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217 Cards in this Set
- Front
- Back
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For each 10mmHg increase in diastolic BP or 20mmHg increase in systolic BP how much does the risk for Cardiovascular disease increase?
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double
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risks of high blood pressure
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heart attack
heart failure (due to ventricular failure) stroke kidney disease |
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What is program that aims to better manage hypertension
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JNC 7 joint national committee on prevention, detection, evaluation and treatment of high blood pressure
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major risk factors for hypertension
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smoking!!!!!!!!!!!!!!!!!
diabetes (HTN and DM both damage smooth muscle of vessels) males over 55 females over 65 (post-menopausal) familial CV disease lipid elevation obesity inactivity |
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organ damage due to HTN
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left ventricle hypertrophy, angina,
MI, coronary angioplasty, stent, graft, heart failure stroke/TIA kidney disease peripheral artery disease retinopathy |
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non drug causes of HTN
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sleep apnea
kidney renovascular disease primary aldosteronism steroid therapy cushing's disease pheochromocytoma: adrenal medulla releases too much epinephrine block alpha and beta receptors coarction of aorta |
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Drugs that cause HTN
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NSAIDS: Cox 2 inhibitors, block prostaglandin synthesis
cocaine, speed, SANS, decongestants steroids, cyclosporine, tacrolimus erythropoietin licorice (carbenoxolone) ephedra (alpha/beta agonist) ma huang |
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blood pressure goals of therapy
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BP under 140/90
under 130/80 if have DM or kidney disease |
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Pseudo-tolerance
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looks like drug is not working, but the body is compensating
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2 compensatory reflexes
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1. sypathetic reflexive tachycardia
2. Renin-Angiotensin-Aldosterone |
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Lifestyle modifications for HTN
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stop smoking
weight reduction (5-20mmHg/10kg loss) eat right (8-14mmHg) reduce sodium (2-8mmHg) physical exercise (4-9mmHg) limit alcohol 1-2 drinks/day (2-4mmHg) |
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Initial drug therapy for HTN
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Thiazide: hydrocholorothiazide and indapamide
distal tubule diuretic that recovers Ca and lets Na go distal tubule job: reabsorb Na and Ca |
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Drug combinations for HTN
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Thiazide diuretic (retain Ca)
+ Ace inhibitor, or angiotensin receptor blocker, or beta blocker, or Ca channel blocker add drugs until goal pressure |
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ischemic heart disease drug therapy
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start with:
beta blocker or verapamil or diltiazem (ca channel blockers) |
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HTN and
Ischemic heart disease MI or post-MI drug therapy or heart failure therapy |
beta blocker (olols) +
Ace inhibitor (prils/sartans) |
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LV dysfunction + HTN drug therapy
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1.ACE inhibition (pril) +
2. Beta blocker (olols) + 3. spironolactone (Aldosterone antagonist, acts on CT) 4. loop diuretic (furosemide, ethacrynic acid, bumetanide) |
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diabetic HTN drug therapy
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2 or more drugs
1. thiazide diuretic (DCT, indapamide, hydrocholorthiazide) 2. Beta blocker (olol) 3. Ace inhibitor (pril) or angiotensin receptor blocker (sartans) 4. loop diuretic (furosemide, ethacrynic acid, bumetanide) |
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HTN and stroke drug therapy
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ACE inhibitor (pril)
Thiazide (DCT diruretic- indapamide, hydrochlorothiazide) |
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What is the red carpet effect?
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when liver cholesterol is low it creates more LDL receptors and calls cholesterol back
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Which types of drugs act on the red carpet effect?
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bile acid resins: cholestipol, cholestyramine
HMGCoA inhibitors: statins |
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What are the goal cholesterol levels?
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<100mg/dl
<70mg/dl if high risk: cardiovascular disease, DM, metabolic syndrome, smoking |
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Which drugs are bile acid resins?
