Cardio drugs Flashcards
What are the effects of quinidine? What other drug do we often administer with it?
- Block open Na+ channel (↑ AP duration, ↑ ERP)
- Muscarinic receptor block (↑ HR)
- Alpha block (→ reflex tachy)
Due to muscarinic block we often give digitalis to slow AV conduction
What is the term for the condition caused by quinidine toxicity? What are main side effects?
Cinchonism:
- Antimuscarinic: constipation, cycloplegia, mydriasis, ↑QT interval → torsades de pointe
- Anti-α: diarrhea (relaxed sphincters), miosis
- Other: CNS excitation, tinnitus
Drug interactions of quinidine:
- Hyperkalemia → enhances effects; hypokalema → reduces
2. Displaces digoxin from tissue-binding sites → higher free conc. → potential toxicity
Toxicities of procainamide
- hapten → hypersensitivity rxn → SLE-like syndrome (also occurs with hydralazine and isoniazid; anti-histone is highly specific serum test)
- metab by N-acetyltransferase → [ ] varies w/ slow/fast metabolizers
- hematotoxicity → do routine CBC, watch for infxn/bleeding
- CV effects (torsades) - has some antimuscarinic activity
Name 3 Class IA antiarrhythmics
- Quinidine
- Procainamide
- Disopyramide
“The Queen Proclaims Diso’s pyramid”
How do Class IB drugs work?
- Block inactivated Na+ channels (so targets depolarized tissue s.a. MI tissue)→ keep channels refractory
- Block slow Na+ “window” current that normally prolongs plateau → ↓ AP duration
These effects allow for increased filling time (diastole) so the heart can function better post-MI
What is the most important Class IB antiarrhythmic and when is it used?
Lidocaine
- post MI
- Open-heart surgery (like MI, lots of depolarized tissue to act on)
- Digoxin toxicity (digoxin depolarizes heart mm. by blocking Na+ pump)
What are the adverse effects of digoxin?
CNS toxicity - seizures
Least cardiotoxic of conventional anti-arrhythmics (this is why we prefer electrical cardioversion > chemical)
Why is lidocaine administered by IV for arrhythmia? What are the forms of lidocaine that can be taken orally?
IV only b/c first-pass metabolism;
Mexiletine and Tocainide
Why are class IC antiarrhthmics only a last resort? What conditions would warrant its use?
They are very proarrhthmogenic (esp. post-MI) and in multiple studies has led to sudden death.
Used in SVTs (including A fib.) and last resort in refractory VT.
IC is Contraindicated in structural and ischemic heart disease
What do class II antiarrhythmics do?
Beta blockade → ↓ cAMP, ↓ Ca 2+ currents → decrease slope of phase 4 depolarization in SA/AV node → suppress abnormal pacemakers
Give 6 examples of class II antiarrhythmics
- metoprolol
- propranolol
- esmolol
- atenolol
- timolol
- carvedilol
What are class II antiarrhythmics used for?
- Prophylaxis post-MI is most common use, not as antiarrhythmic (negative inotropic effect → ↓ O2 demand so angina does not → MI)
- SVT (β-blockers slow AV node conduction especially)
What are the side effects of β-blockers?
Sexual: impotence
Respiratory: exacerbation of COPD and asthma (bronchoconstriction)
CVS: bradycardia, AV block, CHF (depressive effects); exacerbation of vasospasm in Prinzmetal angina (propranolol)
CNS: sedation, sleep alterations
Metabolic: dyslipidemia (↓ lipolysis)
Who should not take β-blockers? How can overdose be treated?
Cocaine users: risk of unopposed α-adrenergic receptor agonist activity
Treat β-blocker overdose with glucagon
What is the mechanism of action of class III antiarrhythmics?
prolonged repolarization
What are the clinical uses for class III antiarrhythmics?
a. fib., a. flutter.
v. tachy
(blocks repol. of all cells so wide use)
Why does amiodarone suck?
T1/2 = 80 days (so it takes forever to get to steady state and to remove from body if toxic)
Why? because it acts as a strong hapten (via iodination) →
1. pulmonary fibrosis (binds to lung proteins → chronic inflamm → irreversible damage)
2. hepatotoxicity
3. hypo/hyperthyroidism (amiodarone is 40% iodine by wt)
4. Deposits anywhere, esp. cornea and skin (→ “smurf” skin b/c iodine + sugar = purple/blue color) → photodermatitis
5. Neurologic effects
6. Constipation
7. CVS effects (brady, heart block, CHF)
What tests should you use to follow patients taking amiodarone?
PFTs, LFTs, TFTs
Besides its effects as a class III antiarrhythmic, what other classes does amiodarone effect?
I, II, and IV (all classes) + alters lipid membrane
List 4 class III antiarrhythmics
Amiodarone Ibutilide Dofetilide Sotalol (AIDS)
Describe the use of sotalol as an antiarrhthmic
- class II and III
- used only for life-threatening ventricular arrhthmias
- Causes torsades de pointes and excessive β-blockade
Which is a more pressing issue: atrial or ventricular arrhythmias?
ventricular → can lead to death quickly vs. atrial which has a main risk of thrombosis
What is the toxicity of ibutilide?
torsades de pointes
What are the only two Ca2+ channel blockers that are approved for use as antiarrhythmics (class IV)?
Verapamil, diltiazem
these vs. dihydropyridine Ca+ channel blockers have high affinity for cardiac channels vs. vascular → no reflex tachy
What is the mechanism of class IV antiarrhythmics?
block slow L-type Ca2+ channels → ↓ phase 0 & 4 slopes in SA and AV node → prevention of nodal arrhythmias (s.a. SVT) and rate control in a. fib.
What are the risks associated with class IV antiarrhythmics?
- CV: AV block, CHF, sinus node depression
- vascular: flushing, edema (for DPH calcium channel blockers, not the cardiac ones verapamil, diltiazam)
- GI: constipation
What drug interactions arise with class III antiarrhythmics?
- Additive AV block w/ β-blockers, digoxin; (↑ PR interval)
- Verapamil displaces digoxin from tissue binding sites → ↑ serum [ ]
Describe the cause of torsade de pointes
anything that prevents K+ efflux (class III antiarrhythmics, antimuscarinics [atropine, antipsychotics, TCAs, antihistamines, meperidine, amantadine, quinidine]) → cells maintained depolarized → ↑ QT interval → torsade
