USMLE Step 1 Web Prep Angina Drugs

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Anti-Anginal Drugs

Anginal pain occurs when oxygen delivery is inadequate Classic angina (angina o e ort or exercise! is due to coronary atherosclerotic occlusion "asospastic (variant! # reversi$le decrease in coronary $lood low %nsta$le (crescendo! # acute coronary vasospas&(AC'! with platelet aggregation(

Drug strategy:

oxygen delivery $y oxygen reqt $y

vasospas& (nitrates ) CCAs!

*"+, C- or $oth (nitrates, CCAs ) $eta $loc.ers!

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Fig. III-5-1. Nitrates and Nitric

!ide "at#$ay

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Nitrates

1or&ation o 2- is triggered $y ACh, 34, 556 ) hista&ine( 2- activates guanylyl cyclase c78* vasodilation via dephosphorylation o &yosin 9C phosphate which prevents its interaction with actin 2itrates or& 2dilation o large veins preload cardiac wor. vasospas& ) cardiac oxygen require&ent( 6hey platelet aggregation collateral $lood low, a terload

5igh doses

arteriolar dilation

2itrates decrease in arct si:e ) post#8; &ortality(

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Nitroglycerin: Isosor(ide:

ral' su(lingual' transder)al * I+ for)s ,ono or dinitrate oral' so)e e!tended-release

Ad-erse:

1lushing, headache, orthostatic hypotension (syncope! +e lex tachycardia ) luid retention (= counter#productive! 6achyphylaxis > require ?rest periods@ o > 12 hr 8ethe&oglo$ine&ia (&ore li.ely with nitrites eg, a&yl nitrite! ;nteractions: watch other vasodilatorsA
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Sildenafil

*hosphodiesterase 5 (*CD5! is in $lood vessels supplying the corpora cavernosu&( 'ildena il inhi$its *CD5 response( c78* vasodilation $lood low erectile

; used with nitrates (or other potent vasodilators! an excessive all in 3* &ay lead to death ro& C" causes including 8;(
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/yanide "oisoning

'odiu& nitrite or a&ylnitrite can $e used in cyanide poisoning( 6hey pro&ote or&ation o &ethe&oglo$in which $inds C2# ions or&ing cyano# &ethe&oglo$in( 6his prevents the inhi$itory action o C2 # on co&plex ;" o the electron transport chain( Cyano#&ethe&oglo$in is then reconverted to &ethe&oglo$in $y treat&ent with sodiu& thiosul ate, or&ing the less toxic thiocyanate ion ('C2 #!(

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Fig III-11. ,ec#anis)s of S)oot# ,uscle /ontraction

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2eta 2loc3ers

2o actions on vasculature # act directly on the heart

5+, orce o

contraction ) Coxygen require&ent( *rophylactic in angina o e ort (not vasospastic! and o set re lex tachycardia caused $y nitrates Carvedilol equivalent to isosor$ide dinitrate(

Drugs in 4nsta(le Angina

2itrates with $eta $loc.ers plus oxygen 5eparin, war arin ) antiplatelets (A'A, ticlopidine! ;;$F;;;a receptor inhi$itors (a$cixi&a$, epti i$atide, tiro i$an!

A 72-year-old woman with mild heart failure is treated overzealously with a thiazide diuretic. A few days later, the woman complains of muscle weakness, and laboratory tests demonstrate hypokalemia. Which of the following is most likely increased in this woman !A" Arterial #$ concentration !%" &lasma aldosterone !'" &lasma sodium !(" &otassium retention !)" *odium retention

Explanations:
The correct answer is B. +hiazide diuretics increase the urinary e,cretion of sodium and water by inhibiting sodium reabsorption in the early distal tubule. +his increases delivery of tubular fluid to the distal tubule, and contraction of plasma volume causes aldosterone secretion to increase. +he net effect is to increase sodium reabsorption at the distal tubules, concomitantly increasing the loss of potassium and hydrogen ions. +he increase in potassium e,cretion has caused hypokalemia !low plasma potassium", which also stimulates aldosterone secretion. +his combination of sodium and potassium depletion acts to generate a metabolic alkalosis. Arterial p# is increased and arterial #$ concentration

(choice A) is decreased with metabolic alkalosis. *odium depletion tends to decrease plasma sodium (choice C) levels, although the effect is usually small. -veruse of the thiazide diuretic has caused depletion of sodium and potassium by the kidneys, not retention of sodium and potassium (choices D and E).