acetylcholine by liaoqinmei

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									Jamie Manuell

   Year 2

Pharmacology &
  Therapeutics
  Drugs and the
Autonomic Nervous
      System
Cholinomimetics
  Directly Acting
  acetylcholine



               Directly acting cholinomimetic
Class

               Neurotransmitter. Acts on
MOA            muscarinic or nicotinic
               receptors. in Autonomic NS



Indications



Side Effects



Other
        Bethanecol

               Directly acting cholinomimetic
Class          Parasympathomimetic

               Choline ester, selective for
MOA            muscarinic receptors, then M3.
               Not acted on by
               acetylcholinesterase so long
               lasting. They increase detrussor
               muscle contraction, by stimulating
               post synaptic receptors
               Gut and Bladder stimulation
Indications    postoperatively




               Bronchoconstriction / secretion,
Side effects   salivation




Other
        Pilocarpine



Class          Directly acting cholinomimetics,
               i.e. muscarinic agonist


MOA            Alkaloid, selective for muscarinic
               receptors. Causes constriction of
               the constrictor pupillae muscles of
               the iris, allowing aqueous humour
               to drain into trabecular meshwork.

Indications    Given to treat glaucoma (by
               causing pupil constriction and
               therefore aiding drainage)


Side Effects   Eye irritation, headache and
               browache, blurred vision,
               hypersalivation, may exacerbate
               asthma.

Other          Not with acute iritis, anterior
               uvetis
Cholinomimetics
  Indirectly Acting
     Neostigmine



               Intermediate lasting
Class          Anticholinesterase



               Inhibits acetylcholinesterase by
MOA            addition of a Carbamyl group to
               the enzyme and so increases the
               amount of ACh in the synaptic
               cleft.
               Used IV to reverse the effects of
Indications    non depolarising blockers. Shows
               some selectivity for the NMJ



Side Effects



               Despite selectivity, atropine is
Other          sometimes co-administered to
               block muscarinic effects of the
               drug.
   Physostigmine



               Intermediate acting
Class          anticholinesterase.



               Inhibit AChE so increasing
MOA            amount of ACh in the synaptic
               cleft. Shows selectivity for the
               postganglionic parasympathetic
               junction.
               Used to constrict the pupil, and
Indications    contract the ciliary muscle in
               glaucoma.


               Initial excitation, followed by
Side Effects   depression, followed by
               respiratory depression and
               unconsciousness.

               Tertiary amine, so can cross the
Other          blood/brain barrier. Central
               effects can be combated by
               atropine.
     Ecothiapate



               Long lasting anticholinesterase.
Class          Organophosphorous compound.
               Irreversible inhibitor of AChE, so
MOA            increasing ACh duration of action
               in synaptic cleft. Inhibit enzyme
               by phosphorylation. Enhance
               muscarinic activity. Moderate
               dose affects all autonomic ganglia,
               high doses causes depolarising
               block at ganglia.
               Treatment of glaucoma
Indications



               Bradycardia, breathing problems,
Side Effects   depolarizing neuromuscular block,
               central effects, and possible death
               form peripheral nerve
               demyelination.
               Phosphorylated enzyme is stable,
Other          so new enzymes have to be
               produced to regain function.
Cholinoceptor Antagonists

    Muscarinic Antagonists
         Atropine


               Non selective Muscarinic
Class          cholinoceptor Antagonist
               Bind to receptor, but has no
MOA            intrinsic activity, effect therefor
               depends on previous level of
               supplied tone by the agonist.
               Reduces gastrointestinal motility,
Indications    cardiac arrest, prevent salivation,
               bronchial secretions, protect heart
               from arrhythmias, particularly
               those caused by neuromuscular
               blockers.
               Dry mouth and skin, raised body
Side Effects   temperature, dilatation of pupil,
               relaxation of ciliary msucle (no
               accomodation) urinary retention,
               irritability and hyperactivity

               Different tissues have different
Other          levels of responsiveness. Salivary,
               sweat, bronchial>parietal cells
               production of gastric acid. Treat
               poisoning with anticholinesterase
               drugs
               The one from the belladonna
               alkaloids, found in deadly
               nightshade.
     Hyoscine
  (Scopoloamine)


               Muscarinic Receptor Antagonist,
Class          antiemetic
               Binds to receptor making it
MOA            inaccessible for ACh to activate
               receptor. Emetic actions in vest.
               Nuclei, NTS, vomiting centre, to
               block VC’s activation.
               Used to prevent bronchial
Indications    secretions and salivations.protect
               heart from arrhythmias,
               particularly those caused by
               neuromuscular blockers.
               Prevention of motion sickness,
               parkinson’s disease.

               Dry mouth and skin, raised body
Side Effects   temperature, dilatation of pupil,
               relaxation of ciliary msucle (no
               accomodation) urinary retention,
               irritability and hyperactivity.
               Drowsiness, slow gut movement.
               Different tissues have different
Other          levels of responsiveness. Salivary,
               sweat, bronchial>parietal cells
               production of gastric acid.
     Tropicamide



               Non-selective Muscarinic
Class          cholinoceptor Antagonist




MOA



               Motion sickness, to dilate the pupil
Indications    to view the retina.



               Low exocrine secretions, initial
Side Effects   drop in HR followed by
               tachycardia. Initial excitation,
               then depression, amnesia,
               tranquility, OD – Coma,
               respiratory depression, death

Other
    Ipratropium
      Bromide


               Muscarinic Receptor Antagonist,
Class          parasympatholytic



               Inhaled, blocks action of
MOA            acetylcholine.



               Used in bronchodilation. For
Indications    asthma and obstructive airways
               disease.


               Systemic effects of blocking
Side Effects   muscarinic cholinoceptors.




Other
Cholinoceptor Antagonists

    Nicotinic Antagonists
    Trimetapham


               Short lasting Nicotinic
Class          cholinoceptor Antagonist (also
               known as ganglion blockade)


               Blocks transmission at all
MOA            autonomic ganglia
               (parasympathetic and
               sympathetic).

               Used clinically to provide 2-3
Indications    minutes of hypotension in surgery



               Drop BP, Impaired postural
Side Effects   reflexes, reduced renin secretion,
               decreased GI motility, impotence,
               impaired bladder emptying,
               inhibition of all glands, dilated
               pupils, poor eye reflex, far vision.
               They Do Not block transmission at
Other          nicotinic receptors in the skeletal
               NMJ. Actions depend on the
               prevailing autonomic tone to the
               target organ.
     Hexamethonium




               Nicotinic Receptor Antagonist
Class



               Blocks transmission at all
MOA            autonomic ganglia
               (parasympathetic and
               sympathetic).

               No longer used clinically
Indications



               Drop BP, Impaired postural
Side Effects   reflexes, reduced renin secretion,
               decreased GI motility, impotence,
               impaired bladder emptying,
               inhibition of all glands, dilated
               pupils, poor eye reflex, far vision.

Other
   Non Depolarising
Neuromuscular Blockers
  Tubocurarine



               Non depolarising Neuromuscular
Class          Blockers
               Competitive


               Competitive neuromuscular
MOA            blocking drug, bind to the
               nicAChR but don’t activate it,
               therefore cause neuromuscular
               block. 80-90% must be blocked
               for its actions to take place.
               Surgery to stop reflexes.
Indications



               Partial ganglion block, mild
Side Effects   histamine release, rare
               hypersensitivity



Other
        Atracurium



               Non-depolarising Neuromuscular
Class          blockers



               Like tubocurarine, but with shorter
MOA            duration of action. Competitive
               neuromuscular blocking drug, bind
               to the nicAChR but don’t activate
               it, therefore cause neuromuscular
               block. 80-90% must be blocked
               for its actions to take place.
               preventing reflexes in surgery
Indications


               Reduction in BP, bronchospasm,
Side Effects   tachycardia and apnoea.



Other
Depolarising Neuromuscular
          Blockers
     Suxamethonium




               Depolarising neuromuscular
Class          blockers, causing phase 1 block.
               Binding to and exciting
MOA            postsynaptic nAChR, but for a
               long period of time (mins vs ms
               for ACh). Eventually, APs can no
               longer be produced because
               voltage sensitive Na channels have
               been inactivated – get flaccid
               paralysis.
               Only one used clinically because
Indications    of its rapid onset and short
               duration of action (4 minutes)
               Initial spasms, resulting in
Side Effects   postoperative muscle pain.
               Muscarinic receptor activation
               resulting in bradycardia.
               (prevented by administering
               atropine). Potassium release from
               muscle giving elevated potassium
               levels.
               Some people with funny AChE
Other          may suffer NMB for hours. In
               myasthenia gravis don’t do
               anything because already have v
               few receptors on end plate.
Adrenoceptor Agonists

     Directly Acting
         Adrenaline




               Non selective α&β adrenoceptor
Class          agonist



               Binds to and excites the α&β
MOA            adrenoceptors, giving its actions.



               Acute anaphylactic reactions –
Indications    inhibits mediators of immune
               response. Cardiac stimulant in
               heart block, prolongs action of
               local anaesthetics
               (vasoconstrictor). Maintain bp
               during spinal anaesthesia.
               Decrease blood flow for use in
               glaucoma.
               Tachycardia, arrhythmia,
Side Effects   hypertension, cerebral
               haemorrhage, pulmonary oedema,
               low mucus secretions, tremor due
               to skeletal muscle effects.

Other
        Salbutamol


               Β2 selective Adrenoceptor Agonist
Class



               Stimulates B2 receptors in the SM
MOA            of the lungs and bronchi, inhibits
               the release of bronchoconstrictor
               substances from mast cells.
               Relative resistance to MAO and
               COMT
               Ventolin (asthma inhaler), uterine
Indications    relaxation (if premature labour)



               Arrhythmias, tachycardia,
Side Effects   vasodilation



               Given by aerosol so limited
Other          systemic effects.
        Dobutamine



Class          Positive Chronotrope, Beta 1
               adrenoceptor agonist

MOA            β1 adrenoreceptors are linked to
               adenyl cyclase and their activation
               leads to increased cAMP levels,
               which leads to and increase in
               intracellular calcium and so to an
               increased cardiac force of
               contraction.

Indications    CCF, all shocks, cardiomyopathy,
               cardiac surgery.


Side Effects   Tachycardia and hypertension




Other          Not to be given to tachyarrhythmic
               patients.
    Isoprenaline



               Non selective beta Adrenoceptor
Class          Agonist



               Simple agonist
MOA



               Treatment of heart block,
Indications



               Reflex tachycardia, dysrhythmias.
Side Effects



               Less susceptible to uptake 1 and
Other          MAO than adrenaline.
Phenylephrine

              Selective for a1 receptors
Class


              Simple agonist (Relatively
MOA           resistant to COMT but not
              MAO)


Indications   Nasal decongestant (Drops/PO)
              Myadriatic (Eye Drops)
              Vasoconstrictor (IV)

              Hypertension
Side
Effects

Other
        Clonidine

               Alpha 2 selective Adrenoceptor
Class          Agonist.



               Reduces sympathetic tone via
MOA            central brainstem action within
               baroreceptor pathway, to reduce
               sympathetic outflow.

               Hypertension and migraine.
Indications



               Drowsiness, hypotension
Side Effects



Other
        Ephedrine



               Indirectly acting Adrenoceptor
Class          Agonist. (promote NA release)



               Taken in by uptake 1 and displace
MOA            NA from the vesicles. Also inhibit
               MAO, so displaced NA can
               continue to have a sympathetic
               effect. Potentiate actions of NA.
               When you need more
Indications    sympathomimetic. Useful in
               restoring blood pressure and tissue
               perfusion in cases of shock.
               Decongestant (vasoconstriction of
               nasal BVs)
               Tachycardia, arrhythmias, dry
Side Effects   mouth, cold extremities, anxiety…
               other α & β stimulation issues.


