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Study Guide – Exam II Block 3 – Rzigalinski - VCOM-DO

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Study Guide – Exam II Block 3 – Rzigalinski - VCOM-DO Powered By Docstoc
					              Study Guide – Exam II Block 3 – Rzigalinski


     Be able to name the major contraindications of all the drugs
     Be able to explain the pharmacotherapy for sleep, which drugs are now
      first choice, etc
Be able to explain the mechanistic differences between BDZ’s and Barbiturates
      - BDZ’s increase the frequency of the GABA channel opening 
           greater Cl- - influx and hyperpolarization
      - Barbituates-- GABA-A receptors; prolong the opening of the Cl- channel
           (think of Barb, like a wire barb—they are tough and will hold it open longer
           than the weak little BZDs!); enhance binding of GABA and BZDs; and inhibits
           excitatory AMPA receptors
      -
Be able to explain how the MOA’s of the newer sleep agents (Zolpidem,
Zolpicone, Ramelteon) differ from the BDZ’s and barbiturates
      - We spend most of our sleep in stage 2 NREM; most sedatives/hypnotics
           decrease sleep latency, stage 3, 4, and REM sleep and increase stage 2;
           exceptions are Zaleplon, Zolpidem(Induces sleep with little change in sleep
           stages, may return sleep patterns to normal. Specific for BDZ1 (w1).) and
           Ramelteon (ML1 and ML2 agonist)
           And that ramelteon is slowly becoming drug of choice for pts that
           initially present with insomnia
Be able to define treatments for BDZ and barbiturate overdose

       -   Barbiturate Poisoning= Supportive measures
       -   Use of CNS stimulants increases mortality rate
       -   Gastric lavage if less than 24 hrs post ingestion
       -   Acidic barbiturates are excreted faster in alkaline vs. acidic urine,
           therefore, alkalinization of urine if often done
       -   Remember no amphetamines                                                       Formatted: Bullets and Numbering


       -   Benzodiazepines OD = Flumazenil – The Benzodiazepine Receptor
           Antagonist, antagonizes benzodiazepine binding
       -   IV administration only
       -   Not for use in barbiturate or antidepressant overdose – seizures may
           result
       -
       -
      Be able to describe major side effects for all drugs – pay particular
       attention to drugs that require monitoring via specific laboratory tests such
       as hematological parameters, liver enzymes, etc.===see charts
Be able to name those anti-seizure drugs with little-no interactions with
other anti-seizure medications: WHEN CHOOSING ADJUNCT USE A
DIFFERENT CLASS

      Ethosuximide Primary treatment for absence seizure
      - MOA= T-type Ca++ channel blockers  reduces low level Ca++ current (T-
         type) in the thalamic neurons.
      - USE: Absence
      -  Does not induce p450s

      Levetiracetam
      - MOA: Inhibits burst firing w/o affecting normal neuronal activity;
      - Use: Partial, secondarily generalized Tonic-Clonic
      - Does not induce and is not metabolized by p450; no interaxns w/ other
         antiepileptic drugs; oral contraceptives, or anticoagulants

      Vigabatrin
      - MOA: Irreversible inhibitor of GABA transaminase (GABA-T), the enzyme
         responsible for the breakdown of GABAleads to increased GABA levels.
      - USE: Partial & Generalized Refractory
      - not metabolized by CYPs; GOOD ADD ON

      Topiramate (Topamax)
      - MOA: Reduces voltage-gated Na+ current, possibly by increasing inactivation
          time, similar to phenytoin
      - Enhances post-synaptic GABA-A current
      - Limits activation of AMPA subtype of glutamate receptors
      - Blocks Kainate Type glutamate receptors
      - USE: broad range of antiseizure activity; Treatment of refractory partial
          seizures (very good), used for Lennox-Gastaut symdrome
      - Rapidly absorbed & excreted unchanged in urine NOT METABOLIZED SO A
          GOOD ADD ON!!!!
      I THINK THESE ARE THE MAIN ONES yep
Be able to name drugs used to treat neuropathy

       Gabapentin Antiseizure med; useful in DM neuropathy &
       trigeminal neuralgia; Exact MOA is unknown
       TCAs: Increase NE and serotoin @ the synapse; Inhibit Na+ channels
        Imipramine
       Amitryptiline
        Nortriptyline

Be able to explain the difference between neuropathic pain and nociceptive
pain

      Nociceptive pain is a specific sensation sensed by nociceptive receptors
       and transmitted via neurons
          o Opioids inhibit transmission of nociceptive pain

          o Neuropathic pain is due to damaged neurons.
      Neuropathic pain responds poorly to opioids (Tricyclic
       Antidepressants or Gabapentin are often drugs of choice for this
       type of pain)

