Chapter 4 CV + hematology drugs - calcium entry blockers and nitrates (antianginals) Flashcards
verapamil (isopten)
calcium entry blockers
- blocks calcium influx
- dilates peripheral arterioles, reducing afterload (amount of pressure that the heart needs to exert to eject the blood during ventricular contraction)
- slows AV node
- prevent reentrant rhythms
- protects myocardium during brief ischemia
- has alpha adrenergic blocking activity
indication
* angina (lessen need for nitrates)
* acute paroxysmal SVT
* slows ventricular response to atrial fibrillation
* HTN
effects
* constipation (decreasing smooth muscle contraction and possibly inhibiting cellular secretion)
* hypotension
* bradycardia
* edema
* CHF
* AV node block (Rare)
* GI upset
* dizziness
contraindicated
IV b-blockers or digitalis
AV node block
sick sinus syndrome
cardiogenic shock
heart failure
hypotension
Vasodilation is induced by calcium entry blockers b/c they inhibit calcium influx
Dilitiazem (cardizem)
- less HR reduction
- reduces afterload by dilating peripheral arteries
- increase o2 suppply to myocardium by preventing sympathetic induced coronary artery spasm
indication
* reduce angina
* inc exercise tolerance in stable angina
* also used as antihypertensive
effects
* edema
* headache
* dizziness
* asthma
* nausea
* rash
contraindication
* AV node block
* sick sinus syndrome (causes slow heartbeats, pauses (long periods between heartbeats) or irregular heartbeats (arrhythmias)
* hypotension
* pulmonary congestion
interaction
* beta blockers and digoxin AV conduction time
* ditilazem inc proporanolol levels
* Cimetidine and drugs metabolized by p-450 increase diltiazem levels
Vasodilation is induced by calcium entry blockers b/c they inhibit calcium influx
Nifedipine (procardia)
- more potent peripheral vasodilation
- fails to dilate coronary arteries
- causes inc in HR and output
indications
* no longer used as single agent d/t toxicity
effects
* MI
* peripheral edema
* dizziness
* nausea
* transient hypotension
* reflex tachycardia
* pulmonary edema
contraindication
hypotension
interactions
* inc risk of severe hypotension
* heart failure
* angina
* nifedipine inc effects of anticoagulants
initial doses can exacerbate angina
isradipine (dynacirc)
- selectively inhibits vascular smooth muscle contraction and SA node conduction with little effect on heart contractility or AV node conduction
indication:
* angina
* HTN
effects
* little tachycardia b/c selective actions
* headache
* peripheral edema
* flushing
high first-pass metabolism
felodipine (plendil)
- peripheral vasodilation
- enhanced myocardial contractility and output
indication
* HTN
effects
* peripheral edema
* flushing
* headache
* dizziness
interaction
increase digoxin levels
amlodipine (norvasc)
- peripheral vasodilation
- enhanced myocardial contractility and output
indication
* HTN
effects
* headache
* edema
* palpitations
Interaction
* increase digoxin
* beta blocker effects
less acute hypotension d/t slow onset
Nisoldpine (sular)
- HTN
nitroglycerin (go nitro)
actions - dilates large myocardial arteries to inc blood supply to heart
* reduce cardiac preload by reducing venous tone; allowing blood to pool in periphery
indication:
* all forms of agina
* immediately before exercise or stress to prevent ischemic episodes
effects:
* hypotension
* rebound tachycardia
* bradycardia
* cerebral ischemia
* contact dermatitis (w/ transdermal prepartion)
* aggravate peripheral edema
sublingual/IV/topical paste/transdermal (for transdermal — tolerance may occur
interaction
* alcohol
* antihypertensive
* vasodilators
* all inc risk of orthostatic hypotension
isosorbide dinitrate (isordil)
- prophylaxis of angina
- not for acute attack
sublingual, oral
beta blockers and calcium entry blockers?
