pharm 2 exam4

agents that act primarily on arterioles are known as 

resistance vessels 

agents that act primarily on veins are known as 

capacitance vessels

adverse effects r/t vasodilation

-postural hypotension:relaxation of smooth muscle on veins cause blood to pool

-reflex tachycardia:arteriole and/or venous; pretreat w/ cardioselective beta blocker

-expansion of blood volume(w/ prolonged use)

hydralazine

selective dilation of arterioles

what does hydralazine cause

-arteriole BP and peripheral resistance falls

-HR and myocardial contractility increase

-inactivated by a metabolic process known as acetylation

adverse effects of hydralazine

-reflex tachycardia

-increased blood volume

-systemic lupus erythematosus like syndrome(fever, joint and muscle pain, nephritis, pericarditis, positive rhumatoid antibodies)

minoxidil

-produces significantly more severe dilation of arterioles than hydralazine

-reserved for pts w/ severe HTN that have not responded effectively w/ safer drugs 

for minoxidil to promote vessel relaxation

-must be metabolized to minoxidil sulfate

-this metabolite will cause potassium channels to open resulting in an efflux of potassium ions out of the cells 

-hyperpolarization of the VSM cells occurs which will reduce their ability to contract 

adverse effects of minoxidil

-reflex tachycardia; minimized w/ beta blocker(metoporolo)

-sodium and water retention; loop diuretics w/ or w/o thiazide diuretics; if ineefective, dialysis is started or drug dc

-hypertrichosis:excessive hair growth

-pericardial effusion;can lead to cardiac tamponade;pericardiocentesis

sodium nitroprusside

-potent and fastest acting vasodilator available

-drug of choice for HTN emergencies

-causes both venous and arteriole dilation 

how is sodium nitroprusside administered

IV infusion only-BP can be adjusted to any level by increasing or decreasing infusion rate

what is administered simultaneously w/ sodium nitroprusside

oral antihypertensives 

sodium nitroprusside can cause

sodium and water retention; give loop diuretic

adverse effects of sodium nitroprusside

-excessive hypotension: when administered too rapidly, requires continuous monitoring of BP

-cyanide poisoning:seen in those w/ liver disease or lack of thiosulfate, if occurs should be dc

-thiocyanate toxicity: occurs id given>3days, plasma levels of thiocyanate should be monitored(need to be <0.1mg/mL), will causes CNS adverse effects

vascular smooth muscle (VSM)

-regulates contraction

-acts on peripheral arterioles and arteries and arterioles of the heart

-no dramatic effect of veins 

heart

-helps regulate fxn of myocardium, SA node, and AV node

-coupled to beta1 adrenergic receptors 

chronotropic

rate of heart

inotropic

force of contractility

dromotropic

how rapidly ventricles are receiving impulses

what effects does CCBs have on chronotropin,inotropic and dromotropic

negative on all 3

nifedipine

at therapeutic leves, acts primarily on arterioles

-if does is toxic, can produce significant cardiac suppression

verapamil and diltiazem

-acts on both arterioles and heart

-direct effect and indirect effects

-net CV effects: vasodliation, reduced arterial pressue, increases coronary perfusion

5 direct effects of verapamil that causes blockade at:

-peripheral arterioles resulting in dilation;decrease arteriole pressure

-arteries and arterioles of heart; increase coronary perfusion

-SA node(reduces HR)

-AV node(decreases AV nodal conduction)

-myocardium(decreases force of contractility)

indirect (reflex) effect of verapamil

activation of baroreceptors reflex causing increased firing of sympathetic nerves to heart 

common ADRs of verapamil

-constipation

-facial flushing

-HA

-edema of ankles and feet

cardiac effects of verapamil

-symptomatic bradycardia

-partial or complete AV heart block

-decreased contractility 

druf interactions w/ verapamil

digoxin and beta adrenergic blockers

cliincal manifestations of verapamil OD

-severe hypotension

-cardiotoxicity (bradycardia, AV block)

tx for verapamil OC

-activated charcoal to prevent further absorption

-IV calcium gluconate counteracts vasodilation and negative inotropic effects

-IV atropine(parasympatholytic)

-IVF-IV norepinephrine

-pacemaker(last resort)

therapeutic uses of nifedipine

angina pectoris and HTN

net effects of nifedipine: direct

-peripheral vasodilation(lowers PR)