Explain the pharmacological treatment for Status epilepticus

   •   Neurological emergency

   •  Treatment goal: Rapid termination of behavioral and electrical seizure
      activity
          • The longer status epilepticus continues, the greater the
              neurological damage and the more difficult the seizure is to control
          • Hypoxic damage to brain cells
          • Prompt drug treatment and attention to hypoventilation and
              hypotension
          • IV drug administration, IM too slow
   Drugs of Choice
          • Diazepam or lorazepam slow IV every 10-15 min until seizure
              stops or max dose is given
          • Fosphenytoin (phenytoin) at same time
          • If failure, give phenobarbital
          • Last resort is general anesthesia
Know the mechanisms that generate seizure in the brain

Reduction in inhibitory neurotransmission or increase in excitatory neurotransmission at
a particular foci, which may spread to neighboring cells followed by dysfunction of
surround inhibition; all of the following lead to a disruption of extracellular ionic
homeostasis
                                    a. Increased Na+ channel activity
                                    b. Decreased GABA inhibitory activity
                                    c. Increased Ca++ channel activity Ca++ channels in
                                       the thalamus cause a pacemaker current that
                                       underlies the thalamic rhythm; and over activation
                                       can cause seizure activity (absence)
                                    d. Excessive glutamate neurotransmissionexcessive
                                       activation of the NMDA-r displaces the voltage –
                                       sensitive Mg2+ block and induces increased Ca++
                                       influx through this receptor; this activates NO and
                                       NOS; NOS makes more NO which goes to the pre-
                                       synaptic cell and further enhances glutamate
                                       release
   Be able to identify the best anti-seizure drugs for each seizure type
Phenytoin:
   • Often drug of choice for initial therapy & Status Epilepticus, esp. in
      adults
   • Effective against all types of partial and tonic-clonic seizures; NOT
      absence seizure
   • Very little sedative actions, no CNS depression
   • Metabolized by CYPs RED FLAG DRUG!!!!! INTERACTS WITH MANY
      DRUGS  Accelerates metabolism of other anti-epileptics
   • Phenytoin induces P450’s that metabolize anticoagulants, oral
      contraceptives, Decreases levels of Vitamin K
Carbamazepine  Primary Generalized partial and generalized tonic-clonic
seizures

   •   Often considered drug of choice for
   •   Limits repetitive neuronal firing by slowing the rate of recovery of voltage-
       gated Na+ channels
   •   Also use-dependent
   •   Suppresses PDS and prevents spread of seizure
   •   Upregulation of adenosine receptors in brain
   •   Blockade of NOREPINEPHRINE REUPTAKE (MOOD-ELEVATING
       EFFECT)

Ethosuximide
   • Primary treatment for ABSENCE SEIZURE (Petit Mal), VAPROATE
     WILL SOON BECOME 1ST LINE
        • Not effective for partial or secondary generalized seizure
        • Mechanism of action: Reduces low level Ca2+ current (T-type) in
           thalamic neurons
        • Does not induce P450
 Be able to identify drugs for RRMS vs other forms of MS




  PRIMARY DRUGS FOR RRMS
       o Glatiramir Acetate (Copaxone)
       o IFNb Two types – IFNb-1a (Avonex, Rebif) , IFNb-1b
         (Betaseron)
       o Differ in peptide sequence
       o Immunoglobulins (IVIg) Suggested to reduce relapses in
         RRMS
       o Rituximab
       o Natalizumab Monotherapy for RRMS, For those who do not
         respond to other treatments
       o Daclizumab Has been effective in pts with poor response to
         IFNb and advanced clinical disease activity
  PRIMARY DRUGS FOR PRMS
       o Mitoxantrone (Novantrone) Very effective in clinical trials
         for secondary progressive and progressive relapsing diseases
       o Not considered for long term therapy due to severe
         cardiotoxicity and potential for liver damage

  PRIMARY DRUGS FOR PPMS
  - Rituximab
Be able to define classic symptoms of opioid overdose and its
treatment

   Symptoms
        o Stupor to coma, depending on dose
        o Depressed respirations, apnea, cyanosis
        o BP may progressively fall
        o Shock may occur
        o Symmetrical pinpoint pupils BUT – if hypoxia is severe, pupils
          dilate
        o Depressed urine formation
        o Hypothermia
        o Relaxed skeletal muscles, jaw relaxation, tongue may block
          airway
        o Convulsions in infants & children
        o Seizures in some cases (meperidine, propoxyphene)
        o Death usually occurs by respiratory failure
Treatment
        o Establish patent airway & ventilate
        o Naloxone is drug of choice
               Caution to not precipitate withdrawal
               Standard dose 0.4 mg (0.01 mg/kg children)
                 administered IV slowly while monitoring respiratory
                 function
               Add doses if no response
               Remember – short half life of antagonists, pt. must be
                 watched.

