drugs from book

Question 1

categories of inotropic drugs & how they work

Answer 1

cardiac glycosides
sympatheomimetic amines
PDE3 inhibitors

all enhance cardiac contraction by increasing intracellular calcium concentration
shift frank-starling curveupward - so fof given Ven filling pressure –> SV & CO increased

Question 2

two desired effects of digitoxin

Answer 2

1) improve contractility of failing heart
2) prolong refractorey period of the AV node in pts with SV arrhythmias

Question 3

MOA of digoxin/digitalis

Answer 3

1) mechanical effect:
inhibition of sarcolemmmal Na/K aTPase pump
increase intracellular Na –> decreases amount of Ca extruded via Na/Ca exchanger–> so more Ca is pumped into SR
-subsequent AP more ca is released –> enhances force of contraction

2) electrical effect –> slows conduction velocity & increases refractoriness at AV node
modifies autonomic nervous system by enhancing vagal tone and reducing sympathetic activity

Question 4

dangers of digitoxin

Answer 4

1) less negative resting potential –> bc inhibition of N/K atpase –> partial inactivation of fast Na channels - slower rise of phase 0 depolarization & reduction in conduction velocity –> can increase risk for reentrant arrhthmias
2) decreased action potential duration –> at high concentrations of dig –> elevated intracellular calcium increased acitvity of CA dependent K_ channel –> opening of thi schannel promotes K+ efflux and more rapid repolarization (also higher intracel Ca inactivates that Ca channels decreasing inward depolarizing curent) –> descrease in AP duration and associated shoretened refractory period increase the time during which cardiac fibers are responsive to external stimulation –> opportunity for propogation of arrhythmic impulses
3) enhanced automaticity –> less neg resting potential (may induce phase 4 depolairzation in nonpacemaker cells) & dig induced increase in Ca may trigger delayed afterpolarizations

Question 5

clinical uses of digoxin

Answer 5

1) historically used to tx HF caused by decreased vent contracility ** only useful in HF if contactility failing
now usef in pts with HF complicated by afib or when symptoms don’t respond to acei, bb and diuretics
*does not prolong life expectancy of pts with CHF but improves QOL

2) antiarrhythmic agent in afib, a flutter and PSVT
(less common bc BB, CCB and amiodarone are more effective)

Question 6

risk factors for dig toxicity

Answer 6

–> further inibits pump
hypomagnesemia
hypercalcemia

Question 7

sympathomimetic amines MOA

Answer 7

bind cardiac Beta1 receptors –> increase acitivty of adenyalte cyclase, –> increased formation of cAMP
-increase cAMP activates protein kinases which promote intracellular Ca influx by phosphorylating L-type calcium channels –> increase calcium tentry triggers corresponding increase in Ca release from SR –> enhances force of contraction

Question 8

names of sympathomimetic amines

Answer 8

dopamine & dobutamine –> used for acute HF (IV)
norepinephrine, epineprhine & isoproterenol

Question 9

dopamine - clincial uses

Answer 9

precursor to norepi
1) low doses–> dopaminegic receptors in renal and mesenteric vascular beds –> local vasodilation & increases renal blood flow and glomerular filtarion, facilitating diuresis
2) medium doses –> increase inotropy by stimulating B1 receptors directly and indirectly promoting release of norepi from sympathetic nerve terminals
3) high doses –> dopa also stimulates alpha receptors –> vasocontriction and elevating systemic resistance –> high dose dopa in hypotensive states such as shock
loses efficacy after one week bc downregulation of receptors

Question 10

dobutamine

Answer 10

synthetic dopamine that stimulats B1,2 &alpha
increase cardiac contractility (b1) but does nto increae peripheral vascular reistance bc balance bw alpha mediated vasocon and b2 mediated vasodil
useful in tx of HF not accompanied by hypotension
loses efficacy after one week bc downregulation of receptors

Question 11

norepinephrine

Answer 11

B1 and alpha activity
B1 –> +inotropinc and chronotropic effects
potent vasocon
useful in pts with warm shock –> bc they have cardiac contactile dysfx and peripheral vasodilation (low BP)

Question 12

epinephrine

Answer 12

alpha, b1 & b2
IV in low doses –> mostly b1 –> increases vent contractilty and speeds impulse generation & b2 –> vasodil reduct TPV and BP
higher doses –> potent vasopressor bc alpha action dominates b2

used most often in cadiac arrest –> combo of inotropic and chronotropic and vasoconstriction also helps in this setting
**not used w beta blockers –> bc unopposed alpha activity –> raise arterial bp

