Drugs for the MAU

							Drugs for the MAU

    Clive Roberts
   Which drugs am I expected to know about??


             Extract from 5th year handbook
You should have a working knowledge of therapeutics. You should know the uses,
dose, side effects, contraindications and alternatives for widely used medication. For
example (in rough order of exposure frequency):

a) Aspirin                                        1. Iron, thiamin and other vitamins
b) Loop and other diuretics (thiazides,           2. Warfarin
   amiloride etc.)                                3. Benzodiazepines
c) Minor analgesics                               4. Digoxin
d) Antibiotics                                    5. NSAIDs
e) Treatments for bronchial asthma                6. Statins
f) Laxatives                                      7. Treatments for type I and type II diabetes
g) Proton pump inhibitors and H2 antagonists      8. Calcium antagonists
h) ACE inhibitors                                 9. Thyroxine
i) Enteral steroids                               10.Major tranquillizers
j) GTN and slow release nitrates                  11.Anticonvulsants
k) Beta blockers                                  12.Amiodarone
l) Antidepressants                                13.The contraceptive pill
    So what are drugs good at treating (or
                preventing)?
•   Pain                   •   Diarrhoea/constipation
•   Inflammation           •   Depression
•   Infection              •   Anxiety/sleeplessness
•   Fluid retention        •   Psychosis
•   Heart problems         •   Metabolic /endocrine
                               diseases
•   High blood pressure
                           •   Malignant disease
•   Epilepsy               •   Degenerative disease
•   Parkinsonism           •   Haematological
•   Asthma / COPD              problems
•   Peptic ulcer disease   •   Etc Etc
• A 45 year old lady presents with
  increasing wheeze over the previous 6
  months. No past history of asthma.
  She is wheezy throughout both lungs
  and has a tachycardia. Her peak flow is
  150 l/min.
• What immediate investigations are
  indicated?
• What immediate measures should be
  taken?
       Acute asthma and COPD -
         available approaches
• Oxygen
• Bronchodilators
   – Salbutamol
   – Ipratropium
   – Aminophylline
• Anti-inflammatories
   – Corticosteroids
      • Intravenous
      • Oral
• Anti-biotics
           Severe asthma
• Sit patient up and give high flow O2
• Check PEFR & O2 sats
• Nebulised bronchodilators salbutamol 5mg
  + ipratropium 500mcg (repeat after 15 min
  if needed)
• Prednisolone 40-50mg po stat
• Consider IV Magnesium sulphate 1.2-2g
  over 20 mins
• ABGs, CXR, FBC, U&Es
     General rules about Oxygen
               therapy
• Correct hypoxia with an appropriate delivery
  device
• Check ABGs if SaO2 <93% or suspicion of
  ventilatory impairment or acidosis
• Some patients (esp. COPD) with chronic
  hypoxia rely on hypoxic drive and will
  hypoventilate on high flow O2
Oxygen delivery devices
   Hudson mask:
variable performance
Nasal cannulae
  Venturi devices:
fixed performance
           Key drug features
• Salbutamol – beta 2 stimulant
  – Easy to administer
  – Watch for tremor and potassium level
• Ipratropium – muscarinic blocker
  – Nebuliser and inhaler
  – Few side effects
• Aminphylline – phosphodiesterase inhibitor
  – Major dosing problems
  – Severe adverse effects on CNS and heart
  – Great caution needed
              Key drug features

• Corticosteroids
  – Safe in acute situations
  – IV hydrocortisone or oral prednisolone
  – Avoid long term or rapidly repeated courses
    because lead to
     • BP+, fluid retention, hypokalaemia, weight gain,
       Diabetes, osteoporosis, myopathy, skin fragility,
       gastric ulcer, reduced host defence, risk of
       hypocorticism
                                                      Antibiotic guidance

                                                                                                Duration of
        Infection                                     Antibiotic Treatment                                               Comments
                                                                                                Treatment

 Infective Exacerbation                                     Amoxicillin 500mg po tds             5-7 days
         of COPD