               Watch out for neglecting ither
Other          things such as kidney.
Adrenoceptor agonists

    Indirectly Acting
         Cocaine



               Sympathetic enhancer
Class

               Strongly inhibits the reuptake of
MOA            catecholamines at NAergic
               neurons and thus strongly
               enhances sympathetic activity.



               Abuse. Occaisionally used as a
Indications    topical anaesthetic by ear, nose
               and throat specialists.

               Toxic psychosis, cardiac
Side Effects   arrhythmias, hypertension, and
               stroke. Psychological dependence,
               but no real physical dependence.
               Chronically produces paranoid
               psychosis, vasoconstriction, tissue
               anoxia at sites of injection,
               damage to fetal brain. Withdrawl
               causes a ↓ in motor performance,
               restorable on provision of the
               drug.
     Tyramine

Class         Weak agonist
              Monoamine compound
              derived from the amino acid
              Tyrosine
              Tyramine competes with
MOA           catecholamines for uptake 1,
              displaces NA from storage
              vesicles into cytosol, this leaks
              into the synapse and stimulates
              postsynaptic adrenoceptors,
              also competes for sites on MAO

Indications   Found in the diet (Cheeses)



              When MAO is inhibited
Side          (Antidepressants – Phenelzine)
Effects       indigestion of food containing
              tyramine may result in a
              hypertensive crisis (Cheese
              Reaction)
Adrenoceptor Antagonist
    Propranolol


               Non selective beta adrenoceptor
Class          antagonist. Anxiolytics.



               Acts by antagonism at β-
MOA            adrenoceptors so that excessive
               catecholamine release does not
               produce the usual sympathetic
               responses.

               Hypertension, angina, arrhythmias,
Indications    good at alleviating signs of
               sympathetic arousal, such as
               palpitations, tremor, sweating and
               diarrhoea. Also useful in socially
               anxious people or musicians with
               stage fright.

               Bradycardia, heart failure,
Side Effects   bronchospasm, peripheral
               vasoconstriction


               Not in people with asthma or heart
Other          failure.
          Atenolol



Class          Negative chronotrope and
               inotropes, beta blocker, beta 1
               selective

MOA            Competitive antagonist for beta 1
               adrenoceptor so reduces
               sympathetic innervation of the
               heart. Lowers tachycardia and
               force of contraction.

Indications    Given after MI, hypertension,
               prophylaxis, anti-arrhythmia,
               thyrotoxicosis, glaucoma and
               anxiety

Side Effects   Bronchospasm, bradycardia, heart
               block, hypotension


Other          At high doses loses selectivity, so
               caution for asthmatics. Not in
               bradycardia, hypotension, AV
               block, and CCF
        Labetalol



               Alpha/beta blocker Adrenoceptor
Class          antagonist



               Lowers BP by a reduction of
MOA            peripheral resistance. This is via
               blockade of α1 in blood vessels
               and β1 effects on neurotransmitter
               renin release. No change in HR or
               CO
               Hypertension
Indications



               Postural hypotension
Side Effects



Other
   Phentolamine



               Non selective α antagonist.
Class



               Causes vasodilation and a fall in
MOA            BP due to blockade of α1/2
               receptors.


               hypertension
Indications



               Increased GI motility, so diarrhoea
Side Effects   a common problem.



               Blockade o f α receptors tend to
Other          increase noradrenaline release
               (enhances the reflex tachycardia
               seen with any bp lowering agent)
        Doxazosin


               α1 adrenoceptor antagonist.
Class


               Cause inhibition of α1 adrenoceptor
MOA            mediated vasoconstriction, so
               reducingPVR and venous pressure.
               Also lower LDL, VLDL, and TGA,
               and increase HDL, reducing risk of
               CAD
               Hypertension, (esp with CCF),
Indications    prostate hyperplasia (reduced
               bladder and prostate resistance) and
               CAD.

               Postural hypotension, dizziness,
Side Effects   headache and fatigue, weakness
               palpitations, and nausea.



Other
False Transmitters
     Methyldopa



               False transmitter, antihypertensive
Class          agent
               Taken up by NAergic neurons,
MOA            where decarboxylated and
               hydroxylated to form α methyl
               NA. Not metabolised by MAO, so
               shunts NA from synaptic vesicles.
               Release as NA but less active that
               NA on post α1 receptors, so less
               vasoconstriction, and more active
               on presynaptic α2 receptor.
               Stimulates vasopressor centre to
               inhibit sympathetic outflow.
               Renal blood flow well maintained
Indications    so a good hypertensive in patients
               with renal insufficiency. Good in
               pregnancy as has no adverse
               effects on foetus.
               Dry mouth, sedation, postural
Side Effects   hypotension, male sexual
               dysfunction, liver looks like
               hepatitis. Orthostatic hypotension.

Other
Drugs and the Heart
   & Vasculature
Positive Chronotropes
          Digoxin



               Positive Chronotrope (cardiac
Class          glycoside)
               These act by inhibiting the
MOA            membrane Na+/K+ ATPase pump.
               This raises intracellular Na,
               decreasing Na gradient, meaning
               less Ca is pumped out in the
               Ca/Na exchanger. Ca levels
               increase, and so does force of
               contraction. Stimulation of vagus
               shorten atrial AP. They decrease
               HR, and reduce AV conductance
               for use in arrhythmias.
               Heart failure and superventricular
Indications    arrhythmias.
               At high doses they raise Sym
Side Effects   stimulation causing arrhythmias
               and heart block. Nausea,
               vomitting, visual disturbances, ab
               pain, diarrhoea.
               Contraindications are heart block
Other          and hypokalaemia. Narrow
               therapeutic window. In toxicity,
               potassium supps and anti-
               arrhythmics given.
        Dobutamine



Class          Positive Chronotrope, Beta 1
               adrenoceptor agonist

MOA            β1 adrenoreceptors are linked to
               adenyl cyclase and their activation
               leads to increased cAMP levels,
               which leads to and increase in
               intracellular calcium and so to an
               increased cardiac force of
               contraction.

Indications    CCF, all shocks, cardiomyopathy,
               cardiac surgery.


Side Effects   Tachycardia and hypertension




Other          Not to be given to tachyarrhythmic
               patients.
        Milrinone



Class          Positive chronotrope,
               Phosphodiesterase II inhibitor

MOA            Phosphodiesterase is responsible
               for the degradation of cAMP.
               Inhibiting this raises cAMP levels,
               so contractility and vasodilation

Indications    Severe acute heart failure, resistant
               to other drugs.



Side Effects   Nausea, vomiting, arrhythmias,
               liver dysfunction, abdo pain,
               hypersensitivity.


Other          Developed to get around adverse
               effects with cardiac glycosides.
Negative Chrono and Inotropes
          Atenolol



Class          Negative chronotrope and
               inotropes, beta blocker, beta 1
               selective

MOA            Competitive antagonist for beta 1
               adrenoceptor so reduces
               sympathetic innervation of the
               heart. Lowers tachycardia and
               force of contraction.

Indications    Given after MI, hypertension,
               prophylaxis, anti-arrhythmia,
               thyrotoxicosis, glaucoma and
               anxiety

Side Effects   Bronchospasm, bradycardia, heart
               block, hypotension


Other          At high doses loses selectivity, so
               caution for asthmatics. Not in
               bradycardia, hypotension, AV
               block, and CCF
        Diltiazem



               Negative chronotrope and
Class          inotrope, rate limiting calcium
               channel blocker


               These bind to and inhibit opening
MOA            of the L-type calcium channels.
               This causes arterial vasodilation,
               so reducing cardiac workload. Has
               –ve chronotropic and inotropic
               effects
               Indications are prophylaxis and
Indications    treatment of angina and
               hypertension. Verapamil and
               diltiazem are given for
               supraventricular arrhythmias
               can cause flushing, headaches,
Side Effects   hypotension, ankle swelling, CCF,
               heart block, constipation

               Not to be given to patients in
Other          cardiogenic shock, severe heart
               failure, those taking beta-blockers,
               and severe bradycardia.
        Verapamil



               Negative chronotropes and
Class          inotrope, Rate limiting calcium
               channel blockers


               These bind to and inhibit opening
MOA            of the L-type calcium channels.
               This causes arterial vasodilation,
               so reducing cardiac workload. Has
               –ve chronotropic and inotropic
               effects
               Indications are prophylaxis and
Indications    treatment of angina and
               hypertension. Verapamil and
               diltiazem are given for
               supraventricular arrhythmias
               can cause flushing, headaches,
Side Effects   hypotension, ankle swelling, CCF,
               heart block, constipation

               Not to be given to patients in
Other          cardiogenic shock, severe heart
               failure, those taking beta-blockers,
               and severe bradycardia.
Drugs reducing Preload &
        Afterload
        Ramipril /
        Enalapril

               Ace Inhibitor to reduce preload
Class          and afterload

               These work by preventing
MOA            angiotensin I to Angiotensin II,
               meaning that the ATI receptors in
               the arterioles and in the adrenal
               cortex are not triggered, resulting
               in increased water and sodium
               excretion in the kidney

               Indications are in CVD, such as
Indications    hypertension, post MI, Diabetic
               neuropathy, Progressive renal
               insufficiency, patients at high risk
               of CVD.

               Adverse effects are hypotension,
Side Effects   dry cough and angioedema.



               Not in pregnancy, renovascular
Other          disease, aortic stenosis
        Captopril



               Ace inhibitor
Class

               These work by preventing
MOA            angiotensin I to Angiotensin II,
               meaning that the ATI receptors in
               the aterioles and in the adrenal
               cortex are not triggered, resulting
               in increased water and sodium
               excretion in the kidney
               Indications are in CVD, such as
Indications    hypertension, post MI, Diabetic
               neuropathy & nephropathy,
               Progressive renal insufficiency,
               patients at high risk of CVD.
               Adverse effects are hypotension,
Side Effects   dry cough and angioedema.



               Not in pregnancy, renovascular
Other          disease, aortic stenosis
        Losartan



               Angiotensin receptor blocker
Class



               Cause inhibition at the angitensin
MOA            II receptor, resulting in
               vasodilation with reduction in
               PVR.

               Hypertension
Indications



               Cough, orthostatic hypotension,
Side Effects   dizzyness, headache, fatigue,
               hyperkalaemia and rash.


               Contraindications in breastfeeding,
Other          pregnancy. Caution in renal artery
               stenosis and aortic stenosis.
        Nicorandil



               Organic nitrate (reducing preload
Class          and afterload). Potassium channel
               activator


               Activates potassium channels of
MOA            vascular SM. Potassium flows out
               of the cells causing
               hyperpolarisation. This inhibits
               the influx of calcium, so inhibits
               contraction – hence vasodilation.
               Prophylaxis of angina
Indications



               Headache, cutaneous vasodilation,
Side Effects   nausea and vomiting



               Cardiogenic shock, left ventricular
Other          failure, hypotension.
    Bendrafluazide




               Thiazide diuretic
Class
               These act on the early distal
MOA            tubule. They inhibit the Na/Cl
               cotransporter in the luminal
               membrane. They increase
               secretion of K and protons into the
               collecting ducts, but decrease Ca
               excretion.
               Hypertension, oedema 2ndary to
Indications    CCF, liver disease, or nephrotic
               syndrome. Sometimes for
               prophylaxis of calcium containing
               renal stones.
               Hypokalaemia, hyperuricaemia,
Side Effects   hyponatraemia, hypercalcaemia,
               and metabolic acidosis.


               Shouldn’t be used in those taking
Other          cardiac glycosides, or diabetes
               mellitus (as may cause
               hyperglycaemia). Or in
               hypokalaemia, hyponatraemia, or
               hypercalcaemia.
     Spironalactone




               Aldosterone antagonist.
Class



               Inhibits the sodium retaining
MOA            effects of aldosterone.



               It is useful in heart failure and
Indications    resistant cases of hypertension.