-increases coronary perfusion

net effects of nifedipine: indirect

reflex cardiac stimulation d/t activation of the baroreceptor reflex; increases HR and contractile force

adverse effects of nifedipine

-same as veraparamil w/ exception (minus) constipation

-reflex tachycardia 

drug and food interactions w/ nifedipine

-beta blockers

-grapefruit juice

-preferred drug for pt w/ AV block, HF, or bradycardia-will not exacerbate d/t minimal blockade of Ca channels in heart

drug of choice for hypertensive crisis

sodium nitroprusside

hypertensive crisis

DBP>120mmHg

3 specific mechanisms of HF

-slowing HR(- chronotropic)

-increasing contractility(+ inotropic)

-reduced cardiac worload

first line drug class used for HF in pts w/ signs of volume overload or hx of volume overload

diuretics

net results of diuretics r/t HF

-decreases venous pressure(preload)

-decrease arterial pressure(afterload)

-reduce pulmonary and/or peripheral edema

-reduce cardiac dilation

aldosterone effects r/t HF

during HF, activation of the RAAS causes aldosterone levels to increase

aldosterone has several harmful effects on the heart:

-promotes myocardial remodeling

-promotes myocardial fibrosis

-activation of the SNS and suppression of NE uptake in heart

-promotion of vascular fibrosis

-promotes baroreceptors dysfunction 

how to ACE inhibitors (-pril) help w/HF

improves functional status and prolongs llife

angiotensin receptor neprilysin inhibitor(ARNI)

sacubitril/ vasartan(entresto)

sacubitril/ vasartan 2 MOA

-increases secretion of natriuretic peptides

-suppresses negative effects of RAAS

aldosterone antagonists

spironolactone and eplerenone

benefits of adding beta blockers to HF tx

-can improve LV ejection fraction

-increase exercise tolerance

-slow progression of HF

-prolong survival 

cardiac glycosides

digoxin

digoxin is exerts a ____ inotropic effect that improves _____ ability of the heart

digoxin is exerts a positive  inotropic effect that improves pumping ability of the heart

what competes w/ digoxin for binding sites to the enzyme

potassium; must monitor levels 

little K+=

lot of K+=

little K+=dig toxicity 

lot of K+=dig is subtherapeutic 

digoxin MOA

-inbibits the Na+-K+-ATPase; blocks K+ uptake and Na+ extrusion

-increase in intracellular Ca ions activates the contractile proteins, actin, and myosin to increase contractility 

neurohormonal benefits of digoxin

can suppress renin release by inhibiting Na+-K+-ATPase in renal tubules 

serious ADR of digoxin

dysrhythmias

-Vfib and V tach are most dangerous

perdisposing factors that can lead to dysrhythmias when taking digoxin

-hypokalemia

-severity of HF/disease

-elevated digoxin levels

what should you encourage your pt to do when taking digoxin

take at the same time each day and monitor HR and rhythm; notify HCP if any changes

CNS manifestations of digoxin toxicity

-fatigue

-visual distubances: blurred vision, halos around light, yellow vision 

GI manifestations of digoxin toxicity

anorexia, N/V

antidote for digoxin toxicity

fab antibody fragments: digibine

nesiritide

used in management of acute decompensated HF; not used routinely; structurally identical to endogenous BNP

3 MOA of nesiritide

-supresses RAAS

-supresses sympathetic outflow from CNS

-direct dilation of arterioles and veins

nesiritide acts to compensate for deteriorating cardiac fxn by…

-reducing preload and afterload

-increases diuresis and excretion of Na

-decreases secretion of neurohormomes, endothelin, and NE

-stimulates production of cyclic cGMP: causes VSM to relax

ADR of nesiritide

severe hypotension and should not be given if SBP is<90mm Hg

milrinone

“indodilator”

possess positive inotropic and vasodilator effects (increases Ca and contractility)

MOA of milrinone

increases levels of cAMP in myocardial cells d/t inhibition of PDE3

adverse effects of milrinone

-hypotension and arrhythmias

-thrombocytopenia

-hepatotoxicity 

modifiable risk factors for angina

-smoking

-hyperlipidemia

-HTN

-DM

-obesity

-physical inactivity 

goal of tx for stable (exertionaly) angina

-decrease cardiac oxygen demand

-use agents that decrease HR, contractility, preload, and afterload

-provides only symptomatic relief 

agents uses to tx stable angin

-organic nitrates: decreased preload

-BBBs:decreases HR and contractility 

-CCBs:decreases afterload, HR , and contractility (- chronotropic, inotropic, dromatropic)