Question 13

isoproterenol

Answer 13

synthetic epi but PURE beta - beta 1 & 2
+ inotropic and chronotropic effects –> increases CO
peripheral vasodilation –> reduction in peripheral resistance

used in emergenceis to increase heart rate in pts with brady or heart block
*not used in pts with my ocardial ischemia

Question 14

milrinone

Answer 14

PDE 3 inhibitor –> inotropic agent
inhibition reduces breakdown of cAMP –> leads to enhanced Ca entry into cell and increaed contraction
in VSM –> increase cAMP results in vasodilation (b/c cAP inhibits myosin light chain kinases)
used to tx acute heart failyre when conventional vasocilators, inotropic agents and diuretics havent worked
potential for serious SE–> only used in hospital in ST

Question 15

vasopressin

Answer 15

natural vasodilator that regulates water
at higher-than-natural doses potent vasoconstrictor bc directly stimulates vascular smooth muscle –> maintains BP for patients in vasodilatory shock

Question 16

why is vasoconstriction initally helpful in HF?

Answer 16

maximaizes LV preload (increases venous tone enhances venous return) and helps to maintain systemic BP (bc of arterial constriction)

Question 17

vasodilator drugs (names)

Answer 17

venodilators –> nitrates
mixed –> nitroprusside, aci, arbs, alpha blockers alpha 2 central agonist, nesiritide
arteriolar dilators–> hydralaizine, minoxidil, ccb

Question 18

effects of acei

Answer 18

decreases systemic arterial pressue, facilitate natriursis, reduce adverse ventricular remodeling
increase BK (bc ace normally breaksdown) –> contributes to antihypertensive effect by stimulating release of NO

Question 19

clincal uses of acei

Answer 19

1) htn –> descrease BP with little change in CO or HR (similar effect to BB & diuretics WITHOUT adversely affecting serum glucose or lipic concentrations so used in diabetic htn bc may slow diabetic nephropathy development
2) HF–> reduces afterload (PVR), reduce cardiac filling pressure (preload) and increase CO (BP unchanged due to balance) –> augmented CO lowers sympathetic stimulation –> so less norepi
improve survival in CHF and following MI

Question 20

arbs

Answer 20

1)compete with angII at AT1 receptors –> more complete block of angII than acei bc alternative pathways
but do not affect BK levels
as effective as acei and are better tolerated
as with acei - htn effect is enhance with concurrent use of thiazide diuretic

2) severt HF - hemodynamic effects similar to acei (used in hf for pts intolerant of acei)

Question 21

direct acting vasodilators - names

Answer 21

hydralazine
minoxidil
soidum nitroprusside
fenoldopam

first two used as LT oral agents
seoncd two IV in acute setting

Question 22

hydralazine

Answer 22

potent and direct arteriolar dilator that acts on precapillary arterioles & no effect on systemic veins
MOA-unknown

fall in BP–> sympathetic activation –> tachy so often given with bblocker
not used often for htn
used to tx hf in pts with systolic dysfx with venodilatoer dinitrate –> improves symtpoms in pts with mild to moderate hf

**acetylated for excretion in liver –> varying degree of acetlyators!
SE- headache, palpitations, flushing, nauseua, anorexia

Question 23

minoxidil

Answer 23

arteriolar vasodilatorion without venous impact
increase K channel permeability –> smooth muscle hyperpolarization and relaxation
often coadministered with BB

used for severe or intractable htn

SE-fluid retention & hypertrichosis

Question 24

soidum nitroprusside

Answer 24

potent dilator of arteries and veins
IV for hypertensive emergencies & for preload and afterload modulation in severe CHF

metabolized by rbc –> liberates NO–> activates guanylate cyclase in VSM
Bblocker concurrently
onset within 30 seconds & peak with in 2 minutes

metabolized into cyanide –> liver transofrms into thiocyanate (levels msut be monitored)

Question 25

effect of CCB in VSM

Answer 25

contraction of VSM depends on cytoplasmic ca concentration --> CCBs promote relaxation of VSM by inhibiting Ca entry thorugh voltage gated channels

Question 26

effect of CCB in cardiac muscle

Answer 26

interfere with excitation contraction coupling and decrease force of contraction also will slow rate of SA and AV firing if binds to open channel (verapamil & diltiazem)