               Can cause hyperkalaemia due to
Side Effects   sodium retention, and steroid like
               side effects like gynaecomastia,
               menstrual disorders, and testicular
               atrophy.
               Due to +ve feedback, more
Other          aldosterone may be produced,
               increasing unwanted side effects.
               Doesn’t prevent aldosterone
               production.
Drugs to control or correct
       Dysrhythmias
        Amiodarone



               Wide spectrum anti-arrhythmic,
Class          potassium channel blockers.



               These are potassium channel
MOA            blockers which prolong cardiac
               action potential duration, and the
               refractory period. It also blocks
               sodium and calcium channels, and
               blocks β and α adrenoceptors.
               For ventricular and
Indications    supraventricular arrhythmias.



               Can cause arrhythmias, thyroid
Side Effects   dysfunction, liver damage,
               pulmonary disorders,
               photosensitivity and neuropathy.

               Not to be given to those with AV
Other          block, sinus bradycardia, or
               thyroid dysfunction
        Diltiazem



               Negative chronotrope and
Class          inotrope, rate limiting calcium
               channel blocker


               These bind to and inhibit opening
MOA            of the L-type calcium channels.
               This causes arterial vasodilation,
               so reducing cardiac workload. Has
               –ve chronotropic and inotropic
               effects
               Indications are prophylaxis and
Indications    treatment of angina and
               hypertension. Verapamil and
               diltiazem are given for
               supraventricular arrhythmias
               can cause flushing, headaches,
Side Effects   hypotension, ankle swelling, CCF,
               heart block, constipation

               Not to be given to patients in
Other          cardiogenic shock, severe heart
               failure, those taking beta-blockers,
               and severe bradycardia.
        Verapamil



               Negative chronotropes and
Class          inotrope, Rate limiting calcium
               channel blockers


               These bind to and inhibit opening
MOA            of the L-type calcium channels.
               This causes arterial vasodilation,
               so reducing cardiac workload. Has
               –ve chronotropic and inotropic
               effects
               Indications are prophylaxis and
Indications    treatment of angina and
               hypertension. Verapamil and
               diltiazem are given for
               supraventricular arrhythmias
               can cause flushing, headaches,
Side Effects   hypotension, ankle swelling, CCF,
               heart block, constipation

               Not to be given to patients in
Other          cardiogenic shock, severe heart
               failure, those taking beta-blockers,
               and severe bradycardia.
          Digoxin



               Positive Chronotrope (cardiac
Class          glycoside)
               These act by inhibiting the
MOA            membrane Na+/K+ ATPase pump.
               This raises intracellular Na,
               decreasing Na gradient, meaning
               less Ca is pumped out in the
               Ca/Na exchanger. Ca levels
               increase, and so does force of
               contraction. Stimulation of vagus
               shorten atrial AP. They decrease
               HR, and reduce AV conductance
               for use in arrhythmias.
               Heart failure and superventricular
Indications    arrhythmias.
               At high doses they raise Sym
Side Effects   stimulation causing arrhythmias
               and heart block. Nausea,
               vomitting, visual disturbances, ab
               pain, diarrhoea.
               Contraindications are heart block
Other          and hypokalaemia. Narrow
               therapeutic window. In toxicity,
               potassium supps and anti-
               arrhythmics given.
          Atenolol



Class          Negative chronotrope and
               inotropes, beta blocker, beta 1
               selective

MOA            Competitive antagonist for beta 1
               adrenoceptor so reduces
               sympathetic innervation of the
               heart. Lowers tachycardia and
               force of contraction.

Indications    Given after MI, hypertension,
               prophylaxis, anti-arrhythmia,
               thyrotoxicosis, glaucoma and
               anxiety

Side Effects   Bronchospasm, bradycardia, heart
               block, hypotension


Other          At high doses loses selectivity, so
               caution for asthmatics. Not in
               bradycardia, hypotension, AV
               block, and CCF
Coronary Vasodilators
        Diltiazem



               Negative chronotrope and
Class          inotrope, rate limiting calcium
               channel blocker


               These bind to and inhibit opening
MOA            of the L-type calcium channels.
               This causes arterial vasodilation,
               so reducing cardiac workload. Has
               –ve chronotropic and inotropic
               effects
               Indications are prophylaxis and
Indications    treatment of angina and
               hypertension. Verapamil and
               diltiazem are given for
               supraventricular arrhythmias
               can cause flushing, headaches,
Side Effects   hypotension, ankle swelling, CCF,
               heart block, constipation

               Not to be given to patients in
Other          cardiogenic shock, severe heart
               failure, those taking beta-blockers,
               and severe bradycardia.
        Verapamil



               Negative chronotropes and
Class          inotrope, Rate limiting calcium
               channel blockers


               These bind to and inhibit opening
MOA            of the L-type calcium channels.
               This causes arterial vasodilation,
               so reducing cardiac workload. Has
               –ve chronotropic and inotropic
               effects
               Indications are prophylaxis and
Indications    treatment of angina and
               hypertension. Verapamil and
               diltiazem are given for
               supraventricular arrhythmias
               can cause flushing, headaches,
Side Effects   hypotension, ankle swelling, CCF,
               heart block, constipation

               Not to be given to patients in
Other          cardiogenic shock, severe heart
               failure, those taking beta-blockers,
               and severe bradycardia.
   Glyceryl
  Trinitrate
              Organic Nitrates
Class


              Release NO which activates
MOA           Guanylate cyclase causing
              more cGMP and more Ca
              storage in the SR, hence
              Venodilation which reduces
              preload and therefore SV and
              CO, also coronary vessel vaso-d

Indications   Angina



              Venodilation causes Postural
Side          hypotension, dizziness, syncope
Effects       and reflex tachy. Arterial
              dilation causes throbbing
              headaches and flushing

Other
        Minoxidil


               K+ channel opener
Class
               Potent vasodilator acting on
MOA            arteries and arterioles by opening
               potassium channels in SM and
               causing hyperpolarisation.


               Used in hypertension control in
Indications    pregnancy




               In the absence of β blockade it
Side Effects   causes reflex tachycardia.




Other
        Doxazosin


               α1 adrenoceptor antagonist.
Class


               Cause inhibition of α1 adrenoceptor
MOA            mediated vasoconstriction, so
               reducingPVR and venous pressure.
               Also lower LDL, VLDL, and TGA,
               and increase HDL, reducing risk of
               CAD
               Hypertension, (esp with CCF),
Indications    prostate hyperplasia (reduced
               bladder and prostate resistance) and
               CAD.

               Postural hypotension, dizziness,
Side Effects   headache and fatigue, weakness
               palpitations, and nausea.



Other
Vasoconstrictors
  Sumitriptan


               Agonist at 5HT1D receptors
Class
               Causes vasoconstriction at some
MOA            large arteries and inhibits
               trigeminal nerve transmission,



               Used to treat migraine attacks
Indications



               Sensation of tingling, heat, chest
Side Effects   tightness



               Contraindicated in patients with
Other          CAD as it causes coronary
               vasoconstriction, hepatic
               impairment, pregnancy and
               breastfeeding.
Anti-Thrombotic &
  Anticoagulants
Thrombolytics (Fibrinolytics)
  Streptokinase



               Tissue plasminogen activator
Class
               This forms a complex with and
MOA            activates plasminogen into
               plasmin, a fibrinolytic enzyme



               Life threatening venous
Indications    thrombosis, pulmonary embolism,
               arterial thromboembolism, and
               acute MI.


               Nausea, vomiting and bleeding.
Side Effects   Derived form streptococcus,
               therefore antigenic. Repeated
               administration could result in
               anaphylaxis.

               Not for use in recent haemorrhage,
Other          trauma, surgery or any form of
               Cerebrovascular disease.
        Alteplase



               Tissue type plasminogen activator
Class
               Binds with and activates
MOA            plasminogen into plasmin, which
               breaks down fibrin in a clot.



               Useful as a fibrinolytic if the
Indications    antigenic streptokinase has already
               been administered once, as it is
               non antigenic. MI, Pulmonary
               embolism

               Nausea, vomiting, and bleeding
Side Effects



               Same as streptokinase, ie any
Other          patient who has recently suffered a
               trauma likely to have required clot
               formation.
Anticoagulants
        Warfarin



               Vitamin K antagonist
Class
               Vitamin K is vital in the post
MOA            transcriptional γ-carboxylation of
               glutamic acid residues of
               prothrombin (factor II) and
               clotting factors VII, IX, and X by
               the liver. This stops clotting
               cascade
               Warfarin can be used in treatment
Indications    of DVT and pulmonary embolism,
               prophylaxis of embolisation in
               atrial fibrillation and rheumatic
               disease and in patients with
               prosthetic heart valves
               haemorrhage
Side Effects

               Warfarin only affects new factors
Other          so takes 72 hrs to take effect.
               Should not be used in Cerebral
               thrombosis, peripheral arterial
               occlusion, peptic ulcers,
               hypertension, pregnancy
           Heparin



               Anticoagulant
Class
               Heparins work by activating
MOA            antithrombin III, which inactivates
               thrombin and factor X. It also
               inhibits platelet aggregation


               Heparin and LMWH given in
Indications    thrombosis and pulmonary
               embolism, MI, prophylaxis against
               PO DVT and pulmonary embolism
               in high risk patients.

               haemorrhage
Side Effects



               Action is immediate so can be
Other          used in emergency. Should not be
               used in haemophilia,
               thrombocytopenia, or peptic
               ulcers.
Anti-Platelet Drugs
              Aspirin


               Cyclo-oxygennase
Class          inhibitor.acetylates the active site.
               This inhibits the COX enzymes,
MOA            which in turn inhibit production of
               thromboxane A2, preventing
               platelet aggregation. Also inhibits
               PGE2, making it an analgesic.
               COX-2 is proinflammatory.
               In overdose can uncouple
Indications    oxidative phosphorylation, causing
               metabolic acidosis.
               Stomach ulcers,
Side Effects   bronchoconstriction. Arachidonic
               acid either forms PGs with COX,
               or Leukotrienes with
               lipoxygenase. LT4 is a powerful
               bronchoconstrictor, more produced
               if COX inhibited. Asthmatics
               vulnerable. Reduced creatinine
               clearance, possible nephritis. Bad
               because effects COX-1 200 fold
               more than COX-2.
               Effects vary according to dose.
Other          Asthmatics can’t take them.
               Aspirin also displaces wafarin
               from plasma causing bleeding, as
               warfarin normally 5% unbound.
        Clopidigrel



               Anti platelet aggregation drug.
Class
               Clopidogrel inhibits activation of
MOA            the IIb/IIIa receptor on the surface
               of platelets, required for
               aggregation to occur.


               Used if patient truly allergic to
Indications    aspirin. Secondary prevention of
               CVD.



               Haemorrhage, ab discomfort,
Side Effects   nausea and vomiting.




Other
        Abciximab



               Glycoprotein IIb/IIIa inhibitor
Class
               It is an antibody fragment
MOA            antagonist of the glycoprotein
               IIb/IIIa receptor on platelets. This
               prevents aggregation.

               Used if problems with other ones.
Indications    Ischaemic cardiac complications in
               open heart surgery. Short term
               prevention of MI in unstable
               angina.

               Haeorrhage, nausea, vomiting
Side Effects   hypotension.