-ranolazine: can be added to enhance benefits 

goal of tx for variant/prinzmetal’s angina

increasing cardiac oxygen supply

agents used to tx variant/prinzmetal’s angina

organic nitrates (tone down vasospams) or CCBs

goal of tx for unstable angina

reduce pain

prevent progression to MI or death 

what is used for relief of acute and as prophylaxis before events known to causes acute angina

nitrates(SL tabs/powder or translingual)

what is used for long term prevention or management of recurrent angina

nitrates: SR oral capsules, topical, transdermal

nitroglycerin

-directly relaxes VSM in blood vessel walls and depresses muscle tone

nitroglycerin produces vasodilation:

-reduces venous pressure and venous return(decrease preload)

-dilates healthy coronary arteries

-dilates peripheral arterioles(modestly)

nitrates must be converted to its active form-

nitric oxide

CNS adverse effects of organic nitrates

HA d/t high lipid solubility (will go away w/time)

CV adverse effects of organic nitrates

orthostatic hypotension and reflex tachycardia(may need BB)

skin adverse effects of organic nitrates

dermatitis from topical applications

what can occur in pts receiving high doses of IV NTG

alcohol intoxication

drug-drug interactions w/ organic nitrates

=PDE5(both increases cGMP; severe hypotension): sildenafil and tadalafil

-BBs and verapamil/diltiazem

how often can you give organic nitrates

q5min for up to 3 doses

how does beta adrenergic blockers help w/ angina

prevents increase in HR and increased intensity of myocardial contraction that occurs w/ sympathetic stimulation; decreases cardiac workload and demand for oxygen

CCBs

-inhibits the movement of Ca ions across the membranes of myocardial and VSM

-depresses myocardial contractility; slows cardiac impulse formation; relaxes and dilates arteries causing a fall in BP and a decrease in venous return; decreases preload and after load

what effect does CCBs have on coronary artery vasospasms

relieves coronary artery vasospasms by increasing blood flow to muscle cells

ranolazine(ranexa)

-reduces number of angina episodes/week andincreases exercise tolerance

-reduce accumulation of Na and Ca in myocardial cells-helps myocardium utilize energy more efficiently 

ranolazine(ranexa) has no effect on..

HR, BP, or vascular resistance

ADRs of ranolazine(ranexa)

-prolongation of QT interval(dose dependent)

-elevation of BP in pts w/ severe renal disease 

4 MOA for oral antidiabetic agents used to tx T1DM

-lowers blood sugar by stimulating the pancreatic beta cells to release insulin

-make target tissues more sensitive to the effects of insulin by increasing the number of receptor sites and by enhancing insulin’s action at post-receptor sites

-work to decrease gluconeogenesis

-decrease intestinal absorption of glucose 

biguanides: metformin (glucophage) MOA

sensitizes insulin insulin receptors for use of glucose by muscles and fat cells, decreases hepatic glucose production, and decreases intestinal glucose absorption

other than tx for T1DM when else is metformin used 

-initiated immediately after T2MD dx

-PCOS

metformin rarely causes

hypoglycemia

serious adverse reaction to metfomin

lactic acidosis***

-may also cause renal failure when given contrast media(stop drug before contrast and hold until 48hrs after contrast)

metformin decreases absorption of what

vitamin B12 and folic acid

sulfonylureas: glipizide(glucotrol) MOA

acts primarily by stimulating the release of insulin from pancreas:

-extent of insulin release is glucose dependent

-ineffective if pancreas unable to synthesize insulin

main ADR of glipizide

hypoglycemia

glipizide stimulates ADH release which results in

SIADH(retaining fluid)

meglitinides: repaglinide MOA

acts primarily by stimulating the release of insulin from the pancreas in the sam eway as sulfonylureas

what is the duration of repaglinide and when should it be taken

 a short duration (3-4hrs) and should be taken w/ each meal; if you skip a meal=skip a dose, if you eat a snack/extra meal=add extra dose

coomon ADR of repaglinide

hypoglycemia