Pharm Flashcards
Centrally acting alpha-2 agonists and route
Clonidine (oral), methyldopa (oral, IV)
Direct vasodilators and route
Hydralazine (oral, IM, IV), minoxidil (oral), fenoldopam (IV), nitroprusside (IV)
a and B antagonists
Labetalol (oral/IV), carvedilol (oral)
Selective a1 antagonists
prazosin, terazosin, doxazosin (all oral)
non-selective a antagonists
phenoxybenzamine (oral), phentolamine (IM/IV)
Clonidine MOA
Stimulates a2 receptors in CNS →↓ symathetic outflow (vasomotor center, baroreceptor control is retained)→↓TPR (a1 on arteries) and ↓ HR, CO (B1 on
heart) decrease seen mostly with clonidine
Methyldopa MOA
- Lipid soluble agent→ access the CNS (activate a2 receptors→ reduce sympathetic outflow from vasopressor centers in the brainstem
- Stimulation of central a2 receptors result in the reciprocal increase in vagal tone and bradycardia
Clonidine clinical usage
- 2nd line for chronic HTN
- HTN urgencies
Clonidine adverse effects
*Sedation/ depression (transdermal route- less
sedation)
*Abrupt withdrawal (hypertensive crisis,
rebound hypertension, symptoms of sympathetic
over- activity)
*Sexual Dysfunction
Methyldopa clinical usage
*Primarily used for hypertension during
pregnancy (Chronic HTN→ HTN that antedates pregnancy, present before the 20th week of pregnancy, or persists longer than 12 weeks
postpartum; Gestational HTN→ after 20 weeks of gestation in the absence of proteinuria)
Methyldopa adverse effects
- Sedation, depression, nightmares, vertigo
* Longterm → (+) Coombs test (discontinuation reverses)
Hydralazine MOA
Vasodilation of Artery → ↓TPR → ↓BP → Activates SNS and ↑Renin which leads to Reflex Tachycardia and Salt & Water Retention → ↑BP and CO (combine
with BB and Loop diuretic to prevent reflex
tachycardia and fluid retention)
Minoxidil MOA
Vasodilation of Artery (through activation of K+ channels on smooth m > resting potential > limits contraction) → ↓TPR → ↓BP → Activates SNS and ↑Renin which leads to Reflex Tachycardia and Salt & Water Retention → ↑BP and CO (combine
with BB and Loop diuretic to prevent reflex
tachycardia and fluid retention)
Hydralazine clinical usage
*Hypertensive urgencies/emergencies;
*Response less predictable than other IV
agents (good agents for pregnant women)
*COMBO with minoxidil = chronic tx for more severe HTN (2nd line)
Minoxidil clinical usage
*Reserve for hypertension patients who do
not respond adequately to maximum
therapeutic doses of a diuretic and 2 other
antihypertensive agents
*COMBO with hydralazine = chronic tx for more severe HTN (2nd line)
Hydralazine and Minoxidil adverse effects
*Excessive vasodilation and hypotension (tachycardia,
Na & H20 retention, flushing, palpitations, dizziness, angina, headache)
Hydralazine adverse effects
Slow acetylators: lupus-like syndrome (fever, arthralgia, skin rash)
Minoxidil adverse effects
- Hypertrichosis
* PERICARDIAL EFFUSION
Fenoldopam MOA
Activates post-synaptic dopamine D1 receptors > decrease TPR and increase renal blood flow
Fenoldopam clinical usage
HTN emergencies
- short-term tx up to 48 hours
- beneficial in pt with renal insufficiency d/t increased renal blood flow, diuresis, natriuresis
Fenoldopam adverse effects
- Hypotension
- Reflex tachy
- flushing
- headache
- increased intraocular pressure
- hypokalemia
Nitroprusside MOA
NO > activate guanylyl cyclase > increase cGMP > activates calcium sensitive K channels > arterial and venous dilation > decreased TPR and decreased venous return (little/no effect on CO)
Nitroprusside clinical use
-HTN emergencies (titrate BP)
-controlled hypotension during surgery
-acute decompensated HF
(IV infusion with rapid onset and very short DOA)
Nitroprusside adverse effects
- CYANIDE TOXICITY (rapid metabolization liberates cyanide, renal failure can increase toxicity)
- HYPOTENSION (headache, dizziness, palpitations)
Labetalol ratio of beta:alpha
3:1 beta to alpha antagonism
Carvedilol ratio of beta:alpha
1:1
Labetalol clinical usage
-HTN urgencies/emergencies
Carvedilol clinical usage
- 2nd line for chronic HTN (inferior to ACEI/ARB/CCB)
- HTN urgency
Labetalol MOA
-inhibits alpha 1, beta 2 (vasodilation) beta 1 (little effect on HR and CO)
Labetalol adverse effects
Bronchospasm, can prolong or enhance hypoglycemia, HF, orthostatic hypotension, sexual dysfunction
Where are alpha 1 receptors?