               Single administration because it is
Other          antigenic, potential anaphylaxis if
               second administration
Statins
 Simvastatin

              HMG-CoA Reductase Inhibitor
Class
              Catalyses the enzyme that is the
MOA           rate limiting step in Cholesterol
              synthesis in the Liver, the fall in
              circulating Cholesterol then
              causes up regulation of LDL
              receptors on hepatocytes cell
              surfaces, also reduces
              circulating VLDL’s and TG’s

Indications   Hyperlipidaemia

              GI upsets
Side          CNS effects (Dizziness, blurred
Effects       vision, headache)
              Cause of abnormal LFT’s
              Myalgia if used with Fimbrates
              Stabilizes atherosclerotic
Other         plaques and reduces
              inflammatory cell migration
              into plaques
NSAIDS
              Aspirin


               Cyclo-oxygennase
Class          inhibitor.acetylates the active site.
               This inhibits the COX enzymes,
MOA            which in turn inhibit production of
               thromboxane A2, preventing
               platelet aggregation. Also inhibits
               PGE2, making it an analgesic.
               COX-2 is proinflammatory.
               In overdose can uncouple
Indications    oxidative phosphorylation, causing
               metabolic acidosis.
               Stomach ulcers,
Side Effects   bronchoconstriction. Arachidonic
               acid either forms PGs with COX,
               or Leukotrienes with
               lipoxygenase. LT4 is a powerful
               bronchoconstrictor, more produced
               if COX inhibited. Asthmatics
               vulnerable. Reduced creatinine
               clearance, possible nephritis. Bad
               because effects COX-1 200 fold
               more than COX-2.
               Effects vary according to dose.
Other          Asthmatics can’t take them.
               Aspirin also displaces wafarin
               from plasma causing bleeding, as
               warfarin normally 5% unbound.
        Ibuprofen



               NSAID, COX-2 antagonist
Class
               Works as a competitive substrate
MOA            for the COX-2 enzyme, preventing
               the arachidonic acid conversion by
               COX-2 into prostaglandins, and
               prostacyclins.

               Mainly for high risk GI patients
Indications    who would get stomach ulcers
               from Aspirin. Drug of choice for
               inflammatory joint disease


               Very few
Side Effects



Other
        Celecoxib



               This is a selective COX-2 inhibitor
Class
               Selective but expensive COX-2
MOA            inhibitor. Used for high risk GI as
               no COX-1 side effects. Also less
               effect on nephrotoxicity.


               High risk GI anti-inflammatory
Indications



Side Effects



               Contraindicated in Inflammatory
Other          bowel disease.
Diuretics
         Mannitol



               An osmotic diuretic.
Class
               Freely filtered at the glomerulus,
MOA            but only partially reabsorbed.
               Means that water leaves tubule
               under osmosis, and more sodium
               is excreted, and there is less free
               reabsorption of water.
               Raised intracranial and intrtaocular
Indications    pressure.



               Chills and Fever
Side Effects



               Contraindicated in congestive
Other          cardiac failure, and pulmonary
               oedema.
  Acetazolamide



               Carbonic anhydrase inhibitor.
Class          Weak diuretics

               Acts in the proximal tubule to
MOA            prevent the usual removal of Na+
               and HCO3-, water follows.
               Prescence of Na+ in the distal
               tubule also increases excretion of
               K+.
               Not normally used as diuretics but
Indications    of value in the treatment of
               glaucoma.



               Loss of carbonate can result in
Side Effects   metabolic acidosis.




Other
          Frusemide


Class         Loop diuretic – powerful diuretic

MOA           Act on thick ascending segment of
              the L of H. Inhibit the Na+, K+,
              2Cl- cotransporter in the luminal
              membrane. This dilutes the
              medullary interstitium and reduces
              the concentrating power in the
              collecting duct. ↑ delivery of Na to
              distal tubule activates Na/K
              exchanger. Gives ↑ urine, ↑
              excretion of Na, K, Cl, Ca, Mg

Indications   Acute pulmonary oedema, oedema
              due to heart failure, liver disease,
              renal disease, hypercalcaemia,
              hyperkalaemia, Acute renal failure

Side          Metabolic acidosis, hypokalaemia,
              loss of Ca, Mg, hypovolaemia,
Effects
              hypotension, nausea, deafness,
              allergies.

Other
Bendrofluazide



Class          Thiazide


MOA            Inhibition of Na and Cl
               reabsorption in the early distal
               tubule. ↑ solute ↓ reabsorption of
               water, ↑ volume, Na, K, Cl, and
               Mg. Reduced loss of Ca. Also
               vasodilation and ↓ insulin
               production due to opening of K
               channels.

Indications    Congestive Heart failure,
               hypertension, Idiopathic
               hypercalcaemia, nephrogenic
               diabetes insipidus

Side Effects   Hypokalaemia, alkalosis,
               hypperglycaemia, uric acid
               retention (gout). Allergies,
               hyponatraemia.

Other
Spironalactone



Class          Aldosterone antagonists,
               potassium sparing diuretic.

MOA            This is a competitive antagonist at
               aldosterone receptors, ↓ Na
               reabsorption, and ↓ potassium and
               proton secretion. Mild diuresis,
               excretion of 2-3% of Na.

Indications    Heart failure and resistant cases of
               hypertension



Side Effects   Hyperkalaemia due to sodium
               retention, and steroid like effects
               like gynaecomastia, menstrual
               disorders, and testicular atrophy.

Other
        Amiloride



Class          Potassium sparing diuretic,
               Sodium Channel Blocker, distal
               tubule

MOA            These block sodium reabsorption
               by the principal cells, thus
               reducing the potential difference
               across the cell, and ↓ potassium
               secretion

Indications    With K losing diuretics to prevent
               K loss. Primary and secondary
               hyperkalaemia.


Side Effects   Better tolerated than
               spironalactone. Hyperkalaemia,
               hyponatraemia, GI disturbances.


Other
Anti-Emetics
 Promethazine
  (Remember
Promet-h-azine)

               Anti-emetic (phenothiazine
Class          derivative) H1>M>D2

               Acts as a competitive antagonist at
MOA            histaminergic (H1), cholinergic
               (M), and dopaminergic receptors.
               (Mostly H1). It acts centrally
               (Labyrinth, NTS, vomiting centre)
               to block activation of the vomiting
               centre.

               Motion sickness (prophylaxis),
Indications    labyrinth disorders (ie Meniere’s
               disease), morning sickness, pre
               and post operatively. Sedative and
               anti muscarinic actions are also
               useful.

               Dizziness, fatigue, Tinnitus,
Side Effects   sedation, Excitation in excess,
               convulsions, Antimuscarinic side
               effects.


Other
 Metoclopramide
   (Remember
metoclopromi-d-e)

Class          Anti-emetic. Receptor antagonist.
               D2>>H1>>M

MOA            Acts on D2 receptors, especially
               centrally at the central trigger
               Zone. Acts in the GI tract ↑ in SM
               motility, ↑ in Gastric emptying.

Indications    Nausea and vomiting associated
               with uraemia, radiation sickness,
               GI disorders, Cancer
               chemotherapy like cisplatin.

Side Effects   Drowsiness, dizziness, anxiety,
               extrapyramidal reactions, no anti-
               psychotic reactions unlike other D
               antagonists.

Other          Competes with other drugs.
               Adsorption and effectiveness of
               digoxin is ↓. Accelerate GI may
               cause nutrient deficiency.
      Hyoscine
   (Scopolamine)


               Muscarinic Receptor Antagonist,
Class          antiemetic
               Binds to receptor making it
MOA            inaccessible for ACh to activate
               receptor. Emetic actions in vest.
               Nuclei, NTS, vomiting centre, to
               block VC’s activation.
               Used to prevent bronchial
Indications    secretions and salivations.protect
               heart from arrhythmias,
               particularly those caused by
               neuromuscular blockers.
               Prevention of motion sickness,
               parkinson’s disease.

               Dry mouth and skin, raised body
Side Effects   temperature, dilatation of pupil,
               relaxation of ciliary msucle (no
               accomodation) urinary retention,
               irritability and hyperactivity.
               Drowsiness, slow gut movement.
               Different tissues have different
Other          levels of responsiveness. Salivary,
               sweat, bronchial>parietal cells
               production of gastric acid.
  Ondansetron
   (Remember
 ondan-s-etron)

Class          Anti emetic, 5HT3 (Serotonin)
               receptor antagonist.

MOA            Blocks 5HT3 receptors in visceral
               afferents and central trigger zone



Indications    Anti emetic in chemotherapy
               induced vomiting, especially
               cisplatin. Radiotherapy induced
               sickness, PO nausea and vomiting.

Side Effects   Headache, sensation of flushing
               and warmth, increased large bowel
               transit time (constipation) due to
               5HT3 receptor block.

Other
  Drugs used for
Gastric & Duodenal
       Ulcers
Antimicrobials
 Metronidazole



               Antiprotozoal and antibacterial
Class          against anaerobic bacteria.
               Antibiotic to eliminate
               helicobacter pylori – bactericidal.
               Metabolised to an intermediate
MOA            that inhibits bacterial DNA
               synthesis and degrades existing
               DNA. Selective because
               intermediate form is not produced
               in mammalian cells.
               Helicobacter pylori eradication in
Indications    peptic ulcer sufferers.



               Mild headache and GI disturbance.
Side Effects   ADRs with alcohol



               Not to pregnant women
Other
  Amoxycillin


               Broad spectrum Penicillin
Class          antibiotic.

               Inihibit bacterial wall synthesis.
MOA            They bind to penicillin binding
               proteins. This results in inhibition
               of peptide crosslinking within the
               cell wall, and indirect activation of
               autolytic enzymes, resultant lysis.
               Broad spectrum so loads of
Indications    applications. Used in eradication
               of helicobacter pylori in peptic
               ulceration.


               Specific and safe but possible
Side Effects   hypersensitivity reactions inc.
               rashes and anaphylaxis. Diarrhoea
               common, neurotoxicity at ↑ CSF
               levels.

               Not for known hypersensitivity
Other          sufferers. Resistance can be due to
               microbial production of a β-
               lactamase enzyme which breaks
               the β-lactam ring of penicillins.
Clarithromycin



               Macrolide.
Class          Bactericidal/bacteriostatic.

               They bind to the bacterial
MOA            ribosome, preventing the
               translocation movement of the
               ribosome along mRNA. Inhibits
               translocation of bacterial tRNA.

               Good against gram +ve bacteria
Indications    and spirochaetes. Haemophilus
               influenzae, mycobacterium avium
               cellulare, and helicobacter pylori.


               GI disturbance
Side Effects



               Resistance due to alteration of
Other          binding site of ribosome.
Inhibitors of Gastric Acid
          Secretion
    Omeprazole


               Proton pump inhibitor in Peptic
Class          ulceration.
               Prodrug converted in acidic pH to
MOA            sulphonamide, which binds
               covalently to the suphydryl groups
               on H+/K+ATPase responsible for
               gastric acid secretion.
                Inihibit acid secretion by >90%.
               Is a weak base so attracted to
               acidic areas like cannaliculi of
               parietal cells. Prevents widespread
               actions.
               Peptic ulceration, reflux
Indications    oesophagitis, H2 receptor
               antagonist resistant patients.

               GI upset, nausea, headaches.
Side Effects   Potential gastric atrophy



Other
        Cimetidine
        ranitidine


               H2 receptor antagonists.
Class
               Block actions of histamine on
MOA            parietal cells



               First line treatment of GORD and
Indications    peptic ulcer disease.




               Dizziness, fatigue, gynaecomastia,
Side Effects   and rash



               Less effective than PPIs at healing
Other          ulcers (60% ↓ in acid secretion).
               Inhibits p450 enzymes, so not to
               be administered with warfarin,
               phenytoin, and theophylline.
Cytoprotective Drugs
    Sucralfate


               Polymer containing aluminium
Class          hydroxide and sucrose octa-
               sulphate. Cytoprotective drugs.
               It acquires a strong negaitve
MOA            charge in acidic environment.
               Binds to +ve proteins forming a
               protective gel over the ulcer, not
               allowing peptins or acids to
               damage. ↑ mucus, PGs and HCO3-
               , ↓ helicobacter pylori.
               Peptic ulcer.
Indications


               Can cause constipation and may ↓
Side Effects   absorption of many other drugs (ie
               antibiotics) through stomach wall.



Other
 Bizmuth chelate




               Polymer structure as with
Class          sucralfate



               Forms protective gel over ulcer
MOA


               Peptic ulcer disease
Indications



               Constipation, ↓ absorption of other
Side Effects   drugs through wall.