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cholestipol
cholestyramine |
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Which drugs block HMGCoA reductase
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Statins
lovastatin simvastatin pravastatin fluvastatin atorvastatin (newest, potent, long acting, active metabolite) |
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What are the 3 classes of drugs used to treat high cholesterol
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bile acid resins
niacin statins |
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What are the bile acid resin drugs and their function
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cholestyramine, colestipol
bind bile acids in gut and take them out with cholesterol the liver makes more LDL receptors (Red carpet) zero bioavailability- never enter vascular compartment block absorption of some drugs/vitamins GI symptoms |
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Which drug decreases triglyceride assembly?
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niacin (nicotinic acid)
SE: flushing (vasodilation) and itching- give with aspirin to block histamine release peptic ulcer myositis: inflammation of voluntary muscle characterized by pain, tenderness, spasm rhabdomyolysis: breakdown of muscle fibers, toxic to kidney |
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Which drugs block cholesterol synthesis?
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statins
block HMGCoA reductase- rate limiting step in cholesterol synthesis liver increases the number of LDL receptors used for high risk patients SE: hepatic toxicity myopathy rhabdomyolysis |
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What is the first dose effect?
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compensations due to hypotension
sympathetic and renin-angiotensin-aldosterone compensations reflexive tachycardia Na and H2O retention K loss |
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What is classical/typical angina?
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angina due to reduced coronary flow
angina of effort |
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What is atypical angina?
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prinzmetal
caused by vasospasm |
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Which drugs lower preload (venodilate)?
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nitrates
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Which drugs lower afterload?
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Calcium channel blockers
beta blockers sympathetic antagonists |
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Which drugs are used to treat angina of effort?
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nitrates (lower preload)
beta blockers, block sympathetic stimulation, calcium channel blockers (lower afterload) |
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Which drugs are used to treat atypical (prinzmetal's) angina?
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calcium channel blockers- relax arterioles
nitrates NO beta blockers |
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What is congestive heart failure?
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ventricle fails to maintain ejection fraction
pressure backs up and creates venous and pulmonary hypertension and edema |
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How is congestive heart failure treated?
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cardiotonics (digitalis-Ca), dobutamine-beta1, amrinone (cAMP)
diuretics- decrease volume ACE inhibitor: lose volume, decrease TPR, reverse myocardial remodeling |
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What are the 4 classes of anti-arrhythmics?
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1. Na channel blockers
2. beta blockers 3. K channel blockers 4. Ca channel blockers |
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How do Na channel blockers work?
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elevate the threshold for depolarization and slow impulse conduction
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What are some examples of Na channel blockers?
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class 1A
quinidine procainamide class 1B lidocaine (IV) tocainide (oral) phenytoin class 1C flecainide |
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Class 1A Na channel blockers
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Quinidine
procainamide atrial/ventricular excitation |
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Class 1B Na channel blockers
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lidocaine (IV)
tocainide (oral) phenytoin used for ventricular extrasystoles |
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Class 1C Na channel blockers
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flecainide
super effective and dangerous |
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antiarrhytmic class 2
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beta blockers
resist NE and epi effects on SA and AV node |
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anti-arrhythmic class 3
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K channel blockers
delay repolarization in phase 3 prolong phase 2 and AP prolong refraction amiodarone sotalol (beta blocker) bretylium |
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anti-arrhythmics class 4
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Ca channel blocker
verapamil diltiazem SA node sinus tachycardia AV node paroxysmal supraventricular tachycardia |
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What does the proximal tubule recover?
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Na
NaHCO3 |
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What does the ascending loop recover?
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everything
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What does the distal convoluted tubule recover?
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Na and CA
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What does the collecting tubule recover?
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aldosterone: recover Na and release K and H
ADH: recover water |
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How do loop diuretics and thiazides work?
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they are weak acids that compete for the organic acid excretion sites in the proximal tubule
uric acid accumulates in the presence of a competing organic acid like lactate (alcohol metabolism related gout) and diuretics |
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Why do diuretics cause hyperglycemia?
