med chem

  1. two causes of arrhythmias
    • cardiac defects
    • drug induced (not necessarily cardiac drugs)
  2. what is the electrophysiology of arrhythmias
    differences in ion concentrations (negative on the inside relative to the outside)
  3. where is the site of blockade in torsades de pointes induced by anti-arrhythmic drugs
    the delayed rectifier IKr
  4. what natural stimulus source paces cells with automaticity
    sinoatrial node SA
  5. two basic abnormalitied in the stimulus to discharge
    • abnormal impulse generation (ectopic foci)
    • abnormal impulse conduction
  6. an abnormal portion of tissue that develops "automaticity"
    ectopic foci
  7. unidirectional blockage of conduction down one path of parellel conduction pathways, feedback loop results in self propagating impulses
    re-entry arrhythmias
  8. most common cause of supraventricular tachycardias
    re-entry arrhythmias
  9. automaticity arrhythmias
    ventricular arrhythmias
  10. this class agent has a MOA - block Na+ channels, slow conduction velocity, prolong refractoriness, decrease automaticity of sodium-dependent tissues
    class I
  11. this subclass of anti arrhythmic block K+ channels (prolonged recovery phase) resuling in QRS widening and QT longation
    subclass 1A
  12. these two subclasses are used in Atrial and ventricular arrhythmias
    • 1A
    • 1C
  13. this subclass does not block K+ channels but shorten repolarization phase
  14. this subclass is used in ventricular arrhythmias not atrial
  15. this subclass has no effect on repolarization phase but profoundly slow conduction velocity resulting in QRS widening
  16. this class has a MAO of beta adrenergic agonist with decreased heart rate by blocking norepinephrine and epinephrine receptors
    antagonizes thyroid hormones effects
  17. this class is indicated for - slow ventricular rate in ventricular rate in atrial flutter/fibrillation and paroxysmal supraventricular tachycardia(PSVT)
  18. side effects of this class include bradycardia and all other side effects that go with beta-blockers
  19. this class has a MOA - block K+ channels leading to prolonged repolarization and QT longation, except ibutilide
  20. this class agent is indicated for
    atrial and ventricular arrhythmias
    conversion of atrial flutter/fibrilation
  21. this class agent MOA - Ca+2 channel blockers decreasing the heart rate
  22. this class agent is indicated for slow ventricualr rate in atrial flutter/fibrillation and PSVT
  23. class IA agent
    80% hepatic metabolism
    2-4 days to reach steady state
    adverse effect of GI irritation
    a polymorphic ventricular tachycardia with hypokalemia and/or hypomagnesium
    metabolized by CYP3A4
    quinidine salts - quinora
  24. class IA agent
    actually two drugs
    30% lupus like syndrome (slow acetylators)
    1% agranulocytosis
    • procainamide HCL - pronestyl
    • N-acetyl - NAPA
  25. class IA agent
    very potent negative inotropic properties
    IND - idiopathic hypertropic subaortic stenosis
    has an inactive metabolite with potent anticholinergic properties
    disopyramide phosphate - norpace
  26. class IB agent
    indication - ventricular arrhythmias only
    extensive first pass effect
    t 1/2 - 1.5 hrs
    hepatic metabolism to two active and potentially neurotoxic metabolites leading to drowsiness
    adverse effects - monitor closely for CNS toxicity, dizziness, speech disturbances, respiratory depression, seizures
    lidocaine HCL - xylocaine
  27. this drug comes in a lidopen auto inj.
