Tx of Angina Flashcards
Name the 5 Dihydropyridines CCBs
“Dipines”
- Amlodipine
- Nifedipine
- Felodipine
- Nicardipine
- Isradipine
Name the 2 non-dihydropyridines CCBs
- Verapamil
2. Diltiazem
Uses of CCBs:
- Angina
- HTN
- Arrhythmias
What type of calcium channels do CCBs act on, and why do they not have significant side effects?
L-type calcium channels
- other types of Ca2+ channels are insensitive to CCBs
MOA of all CCBs
Increase the time that Ca2+ channels are closed which:
- reduces the magnitude of Ca2+ current (and therefore less contraction)
- Induce relaxation of Arterial smooth muscle only
- Effect AFTERLOAD (not preload)
Addition MOA of non-dihydropyridine CCBs
Increase the time that Ca2+ channels are closed which:
- reduces the magnitude of Ca2+ current (and therefore less contraction)
- Slow recovery of the channel
*reduce inotropy, slow AV conduction, and slow SA firing
Selectivity of Dyhydropyridine CCBs in the CV system?
- Peripheral vasodilation
2. Coronary vasodilation
Selectivity of non-Dyhydropyridine CCBs in the CV system?
- Peripheral and Coronary vasodilation
2. Cardiac tissue (Myocytes)!
Potential side effect of Dyhydropyridine CCBs?
- Reflex tachycardia (Increase HR)
- Reflex increase in myocardial contractility
- Increase O2 demand
*should only use in combo with B-Blocker to modulate these effects
Pharm effect of non-Dyhydropyridine CCBs
- Decrease inotropy (Contractility)
- Decrease HR
- Slow conduction
- Vasodilate
What type of binding to L-type Ca2+ channels do non-Dihydropyridines (Diltiazem/Verapamil) demonstrate?
Use-dependent binding
- bind to channels with higher activity because it is more likely that they will encounter an open channel to inhibit
(i.e. channels in Cardiac cells)
What type of binding to L-type Ca2+ channels do Dihydropyridines CCBs demonstrate?
Voltage-dependent binding
- bind to channels that have very slow changing voltages
(i.e. Channels in Smooth muscle cells)
Absorption of CCBs?
Absorbed in the GI tract
*extensive 1st-pass hepatic metabolism reduces bioavailabilty
Metabolism of CCBs
Hepatic metabolism
- reduce dose in hepatic disease
- CYP3A4 interactions (verapamil > Diltiazem)
Adverse effects of Dihydropyridine CCBs?
- excessive vasodilation (dizziness, hypotension, headache)
- GI irritation (nausea)
- Peripheral Edema
- Paradoxical exacerbation of Angina (Coronary steal- less common in slow-release form)
- Fetotoxicity
Adverse effects of non-Dihydropyridine CCBs?
- Bradycardia, Asystole, AV Block
- Constipation
- Fetotoxicity
**Do not use w/ B-Blocker (slows conduction) or in CHF (neg-iontropic effects)
Drug interactions with Verapamil and Diltiazem?
- CYP3A4 drugs (Macrolides, Azoles, Statins, Grapefruit juice)
- B-Blockers
Pharmalogical effects of Nitrates?
- Venodilation (Reduced Preload)
2. Coronary Vasodilation
Overall effect of Nitrates on hemodynamics?
BP: Unchanged or slight decrease
HR: Unchanged or slight increase
Pulm Vascular Resistance: Decreased
CO: Slight reduction
Adverse effects of Nitrates
- Hypotension
- may trigger reflex tachycardia, increased contractility and decrease coronary (paradoxically worsen angina)
- Dizziness, orthostatic hypotension, syncope in PTs who are sensitive to reduced preload - Headache *most commonly
- Rash - seen w/ longer acting nitrates and w/ cutaneous administration
Contraindications for Nitrates
Boner Pills (Sildenidil- Viagra)
Biggest problem with nitrate therapy? And how to deal with it?
Loss of efficacy due to repeated exposure (Tolerance)
*Cycle its use with 8-12 hour “nitrate free” intervals
What happens if you abruptly stop IV nitroglycerin in unstable angina? How do you prevent this?
Anginal Rebound - coronary vasospasms
*bridge with transdermal or oral form
Drugs that Tx Angina
- Nitrates
- B-Blockers
- CCBs
- Ranazoline