Other
  Misoprostol



               PGE1 analogue
Class


               Mimics actions of PGE1 which
MOA            stimulates mucus secretions in the
               gastroduadenal lining.


               Peptic ulcer disease
Indications



               Diarrhoea, uterine contractions, ab
Side Effects   cramps.



               May be co prescribed with
Other          NSAIDs to counteract their anti
               PG effect chronically and prevent
               peptic ulcers.
      Drugs for
Inflammatory Bowel
       Disease
Glucocorticoids
  Hydrocortisone




               Natural glucocorticoid with some
Class          mineralocorticoid actions.
               Move into cells where they
MOA            activate glucocorticoid receptors.
               These receptors are translocated to
               the DNA where they cause
               transcription of corticosteriod
               responsive genes. These have
               diverse effects on target tissues.
               See prednisolone. Can also turn
               off genes (reduced antigen
               presentation, reduced production
               of adhesion molecules, COX, NO,
               cytokines such as IL-1 and TNFα)
               IBD (crohn’s, Ulcerative colitis),
Indications    Anti-inflammatory,
               immunosuppression
               Cushing like appearance. See
Side Effects   separate slide. Adrenal
               suppression and atrophy.
               Withdraw slowly to avoid adrenal
Other          insufficiency crisis. Normal
               markers of infection suppressed so
               must be aware.
  prednisolone



               Synthetic glucocorticoid. Anti-
Class          inflammatory,
               immunosuppressant.
               These induce lipocortin which
MOA            inhibits the conversion of
               membrane phosphilipid to
               arachidonic acid by phospholipase
               A2. Leukotrienes and prostanoids
               are therefore not produced,
               suppressing inflammation and
               chemotaxis of immune agents.
               IBD (crohn’s, UC)
Indications

               As for hydrocortisone.
Side Effects



Other
 Budesonide

              Synthetic glucocorticoid. Anti-
Class         inflammatory,
              immunosuppressant.
              Budesonide in comparison with
MOA           prednisolone has been
              associated with fewer bone
              density losses and unlike other
              corticosteroids has little
              influence on the hypothalamic-
              pituitary-adrenal axis which
              also limit the need of tapering
              before discontinuation. Overall,
              it has a lower incidence of
              systemic manifestations than
              similar medications.

Indications   IBD (crohn’s, UC)


              As for hydrocortisone.
Side
Effects

Other
Aminosalicylates
Sulfasalazine



               Aminosalicylate
Class

               Broken down in the gut to 5-ASA.
MOA            These scavenge free radicals.
               Fewer anti-inflammatory actions
               and no immunosuppressive ones.
               AI actions are ↓ inflammatory
               cytokine production, ↓ PG and LT,
               ↓ leukocyte infiltration. Activated
               by gut flora from moiety.
               Maintain remission and prevent
Indications    relapse of inflammatory bowel
               conditions

               Sulfaphrindine (non active part of
Side Effects   sulfasalazine) reaponsible for
               Nausea, vomiting, headache and
               rashes., hypospermia, anorexia

               Not to people with renal
Other          impairment, or salicylate
               intolerance
    Mesalazine



               Aminosalicylate (5-ASA)
Class


               Same as sulfasalazine, but without
MOA            nasty side effects.



               Inflammatory bowel syndrome.
Indications



               Few, no sulfapyridine to worry
Side Effects   about.




Other
Immunosupressants
 Azothioprine



              Immunosuppressive
Class
              Activated by gut flora to 6
MOA           metcaptopurine, a purine analogue,
              interferes with DNA synthesis.
              Inihibits cell replication, cell and
              antibody mediated immune
              reponses, lymphocyte proliferation,
              mononuclear cell infiltration,
              synthesis of antibodies.
              Inflammatory bowel syndrome.
Indications   Used to maintain remission in CD


Side
Effects

              More effective than other
Other         immunosuppressives so can get
              away with fewer GCs. Not good in
              gout treatment because it is
              metabolised by Xanthine Oxidase
              (target of gout treatment).
Anti-TNFα
     Imfliximab



Class


               Crohn’s is a type 1 autoimmune
MOA            response. TNF-α plays an
               important role in pathogenesis.
               Anti reduces activation of anti-
               TNFα receptors in the gut.
               Promotes apoptosis of activated T-
               cells.
               Inflammatory bowel disease and
Indications    other Th1 mediated AI diseases


               ↑ incidence of extra pulmonary
Side Effects   TB. Worsening of heart failure,
               can be immunogenic, specialist
               use.

               1 IV every 8 weeks
Other
  Drugs used in
Respiratory Disease
        Salbutamol


               Β2 selective Adrenoceptor Agonist
Class



               Stimulates B2 receptors in the SM
MOA            of the lungs and bronchi, inhibits
               the release of bronchoconstrictor
               substances from mast cells.
               Relative resistance to MAO and
               COMT
               Ventolin (asthma inhaler), uterine
Indications    relaxation (if premature labour)



               Arrhythmias, tachycardia,
Side Effects   vasodilation



               Given by aerosol so limited
Other          systemic effects.
   salmeterol



               β-2 receptor agonist
Class

               Stmiulation of β2 receptors in the
MOA            airway SM leads to rise in
               intracellular cAMP levels and SM
               relaxation. Also prevent mast cell
               activation. This has potent β2
               effects but limited β1 actions, so
               fewer cardiac side effects.
               Alone to treat mild asthma and
Indications    bronchospasm, but more often
               with corticosteroids

               Fine tremor, tachycardia and
Side Effects   hypokalaemia after high doses.




               Not in hyperthyroidism, CVD,
Other          arrhythmias.
  aminophylline



               Phosphodiesterase inhibitor
Class

               Acts by raising the cAMP levels
MOA            (which relaxes SM), by inhibiting
               phosphodiesterase, the enzyme
               responsible for converting cAMP
               to AMP. Aminophylline is the IV
               xanthine used in severe asthma
               attacks.
               Status asthmaticus
Indications

               Nausea, vomiting, tremor,
Side Effects   insomnia, and tachycardia.




               Not often used because PDE exists
Other          everywhere in the body, cAMP is
               very common. Not for use in
               CVD, hypertension, hepatic
               impairment, have many drug
               interactions.
    Ipratropium
      Bromide


               Muscarinic Receptor Antagonist,
Class          parasympatholytic



               Inhaled, blocks action of
MOA            acetylcholine.



               Used in bronchodilation. For
Indications    asthma and obstructive airways
               disease.


               Systemic effects of blocking
Side Effects   muscarinic cholinoceptors.




Other
Drugs of Abuse
Opiates
        Morphine


               Strong opioid analgesic
Class
               Acts on opiate receptors. These
MOA            exist in the dorsal horn relay
               neurones, descending inhibitory
               NA fibres from the brainstem, and
               descending seratonergic fibres
               from the brainstem, all of which
               block sensory information from
               travelling in the dorsal column,
               leading to analgesia.
               Drug of choice for severe pain in
Indications    terminal care.
               Drowsiness and sedation – initial
Side Effects   excitement followed by sedation
               and coma (in OD). ↓ in sensitivity
               of resp centre to CO2 leading to
               shallow and slow respiration,
               tolerance and dependence,
               suppression of cough (antitussive),
               vomiting due to CTZ stimulation,
               pupillary constriction due to
               stimulation of parasympathetic 3rd
               CN nucleus, hypotension and ↓
               CO, due to reduced hypothalamic
               sympathetic outflow.
               Bronchospasm, flushing and
               arteriolar dilation due to histamine
               release.
         Heroin
               (dimorphine)


                 Opioid drug of abuse, sometimes
Class            analgesic

                 Acts on opioid receptors. Twice
MOA              as potent as morphine owing to its
                 greater penetration of the BBB,
                 metabolised to morphine in the
                 body.


                 Severe pain, post operative, MI
Indications      and acute pulmonary oedema. Not
                 used as much as morphine due to
                 added euphoria and dependence.
                 Causes less nausea and
Side Effects     hypotension than morphine, but
                 more euphoria.




Other
         codeine



               Weak opioid analgesic
Class

               Acts on opioid receptors. Only
MOA            1/12 analgesic potency of
               morphine.




               Mild to moderate pain, Anti-
Indications    tussive and anti diarrhoeal effects
               (taking advantage of side effects).

               Nausea and constipation
Side Effects




Other
    methadone



               Long acting opioid analgesic.
Class

               Acts on opioid receptors.
MOA            Withdrawl symptoms are more
               prolonged but less intense than
               withdrawl from heroin.



               Weaning opioid addicts from their
Indications    addiction


               As opioid general ADRs, but not
Side Effects   too marked.




Other
Opiate Receptor Antagonists
        Naloxone



               Opiate receptor antagonist
Class

               Acts as a competitive inhibitor at
MOA            opiate receptors.




               Used in heroin or other opioid
Indications    overdose IV, along with
               respiratory support.

Side Effects




Other
Reuptake Inhibitors
         Cocaine



               Sympathetic enhancer
Class

               Strongly inhibits the reuptake of
MOA            catecholamines at NAergic
               neurons and thus strongly
               enhances sympathetic activity.



               Abuse. Occaisionally used as a
Indications    topical anaesthetic by ear, nose
               and throat specialists.

               Toxic psychosis, cardiac
Side Effects   arrhythmias, hypertension, and
               stroke. Psychological dependence,
               but no real physical dependence.
               Chronically produces paranoid
               psychosis, vasoconstriction, tissue
               anoxia at sites of injection,
               damage to fetal brain. Withdrawl
               causes a ↓ in motor performance,
               restorable on provision of the
               drug.
MethyleneDio
xyMethAmpet
   amine
               (ecstasy)
               Serotonin (5-hydroxytryptamine)
Class          reuptake inhibitor

               Release of monoamines, inhibition
MOA            of monoamine uptake. Especially
               acts on serotonergic neurons,
               potentiating 5-HT.



               Drug of abuse
Indications


               Stimulant and hallucinogenic
Side Effects   properties, euphoria, arousal, and
               perceptual disturbances are
               common. Feelings of euphoric
               empathy so that social barriers are
               reduced. Withdrawl like
               amphetamines. Toxicity results in
               hyperthermia, exhaustion,
               dehydration. Seratonergic
               neurodegeneration chronically.
Alcohol
        Ethanol
               Alcohol
Class

               Acts as a volatile anaesthetic agent
MOA            producing general CNS
               depression. Cellular mechanisms
               involve inhibiting calcium entry,
               and so reducing NT release, as
               well as potentiation of GABA
               transmission.
               Antidote to methanol poisoning.
Indications
               Physical and psychological
Side Effects   dependence occur. Withdrawl
               hangover. Late stage involves
               delirium, tremor, hallucinations,
               and confusion. Acute toxicity
               causes ataxia, nystagmus, coma,
               resp. depression, and death.
               Chronically causes
               neurodegeneration (worsened by
               vit deficiency), dementia, liver
               damage, pancreatitis, and
               accompanying depression. ↓
               vasopressin secretion causing
               diuresis and delayed parturition at
               term due to inhibitory effects at
               the hypothalamus. Action at ant.
               Pit. Causes ACTH production
               leading to adrenal steroid
               production. This leads to
               feminisation in males. Helped by
               enhanced testosterone inactivation
               in the liver.
Ethanol Aversion Therapy
    Disulfiram



Class

               Inhibits action of Acetaldehyde
MOA            dehydrogenase and so inhibits
               conversion of Acetaldehyde to
               Acetic acid



               Ethanol aversion therapy
Indications

               flushing of the skin, accelerated
Wanted         heart rate, shortness of breath,
Side Effects   nausea, vomiting, throbbing
               headache, visual disturbance,
               mental confusion, postural fainting
               and circulatory collapse

Other
Antimicrobial Drugs
Drugs which interfere with the
 synthesis / action of Folate
  Sulfamethoxazole




               Sulfonamide – anti folate
Class

               Folate necessary to make DNA.
MOA            Man has uptake processes, bacteria
               have to produce theirs, and need p-
               aminobenzoic acid. Sulfonamide
               is an analogue of this, meaning it
               isn’t produced, so bacteria can’t
               replicate. Bacterostatic, then host
               system can erradicate infection.
               Not used much except in co-
Indications    trimoxazole.