  28. class IB
    ind - ventricular arrhythmias only
    adverse effects - monitor closely for CNS toxicity
    possible agranulocytosis and pulmonary fibrosis
    mexiletine HCL - mexitil
  29. class IC agent
    uses dropped off due to increased mortality
    decrease left ventricular function due to negative inotropic properties
    IND - PSVT, paroxysmal atrial fibrillation/flutter
    t 1/2 - 20hrs
    flecainide acetate - tambocor
  30. class IC agent
    ind - PSVT, paroxysmal atrial fibrillaton/flutter
    100% hepatic metabolism to a metabolite that has active beta-blocker properties
    drug interactions - inhibits hepatic metabolism of some drugs
    propafenone HCL - rythmol
  31. class IC agent
    ind - PSVT, paroxysmal atrial fibrillation/flutter
    capable of inducing its own metabolism
    adverse effects - N/V
    moricizin HCL - ethmozine
  32. class III agent
    clearly demonstrated to decrease arrhythmia in post MI and heart failure patients
    t 1/2 - 45 days
    adverse effects hypo/hyperthyroidism
    containd Iodine
    amiodarone HCL - cordarone
  33. how can we avoid accumulation and toxicity in class III agents
    add and ester group
  34. new product for 2009
    non-iodinated analog of amiordarone
    no thyroid, pulmonary, ocular toxicity
    MOA - unknown because it has all 4 properties of vaughn-williams classes
    dronedarone - MULTAQ
  35. class II agent
    IV only
    adverse effects because of IV faster drug infusion - hypotension, N/V
    digoxin toxicity is aggravated by catecholamines that are released by this drug
    bretylium tosylate
  36. a class II & III agent
    MOA - beta blocker and K+ channel blockade
    100% absorbed
    excreted unchanged in the urine
    racemic mixture - pure d-enantionmer has been shown to increase mortality by 65%
  37. class III agent
    blocks K+ outflow
    dofetilide - tikosyn
  38. class III agent
    promotes Na+ influx
    may mask arrhythmias caused by digoxin
    ibutilide - corvert
  39. class IV agents
    only 2 approved by the FDA for arrhythmias
    posible alternative medicines to beta-blockers for arrhythmias
    contraindicated in systolic dysfunction due to negative inotropic effects
    CYP inhibitors
    • verapamil
    • diltiazem
  40. these three drugs are L-type Ca+2 channel blockers
    • verapamil
    • diltiazem
    • 1,4-dihydropyridine
  41. misc agent
    MOA - acts at purine receptors to slow or block conduction through the AV node
    diagnostic aid in determining wide QRS complex
    t 1/2 - 1-10 sec.
    contraindicated in sich sinus syndrome, second or third degree AV block, patients with asthma or COPD
    drug interactions - caffeine and theophylline block their receptors, large doses are needed
    adenosine - adenocard
  42. misc agent
    low adenosine A2A receptor agonist - increases vasodilation and coronary blood flow
    IND - radionuclide myocardial inaging
    Interactions - no methylxanthine 12 hours before
    aminophylline can reverse persistant adverse reactions
    regadenoson - lexiscan
  43. interventional cardiology method treatment to kill off the problematic tissue
    radio frequency ablation (RFA)
  44. patients reposition pacemaker so it comes out of place and can pull the lead out
    twiddler syndrome
  45. these cardiovascular agent consist of 5 protein subunits
    regulate smooth (cardiac) muscle contraction
    calcium channel blockers
  46. three prototypical chemical classes of Ca+2 blockers
    • phenylalkylamines
    • 1,4 dihydropyridines
    • benzothiazepine
  47. name the three status equilibrum states that are a function of stimulus frequency and membrane potential
    • open
    • resting
    • inactivated
  48. what status of equilibrium does phenylalkylamines and benzothiazepine bind to
    AFTER the channel is open
  49. what status of equilibrium does 1,4-dihydropyridines act on
    open or closed
  50. indication of calcium channel blockers
    control of angina and hypertension
  51. verapamil and diltiazem have both cardiac and vascular actions?
  52. 1,4-dihydropyridines have more pronounced what actions
  53. two side effects of calcium channel blockers
    • may precipitate CHF
    • edema of the hands and feet
  54. calcium channel blocker
    a benzothiazepines
    Slow release products only
    incompatible with furosemide
    diltiazem HCL - cardizem
  55. calcium channel blocker
    IND - chronic stable angina
    bepridil HCL - vascor
  56. calcium channel blocker
    prinzmetals angina
    unstable angina
    • verapamil - calan
    • bepridil HCL - vascor
  57. calcium channel blocker
    1,4 dihydropyridines
    IND - hypertension
    extended release
    nisoldipine - sular
  58. calcium channel blocker
    1,4 dihydropyridines
    IND - chronic stable angina
    generic and extended release
    nifedipine - procardia
  59. calcium channel blocker
    IND - hypertension (immediate and SR only)
    chronic stable angina (immediate release products only)
    nicardipine HCL - cardene
  60. calcium channel blocker
    IND - hypertension
    isradipiine - dynacirc
  61. calcium channel blocker
    chronic stable angina
    prinzmetals angina
    amiodipine - norvasc
  62. 1,4-dihydropyradine - 3rd generation 
    IND - injectable for IV when orals are not feasible
    contraindicated in soy or egg allergy
    rapid onste 2-4 minutes
    cleviprex - clevidipine butyrate
Card Set
med chem
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