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K flows out of cell
K conductance stops when glucose enters insulin is released loop diuretics or thiazides lead to hypokalemia outside the cell so there is faster conductance of K out by diffusion, more glucose is needed to turn off the K channel and less insulin is released |
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ADH (vasopressin)
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V1: vasoconstrictor
V2: collecting duct water recovery desmopressin only does collecting duct water recovery |
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What is an ADH antagonist?
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lithium ion (blocks V2: collecting duct water recovery)
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What is lithium induced DI treated with?
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desmopressin (not ADH)
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Which diuretics act on the proximal tubule?
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acetazolamide
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Which diuretics act on the ascending loop?
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furosemide
ethacrynic acid bumetanide |
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Which diuretics act on the distal convoluted tubule?
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indapamide (vasodilator)
hydrochlorothiazide |
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Which diuretics act on the collecting tubule?
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amiloride
triamterene spironolactone- target aldosterone |
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Which are the urine alkalinizing diuretics?
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Acetazolamide
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Which are the loop diuretics
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furosemide
bumetamide ethacrinic acid act on ascending tubule |
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which are the K sparing diuretics
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spironolactone
amiloride triamterene act on collecting duct |
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which are the thiazide diuretics?
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hydrochlorothiazide
indapamide (also a vasodilator) |
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What are the effects of acetazolamide?
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Carbonic anhydrase inhibitor
act on proximal tubule block reabsorption of NA and NaHCO3 recover H creating acidic blood and alkaline urine acidic blood stimulates respiratory compensation in altitude sickness used to treat glaucoma |
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Loop diuretics
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furosemide
ethacrynic acid bumetanide block recovery of everything used to treat edema, pulm edema, CHF, hypercalcemia, HTN ethacrynic acid- ototoxic furosemide and bumetanide- sulfa sensitivity hypokalemia, alkalosis, hypovolemia, hyperuricemia, hyperglycemia |
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Ca sparing diuretics
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Thiazides:
indapamide (vasodilator) hydrochlorothiazide act on DCT (DCT recovers Na and Ca) CALCIUM SPARING NaCl diuresis reduce formation of Ca stones, benefit osteoporosis tx: HTN, CHF, nephrogenic DI |
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K sparing diuretics
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spironolactone- target high aldosterone
amiloride triamterene use with thiazide or loop to neutralize K loss |
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mannitol
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osmotic diuretic
used to treat glaucoma or edema |
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drugs to treat glaucoma
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mannitol
acetazolamide |
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Explain the renin angiotensin system:
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when low renal artery BP or when Beta 1 stimulated
JG cells release renin Angiotensin 1 is converted to Angiotensin 2 by angiotensin converting enzyme (from lungs) Bradykinin is inactivated by ACE or peptidyl dipeptidase |
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What are the effects of angiotensin 2?
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vasoconstriction
aldosterone release increase SANS retain Na and H2O increase BP |
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What are the effects of bradykinin?
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inactivated by ACE
vasodilator decrease arterial resistance and increase venous capacitance proinflammatory: pain, swelling, angioedema bronchoconstrictor: airway irritability, cough, airway obstruction |
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What do ACE inhibitors do?
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decrease angiotensin 2
increase Bradykinin: cough, resp. irritability, angioedema dilate arterioles and venules low aldosterone- reduce BP in patients with elevated PRA decrease extracellular fluid and blood volume |
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Name the ACE inhibitors:
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direct acting:
captopril lisinopril prodrugs: enalapril benazepril |
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Which drugs block the angiotensin 1 receptors?
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losartan
valsartan avoid bradykinin SE |
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How is Ca released in the cell?
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NE binds G protein receptor
PLC activated PLC causes release of DAG and IP3 DAG activates phosphokinase C IP3 causes release of Ca from smooth muscle |
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What does nitric oxide do?