                               •Penicillin allergic         •Doxycycline 100mg po bd             5 -7days




 Community Acquired            Non-severe               •Amoxicillin 500mg–1gram po tds          •5-7 days      •*Amoxicillin monotherapy may be
    Pneumonia                                           plus* Clarithromycin 500mg po bd                        considered for (i) those previously
     Risk Factors in CAP                                 Amoxicillin 500mg-1gram IV tds                          untreated in the community or (ii)
         (CURB-65)                                                                                             those admitted to hospital for non-
                                                        plus* Clarithromycin 500mg IV bd
C = Confusion MTS 8 or less                                                                                   clinical reasons who would otherwise
                                                        can be used if a patient is unable to                      be treated in the community.
     U = Urea > 7mmol/l
                                                            swallow or is not absorbing.
 R = Resp. Rate >/= 30/min
B = BP Systolic < 90 mmHg
 +/- Diastolic </= 60 mmHg
                                 Non-severe                 Moxifloxacin 400mg po od             •5-7 days
     65 = age >/= 65 yrs
 3 or more of the above risk   Penicillin allergic
  factors (CURB-65 Score
 >/=3) = Severe Community
    Acquired Pneumonia              •Severe                •Co-amoxiclav 1.2grams IV tds         •7-10 days       •If systemic sepsis add
                                                         •plus Clarithromycin 500mg IV bd                        Gentamicin 5mg/kg IV stat
                                                       •(Switching to Co-amoxiclav 625mg po                       pending culture results
                                                        tds plus Clarithromycin 500mg po bd)


                                   •Severe                 •Levofloxacin 500mg IV bd             •7-10 days
                               •Penicillin allergic    •(Switching to Moxifloxacin 400mg po
                                                                        od)
• A 45 year old man known to be alcoholic
  and addicted to Valium is admitted
  following three tonic clonic seizures
• What might be the possible causes?
  –   Effect of alcohol on brain
  –   Metabolic abnormality 2ndry to alcohol
  –   Alcohol withdrawal
  –   Drug withdrawal
  –   Head injury
  –   Overdose of something
• What specific urgent investigations are
  indicated?
• CT scan
• Glucose and electrolytes, serum
  Calcium
• Toxicology
      What will you prescribe?

• Correct electrolytes, dehydration,
  hypoglycaemia
• Oxygen
• Treat alcohol withdrawal Vit B complex
  (Pabrinex)
• Give anti-epileptic treatment
 Urgent anti-epileptic treatment for
           repeated fits
• Lorazepam 4mg iv (repeat once after 10 mins if fits
  again)
• If no control after 30 mins Phenytoin 15mg/kg iv (1g for
  70kg person over 20 mins), monitor BP & ECG, then
  maintenance dose of 100mg every 6-8hrs
• Consideration of ITU at 60 mins
• Subsequently:-
   – Consider need for maintenance treatment
      •   Carbamazepine
      •   Valproate
      •   Phenytoin
      •   Lamotrigine
• Advise not to drive
        Key features of drugs
• Lorazepam – potent benzodiazepine with
  short half life
• Phenytoin –
  – highly effective in controlling status epilepticus
    / repeated fits
  – Low therapeutic ratio / complex
    pharmacokinetics / many adverse effects /
    precautions / drug interactions
        Key features of drugs
• Carbamazepine
  – Effective prophylactic in most common epilepsies
  – Powerful enzyme inducer
  – Toxicity includes hepatic and blood disorders and
    hyponatraemia (SIADH)
• Valproate
  – Also widely effective including absence seizures
  – Possibly less problematic
• A 60 year old man presents with severe
  shortness of breath at rest and
  orthopnoea. He has been waking at
  night with frightening episodes of
  dyspnoea. He is distressed and sweaty.
  Examination reveals elevated JVP
  some oedema of ankles. Crepitations
  throughout the lungs. Gallop rhythm at
  120/min. BP 140/90.
• He had suffered an anterior myocardial
  infarction 3 years previously and has
  been on tablets for blood pressure.
     Heart failure - approaches
• Improve oxygenation
• Reduce pre-load
   – Reduce blood volume – Diuretics
   – Increase vascular capacity – Nitrates and other
     vasodilators
• Reduce afterload
   – ACE inhibitors / AII blockers
• Reduce demands on myocardium
   – Beta blockers
   – (calcium channel blockers)
• Increase force of contraction
   – Digoxin
• Reducedistress
   – Morphine
• Avoid fluid overload, sodium retaining drugs, negative
  inotropes, arrhythmogenic
`
         Severe heart failure
• Acute SOB, frothy sputum, tachypnoea, course
  crackles, hypoxia. May be cardiac history, ECG
  usually abnormal.
• Is there a precipitating cause?
• Need to exclude acute MI or arrhythmia
• Urgent ECG, CXR, bloods (inc TnI), ABGs
• Pay close attention to BP
Severe heart failure - treatment
• Sit patient up, give high flow O2 (60-
  100%)
• Furosemide 40-120mg iv
• Diamorphine 2.5-5mg iv
• Metaclopramide 10mg iv
• GTN spray s/l then GTN (isoket) infusion
  1-10mg/hr (monitor bp)
            Key drug features
• Furosemide – loop/high ceiling dose diuretic
  – Safe for rapid IV injection, rapid diuresis but
    depends on renal function
  – Risk of over-diuresis, hypokalaemia, and in
    longer term gout and hyponatraemia
• ACE inhibitors
  – Risk of early drop in BP and renal function
  – Minor hyperkalaemia and cough in long term
                Key drug features
• Digoxin – NA/K ATPase inhibitor
  – Negative chronotrope/positive inotrope
  – Most useful in atrial fibrillation / limited in SR
    (except in children)
  – Risk of AV block / supraventricular and
    ventricular tachyarrhythmias esp if low K+
  – Elderly and renal impairment predispose to
    toxicity which starts with nausea and
    progresses to CNS effects.
• Morphine – CNS effects – also venodilator
          Key drug features
• Nitrates – venodilators
  – Reduce pre-load therefore good in LVF with
    preserved cardiac output
  – Sublingual / iv infusion
  – Risk to BP
• Beta blockers
  – Reduce mortality in heart failure in long term
    by decreasing sympathetic drive but use only
    when stable or if severe tachycardia
                      Acute Pain
• Paracetamol
  – Effective as aspirin, antipyretic but not anti-inflammatory, not GI
    adverse effect, dangerous in o/d
• Codeine
  – Opioid so causes drowsiness and constipation
• NSAIDs
  – Effective in somatic pain but risk of/in GI, renal, heart failure,
    hypertension, hypersensitivity, hepatic damage, alveolitis, skin
    diseases, pancreatitis. Drug interactions ++
• Opiates, Morphine and diamorphine
  – Vary in potency for somatic and visceral pain and adverse effect
    but all tend to affect mood, respiration, GI motility. Risk of
    addiction
• A 90 year old lady is admitted coughing up
  blood and with pleuritic pain in her R side
• She had had bilateral ankle swelling
• CXR clear, D dimer raised, S1Q3T3 on
  ECG
• Current treatment amoxycillin –just
  started, carbamazepine for trigeminal
  neuralgia, aspirin prophylactic, diclofenac
  for shoulder pain.
    Outline of treatment regime
• Low molecular weight heparin for 5 days
• Load with warfarin
• Daily INR
• Adjust warfarin according to
  recommendation on chart
• Deal with over anti-coagulation according
  to BNF
 Key features of anticoagulants
• Warfarin
  – suppresses synthesis of Vit K dependent
    clotting factors in liver (II,VII,IX and X).
    Therefore slow onset and offset.
  – Effect easily monitored by prothrombin time
    (INR)
  – Dose requirement highly susceptible to
    pharmacokinetic and pharmacodynamic
    variation from disease states, drug interaction
    and compliance.
  – Many people die from over anti-coagulation
    each year
WARFARIN- Indications