Question 27

CCB clinical uses

Answer 27

1) angina pectoris --> decrease myocardial o2 comsumption & increae supply (dilation) 2) coronary artery spams --> vasodilate 3) htn --> arterial smooth muscle relazation 4) SV arrthymias --> decrease conduction velocity & increase refrcatoriness of AV node **often used in htn --> more than bb and aci espeically in elderly pts

Question 28

organic nitrates (nitroglycerin)

Answer 28

produce vsm relaxation --> drug converted to NO which activates guanylate cyclase to product cGMP --> increase intracellular cGMP leads to SM relaxation

Question 29

clinical use of nitroglycerin

Answer 29

primary to tx angina pectoris --> venodilation leading to reduced LV preload --> smaller V size lowers venti wall stress and myocardial o2 consumption alleviates o2 imbalance

Question 30

nesiritide

Answer 30

human recombinant b type natriuretic peptide --> promote vasodilation and result in sodium and water excretion, augments CO not really used clinically --> doesn_t improve survival in HF

Question 31

central adrenergic inhibitors (alpha 2 agonist)

Answer 31

alpha 2 receptors in presynaptic neurons oc CNS --> when stimualted by alpha 2 agonist --> diminished sympathetic outflow from medulla reduces PVR and dec cardiac stimulation --> dec bp and hr used to be used commonly as anti htn clonidine can be used as skin patch - 1 week SE dry mouth, brady, sedation

Question 32

reserpine

Answer 32

inhibitsuptake of norepi into storage vesicles in postgan and central neurons --> norepi degradation depletion of catecholamines --> dec mycoardial cont and total peripheral resistance SE cns toxicity - depression = not used

Question 33

alpha 1 receptor selective antagonists & use

Answer 33

prazosin, terazosin, doxazosin had been used for htn btu more adverse events than diuretics so not used as often now mostly used to tx symptoms of benign prostatic hyperplasia

Question 34

nonselective beta antagonist

Answer 34

carvedilol - also alpha labetalol - also alpha propranolo nadolo timolol

Question 35

beta 1 selective antagonists

Answer 35

atenolol metopolol

Question 36

uses for bb

Answer 36

1) ischemic heart dz --> dec o2 demand & increase survival post mi 2) htn --> lt effect not really known 3) HF --> clinically stable hf --> may blunt cardiotoxicity of circulationg catecholamines 4) tachy arrhythmias

Question 37

adverse effects of bb

Answer 37

1) bronchospasm 2) impair AV node conduction by b1 3) b2 can worsen raynaud (arterial vasospasm) 4) cant withdraw abruptly 5) reduce HDL 6) can mask hypoglycemia in diabetics

Question 38

classes of antiarrhythmics

Answer 38

1. Class I drugs block the fast sodium channel responsible for phase 0 depolarization of the action potential. They are further divided into three subtypes based on the degree of sodium channel blockade and the effect of the drug on the cell_s action potential duration. 2. Class II drugs are -adrenergic receptor antagonists ( -blockers). 3. Class III drugs block potassium channels responsible for repolarization, thereby prolonging the action potential with little effect on the rise of phase 0 depolarization. 4. Class IV drugs block the L-type calcium channel.

Question 39

tx aims for arrythymia by increased automaticity

Answer 39

1) reduce slope of spontaenous depolarization of phase 4 2) prolong ERP

Question 40

aims to stop reentry circuits

Answer 40

1) prolong ERP 2) impair impulse propagation wthin already slowed retrograde limb --> blockade of Na channels responisble for phase 0

Question 41

aim to stop triggered arrhythmia

Answer 41

supression of early and dealyed after depolarizations

Question 42

class IA uses

Answer 42

1) reentrant arrhythmia --> 2) ectopic supraventricular tachy 3) vent tachy procainamide

Question 43

class I B uses

Answer 43

inhibit the fast Na channel but SHORTEN AP (unlike class I) only work on depolarized cell --> target damaged cells 1) Vent arrhythmias esp those associated with ischemia or dig tox little effect on atrial tissue (bc of shorter AP of atrial tissues) lidocaine - IV administration only

Question 44

class IC uses

Answer 44

most potent Na channel blockers markedly decrease upstroke of AP and conduction velocity in atrial, ventricular and purkinje fibers prolong AV ERP (but not elsewhere) tx supraventricular arrhythmias flecainide

Question 45

use of class II

Answer 45

used in both supravent and vent arrhythmias slow vent rate in atrial flutter and fib by impairing conduction and increasing refractoriness of AV node inhibit beta adeneregic effect of more rapid upslope of phase 4 depolarization & increased firing of SA node (reduce automaticity) & ltos more

