IHD Treatment Flashcards
(28 cards)
What are the dihydropyridine CCBs?
Nifedipine, Amlodipine, Felodipine, Nicardipine, Isradipine
What are the non-dihydropyridine CCBs?
Verapamil, Diltiazem
How are CCBs cardioselective?
They work on L-type voltage-dependent Ca2+ channels that are responsible for phase 2 of the cardiac & pacemaker action potential. They have large conductance and slow inactivation.
What is the mechanism of action of CCBs?
- increased time that channels are closed, which reduces the magnitude of the current and therefore contraction
- induce relaxation of arterial smooth muscle to reduce afterload
- non-DHPs reduce inotropy, slow AV conduction, and slow pacemakers
- slow recovery of the Ca2+ channel
What are the differences between the two classes of CCBs?
- Dihydropyridines: selective vasodilators in periphery and heart
- can cause reflex tachycardia
- Must use with beta-blockers
- voltage-dependent binding - bind to channels responding to slow changes in voltage (smooth muscle cells)
- can cause reflex tachycardia
- Non-DHPs: equal effects on cardiac tissue & vasculature
- use-dependent binding - bind to channels constantly opening & closing (cardiac cells)
- Never use with beta-blockers
How are CCBs metabolized?
- absorbed from GI tract
- extensive first-pass metabolism
- eliminated via hepatic metabolism
- reduce dose in hepatic disease
- metabolized by & inhibit CYP3A4
Why are CCBs formulated for slow release?
- most have short plasma half-life
- absence of bolus effect that causes reflex tach, headache, & coronary steal
What are the adverse effects of dihydropyridines?
- pregnancy category C, crosses placenta & breast milk
- excessive vasodilation → dizziness, hypotension, headache
- GI irritation
- peripheral edema
- coronary steal worsening angina
What are the adverse effects of non-dihydropyridines?
- bradycardia, asystole, AV block
- NEVER GIVE WITH BETA-BLOCKERS
- CHF
- constipation
- pregnancy category C
What are the drug interactions of non-DHPs?
- metabolized and inhibit CYP3A4
- can increase plasma levels of statins
- rifampin will decrease levels
- verapamil reduces clearance of digoxin
- beta-blockers cause increased risk of SA or AV block
What is the molecular mechanism of action for nitrates?
- Organic nitrate ester reductase induces denitration and releases NO
- NO activates guanylate cyclase to cause an increase in cGMP
- cGMP activates PKG
- PKG induces smooth muscle relaxation by reducing [Ca2+]
What are the CV effects of nitrates?
- venodilation decreases preload
- decreased pressure in diastole improves coronary a perfusion
- coronary vasodilation
- reverses/prevents vasospasm
- hemodynamic changes
- BP unchanged or slight decrease
- HR unchanged or slight increase
- pulmonary vascular resistance decreased
- cardiac output slightly reduced
What are the adverse effects of nitrates?
- hypotension
- reflex tachycardia that worsens angina
- dizziness, orthostatic hypotension, syncope
- headache (transient)
- drug rash (with long-lasting and cutaneous)
Why should nitrates never be taken with Sildenifil (Viagra)?
- Sildenifil is type V PDE inhibitor
- increases cGMP by preventing breakdown
- exaggerated cGMP response can cause profound hypotension and MI from blood pooling
What is the mechanism of nitrate tolerance?
- depletion of tissue cystein required for conversion to NO
- volume expansion, neurohumoral activation
What drugs are used to treat angina?
Nitrates (drug of choice), beta-blockers, CCBs, & Ranazoline (Ranexa)
How do you treat angina?
- increase coronary blood flow
- reduce myocardial O2 consumption
- decrease chronotropy
- decrease inotropy
- decrease preload (venodilation) or afterload (vasodilation)
- prevent platelet aggregation with aspirin
What are the indications for using dihydropyridine CCBs in angina?
- when combined with a beta-blocker
- with sinus bradycardia, SA/AV block
- valvular insufficiency due to reduction of aftelroad)
What are the indications for using non-dihydropyridine CCBs in angina?
- asthma or COPD
- insulin-dependent diabetes
- severe peripheral vascular disease
- depression
- must have good LV function
Why are CCBs reserved for treating angina when beta-blockers can’t be administered or aren’t fully effective?
- fail to reduce reinfarction or death in pts with CHD
- increase morbidity & mortality in patients with LV dysfunction
- significantly higher rates of MI & CHF when used for hypertension
How do beta-blockers treat angina?
- decrease oxygen demand by reducing HR and contractility with exercise
- also increases coronary artery perfusion
- decrease afterload
- do not prevent vasospasm
- combined with nitrates or dihydropyridine CCBs to prevent reflex tachycardia and increases in inotropy
When are beta-blockers contraindicated with acute MI/unstable angina?
with CHF, hypotension, sinus bradycardia, heart block
What is the mechanism of action of Ranolazine?
- FA oxidase inhibitor - increases glucose oxidation and O2 utilization efficiency
- late Na+ current inhibitor - prevents Ca2+ overload and reduces diastolic wall stress
- no effect on HR and BP
What are the indications fo Ranolazine use?
- chronic stable angina with amlodapine, beta-blockers, or nitrates
- not for acute angina