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1. enters the cell
2. binds guanylate cyclase 3. GTP is converted to cGMP 4. cGMP causes relaxion of vessel walls by inhibiting calcium |
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vasodilators
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nitrates: isosorbide dinitrate
sodium nitroprusside hydralazine minoxidil diazoxide |
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causes of high TPR
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vasoconstriction
renin-angiotensin cortisol sympathetic stimulation licorice Na Ca |
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What causes high Cardiac output
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increased volume (Na hyperaldosteronism, kidney failure)
SANS pheochromocytoma renin-angiotensin |
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What do vasodilators do?
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reduce TPR
activate K channels interfere with Ca channel function promote NO synthesis by vascular endothelium to target smooth muscle |
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What are the side effects of vasodilators?
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hypotension (excessive vasodilation)
reflex tachycardia: with decreased BP, sympathetic reflex will be invoked and HR will increase coronary steal syndrome-> angina pectoris renin-angiotensin-aldosterone compensation |
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which vasodilator works on the arteriole? and what are the side effects?
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hydralazine
minoxidil |
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Which vasodilators cause excessive hair growth?
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minoxidil
nitrate diazoxide |
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Which vasodilators act on the venules and arterioles
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nitrates
sodium nitroprusside |
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What are the side effects of hydralazine?
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LUPUS syndrome
headache, flushing, dizziness, hypotension, tachycardia, angina pectoris |
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Which drug is used to reverse emergency hypertension?
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diazoxide
causes hyperglycemia and hypertrichosis |
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How do Ca channel blockers work?
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block Ca release from arterioles and heart
cause arterioles to relax BP drops heart automaticity and ventricular contractility decrease used to treat angina and HTN SE: Hypotension |
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Calcium channel blockers
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Nifedipine
nimodipine Verapamil diltiazem |
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Calcium channel blockers that act on the arteries and heart
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verapamil
diltiazem |
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calcium channel blockers that act only on the arterioles
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nifedipine
nimodipine |
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Which Ca channel blockers resist the sympathetic reflex?
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verapamil
diltiazem |
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What controls sympathetic stimulation
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vasomotor center
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alpha 2 agonists
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clonidine
guanabenz alpha methyldopa (prodrug) |
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nonselective alpha antagonist
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phentolamine
phenoxybenzamine (irreversible) |
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alpha 1 selective antagonist
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doxazosin
prazosin relax sphincters miosis: constrict pupil lower BP SE: 1st dose effect: precipitous drop in BP on starting the drug or increasing the dose postural hypotension reflexive tachycardia urinary incontinence/diarrhea GI hyperactivity miosis |
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nonselective beta blockers
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propranolol
nadolol pindolol (ISA) labetalol (mixed alpha beta blocker) |
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B1 (cardioselective)blockers
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acebutol (ISA)
metoprolol atenolol |
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alpha 1 agonists
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EPI
NE cocaine amphetamine vasoconstriction increase TPR, CO, BP contract GI sphincter, stop gut, retain urine mydriasis(dilate pupil) |
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alpha 2 agonist effects
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decrease vasomotor action
decrease sympathetic stimulation inhibit neurotransmitter release pre-synaptic negative feedback SE: CNS depression rebound phenomenon low BP |
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alpha blocker uses
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HTN
pheochromocytoma (only allows Beta stimulation) BPH epinephrine reversal (hypertension to hypotension) |
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alpha blocker side effects
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loss of TPR- hypotension
congestion 1st dose effect: precipitous drop in BP on starting drug or decreasing dose, postural HTN reflexive tachycardia urinary incontinence GI hyperactivity miosis |