Arterial smooth muscle, venous smooth muscle, trigone, prostatic smooth muscle
Zosin MOA
Blocks alpha 1 on arteries > vasodilation > decrease TPR, reflex tachy, reflex H2O and Na retention > decrease BP, increase CO
and veins > venodilation > decrease venous return > decreased CO (long-term little/no change in HR/CO)
End result of alpha-1 antagonists
With chronic use, any short-term effects on HR, CO, and plasma renin activity return to pretreatment levels
-reduction in BP achieved via vasodilation induced decrease in TPR
Zosin clinical usages
-BPH (increase urine flow)
-Raynaud’s (CCBs first line)
-2nd line for chronic HTN (good for pt with BPH)
(increased risk of HF compared to thiazides)
Zosin adverse effects
Orthostatic hypotension (severe with syncope> “first dose” effect; little with long-term)»_space; take @ bed
- Reflex tachy
- Headache, weakness, dizziness
- Edema (Na and H2O retention)
Phenoxybenzamine and phentolamine use
Pheochromocytoma (blocks alpha 1 receptors from catecholamine-producing tumor)
-Phentolamine can also be used in HTN urgencies/emergencies > limited use in severe HTN d/t alpha 2 inhibition)
Phenoxybenzamine and phentolamine adverse effects
- Orthostatic hypotension
- Nasal stuffiness
- Tachy (arrhythmias)
- inhibited ejaculation
- fatigue
- sedation
- nausea
Cardiac Glycosides
Digoxin
Digoxin MOA
Blocks Na/K ATPase -> increases cytoplasmic levels of Na and decreases drive of Na/Ca exchanger -> high levels of Ca in cytoplasm -> more Ca absorbed into SR via SERCA2 -> allows for more Ca in SR and stronger contraction
Digoxin Clinical Usage
used with diuretics, ACEI, and BB
Useful in A-fib
Stage C & D HF patients when ACEI and BB fail to control symptoms
NOT FOR ACUTE DECOMPENSATED HF
Improves clinical symptoms and quality of life but DOES NOT improve survival
Digoxin Adverse effects
sinus bradycardia AV block Increased sympathetic tone, tachycardia Ca overload Hypokalemia and hypercalcemia increase the action/toxicity of digoxin Narrow TI Cardiac arrhythmias Anorexia, diarrhea, N/V Dizziness, confusion Blurred vision Green & yellow halos around objects
Digibind
digoxin antidote
fab fragment of digoxin specific antibody
Use in life threatening cases of digoxin toxicity
Vasodilator Drugs
Isosorbide Dinitrate
Hydralazine
Isosorbide Dinitrate MOA
venous dilator -> reduces preload
stimulates intracellular cGMP, relaxes arterial and venous smooth muscle
Hydralazine MOA
arterial dilator -> reduce afterload
Help increase forward CO
Isosorbide Dinitrate & Hydralazine Clinical Usage
Recommended to use together
Patients who cannot use ACEI or ARB
Stage C HF
Persistently symptomatic blacks that are already on optimal therapy with a diuretic, ACEI, BB
Ivabradine MOA
reduces cardiac rate through blockade of the If current
Ivabradine Clinical Usage
NYHA class II to III, Stage C EF< 35%, HR > 70 On maximally tolerated doses of B or who are contraindicated to use a BB
Ivabradine Adverse Effects
Bradycardia
HTN
Afib
Ivabradine Contraindications
acute decompensated HF
BP< 90/50
AV block or bradycardia
severe hepatic impairment
Sacubitril/Valsartan MOA
Sacubitril -> inhibits neprilysin (enzymes that degrades natriuretic peptides)
Valsartan -> ARB
Oral administration
