Antiarrhythmic Drugs Flashcards
where do supraventricular arrhythmias originate
in atria
where do ventricular arrhythmias originate
ventricles
what are two abnormalities that lead to arrhythmias
- abnormal impuses from ectopic foci
multiple spontaneous rhythms generated
- abnormal propagation: generation of re-entrant rhythm –> the damaged area conducts in one direction only –> permits continuous circilation of impulse to occur
what are the phases of cardiac action potential
- rapid depolarization
- partial repolarization
- plateau
- repolarization
- pacemaker depolarization
what are anti-arrhythmic drugs (AARD’s) used to treat
- tachyarrhythmias (vaughan williams classification –> class 1, 2, 3, 4 and digoxin)
- bradyarrhythmias (muscarinic antagonists, B-agonists, methylxanthines)
what is the mechanism of action of class 1 anti-arrhythmic drugs
- block sodium channels
- reduce the rate of depolarization during phase 0
- reduce slope of phase 0
use-dependent channel block
how are class 1 AARD’s subdivided
class 1a- intermediate dissociation
-prolong APD & RP
class 1b- fast dissociation
-slightly decrease APD & RP
class 1c- slow dissociation
-no effect on APD or RP
what is the major indication of class 1a AARD’s
hemodynamically significant or life threatening ventricular arrhythmias
to convert atrial fibrillation to sinus rhythm (quinidine in horses)
what are the side effects of class 1a AARD’s
what are the major indications of class 1b AARD’s
hemodynamically significant or life threatening ventricular arrhythmias
lidocaine effetive in recent onset arrhythmia in dogs
what are the side effects of 1b AARD’s
- tremor, shivering
- muscle fasciculations
- seizures
lidocaine also local anaesthetic
what are examples of class 2 AARDs
B-blockers
what are the types of B-blockers
- B1 and B2 receptors: Propanolol, Sotalol
- B1 receptors: Atenolol
- B1, B2, a1 receptors: Carvedilol
what are the effects of B-blockers
- reduce sympathetic drive: slow AV node conduction, negative inotropes
- reduce oxygen consumption: improve oxygenation
what are the indications of B-blockers
- arrhythmias (both SVA & VA)
- hypertrophic cardiomyopathy
- heart failure
what are the side effects of B-blockers
- worsening CHF
- negative inotropy
- lethargy, depression
- bradycardia
- bronchspasm
what are examples of class 3 AARDs
amiodarone, sotalol, bretylium
what are the effects of class 3 AARDs
block outward K channels
increase APD and RP
amiodarone –> Na channel blockade, a and B blocker, Ca channel blocker
what are the pharmacokinetics of class 3 AARDs
long t1/2
lipophilic
what are the side effects of AARDs
- elavated liver enzymes
- GI disturbances
- pulmonary fibrosis
- thyroid effects
what are examples of class 4 AARDs
verapamil, diltiazem
what are the mechanism of action of class 4 AARDs
calcium channel blockers
block L-type calcium channels –>
profound effect on nodal tissue (reduce AP height, prolong AP)
cardiomyocytes –> shorten AP (negative inotropes, positive lusitropes)
what are the indications of class 4 AARDs
supraventricular arrhthymias
hypertrophic cardiomyopathy
what is an example of cardiac glycosides
digoxin
what are cardiac glycosides from
foxgloves and related plants
what are the 3 components of cardiac glycosides
sugar, steroid, lactones
what are the pharmacodynamics of cardaic glycosides
- antiarrhythmic effects
- baroreceptor/neuroendocrine effects
- positive inotropic effects
- diuretic effects
how do cardiac glycosides lead to antiarrythmic effects
- increases parasympathetic activity –> decreases sinus rate
- inhibit AV node conduction –> prolong RP
overall: slow ventricular response to atrial flutter/fibrillation (supraventricular arrhythmias don’t pass down)
how do cardiac glycosides effect baroreceptors
baroreceptors functions are decreased in heart failure
glycosides increase function –> decrease sympathetic activity, and decrease [catecholamine]
not a primary indication of digoxin
how do cardiac glycosides have a positive inotropic effect
- inhibits Na/K ATPase
–> increases [Na+] in the cardiomyocyte –> slows extrusion of Ca via the Na/Ca exchange transporter –> increases [Ca] stored in SR –> increase Ca released by each AP
mild positive inotrope
explain what this data is showning
control: when cell is stimulated Ca increases and increases contraction
after cardiac glycoside is added: the transient Ca is larger and therefore the contraction is larger
how do cardiac glycosides cause diuretic effects
Na/K ATPase on basolateral aspect of renal tubular epithelial cells –> promote tubular reabsorption of sodium
inhibition –> diuretic effect
what are the pharmacokinetics of digoxin (6)
- oral admin 60-75% bioavailability
- 25% plasma protein bound
- large Vd (skeletal muscle reservoir)
- t1/2 dog 24-30 hours (cats 36 hours)
- approx 7 days to steady state
- renal excretion
what are the adverse effects of cardiac glycosides (3)
- disturbances of rhythm: block AV conduction, increased ectopic pacemaker activity
- effects of glycosides increased if plasma [K+] decreases
- narrow therapeutic index: excessive borborygmi, depression, anorexia, vomiting, diarrhea, cardaic arrhythmia
what are predispositions to cardiac glycoside toxicity (9)
- thin, cachexic
- obese
- ascites
- hypoproteinemia
- hypothyroidism
- impaired renal function
- electrolyte disturbance
- other drugs
- dobermans
how is cardiac glycoside toxicity prevented (5)
- start on low dose
- dose by body surface area
- avoid loading dose
- reduce dose if predisposed
- check serum level after 7 days
how is cardiac glycoside toxicity dealt with
- stop for 3-5 days
- start again at lower dose
- check electrolytes, acid base balance
- treat arrhythmias
- overdose –> activated charcoal/cholestyramine resin, digibind (if in circulation antibody used to encapsulate drug)
what is the mechanism of action of muscarinic antagonists
antagonism of muscarinic acetylcholine receptors
when are muscarinic antagonists indicated
bradyarrhythmias associated with high vagal tone
what are the side effects of muscarinic antagonists (4)
- constipation
- sinus tachycardia
- urinary retention
- dry mucous membranes
what are examples of muscarinic antagonists
atropine
propanthaline
what are examples of B-agonists
isoprenaline (B1)
terbutaline (B2)
what are the mechanism of action of B-agonists
stimulation of B-adrenergic receptors
what are the indications of B-agonists
sinus arrest, AV block
bronchodilator
what are the side effects of B-agonists
- isprenaline: ventricular arrhthymia
- terbutaline: tremor, tachycardia, hypotension
what are examples of methylxanthines
theophylline, aminophylline, etamiphylline
what is the mechanism of action of methylxanthines
mild PDE inhibition
enhanced sympathetic drive –> mild positive inotropic and chronotropic effects
what are the indications of methylxanthines
widely used in HF in past
now bronchodilation