- used in tx of stable angina
- unstable angina is treated with aspirin, heparin
Calcium entry blockers
- smooth muscle relies on influx of extracellular Ca++ for contraction
- Blockade of influx prevents contraction => l/t vasodilation
- smooth muscle is also responsible for propulsion in GI => constipation
- Cardiac muscle and conducting tissue rely on rapid influx of sodium and slow influx of calcium through separte channels for contraction
- the slow ca++ channel is particular important in SA and AV => blockade of these channels => slows the heart
- skeletal muscle are exception b/c they need rapid influx of siudm which triggers release of Ca++ from SR; they do not rely on extracellular calcium (CCBs fail to affect them)
treatment of stable angina
- aspirin reduces rate of CV event by 1/3 in patients with stable angina, should be given to all pts unless contraindicated
- beta blockers and calcium channel blockers equally effective in reducing anginal symptoms in stable angina
- short acting CCB such as nifedipine should be used w/o beta blocker
- CCB => vasospastic angina
- similar to above, nitrates improve exercise tolerance and time to onset of angina in pts w/ exertional stable angina
- nitrates contraindicated in patients taking sildenafil (since it potentitates hypotensive effects of nitrates)
treatment of unstable angina
- rupture of an unstable plaque and resulting thrombus formation l/t to unstable angina
- Arterial plaque is made up of materials that enter the artery wall from the bloodstream. These include fat, cholesterol, calcium, waste products from cells, and a clotting agent called fibrin.
- Plaque can also rupture and create a blood clot at the rupture site, as your body’s natural processes try to repair the “injury.” The blood clot can cut off blood flow through the artery and starve your body’s tissues of oxygen and nutrients. Thus, a ruptured plaque can be serious, as it’s the most common cause of a heart attack or stroke.
- heparin primary anticoagulant
- o2 therapy — help with hypoxemic pts from CHF or underlying lung disease
- morphine reduces pain and anxiety that can worsen sx in pt’s
- Beta blockers reduce ischemic burden by dec HR and BP (10-20%)
- Nitrates — reduce BP and induce coronary vasodilation
- CCB (two classes, dihydropyridines [nifidipine] & non-dihydropyridines [diltiazem]) —– nifiedipine can be hazardous d/t l/t higher rate of MI or recurrent angina if given without a beta blocker
- diltiazem can be safely used and may reduce rate of death or recurrent MI (best choice if contraindicated for beta blokers)
- Heparin proven effective in setting of unstable angina (up to 35%) when used with aspirin
- lower molecular weight heparin (enoxaparin for e.g) prove to superior over unfractionated heparin
- aspirin reduce rate of recurrent ischemia (decreased blood flow and oxygen to the heart muscle), infarctions, and death by more than 50% (antiplatelet therapy)
- newer antiplatelets — ticlopidine (ticlid) or derivatives of thienopyridines — reduced rates of vascular events compared to aspirin
- however inc risk of neutropenia and rarely cause thromobotic thrombocytopenic purpura (TTP, blood clots form in small blood vessels throughout your body. The clots can limit or block the flow of blood to your organs, such as your brain, kidneys, and heart. This can prevent your organs from working properly and can damage your organs)
- clopidogrel (plavix) was more effecitve in preventing reccurent ishcemic events in pts w/ vascular disease
- both above 2 are acceptable substitutes for pts that cannot take aspirin
adjunctive tx of MI
- thrombolytic therpay reduces risk of death by 20% if given within 12 hrs of an acute infart
- drugs (plasminogen activators) should only be used in the setting of ST elevation
- thrombolysis not effect when patient’s ECG shows ST depression or no diagnostic changes [especially dangerous with non-ST elevation ishcemic syndromes]
Drugs that inhibit clot formation and extension:
1) heparin or low molecular weight heparin
2) IIb/IIIa inhibitors (prevent platelets from sticking) – -tirofiban, eptifabtide, and abciximab
3) aspirin
- aspirin itself (reduces risk of infarction death by 23%)
- additive effect when used in combination w/ thrombolytic medication
- ASPIRIN always used for infarction unless pt has active GI bleed or true allergy to aspirin (clopidogrel can be substitued)
- beta blockers reduce cehst pain, myocardial wall stress and infarct size (during infarct)
- great reduce death after myocardial infarction and these drugs should be given in all patients with acute myocardial infarction who do not have clear contraindications such as pulmomary edema, hypotension, bradycardia, advanced heart block or asthma
- angiotensin inhibitors dec death rates in pts w/ reduced left ventricular dysfunction after infarction (relative risk reduction of death after MI much less powerful)
- ACE inhibitors redue the rate of progression to HF; should be given in all patients presenting w/ acute MI unless have renal failure, hypotension or angioedema
- nitrate therapy not considered
- CCBs do not reduce mortiality during or after acute MI