Sacubitril/Valsartan Clinical Usage
HF NYHA class II-IV , Stage C and reduced ejection fraction
Sacubitril/Valsartan Adverse Effects
Hypotension
Hyperkalemia
Sacubitril/Valsartan Contraindications
Pregnancy - BBW
Positive Inotropic
Dobutamine
Dopamine
Inamrinone
Milrinone
Acute Decompensation (vasodilators)
Nitroglycerin
Nitroprusside
Nesiritide
Dobutamine MOA
activates B1 receptors with some effect on B2 and a1
Increases SV & CO
Modest decrease in TPR
Dopamine MOA
activates B and a receptors
Low dose -> vasodilation of renal and mesenteric artery beds
High dose -> positive inotropic
Higher dose -> vasoconstriction of arteries
Milrinone and Inamrinone MOA
increase cAMP -> increase force of contraction in heart, increase velocity of relaxation, vasodilation
Positive inotropic drug Clinical Usage
IV infusion - severe refractory HF
Alleviate symptoms
Stage D
NOT TO BE USED IN LONG-TERM treatment
Pharmacologic agents for ADHF
Stage C - loop diuretics (volume overload) & nitroglycerin, nitroprusside, or nesiritide (vasodilators)
Stage D - dobutamine/dopamine or phosphodiesterase inhibitors - milrinone or inamrinone (inotropic agents)
Nitroglycerin MOA
Forms free radical NO
Activates guanylyl cyclase -> increased cGMP levels -> dephosphorylation of myosin light chains -> smooth muscle relaxation
Prominent effect in veins & decreases preload
Nitroglycerin Contraindication
Inferior ST-elevated MI
Nesiritide MOA
recombinant human BNP
binds to guanylyl cyclase and increases cGMP levels in smooth muscle -> dilates arteries and veins
In kidneys causes natriuresis
Induces diuresis
Nesiritide Adverse Effects
Renal Damage
Hypotension
Headache
Vasodilator Clinical Usage
Nitroglycerin, Nesiritide, Nitroprusside
IV for acutely decompensated HF
Added to diuretics for pt with severe symptomatic fluid overload but NOT Stage D
Nitroglycerin - relief on angina
Control of HTN complicating HF
ACE Inhibitors
Captopril
Enalapril
Lisinopril
ARBs
Losartan
Valsartan
Selective beta-1 blockers
Metoprolol
Bisoprolol
Atenolol
Nonselective beta-blockers
Propranolol
Beta blocker that blocks beta 1 and 2 and alpha 1
Carvedilol
Loop diuretics
Furosemide
Bumetanide
Ethacrynic acid
Thiazide diuretics
Hydrochlorothiazide
Chlorthalidone
K-sparing diuretics
Spironolactone
Eplerenone
Amiloride
Triamterene
CCBs
Amlodipine
Dilitiazem
Verapamil
Loop diuretics MOA
Blocks NKCC2 in thick ascending limb (competes Cl-)
Lasts 4-6 hours; after 6 excretion falls d/t volume depletion
Loop diuretics clinical usage
- DOC for acute circumstances
- Edema > resulting from cardiac, renal, or vascular disease that reduce blood flow to kidney
- HF (prevent or treat fluid retention for stage C and D - most commonly used)
- Interstitial or pulmonary edema
- For severe HTN and/or pt with reduced renal fxn
Loop diuretics adverse effects
- Fluid and electrolyte loss
- hypokalemic metabolic alkalosis
- ototoxicity
- hyperuricemia
- hypomagnesemia
- allergic rxn (except ethacrynic acid)
Thiazides MOA
Blocks NCC channel in DCT at Cl- site > enhances calcium reabsorption > induces vasodilation
Thiazides clinical usage
- HTN first line (low dose > high dose just adds diuretic effect with little effect on BP)
- HF in combo with furosemide (if needed) for stages C and D