Question 46

amiodarone

Answer 46

major therapeutic effect is to prolong AP duraction and refractoriness of all cardiac regions -dpresses phase 0 depolarization slope through Na channel blockade -b blocking effect and weak ccb -dec SN diring rate, suppress automaticity, interrupt reentrant circuits and prolong PR, QRS, QT intervals also vasodilator and negative inotrope

Question 47

uses of amiodarone

Answer 47

1) afib 2)a flutter 3) vent tachy 3) vent flutter 5) SVT including bypass tracts

Question 48

sotalol

Answer 48

nonselective b beta bocker but also oral antiarrh drug bc additional class III properties --> prolongs AP duration, increase RP of atrial and vent tissues and inhibits conduction in accessory bypass tracts tx both SV and V arrh

Question 49

class IV

Answer 49

verapamil & diltiazem --> impact SA and AV nodes -dec rate of rise of phase 0 depol and conduction velocity and lengthens RP of AV node

Question 50

use of class IV

Answer 50

primary used for tx of reentrant SVT (eg AVNRT)

Question 51

adenosine

Answer 51

most effective drug for rapid termination fo reentrant SVT (eg AVNRT) binds adenosine receptors --> activates K channels --> hyperpolarizes membrance --> suppresses spontaneous depol of SA node and slows conduction through AV node -decreases intracellular cAMP --> decrease in inward pacemaker current (If) and inward calcium current) 10 second half life

Question 52

statins

Answer 52

inhibit hmg coA reductase - most effective drugs for reducing LDL cholesterol rate controlling step in cholesterol synthesis lower cholesterol by reducing pool so more LDLR --> more taken out of blood reduce serum LDL by 20-55% & decrease plasma TG by 7-30% & HDL increase 5-15%

Question 53

bile acid sequestrants

Answer 53

cholestyramine, colestipol & colesevelam bind bile acids in intestine and prevent reabsorption --> to make up for loss more hepatic cholesterol is converted into newly produced bile acids dec pool --> increase LDLR but since increase in VLDL production --> elevated TG

Question 54

cholesteroal absorption ihibitors

Answer 54

ezetimibe --> competitively inhibits transport NPC1L1 --> reduced chylomicron production ---> increase LDLR on liver to make pool bigger

Question 55

niacin

Answer 55

raises HDL cholesterol and reduced LDL and TG, reduces LPL(a) inhibits lipolysis --> less FA into liver and less VLDL also enhances LPL at adipose and muscle cells *flushing as side effects

Question 56

fibrates

Answer 56

gemfibrozil and fenofibrate --> reduce TG by 50% and raise HDL by 20% but LDL effect variable acton PPAR alpha --> dec TG by augmenting FA ox, increased VLDL cata b--> inc LDL :( --> actviate gene for apoprotein A1--> increase HDL

Question 57

tx to prevent recurrent ischemic episodes

Answer 57

BB -> decrease recurrent MI and mortality following acute MI organic nitrates --> purely symptomatic relief no improval in survival CCB

Question 58

clopidogreal

Answer 58

novel antiplatelet agent that blocks platetely P2y12 receptor --> preventing platelet activation and aggregation can be used in pts allergic to aspirin or in combo with aspirin

Question 59

two types of diuretic

Answer 59

thiazide - HCTZ | Loop - furosemide

Question 60

non selective alpha inhibitor

Answer 60

phenoxybenzamine

Question 61

selective alpha blocker

Answer 61

prazosin

Question 62

central alpha blcoker

Answer 62

clonidine

Question 63

aldosterone antagonist

Answer 63

spironolactone

Question 64

arterial vasodilators

Answer 64

``` hydralazine sodium nitroprusside (IV drip) ```

Question 65

venodilators

Answer 65

nitrates

Question 66

Inotrope Pressor Vasoactive drugs

Answer 66

a. Epinephrine b. Norepinephrine c. Dopamine d. Dobutamine e. Isoproterenol f. Phenylephrine g. Milrinone

Question 67

Acetylcholinesterase inhibitors

Answer 67

edrophonium, physostigmine, neostigmine

Question 68

Class I (Na channel blockers)

Answer 68

a. Ia Procainamide/Quinidine b. Ib Lidocaine c. Ic Flecainide

Question 69

Class III (K channel)

Answer 69

Amiodarone, Sotalol