               Nausea &vomiting, headache,
Side Effects   mental depression. Potential
               severe: hepatitis, hypersensitivity,
               bone marrow suppression.


               Widespread resistance to these
Other          drugs.
   Trimethoprim



               Folate antagonist.
Class

               Inhibits Dihydrofolate reductase,
MOA            an enzyme which is more sensitive
               in bacteria to interference. DNA is
               stopped from replicating.



               Urinary and respiratory tract
Indications    infections.


               Nausea & vomiting, skin rashes,
Side Effects   hypersensitivity




Other
  Co-trimoxazole




               Folate buggerer – sequential
Class          blockade. (actually trimethoprim
               and sulfamethoxazole)
               Trimethoprim blocks
MOA            dihydrofolate reductase in bacteria,
               blocking cell replication.
               Sulfamethoxazole affects folate
               synthesis (earlier in same
               pathway). They potentiate one
               another, meaning that1/10th the
               dose is needed.
               Infections with pneumocystis
Indications    carinii, which causes pneumonia in
               AIDS patients. Used in high
               doses.
               Combination of effects from
Side Effects   trimethoprim and
               sulfamethoxazole.



Other
Drugs which interfere with the
  synthesis of Peptidoglycan
     Penicillins


               β-lactam antibiotics. Cell wall
Class          targetting
               Has a thiazolidine ring linked to a
MOA            β-lactam ring. Prevents
               transpeptidisation. Antibiotic
               bonds to normal peptidoglycan
               which then can’t join with others
               to form a lattice. Bacterium open
               to osmotic pressures so lyses.

               Do not cross BBB.
Indications
               Hypersensitivity (antigenic), skin
Side Effects   rashes and fever but can be
               anaphylactic shock. Can also
               interfere with gut flora causing GI
               disturbance.

               Amidaze and β-lactamases can
Other          destroy the anti-biotic, normal
               defence mechanism. Using a β-
               lactamase inhibitor (clavulanic
               acid) normally gets round this
               problem. Other resistance stems
               from impermeability of the outer
               membrane, and modified penicillin
               binding sites.
        cefotaxime



               Cephalosporin. Peptidoglycan
Class          targetting.

               Like penicillins targets the
MOA            peptidoglycan synthesis. Can
               combine two or more
               synergistically which target
               different binding sites to ↑
               efficiency.


               Meningitis due to G-ve intestinal
Indications    bacteria


               Hypersensitivity as seen in
Side Effects   penicillins. Nephrotoxicity,
               alcohol intolerance, diarrhoea.



               Nearly all gram –ve bacteria
Other          possess β-lactamase, very effective
               against cephalosporins.
Drugs which affect Bacterial
     Protein Synthesis
   tetracyclin



               Broad spectrum antibiotics
Class

               Inhibit bacterial protein synthesis.
MOA            Actively transported into bacteria
               where they interfere with protein
               synthesis. Competes with tRNA
               for the binding site, doesn’t kill,
               just stops growth.


Indications


               Form an insoluble complex with
Side Effects   metal ions, so work best without
               food. GI disturbances common,
               because chelate calcium can stain
               teeth and lead to bone deformities.
               Some (doxycycline) produce
               sensitivity to sunlight.
               Resistance based around
Other          tetracyclines being transported out
               of the cell, but also on alterations
               of the target, the bacterial
               ribosome.
chloramphenicol



               Broad spectrum ribosome binding.
Class

               Inhibits protein synthesis by
MOA            reversibly binding to the 50S
               subunit of the ribosome and
               inhibiting transpeptidation
               (formation of peptide bonds).
               Both bactericidal and
               bacteriostatic

               Broad spectrum. V. toxix so
Indications    reserved for life threatening
               infections such as typhoid fever
               and meningitis.
               Depression of the bone marrow
Side Effects   leading to pancytopenia. Not in
               babies because inadequate
               excretion can result in grey baby
               syndrome (40% mortality).

               Not to pregnant women or
Other          neonates. Resistance due to
               choloramphenicol acetyl-
               transferase, plasmid mediated so
               resistance easily transferred
    gentamicin



               Aminoglycosides
Class
               Inhibit bacterial protein synthesis
MOA            by binding to the 30S subunit of
               the ribosome, causing an alteration
               in codon:anticodon recognition.
               mRNA is read wrong, so faulty
               proteins produced. Transported in
               by O2 dependent active transport
               which chloramphenicol can block.
               Streptococcus lysteria or
Indications    pseudomonas. Mostly gram-ve,
               some +ve. Polar so not absorbed –
               IV or IM. Not cross BBB.
               [Tissue] can become toxic.
               Ototoxicity – destruction of cells
Side Effects   in the vestibular and cochlear
               regions. Damage to kidney
               tubules (so can’t be excreted –
               viscious circle)
               Not good anaerobically. Enhanced
Other          by cell wall disrupting agents.
               Resistance due to conformational
               binding changes, failure of
               penetration, or inactivation by
               microbial enzymes.
Anti-Mycobacterial Agents
        isoniazid



               Antimycobacterial agent.
Class

               Passes freely into mammalian cells
MOA            and inhibits synthesis of mycolic
               acids, important constituents of the
               cell wall peculiar to mycobacteria.



               Mycobacterium (leprosy and
Indications    tuberculosis). After phagocytosis,
               both can survive inside the
               macrophage.
               Rare skin eruptions, fever, GI
Side Effects   disturbances.




Other
        rifampicin



               Antimycobacterial agent
Class

               Binds to and inhibits DNA-
MOA            dependent RNA polymerase in
               prokaryotic but not eukaryotic
               cells. One of best anti-tuberculosis
               agents known. Active against
               most gram +ve and some gram-ve.


               Antimycobacterium, mostly
Indications    tuberculosis.


               Rare side effects including skin
Side Effects   eruptions, fever and GI
               disturbances.




Other
 pyrazinamide



               Anti-mycobacterial. Related to
Class          nicotinamide

               Inactive at neutral pH but active in
MOA            acidic pH. Effective once agent
               has been phagocytosed, as acidic
               in phagolysosomes. Involves
               metabolism of drug inside
               bacterium to produce a toxic
               product, pyrazinoic acid.

               Anti-mycobacterial (tuberculosis,
Indications    leprosy


               Hepatotoxicity, and raised plasma
Side Effects   urate levels can lead to arthralgia
               and gout.



               Resistance can be rapid.
Other
Antifungal Agents
        nystatin



               Polyene macrolide
Class

               Acts by forming a transmembrane
MOA            ion channel in fungal cells,
               affecting permeability and
               transport functions. Not absorbed
               so used in GI tract or on skin.
               Affects fungi and some protozoa,
               mild mammalian effects, not at all
               to bacteria. Selective due to
               ergosterol rather than cholesterol
               in mammal membranes.
               skin or GI infections.
Indications


               Rare. Some GI disturbance in
Side Effects   high dose, v. rare rash.




Other
    miconazole



               Broad spectrum anti mycotic of
Class          the azole group.

               Azoles block the synthesis of
MOA            ergosterol by interating with the
               enzyme needed to convert
               lanosterol to ergosterol. This
               alters the fluidity of the membrane
               which interferes with action of
               membrane associated enzymes.
               Also prevents the transformation
               of yeast cells into hyphae, the
               invasive and pathogenic form of
               the parasite.
               Orally for GI, IV for systemic
Indications    fungal infections
               Rare, some GI disturbance, also
Side Effects   pruritus, blood dyscrasias.




Other
Anti-Viral Agents
        acyclovir



               Nucleic acid synthesis inhibitor.
Class          A guanosine derivative.
               Acyclovir is converted to the
MOA            monophosphate form by
               thymidine kinase – the virus’s own
               kinase is more effective at
               converting it than the host cell’s
               own kinase, and then converted to
               the active triphosphate. Therefore
               it is only activated in infected
               cells. It is used as a guanine
               substitute, which prevents DNA
               synthesis.
               Herpes simplex virus
Indications
               Minimal. Local inflammation
Side Effects   around injection site if extravasion
               occurs (alkaline solution so
               irritant). Renal dysfunction
               reported. Nausea and headache.
               Resistance due to changes in viral
Other          genes coding for thymidine kinase
               or DNA polymerase, and acyclovir
               resistant form have caused
               pneumonia and encephalitis in
               immunocompromised patients.
    Zidovudine
                 (AZT)


               Analogue of thymidine, reverse
Class          transcriptase inhibitor.
               Active inhibitor of reverse
MOA            transcriptase. Phosphorylated to the
               triphosphate form, where it competes
               with cellular triphosphates, essential
               for formation of proviral DNA by viral
               reverse transcriptase (viral RNA
               dependent DNA polymerase). It is
               incorporated into the growing DNA
               strand which results in chain
               termination.
               In retroviruses such as HIV virus.
Indications    Reduces risk of transmission from
               mothers, reduces chance of
               opportunistic infection, HIV associated
               dementia etc.
               Anaemia and neutropenia,
Side Effects   abnormalities of liver function and
               myopathy, GI disturbances, confusion,
               anxiety, depression, rash.

               Mammal α-DNA polymerase is
Other          resistant but mitochondrial γ-DNA
               polymerase is susceptible. Resistance
               is due to changing a.a. in the viral
               reverse transcriptase, so it is a
               constantly moving target.. Also ↓
               phosphoylation of zidovudine to its
               active form, ↑ in viral load, and
               increased virulence of the pathogen.
Anxiolytics
        Diazepam


               Benzodiazepine (long acting,
Class          32hrs)
               Benzodiazepines potentiate the
MOA            action of GABA by binding to a
               site on GABAA receptors,
               increasing their affinity for
               GABA. This results in an
               increased opening fluctuations of
               these ligand gated Cl- channels,
               thus increasing the inhibitory
               effects on postsynaptic firing.
               Short term relief of severe anxiety
Indications    and severe insomnia, preoperative
               sedation, status epilepticus, and
               acute alcohol withdrawl.
               Drowsiness, ataxia, reduced
Side Effects   psychomotor performance,
               dependence after 4-6 weeks. If
               taken in combination with alcohol,
               fatal respiratory depression can
               result. OD treated with flumazenil

               Not be given to people with
Other          bronchopulmonary disease, and
               have combination effects with
               other depressants such as alcohol,
               barbiturates, and antihistamines.
        oxazepam



               Benzodiazepine (short acting,
Class          8hrs)
               Acts to potentiate effects of
MOA            GABA, by binding to GABAA
               receptors and increasing their
               affinity for GABA, therefore
               increasing the frequency with
               which Cl- is allowed into the cell
               and ↑ the inhibitory effect on the
               postsynaptic cell.
               Short term relief of severe anxiety
Indications    and insomnia, preop sedation,
               statuss epilepticus, and acute
               alcohol withdrawl.
               Drowsiness, ataxia, and ↓
Side Effects   psychomotor performance are
               seen. Dependence develops after
               4-6 weeks, fatal respiratory
               depression if taken in combination
               with alcohol (or other CNS
               depressants)

Other
        Buspirone


               Anxiolytic, Azapirones, act on 5-
Class          HT (serotonergic) receptors
               In the raphe nucleus, dendrites of
MOA            the serotonergic neurones have
               autoreceptors (5-HT1A)which ↓ the
               firing of 5-HT neurons.
               Azapirones act as partial agonists
               at these receptors.


               Short term relief of general anxiety
Indications    disorder.


               Nervousness, dizziness, headache
Side Effects   and light headedness. Does not
               cause sedation or cognitive
               impairment, doesn’t potentiate
               alcohol, and only has a minimal
               risk of dependence.