Thiazides adverse effects
- Hypokalemic metabolic alkalosis
- Hyperuricemia
- hyponatremia
- hyperglycemia
- hyperlipidemia
- hypersensitivity rxn
- hypercalcemia
Spironolactone and eplerenone MOA
competitive antagonist at aldosterone receptor
Amiloride and triamterene MOA
Blocks ENaC channel directly
K sparing diuretics clinical usage
- Mineralocorticoid excess or hyperaldosteronism
- Hypokalemia caused by other diuretics
- Select pt who have LVEF of 35% or less and are already on ACEI and BB and stage C, NYHA class II-IV
- recommended for pt w/ moderate-severe symptoms of HF (monitor renal fxn and K)
K sparing diuretics adverse effects
Hyperkalemia
Tumorigenic - S
Gynecomastia - S
ACEI MOA
Inhibits conversion of AngI to AngII;
Inhibits inactivation of bradykinin
ACEI Clinical Usage
- First line HTN, CVD, CKD
- Used with diuretics to block RAAS - prevent destruction of bradykinin
- HF (stage A, pt at risk of artherosclerotic vascular disease, DM, or HTN and associated CV factors)
- HF - asymptomatic LV systolic dysfunction (stage B, hx of MI, reduced EF)
ACEI adverse effects
- hypotension > usually with 1st tx
- functional renal insufficiency
- hyperkalemia
- cough and angioedema
ARBs MOA
AT1 receptor antagonists
ARBs clinical usage
Use when ACEI is effective but causes cough
ARBs adverse effects
-renal insufficiency, hypotension, hyperkalemia, angioedma
Aliskiren MOA
Inhibit renin
Aliskiren clinical usage
hypertension
Amlodipine MOA
Decrease TPR (vasodilator) less cardiac depressant effect d/t reflex tachy
Non-dihydropyridines MOA
- Direct effect on SA node
- Decrease contractility> decreased CO
Dihydrophyridine clinical usage
1st line HTN, CV
Nimodipine > subarachnoid hemorrhage
Nondihydropyridine clinical usage
Can be given in rate control in pt with a fib or control of angina
Dihydropyridine adverse effects
Reflex tachy
Nondihydropyridine adverse effects
Diminish cardiac contractility and slow cardiac conduction, exacerbate HF or pulmonary edema
CCB adverse effects
constipation (V), flushing, headache, dizziness, peripheral edema
metoprolol MOA
blocks beta1 receptor > decrease HR; decrease renin> decrease contractility; decrease TPR > decrease CO
atenolol MOA
ISA > mild peripheral vasodilation w/o reducing CO (partial agonist)
BB clinical usage
- HTN with COMPELLING INDICATION
- Hyperthyroidism
- asymptomatic LV systolic dysfunction (stage B), hx of MI, reduced EF
BB adverse effects
- Heart - exercise fatigue, bradycardia, AV conduction abnormalities
- Increased airway resistance
- CNS - depression, fatigue, sexual dysfunction
- BB withdrawal - accelerated angina, MI, sudden death
- Lipid metabolism - increased TGs, decrease HDL
- Glucose intolerance - inhibit glycogenolysis in liver, masks hypoglycemia, inhibit insulin secretion
- Exacerbation of PVD - unopposed vasoconstriction from blocking B2 activity > primarily non-selective beta antagonist
- Worsening HF
BB contraindications
ADHF, symptomatic bradycardia or heart block w/o pacemaker, hx of asthma, symptomatic hypotension, fluid overload
Aldosterone antagonist clinical usage
- LVEF 35% or less and are already on ACEI and BB and stage C, NYHA II-IV
- recommended for pt w/ moderate-severe symptoms of HF
- monitor renal function and K