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Beta 1 receptor effects
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Heart: stimulate contractility, conduction
kidney: release renin-> antiotensin 2 (vasoconstriction) -> aldosterone release |
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beta 2 receptor effects
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bronchodilate
vasodilate decrease GI tone convert glycogen to glucose |
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beta blocker effects
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decrease Heart contraction, conduction
decrease renin-angiotensin 2-aldosterone non-selective antagonize glycogen breakdown and increase GI tone suppress ventricle arrhythmias decrease positive feedback at VMC decrease work in coronary artery disease |
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nonselective alpha blockers
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phentolamine (injectable)
phenoxybenzamine (irreversible) |
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alpha 1 selective antagonists
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doxazosin
prazosin |
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alpha 2 agonists
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clonidine
guanabenz alpha methyldopa (prodrug) |
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nonselective beta blockers (drug names)
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propranolol
nadolol pindolol (ISA)- partial agonsit labetalol (mixed alpha/beta blocker) |
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β1 blocker drug names
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acebutol (ISA)
metoprolol atenolol |
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nonselective alpha blocker function
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decrease vasoconstriciton
treat HTN pheochromocytoma SE: reflex tachycardia, diarrhea, epinephrine reversal |
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alpha 1 antagonists SE
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less reflex tachycardia than non-selective alpha blockers
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alpha 2 agonist drugs, effects, and SE
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clonidine,
guanabenz, alpha-methyl dopa decrease CO and TPR and thus BP negative feedback inhibition of vasomotor center SE: CNS depression, dry mouth/eyes/nose, drowsiness, rebound hypertension, tachycardia |
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alpha 2 antagonists
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yohimbime- used for male impotence, increases sympathetic stimulation, can cause HTN
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nonselective beta blockers general facts
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-olol
decrease renin used to treat HTN, angina, arrhythmias SE receptor upregulation and rebound phenomenon- extreme tachycardia, ventricular arrhythmia cardiac depression sedation diabetic hypoglycemia |
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beta 1 blockers
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AMA
atenolol- less CNS effects metroprolol, acebutol: with ISA use in asthmatics, DM, PVD decrease renin release SE: cardiac depression rebound phenomenon |
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mixed beta blocker (alpha and beta)
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labetalol
SE: hypertensive crisis pheochromocytoma clonidine withdrawal rebound phenomenon- upon withdrawal |
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ganglionic block
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mecamylamine
lose dominant tone on an organ use to treat HTN |
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NE depleter that blocks biosynthesis
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alpha methyl tyrosine
blocks tyrosine hydroxylase and inhibits synthesis of Dopamine, NE, epi Tx: severe pheochromocytoma SE: depression, hypotension, extrpyramidal symptoms |
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NE depletor that blocks storage
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reserpine
bind NE and serotonin and block storage SE: CNS depression (amine hypothesis), GI hyperactivity |
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NE depletor that displaces NE in vesicles
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guanethidine
does not cross BBB SE: no CNS depression, GI hyperactivity |
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depolarization cycle
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0: Na channels open- depolarize
1: overshoot, Na channels close 2. ca channels open 3. Ca channels close, K channels open 4. Na/K pump resets conc. gradient Na/Ca pump restores normal Ca levels |
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effective refractory period
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no stimulus regardless of size will cause a response
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relative refractory period
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a strong enough stimulus will induce a response
can produce arrhythmias |
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conductance
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rate of spread of an impulse
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conductance determined by
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vmax- rate of phase 0 depolarization (lower vmax, lower conduction)
threshold potential: the less -, the less Na channels needed, the slower the conduction velocity resting membrane potential: the more negative, the faster the recovery of channels |
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automaticity