               Not in epileptics. Effects evolve
Other          over 1-3 weeks.
Sedatives / Hypnotics
        Temazepam


               Short lasting benzodiazepine
Class
               Potentiates the effects of GABA
MOA            by binding to a site on GABAA
               receptors, ↑ their affinity for
               GABA, ↑ amount of Cl- entering
               the cell and so inhibiting the firing
               of the neurone.


               Given in short term relief of severe
Indications    anxiety and insomnia, preop
               sedation, status epilepticus, and
               acute alcohol withdrawl.
               Drowsiness, ataxia, and ↓
Side Effects   psychomotor performance are
               seen. Dependence develops after
               4-6 weeks, fatal respiratory
               depression if taken in combination
               with alcohol (or other CNS
               depressants)

Other
    amobarbital



               barbiturates
Class
               These prolong the time Cl-
MOA            channels are opened at GABA
               receptors whereas benzodiazepines
               ↑ the firing frequency.



               Sedation, reduction of anxiety.
Indications    Not used now


               More depressant than
Side Effects   benzodiazepines as they ↑ Cl-
               conductance directly, decreasing
               the neurones sensitivity to
               excitatory transmitters.


Other
Chloral hydrate




Class          Hypnotic


MOA            Chloral hydrate is metabolised to
               trichloroethanol, which I an
               effective hypnotic. Cheap but no
               advantage over newer
               benzodiazepines.

Indications    Previously popular hypnotic for
               children, but worse than
               benzodiazepines and children
               shoudn’t be sedated anyway.

Side Effects   Gastric irritation




Other
Anticonvulsants
        Phenytoin


               Sodium channel inhibitors, anti
Class          epileptic / arrhythmic.

               Bind preferentially to the closed Na+
MOA            channels, preventing them from
               opening, and so preventing
               depolarisation. In a seizure, the number
               of channels susceptible to blockade is
               higher, meaning that normal
               transmission is relatively unaffected.

               Seizures, except absence seizures
Indications
               Dosage effects: Affect
Side Effects   cerebellovestibular system, leading to
               ataxia, blurred vision, and hyperactivity.
               Acute toxicity leads to sedation and
               confusion.
               Non dosage effects: collagen effects
               such as gum hypertrophy, coarsening of
               facial features, allergic reactions (rash,
               hepatitis, lymphadenopathy),
               haematological effects (megaloblastic
               anaemia), hirsutism, teratogenic effects
               (congenital malformations)

               This drug is liver saturable – will build
Other          up in system until effects become
               marked suddenly, like beer.
               Fosphenytoin is a water soluble pro-
               drug.
  Carbamazepine




Class          Na+ channel blockers


MOA            Inhibits fast Na+ channels involved
               in neuronal excitation. Prevents
               excessive depolarisation




Indications    Seizure suppression



Side Effects   Limited to NS – ataxia,
               nystagmus, dysarthia, vertigo, and
               sedation.



Other
         Sodium
        valproate

Class          anticonvulsant


MOA            Like phenytoin causes use
               dependent block of voltage gated
               Na+ channels. Also Inhibit
               GABA metabolism by GABA
               transaminase


Indications    All forms of epilepsy



Side Effects   GI upset, liver failure.




Other          Hepatic toxicity exacerbated when
               used with other anti-convulsants.
               First line for many types of seizure
               syndromes.
        vigbatrin



               Anti convulsant
Class

               Inhibit GABA metabolism by
MOA            irreversible inhibition of GABA
               transaminase.




               Tough epilepsy
Indications


               Drowsiness, dizziness, depression,
Side Effects   and visual hallucinations




               Side effect of hallucinations, so
Other          not in people with history of
               psychosis. New drug used in
               conjunction with other therapies.
   Lamotrigine



               Anti epileptic
Class

               Acts by effect on sodium channels,
MOA            and inhibiting release of excitatory
               amino acids.




               Monotherapy and treatment of
Indications    partial and generalised tonic clonic
               seizures. Neuralgic pain (nerve
               root pain) (by stabilising neurones
               involved, limiting activation)
               Rashes, fever, malaise,
Side Effects   drowsiness, hepatic dysfunction




               Not in hepatic impairment
Other
Anaesthetics
Local Anaesthetics
          Cocaine
          (Ester)

               Local anaesthetic
Class

               Blocks Na+ channels. Also
MOA            prevents the uptake of NA at the
               synapse.




               Ear, nose and throat surgeons
Indications


               Does not cause CNS depression
Side Effects   like the other local anaesthetics
               because it causes euphoria through
               long lasting chatecolamine action.



Other
        Procaine



               Local anaestheic.
Class

               Basically a synthetic derivative of
MOA            cocaine. Causes sodium channel
               block




               Seldom used because of its CNS
Indications    side effects


               Causes CNS depression the worst
Side Effects   out of all the local anaesthetics.
               Resp depression, myocardial
               depression and vasodilation, visual
               disturbances and twitching.


Other
          Lidocaine
        (lignocaine)


               Local anaesthetic
Class          Amide


MOA




               Widely used in all applications,
Indications    EMLA


               Caused by leaking into the
Side Effects   circultion. Restlessness, tremor,
               confusion, agitation, CNS
               depression.



Other
    Bupivicaine


               Local anaesthetic
Class

               Slow onset, long lasting local
MOA            anaesthetic, with moderate tissue
               penetration.




               Epidural and spinal anaesthesia
Indications


               Systemic problems as with the
Side Effects   others.




Other
General Anaesthetics
Nitrous Oxide

               Inhalational GA
Class

               Blockade of NMDA type
MOA            Glutamate receptors




               Rapid control of depth of
Indications    anaesthesia


Side Effects




Other
    Halothane
   & Enflurane

               Inhalational GA
Class
               Potentiate GABAa receptor (and
MOA            Glycine receptors in the spinal
               cord to educe reflexes), inhibition
               of nicotinic Ach receptors &
               facilitate TREK (backround leak
               of Potassium due to channel
               opening leading to reduced
               neuronal activity)

Indications


Side Effects




Other
     Propofol &
     Etomidate
               IV GA
Class
               Potetiates the action of GABAa
MOA            receptors, most effective when Beta
               subunits of the GABAa receptor
               complex predominate, anaesthesia
               from depression of Thalamocortical
               neurones and influence on the
               reticular activating system, amnesia
               from depression of the synaptic
               transmission at the Hippocampus
               and Amygdala

Indications


Side Effects




Other
      Usual GA
     Cocktails
• Loss of Consciousness (Induction by IV
  GA – Propofol)
• Supression of Reflexes (Maintainance
  with Enflurane)
• Analgesia (Fentanyl)
• Muscle Relaxation (Suxamethonium)
• Amnesia (Midazolam – BDZ)
Anti-Parkinsonian Drugs
          L-dopa
              Exogenous precursor to
Class         Dopamine
              Allows the remaining (30% or
MOA           lower) DA-ergic neurones to
              function by having more of a
              reservoir of DA to use

Indications   Treats rigidity & tremor
              Start with low dose of the drug
              and increase dose until
              maximum benefit without side
              effects
              Effectiveness of L-DOPA
              declines with time!

              Acute (N&V, Hypotension and a
Side          Schizophrenic like syndrome)
Effects
              Chronic (Dyskinesias and
              On/Off fluctuations)

              To prevent N&V formulations of
Other         L-DOPA have been created with
              a peripheral DOPA
              decarboxylase inhibitor
              Sinamet (+ Carbidopa)
              Madopar (+Benserazide)
  bromocriptine



               DA2 receptor agonist.
Class

               Simple Agonist, no need of
MOA            functioning DA-ergic neurones as
               in L-DOPA therapy



               Acromegaly,, Benign breast
Indications    tumour relief, Acromegaly,
               Parkinson’s, prolactinoma

               Nausea, vomiting, ab cramps,
Side Effects   psychomotor excitation,
               dyskinesias, postural hypotension,
               vasospasm in fingers and toes


               Caution in Raynauds disease
Other          where vasospasm in fingers and
               toes happens already.
     Deprenyl
    (Selegiline)
               Selective for MAO-B,
Class          predominates in dopaminergic
               areas of CNS. Actions are without
               peripheral side effects of none-
               selective MAO-I’s
               Increases available DA
MOA

Indications    Can be given alone in the early
               stages of the disease.
               Or in combination with L-DOPA,
               reduce the dose of L-DOPA by 30-
               50%


Side Effects   Side effects are rare - hypotension,
               nausea/vomiting, confusion and
               agitation.


Other
 Entacapone
              Peripheral and CNS COMT
Class         inhibitor


MOA           CNS - Prevents breakdown of
              dopamine in the brain
              Peripheral - COMT in the
              periphery converts L-DOPA to
              3-0-methyl-DOPA (3-0MD). 3-
              OMD and L-DOPA compete
              for same transport system into
              the brain. COMT inhibitors
              stop 3-OMD formation thus
              increasing the bioavailability of
              L-DOPA, Thus more L-DOPA
              converted to dopamine in the
              CNS. Reduce L-DOPA dosage!


Indications

Side
Effects
Other
Neuroleptic Drugs
   chlorpromazine


               Typical antipsychotic
Class

               CNS Antagonist against D2, Ach
MOA            and H

               Acute and Chronic Psychoses,
Indications    Schizophrenia and the manic phase
               in Bipolar disorder

               Less incidence of extra pyramidal
Side Effects   disorders in contrast to the more
               potent neuroleptics (Haloperidol)
               most SE from the drugs Anti Ach
               activity (sedation, dry mouth,
               constipation, urinary retention)

Other
 haloperidol

              Typical antipsychotic
Class
              CNS Strong Antagonist against
MOA           D2 (and to a lesser extent Ach
              & H)


Indications   Schizophrenia

              Extrapyramidal symptoms like
Side          acute dyskinesias (Too much
Effects       Ach), Tardive Dyskinesia
              (Upregulation of DA receptors),
              Parkinsonian like syndrome and
              possible increase in Prolactin
              levels
              Can be used as an anti emetic
Other
        sulpiride

              Selective CNS D2 receptor
Class         Antagonist
              Simple antagonist
MOA


Indications   Schizophrenia

              Extrapyramidal symptoms like
Side          acute dyskinesias (Too much
Effects       Ach), Tardive Dyskinesia
              (Upregulation of DA receptors),
              Parkinsonian like syndrome and
              definite increase in Prolactin
              levels (Breast Cancer?)


Other
     clozapine

              Atypical antipsychotic
Class
              CNS Antagonist against D2,
MOA           Ach, H & 5HT (Hence
              Atypical)


Indications   Schizophrenia

              Agranulocytosis and
Side          myocarditis it may rarely lower
Effects       seizure threshold, cause
              leukopenia, cause hepatic
              dysfunction, weight gain and be
              associated with type II diabetes.
              More common side effects are
              predominantly anticholinergic
              in nature, with dry mouth,
              sedation and constipation

Other
Cytotoxic Drugs
cyclophosphamide
              Alkylating agent
Class
              Highly reactive molecules that
MOA           bind irreversibly to cell
              macromolecules causing intra
              and inter chain cross links
              (Notably DNA / RNA) binding
              sites N7 of G, N1 & N3 of A
              and N3 of C

Indications   Chemotherapy (&
              immunosupression at lower
              doses)
              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
methotrexate
              Antimetabolite
Class
              Folate antagonist and so
MOA           reduces the synthesis of Purine
              nucleotides (Reduction of the
              enzyme DHFR)


Indications   Chemotherapy (&
              immunosupression at lower
              doses)
              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
Azathioprine

              Antimetabolite
Class
              Purine analogue, inhibit Purine
MOA           synthesis and is incorperated
              into DNA itself


Indications   Chemotherapy (&
              immunosupression at lower
              doses)
              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
    bleomycin

              Cytotoxic Antibiotic
Class
              Causes fragmentation of DNA
MOA           chains and can act on non
              dividing cells. Bleomycin is a
              metal chelating glycopeptide
              antibiotic which uses Iron ions
              to create ROS which then cause
              DNA damage

Indications   Chemotherapy

              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
 doxorubicin

              Cytotoxic Antibiotic
Class
              Topoisomerase II inhibitor and
MOA           in such creates DNA strand
              breaks

Indications   Chemotherapy

              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
   vincristine

              Vinca Alkaloid
Class
              Spindle Poisons and exert there
MOA           actions by binding to tubulin
              causing depolymerisation of
              microtubules and therefore
              producing metaphase arrest

Indications   Chemothrapy

              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
     etoposide

              Podophyllotoxin
Class
              Topoisomerase II inhibitor,
MOA           prevents DNA replication and
              causes strand breaks


Indications   Chemotherapy

              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
procarbazine

              Miscellaneous anticancer drug
Class         (MAO-I)
              Inhibition of incorporation of
MOA           Thymidine and adenine into
              DNA


Indications   Chemotherapy

              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V

Other
        cisplatin

              Miscellaneous anticancer drug
Class         (Platinum Compound)
              After dissociation of a Cl- from
MOA           the drug this generates a
              reactive complex that cross
              links between G units in DNA
              (Similar to alkylating agents)

Indications   Chemotherapy

              General toxic side effects
Side          Myelosupression
Effects       Impaired wound healing
              Depression of Growth
              Sterility
              Teratogenicity
              Loss of Hair
              N&V (WORST SIDE
              EFFECT!)