Be able to list the side effects of opioids

      -   Nausea, vomiting, respiratory depression, dizziness, mental
          clouding, dysphoria, pruritus, constipation, biliary colic, urinary
          retention, hypotension
      -   Metabolism by liver warrants caution in patients with hepatic
          diseases
      -   Use caution in pts with renal disease or prostatic hypertrophy
      -   Use caution in pts with respiratory dysfunction (emphysema,
          asthma)
      -   Contraindicated in head injury (generally)
      -   Hypotension
      -   Histamine release may cause bronchoconstriction & vasodilation
          (fentanyl does not)
Be able to explain which opioids have the best vs worse bioavailability and pain
relief, and what routes of administration are available
Be able to explain the basic effects of tolerance, particularly how
it effects opioid-induced miosis

       -   Tolerance – During repeated use, drug looses effect and increased
           dose required to produce same effects
       -   Opioids are cross tolerant
       -   Down regulation of opioid receptors
       -   At equi – analgesic doses, the more efficacious opioid will occupy
           a lesser number of receptors and therefore induce less tolerance
       -   No tolerance to miosis or constipation
       -
      Be able to name opioids used to treat Post-anesthetic shivering ===cant
       find this one

Be able to describe the CNS systems involved in MS, PD, AD
   Diseases of POST-MITOTIC neurons; Loss of neurons from SPECIFIC
   regions of the brain (Selective Vulnerability)

       -   MS Any condition characterized by destruction of the myelin
           sheaths of nerves.
       -   Involves loss or dysfunction of myelin in the central or peripheral
           nervous system.
       -   PD  Loss of dopaminergic neurons in the subsantia nigra and
           basal ganglia
       -   Intracellular inclusions – Lewy Bodies Contain a-synuclein –
           important in ER/golgi trafficking; Misfolding and fibrilization Oxidation
           and nitration
       -   AD  Loss of hippocampal and cortical neurons 
       -   Atrophy of cerebral cortex, esp. hippocampus
       -   Neuronal loss, particularly cholinergic
Be able to explain the differences between levodopa and
dopamine receptor agonists (ropinarole, etc)

       Dopamine Receptor Agonists
   •   Agonists of striatal dopamine receptors
   •   Enzymatic conversion not required
   •   Longer duration of action, less fluctuations (no “on/off”)
   •   Reduced free radical damage from dopamine
          • Metabolism does not generate free radicals
          • Current data suggests they may scavenge free radicals and be
             neuroprotective
   •   Currently utilized as adjunct to levodopa  becoming first line therapy
          • Lowers necessary dose of levodopa
          • Reduces risk of levodopa-related motor complications
   •   Many authorities recommend these as first line therapy
   •   As monotherapy, delays time to levodopa by about 3 yrs

          • Ropinirole – Agonist at D2 and D3 (D3>D2), no activity at D1,
            also used for restless legs syndrome
         • Pramipexole - Agonist at D2 and D3 (D3>D2), no activity at D1
         • Rotigotine
                • D3>D2>D1
                • Transdermal patch for once daily dosing
                • Used in conjunction with levodopa in later stages
Also used for restless legs syndrome

       Levodopa
   •   Converted to dopamine after crossing the BBB
   •   Provides dopamine to replace lost dopaminergic neurons
   •   Acts at D1 and D2 receptors
          • Affects multiple targets inc. serotonin receptors
   •   SOME dopaminergic neurons must be left in the brain for levodopa to be
       successful
Be able to explain how AADC and COMT inhibitors act in PD
   Inhibition of AADC in the periphery increases the available substrate for
    COMT (3-O-MD). 3-O-MD competes with L-Dopa for transport across
    BBB. Therefore, inhibition of COMT and AAD makes sense. Inhibition
    resuls in an increase in levodopa bioavailability
  AADC Inhibitors
  • Inhibits aromatic amino acid decarboxylase
  • Prevents conversion of levodopa to dopamine in the periphery
  • Benzaseride, Carbidopa

  Catechol-o-methyltransferase (COMT) Inhibitors
  • Clinical trials show reduced “on/off” of levodopa and improved motor
     scores in combination therapy
  • Increases bioavailability to approx. 10%
  • Tolcapone
     - Long duration of action
     - Central & peripheral COMT inhibition
  • Entacapone
     - Short duration
     - Peripheral COMT inhibition
     - Entacapone use largely replaced by tolcapone
  •

Be able to explain the reasons for cautionary use of
anticholinergics in AD
  Anticholinergic Drugs May Increase Cognitive Decline in AD
  • Recent retrospective study (2008) found that anticholinergic drug
     treatment was associated with decline in cognitive performance in older
     individuals.
  • Physicians should take this into account when prescribing anticholinergics
     to this group of pts.
  • Includes drugs like tolterodine (Detrol, overactive bladder), some PD
     meds, warfarin, furosemide, hydrochlorthaizide, ranitidine.



CASE STUDY QUESTIONS. BE ABLE
 TO EXPLAIN THE MOA’S FOR ALL
  DRUGS ON THE CHARTS. NOTE
        THIS IS IN RED

				
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posted:3/22/2013
language:English
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