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ability to spontaneously depolarize, phase 4 slope
in the heart, the tissue with the fastest phase 4 slope will be the pacemaker of the heart |
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arrhythmias caused by disturbances in
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impulse generation
impulse conduction |
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factors that increase the slope of phase 4 depolarization
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cause tachycardia
-sympathetic -hyperthyroidism -atropine (ACH blocker) -hypokalemia -digoxin |
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factors that decrease the slope of phase 4 depolarzation
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cause bradycardia
beta blockers Ca channel blockers |
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hyperpolarize (supress depolarization)
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vagal, parasympathetic activity
muscarinic agonists, acetylcholinesterases digoxin action on SA or AV node |
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elevate threshold for depolarization- suppress impulse generation
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Na channel blockers
cause bradycardia |
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early afterdepolarizations
|
occur in phase 3
can trigger ventricular tachycardia or torsades des pointes drugs that slow the rate (beta blockers), lengthen QT or action potential duration (class 3, K blockers), and cause hypokalemia (diuretics) |
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delayed afterdepolarization
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phase 4
due to elevated intracellular calcium (digoxin) hypokalemia- diuretics excessive catecholamines (sym, hyperthyroidism, drugs) ischemia (MI, coronary disease) |
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ventricular tachycardia
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3 extra systoles in a row
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impulse conduction problems
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AV node unloading: AV node normally prevents excessive activity
AV node depression: digoxin, beta blockers (propranolol), artiolar and cardiac calcium channel blockers (verapamil, diltiazem), adenosine accessory pathway-bypass AV node, avoid everything used to suppress the AV node reentry: AV node and purkinje system cause a cyclic conduction pathway that depolarizes surrounding tissue, major cause of atrial tachycardias |
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4 classes of antiarrhythmics
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1. Na channel blockers
2. beta blockers 3. K blocker 4. Ca channel blockers |
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class 1 antiarrhytmics
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1. Na blockers
1A: quinidine, procainamide 1B: lidocaine IV, tocainide (oral), phenytoin 1C: flecainide |
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Sotalol
|
Class 2 and 3 anti-arrhytmic
Beta and K blocker AV depressant Long QT- torsades de pointes increase AP duration |
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bretylium
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class 3 (k blocking) anti-arrhythmic
depletes NE decreases BP use for ventricular ischemic events |
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Ca channel blocker side effects
|
bradycardia
asystole AV depression vasodilation hypotension constipation |
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arteriolar calcium channel blockers
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nifedipine
nimodipine |
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arteriolar and cardiac channel blockers
|
verapamil
diltiazem used for arrhythmias block Ca channels at SA, AV nodes decrease conduction |
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Adenosine
|
classless anti-arrhytmic
IV- instant, short half-life (8 seconds) opens K channels in AV node reverse AV node events SE: bronchospasm, vasodilation |
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Digoxin
|
classless anti-arrhythmic
AV nodal depressant invokes muscarinic ACH effect suppress AV node to protect ventricle SE: extra ventricular systoles, DADs ventricular tachycardia esp with diuretic and hypokalemia AV depression or block- with verapamil (ca channel blocker), propranolol, or adenosine |
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class 1A anti-arrhytmics
|
Na channel blockers
Quinidine, Procainamide decrease vMax increase effective refractory period |
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Class 1B anti-arrhytmics
|
Na channel blockers
target the ventricle lidocaine, tocoainide, phenytoin |
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class 1C anti-arrhytmics
|
flecainide:
super Na blocker, dangerous, last resort, emergency like 1A: slow Vmax, increase ERP |
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commonalities between anti-arrhythmics class 2 (beta blockers), 4 (calcium channel blockers), adenosine, and digoxin
|
all increase AV effective refractory peiod
all used at AV node to protect ventricle |
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class 3 drugs
|
K blockers
amiodarone, sotalol, bretylium increase ERP everywhere |
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atrial flutter or fibrillation
|
digoxin- AV depression
verapamil: ca channel blocker (class 4) beta blocker (class 2) class 1A: suppress Na driven ectopic focus |
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supraventricular tachycardia: atrial or AV node reentry circuit
|
verapamil suppresses AV
other AV depressants caused by atrial wall reentry 1. inhibit initiation of action with class 1A- quinidine 2. increase refractoriness with class 3: amiodarone |
