K+ and Ca2+ blockers Flashcards
How do we achieve the goal of antiarrhythmics?
- decrease or increase conduction velocity
- Alter the excitability of cardiac cells by changing EFP
- Suppress abnormal automaticity
What are class III antiarrhythmics and what do they act on?
K channel blockers
- block them slows repolarization
- increases AP duration and ERP
What are Class III antiarrhythmics useful for?
- suppressing reentry
- prolong time cell is unexcitable
- Prolongs QT
What is common a Class III AA drug? what other effects does it have on CV system?
Amiodarone
- prolongs AP
- also a potent to blocks Na+
- Weak B-blocker
- Weak Ca2+ blocker
What are some extra-cardiac effects and therapeutic uses of Amiodarone?
Vasodilation
V-Tach, V-fib and A flutter/fib
What are the pharmacokinetics of Amiodarone?
Hepatic and metabolite is bioactive
- 1-3 month long 1/2 life
- Substrate for CYP3A4 (Statins)
- Inhibits several P450’s like Warfarin and Digoxin
What is the toxicity of Amiodarone?
Bradycardia and heart block in pts with preexistingSA and AV node dz.
- Heart lung liver skin and tears accumulation
- Blocks T4–>T3 conversion
What does increasing T3 lead to?
Increase in beta receptors in the heart
- increase HR, Force and contraction
- Leads to increase CO
What is the most important adverse effect of Amiodarone?
Pulmonary toxicity
- dose related
What are some other causes of amiodarone toxicity?
- hypersensitivity hepatits
- Photodermatitis, gray blue skin in sun exposed areas. Skin deposits
- Corneal micro-deposits- Halos develop in periph visual fields
What is Dofetilide?
Class III AA
- Very selective K channel blockers
- Prolongs AP
- Increase QT
- increase refractory in His-Purkinje system
What is the toxicity, pharmacokinetics and therapeutic use of Dofetilide?
- life threatening Ventricular arrhythmias
- CPY3A4 metabolism
- Maintenance and restoration of normal sinus rhythm in A-fib.
- Contraindicated in Long QT, Bradycard and hypokalemia
What is the mnemonic for Class III AA?
AIDS Amiodarone Dofetilide Ibutilide Sotalol
What is the cardiac effects of ibutilide?
- Prolongs AP
- Also slow inward Na ACTIVATOR (delays repole)
- inhibits Na inactivation (increase ERP)
What is the toxicity, PK and therapeutic use?
- Excessive qt interval prolongation leading to Torsades and life threatening ventricular arrhythmias
- Hepatic metab
- Acute conversion of a-fib and fibrillation to NS rhythm
- more effective for termination of flutter in 20 minutes
Why is amiodarone contraindicated in pts with heart block and SA node dysfunction?
Because of its Class IV effects causing bradycardia and atrioventricular block
What is the MOA of class IV AA?
bind to L-type Ca2+ channels located on VSM, cardiac myocytes and SA/AV nodes
What are the Class IV AA effects then?
- Vasodilation
- Decreased myocardial contractility
Which phase of the AP curve does Class IV affect?
Phase 2
- blocking Ca thus shortens phase 2
- shortens AP (increase ERP)
- reduces force of contraction
- less available for trop to bind to
What does blocking Ca like Class IV AA do to the nodal cells?
Blocks pacemaker currents
- slows HR
- Decreased conduction velocity (mainly Av node)
- prolong PR
What are Class IV AA’s commonly used for?
HTN
-Resistance= x/r^4
Why are Class IV AA indicated for angina?
- Vasodilation
- Leads to reduced art pressure decrease afterload and thus oxygen demand
- Decrease HR and contractility
- Reverse or prevent vasospasm
What else are Class IV useful for?
- Ectopic foci causing aberrant AP firing
2. Helps block reentry which can cause SVT by prolonging repole
What are the 2 subclasses of Class IV AA’s?
- Dihydropyridines
- Non-dihydropyridines
- differ in specificity for cardiac vs vascular L type Ca2+ channels
What are Diydropyridines mainly used for?
Smooth muscle selective class
- Reduced systemic vascular resistance and art pressure to treat HTN
- NOT ANGINA- leads to reflex tachycardia
What are the two non-dihydropyridines?
- Verapamil
- Diltiazem
- only two used clinically
What is Verapamil mainly used for?
Selective in myocardium
- less effective in vasodilator drug
- good for angina, arrhythmias, reducing cardiac O2 demand and treating vasospasms
What is diltiazem mainly used for?
Between Verpamil and Dihydropyridines for Vascular selectivity
- reduce arterial pressure without tanking it
What is contraindicated with Class IV AA drugs?
B-blockers
What are some side effects and contraindications of Class IV drugs?
Flushing, edema, constipation, HoTN, reflex tach, nervousness, lack of energy
- Preexsting bradycard, conduction defect or HF
What is the therapeutic use of Varapamil?
SVT, a-fib and flutter
– Contraindicated in Wolff-Parkinson-White
What is the MOA of Adenosine?
Activation of K channels and inhibition of L-type Ca channels
- Hyperpolarization
- suppression of Ca dependent AP’s ( Nodal tissue)
What blunts the action of adenosine because they are adenosine receptor antagonists?
Caffeine
Theophylline
What is adenosine used for?
SVT
- 15 sec 1/2 life
What are some SE of adenosine?
-Flushing and HA
-AV block
-Rapid arterial HoTN and reversed shortly after infusion
-SENSE OF IMPENDING DOOM
- bronchospasm
-
Who is adenosine contraindicated from?
2 and 3rd degree AV blocks pts
What is the cardiac glycoside drug used in the US and for what?
Digitalis
- HF mainly
- a-fib/flutter
- some reduction of Ventricular rate when driven from above
What is the MOA of Digitalis?
Inhibits Na/K/ATPase pump
- increase intracellular Na
- shutting down Na/Ca pumpt
- increase intracellular Ca
- Increase contractibility
- Increase SV but decreased HR to keep
What happens to the membrane potential with someone on digoxin?
Depolarized
- decreased intracellular K and increase intracellular Na
How does digitoxin affect conduction?
decreased it through the SA and AV–> increasing refractory period
- Increase intracellular Ca leads to decreased extracellular. Thus less to influx of the funny channels thus slowing the rate.
What are some side effects of digitalis?
Extreme AV block
- Hyperkalemia
- cholinergic effects–> N, v, d, blurry yellow vision, arrhythmias
When is digitalis contrindicated?
- AV block
- Hypokalemia
- WPW
- Renal failure
- Class I, II, III, IV,, NSAIDS and diuretics
Arrhythmias cause by what from digitalis?
Increase automacity and decrease AV conduction