Long-term anti-thrombotic treatment
• Treatment of DVT or PE
• Prevention of arterial thrombosis in……
  – Atrial fibrillation
  – Mechanical or bio-prosthetic valves
  – Peripheral vascular disease
  – Cerebrovascular disease
  – Ischaemic heart disease
WARFARIN- Important interactions

• Assume all co-prescriptions will alter warfarin
  dose response
Cause                      Cause
over-anticoagulation       under-anticoagulation

Amiodarone                Barbiturates
PPI’s                     Carbemazepine
Statins                   Rifampicin
Fluconazole               Cholestyramine
Erythromycin

•Anti-platelet agents increase bleeding risk
Description & action- HEPARIN
• Parenteral anticoagulant
• Naturally occurring glycosaminoglycan
• Mixture of different length molecules
  (UFH av. 50 LMWH av. 15-20)

How it works
• Increases activity of plasma Antithrombin

• Inhibits active clotting factors esp. factors IIa and Xa
 (LMWH inhibits Xa better)
    PHARMACOLOGY OF HEPARINS
                  UF HEPARIN     LMW HEPARIN

Route                  IV             SC

Bioavailability     Variable,     Predictable,
                      poor           good

Metabolism         Complex,       Predictable
                  mostly renal       renal

T1/2 (hours)          1-2             4-6
 Presentation- UF Heparin
• Vials containing..
25,000   IU/ml (sc)
5,000    IU/ml
1,000    IU/ml (flush)
10       IU/ml (flush)


Typical dose
5000 IU loading then
30,000 IU by iv infusion
  / 24 hrs
  Presentation- LMW heparin
• 4 generic preparations
 eg Tinzaparin (Innohep)
      Enoxaparin (Clexane)

• Pre-filled syringes
Clexane 100 mg/ml; 20, 40, 60,
80, 100, 120, 150 mg syringes

Typical doses
40mg sc once daily ‘prophylactic’
100 mg sc once daily ‘treatment’
 HEPARINS- Indications
Anti-thrombotic activity with rapid onset /offset

• Initial treatment of DVT or PE          LMWH
• Acute coronary syndromes                LMWH
• Cardiothoracic surgery                    UFH
• Other extra-corporeal circuits           UFH
• Warfarin unsuitable esp pregnancy       LMWH
• Prophylaxis against venous thrombosis   LMWH