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premature ventricular contraction, extra systoles, early after depolarization, delayed after depolarizaiton
|
may start by extra Ca
Na will cause it to depolarize lidocaine- class 1B beta blockers- class 2 if sympathetic, hyperthyroidism, beta 1 drug administration class 1 drugs |
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ventricular tachycardia
|
caused by repeated ectopic depolarizations in conducting tissue or by a conducting path reentry circuit
Na driven life threatening-cardioversion lidocaine- class 1B Class 1A (quinidine or procainamide) Class 3: K blockers (amiodarone, sotalol, bretylium) |
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anti-arrhythmic classes that work on ventricle
|
1, 3
|
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ventricular fibrillation
|
cardioversion will synchronize the depolarizations and drugs will slow the initiation of such events
treat with Class 1A (quinidine, procainamide) Class 1B (lidocaine, tocainide, phenytoin) Class 3: K blocker (sotalol, amiodarone, bretylium) |
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digitalis induced arrhythmias
|
extrasystole or ventricular tachycardia with danger of AV node depression
Class 1B: lidocaine, tocainide, phenytoin, increase AV conduction |
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congestive heart failure
|
heart progressively fails to maintain adequate output to support normal blood pressure
progressively fails to move venous return and allows development of high venous blood pressures leading to pulmonary and systemic edema |
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CHF progression
|
1. inadequate CO-> decrease in BP
2. HR increases due to low CO 3. resistance in vessels increases 4. BP increases 5. low blood flow to kidney 6. kidney secretes renin-> angiotensin-> aldosterone excess venous blood pulmonary and systemic edema |
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CHF drug targets
|
1. stimulate ventricle to contract more forcefully
2. use diuretic to improve kidney function and decrease volume 3. vasodilate venous or arteriole side 4. counteract compensations |
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CHF drug target: stimulate ventricle to contract more forcefully
|
improve stroke volume improves BP and reduces vasoconstriction of vessels, more blood reaches the kidneys and less renin is released
|
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CHF drug target: use diuretic to improve kidney function
|
diuretic decreases the volume needed to be pumped, lower work-load for the heart
support the kidney |
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CHF drug target: vasodilate venous or arteriole side
|
Vasodilators arterioles:
hydralazine minoxidil diazoxide vasodilate venules and arterioles Na Nitroprusside Nitrates Isosorbide Dinitrate |
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Counteract compensations
|
ACE inhibitor- block angiotensin 2 vasoconstriction
block angiotensin 2 receptors: Sartans block aldosterone: spironolactone |
|
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Proximal tubule diuretic: name
|
Acetazolamide
|
|
|
loop diuretics: names
|
furosemide
bumetamide ethacrinic acid |
|
|
K sparing diuretics
|
spironolactone
amiloride triamterene |
|
|
thiazide diuretics
|
hydrochlorothiazide
indapamide (also a vasodilator) |
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Calcium sparing diuretics
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hydrochlorothiazide
indapamide (vasodilator) work on DCT decrease reabsorption of Na vasodilate hypokalemia hypercalcemia |
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Loop diuretic drug names and effects
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ethacrynic acid (ototoxic)
furosemide (sulfa sensivity) bumetamide (sulfa sensitivity) decrease recovery of everything |
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diuretics that act on the collecting duct
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spironolactone- targets aldosterone, K sparing
amiloride triamterene retain K use with loop and thiazide |
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vasodilator: arteriolar only
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hydralazine
minoxidil (always use with vasodilator and beta blocker) diazoxide (reverse emergency HTN) decrease afterload |
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vasodilator: venules
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isosorbide dinitrate
sodium nitroprusside decrease preload |
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beta blockers used in CHF
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metoprolol
carvedilol usually considered cardio depresants but MAY SUPPRESS SYMPATHETIC DRIVEN VENTRICULAR TACHYCARDIA can aggravate digitalis induced depression |
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Digitalis
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blocks Na-K-ATPase
improves calcium contractility in cardiac cells residual Na decreases the gradient to run the NaCa antiport Ca remains in the cell long term improvement in cardiac contractility AV node depression SE: ventricular extrasystole, ventricular tachycardia, ventricular fibrillation AV node depression |
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difference between digoxin and digitoxin
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digitoxin is detoxified by the liver
digoxin is excreted unchanged |
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beta 1 agonists
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dobutamine, NE, epi, isoproterenol
potentiate B1 by improving signaling by cAMP |
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phosphodiesterase inhibitors
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inamrinone (amrinone)
