Cardiovascular II - CA++ antagonists Flashcards
Calcium channel antagonists:
- Selective antagonism of what channel?
- What are the primary uses of Ca++ channel antagonists?
- L-type potential operated channel (thus no effect on neural tissue or skeletal muscle)
- Myocardial ischemia, hypertension, hypertensive emergencies (only DHPs), and cardiac arrythymias (supraventricular tachycardia, atrial fibrillation/flutter - no use of DHPs)
What are other potential uses of calcium channel antagonists?
cardioprotection, esophageal spasm, subarachnoid hemorrhage, hypertrophic cardiomyopathy, and migrane (much better migrane drugs)
What are the three classes of calcium channel antagonists?
1,4 Dihydropyridines
Phenylalkylamines
Benzothiazepines
Example of a 1,4 DHP?
Nifedipine
Example of a phenylalkylamine?
Verapamil (the only drug in this class)
Example of a benzothiazepine?
Diltiazem (the only drug in its class)
Calcium antagonists have four target organ characteristics:
- Relative population of __ type channels - most prevalent in ___ tissues.
- Dependence of tissue on ___ ___ (examples of tissues)
- L, CV
- external Ca++; heart, arterioles, large coronary arteries, cerebral arteries (therefore NOT skeletal muscle)
Calcium antagonists have four target organ characteristics:
- Theoretical ____ of binding sites.
- ____ and frequency dependence of binding sites: binding is greater in the ___ state. Thus, different resting membrane potentials may affect drug effectiveness. Increased frequency of stimulation leads to ____ effectiveness. What drug binds best when the channel is inactive? Second best?
- selectivity
- voltage; depolarized; increased; verapamil; diltiazem
The effects of one type of calcium channel antagonist should never be?
Extrapolated to another type because there is a slight variation in action
Nifedipine, Nicardipine, and Nimodipine:
- Where do the dihydropyridines inhibit L channels?
- They are more potent ____ than verapamil or diltiazem.
- Arterial resistance vessels and large coronary/cerebral arteries
- vasodilators
Nifedipine, Nicardipine, and Nimodipine:
These are potent vasodilators because they inhibit?
cyclic nucleotide phosphodiesterase
Nifedipine, Nicardipine, and Nimodipine:
The DHPs exhibit little dependence on the ___ of ____ and do NOT inhibit ___ conduction at clinical doses. They are ____ inotropes in vitro but in vivo this is reversed by?
frequency; stimulation; A-V; negative; reflex activation of the SNS
Verapamil:
- Drug class?
- It is a less potent dilator of arteries than the ____.
- It produces potent inhibition of?
- Inotropic and chronotropic effects? Results in?
- Phenylalkylamine
- dihydropyridines
- AV conduction
- Negative inotrope/chronotrope –> decreased oxygen demand
Diltiazem
- Drug class?
- As potent as Nefedipine in what function? But?
- Less potent than Verapimil in what action?
- Benzothiazepine
- dilating the coronary arteries but has fewer side effects
- inhibiting AV conduction
Bepridil
- Treatment of?
- It significantly prolongs the cardiac ___ ___ and in suceptible patients it may cause?
- angina
- action potential; torsade de pointes
Bepridil is absolutely contraindicated in what patients?
Those with serious arrhythmias or prolonged QT
Therapeutic uses for calcium channel antagonists?
Hypertension, angina, and cardiac arrhythmias
Use in hypertension:
- What drug is a better choice for severe hypertension? Why?
- These antagonists do not cause what two things associated with other drugs for hypertension?
- Potential for cardiac depression is potentiated by concurrent administration with?
- Nifedipine; reflex cardiac effects are less than those seen with other vasodilators
- Fluid retention or postural hypotension
- Beta blockers
All forms of angina are responsive to Ca++ antagonists; however calcium blockers, especially ____, can ____ angina.
Nifedipine; aggravate
Therapeutic uses in cardiac arrhythmias:
Verapamil and Diltiazem are effective for what problems?
supraventricular tachycardias, reentry tachycardia through the AV node, and atrial fibrillation
Side effects and contraindications:
Ca++ antagonists are not recommended in patients with?
SA or AV node conduction abnormalities or heart failure
Side effects and contraindications:
What side effects are more common with nifedipine?
Hypotension, headache, and peripheral edema
Side effects and contraindications:
What side effects are more common in verapamil?
Most common is cardiodepression – also potential hypotension, peripheral edema, or AV block
Side effects and contraindications:
What side effects are most common for Diltiazem?
This drug has the least side effects; very minimal likelihood to cause hypotension, AV block, or cardiodepression
Pharmacokinetics:
- The calcium channel antagonist subtypes are all orally active, ____ protein bound, and ____ metabolized.
- What is much more bioavailable?
- extensively, highly
- Nifedipine