Other
        goserelin

               GnRH agonists.
Class

               Blocks oestrogen production,
MOA            constant bombardment of the
               adenohypophesis with the GnRH
               agonist causes down regulation of
               the GnRH receptors


               Breast cancer in pre menopausal
Indications    women.


Side Effects



               Can also block oestrogen actions
Other          using enzymatic inhibition, or just
               inhibit the actions of oestrogen
               within the tumour cell.
Drugs for Endocrine
     Disorders
        tamoxifen



               Estradiol analogue – anti-
Class          oestrogen

               Works by acting as a competitive
MOA            inhibitor at the ER on the breast
               cell tumours. This stops the effect
               and holds the cell at the G1 phase.



               Endocrine treatment of choice for
Indications    postmenopausal women


Side Effects




Other
        Ferrous
        sulphate


               Oral iron compound
Class

               Ingested and solves iron deficiency
MOA




               Iron deficiency anaemia
Indications


               none
Side Effects




Other
    cabergoline



               DA2 receptor agonist with some
Class          DA1 actions.


MOA




               Hyperprolactinaemia. Not as good
Indications    as bromocriptine but side effects
               are less pronounced and it is
               longer lasting.

Side Effects



               Mutual antagonists with anti-
Other          psychotics. Sympathomimetic
               toxicity is increased. Exacerbates
               effects of alcohol.
   Octreotide


               Somatostatin analogue
Class

               Imitates actions of somatostatin by
MOA            inhibiting production of Growth
               hormone.




               Acromegaly – short term treatment
Indications    before pituitary surgery.


Side Effects




Other
  Ethinyloestradiol
          &
medroxyprogesterone



               TSH & LH replacement therapy
Class

               Replaces actions of progesterone
MOA            and oestrogen.




               Hormone replacement in cases
Indications    where gonadotrophins are no
               longer produced in pan
               hypopituitarism

Side Effects




Other
 Terlipressin


               V1 receptor agonist.
Class

               Acts at V1 receptors as an agonist
MOA            casuing an increase in IP3/DAG
               and so causing vasoconstriction,
               platelet aggregation, hepatic
               glycogenolysis, ↑ vWF and Factor
               VIII, ↑ ACTH and so cortisol.


               Stopping bleeding from
Indications    oesophageal varices, prolongs the
               actions of local anaesthetics.


Side Effects




Other
  Desmopressin



               V2 receptor agonist
Class

               Imitates actions of vasopressin in
MOA            the distal collecting duct as an anti
               diuretic




               Given in central diabetes insipidus.
Indications    Has no effect with nephrogenic
               diabetes. Thiazides used for
               nephrogenic diabetes insipidus.

Side Effects




Other
    Lithium &
 dimethylchlor
 otetracycline
               Inhibitors of vasopressin action on
Class          the distal tubule

               Prevents anti-diuretic actions of
MOA            excessive vasopressin




               Excessive vasopressin production.
Indications


Side Effects




Other
 Levothyroxine


               Thyroxine analogue
Class

               Acts to raise metabolism in tissues
MOA            – replacing T4




               hypothyroidism
Indications


Side Effects




Other
  Liothyronine



               T3 analogue – tri-iodothyronine
Class

               Replacement of T3. binds to
MOA            intracellular receptor where I tis
               transported to the DNA and causes
               transcription of tissue specific
               DNA regulated effects, ie raising
               BMR, sesnsitising tissue to
               sympathetic stimuli etc.

               Hypothyroidism. At birth to
Indications    prevent cretinism


Side Effects




Other
    Protirelin


               Thyrotrophin releasing hormone
Class          analogue

               Stimulates release of thyroxine
MOA            from the thyroid gland




               Used in stimulation tests of the
Indications    thyroid to test function.


Side Effects




Other
    Metformin


               Insulin sensitiser (Biguanide)
Class

               Requires endogenous insulin
MOA            production. Works by decreasing
               glucose output by the liver and
               increasing its uptake by liver and
               peripheral cells.


               Type 2 Diabetes mellitus in fat
Indications    people whose diet control hasn’t
               worked properly

               Lactic acidosis, ↓ vitamin B12
Side Effects   absorption. Nausea and vomiting,
               headache, anorexia.



               Not in renal insufficiency or
Other          hepatic impairment.
  Glibenclamide



               Sulphonurea
Class

               These block ATP dependent
MOA            potassium channels in the
               membranes of the pancreatic β
               cells, causing depolarisation,
               calcium influx, and insulin release.


               Type II Diabetes Mellitus where
Indications    there is still β cell activity in the
               pancreas

               Potential hypoglycaemia in people
Side Effects   with renal or hepatic insufficiency.




               Contraindications in people with
Other          ketoacidosis
 Rosiglitazone



               Thiazolidinediones. Insulin
Class          sensitisers

               Work by reducing peripheral
MOA            insulin resistance, leading to a
               reduction in plasma glucose




               Uncontrolled Type II DM
Indications


               Weight Gain, potential liver
Side Effects   failure.




               Must only be used in combination
Other          with a sulphonylarea or
               metformin.
        Acarbose


               α glucosidase inhibitor
Class

               Inibits the breakdown of
MOA            oligosaccharides (starch and
               sucrose), therefore delays CHO
               absorption. This reduces the –
               CHO peaks a bit like metformin.


               Useful in the obese diabetic
Indications    patient.


               GI gas
Side Effects



               Not in pregnancy, breastfeeding,
Other          bowel problems.
 carbimazole


               Thiourylenes – also includes
Class          propylthiouracil

               Blocks thyroperoxidase which is
MOA            responsible for the production of
               thyroglobulin and T3 & T4
               synthesis. May also ↓ antibody
               production in Grave’s disease and
               ↓ the conversion of T4 to T3 in
               peripheral tissues.

               Hyperthyroidism
Indications


               Hypothyroidism
Side Effects




Other
              Iodide


               Anion inhibitor
Class

               Inhibit the conversion of T4 to T3,
MOA            of organification and of hormone
               secretion. They also reduce the
               size and vascularity of the gland



               Hyperthyroidism
Indications


               Allergic responses
Side Effects




Other
  Radioiodine


               Anti hyperthyroid
Class

               Selectively taken up by the thyroid
MOA            gland where it has very local
               cytotoxic effects due to β particles.
               The γ particles pass straight out.
               Can destroy the over producing
               thyroid follicular cells.


               Low dose test of thyroid function,
Indications    high dose, hyperthyroidism or
               thyroid tumours.

               Not in children or pregnancy
Side Effects




Other
Miscellaneous Drug
    Information
     SYMPathetic
α1    located postsynaptically, Their activation
      causes SM contraction (except in non sphincter
      GI), glycogenolysis in the liver, and potassium
      release from the liver & salivary glands. G-
      protein linked, & by increase in 2 nd messengers.


α2    Located most pre, but post on hepatocytes,
      platelets and BV SM. Activation of pre inhibits
      NA release and provides end product negative
      feedback. Activation of post causes BV
      constriction & platelet aggregation. G-protein
      linked & by decrease in 2nd messengers.

β1    Mostly postsynaptic in the heart, platelets and
      non sphincter GI. Activation causes rise in rate
      and force of contraction of the heart, relaxation
      of GI, platelet aggregation, rise in NA, lipolysis
      in Fat, amylase secretion from salivary glands.
      G-protein and rise in 2nd messenger cAMP.

β2    Located post, SM relaxation, glycogenolysis in
      liver, inhibition of histamine from mast cells,
      tremor in skeletal muscle. G-protein and and
      increase in cAMP.
Parasympathetic

M1   Neuroparietal normally found in the CNS,
     peripheral neurons, and gastric parietal cells.
     Effects are excitatory, depolarizing membranes
     through a decrease in K conductance.
     Activation causes central excitation and gastric
     acid secretion, transduction through G-proteins
     and Increase in 2nd messengers.

M2   Neurocardiac are found in the heart and on
     peripheral neurons. Effects are inhibitory
     raising K conductance(<rate), and inhibiting
     calcium channels(<force). G-protein
     transduction with decrease of 2nd messengers.

M3   Smooth muscle-glandular found in obvious.
     Excitatory by increasing Na conductance.
     Causes SM contraction and secretions such as
     saliva and sweat. G-proteins and increase in 2nd
     messengers. Also on vascular epitelium,
     activation of which causes EDRF (NO).

M4   Eye. Causes constriction of the pupil and
     accomodation for near vision. Transduction is
     via G-proteins and a decrease in 2nd messenger.
Multiple drug
  therapies


Helicobacter   Metronidazole/amoxycillin,
pylori         clarithromycin, Omeprazole

Tuberculosis   1st phase of 2 months:
               isoniazid, rifampicin,
               pyrazinamide (+ethambutol if
               resistant)
               2nd phase of 4 months:
               Isoniazid and rifampicin
     Histamine

H1   Histamine in hypersensitivity reaction.
     •Capillary and venous dilation (systemic
     hypotension
     •↑ vascular permeability (oedema)
     •Contraction of SM (bronchial and GI
     contraction)
     •↑ mucus secretion by goblet cells

H2   Regulation of gastric acid secretion.
     -H2 receptors respond to histamine secreted from
     enterochromaffin like cells that are adjacent to
     the parietal cells.
     -Negative feedback if on mast cells and
     basophils.
     -Increases vasopermeability & dilation and
     stimulates exocrine glands.

H3   Neurotransmission. Not sure what. Possible
     presynaptic inhibition of NT release in the CNS
     and autonomic NS? Role in pain perception?
     Vasopressin
      Receptors

V1   Vascular smooth muscle (prevention of blood
     loss from oesophageal varices), non vascular
     smooth muscle, anterior pituitary, Liver,
     platelets (Stimulation of factor VIII and von
     Willbrandt factor), Brain and CNS




V2   Kidney (distal collecting duct), CNS
Glucocorticoid
      SE
osteoporosis           ↑ osteoclast activity, ↓
                       osteoblast activity

Gastric ulceration     ↓ PG production in
                       stomach (lipocortin ↓
                       arachidonic acid.)

Suppression of HPA     -ve feedback on pit. &
                       hypothalamus

hypertension           Na+ Cl-, water retention; ↑
                       adrenoceptors hence ↑
                       response.

infection              Immunosupression

Skin thinning          ↓ connective tissue, ↓
                       tissue turnover and repair

Muscle wasting &       ↓ storage of glucose in
buffalo hump           muscle, leads to an ↑ in
                       fat deposition.

Cataracts & glaucoma

								
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