potentiate B-1 action by improving signaling by cAMP |
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brain natriuretic peptide
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nesiritide
increase cGMP relax smooth muscles in arterioles and venules short term |
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AV depressants
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beta blockers
Ca channel blockers adenosine can aggravate digitalis induced AV depression |
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Major concept in pharmacology
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use drugs with different mechanisms of action and different toxicities
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CHF main treatment
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diuretics and ACE inhibitor (captopril, lisinopril, enalapril, benazepril)
cardiotonics to support CO |
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3 drug classes used to treat angina
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1. nitrates (venodilate)
2. beta blockers 3. calcium channel blockers |
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classical angina
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stable, classical, typical, angina of effort, lead pipe coronary
coronary blood flow is regulated by perfusion pressure -limited blood flow adjustment -heart work that exceeds the limits of blood flow will cause ischemic damage/pain -induced by cold, stress, exercise -coronary hypoperfusion can be caused by vasodilator |
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variant angina
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prinzmetal's angina, angina at rest
-atherosclerosis may contribute -caused by coronary vasospasm -at rest the predominant tone is parasympathetic |
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unstable angina
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aka crescendo angina
-emergency -will get worse -atheromatous disease -vasospasm -PLATELET PLUGS AND COAGULATION -will cause MI |
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treatment goal for classical angina
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reduce heart work
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treatment goal for variant angina
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reduce coronary vasospasm
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treatment goal for unstable angina:
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reduce heart work
reduce vasospasm stop platelets and fibrin go to the ER |
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Typical angina: Drug therapy to reduce heart work
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reduce preload- venodilate- nitrates
decrease sympathetic drive: Beta blockers decrease afterload: Ca channel blockers (verapamil, diltiazem, nifedipine) verapamil and diltiazem also resist cardiac response to sym. |
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variant angina: drug therapy to reduce coronary vasospasm
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vasodilator
venodilate: nitrates Ca channel blocker NO BETA BLOCKERS |
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how do nitrates work?
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1. release NO
2. activates guanylate cyclase 3. forms cGMP which dephosphoryates myosin light chain kinase 4. smooth muscles relax |
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What are the effects of nitrates? and their side effects
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venodilation
arteriolar dilation SE: dependence tolerance headaches dizziness, fainting, hypotension |
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Name the nitrate drugs
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sodium nitroprusside
nitroglycerin: PO, avoid 1st pass metabolism for rapid onset, many routes of administration isosorbide mono (longer duration) and dinitrate |
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What is coronary steal syndrome?
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when vasodilators steal perfusion pressure
can cause angina and sympathetic reflex- tachycardia |
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Ca channel blockers used in angina
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nifedipine
-works at arteriole -use alone in variant angina or with a beta blocker in common angina -can cause angina, hypotension, reflex tachycardia, coronary steal -variant angina- might be able to tolerate tachycardia if they can exercise without angina |
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Ca channel blockers used prophylactically in variant angina
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verapamil, diltiazem
vasodilate heart and arteries |
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beta blockers are used with other drugs
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to prevent reflex tachycardia
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heparin
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IV anti-coagulant
potentiates antithrombin 3 reversed with protamine sulfate |
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Warfarin
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oral anti-coagulants
blocks clotting factor synthesis by inhibiting recycling of vitamin K (required cofactor) reverse with vitamin K or clotting factors |
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fibrinolytics
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streptokinase
urokinase alteplase promote activation of plasmin (proteolytic enzyme that retracts clots and digests fibrin) |
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Aspirin
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irreversible blocks COX1 and COX2
stops synthesis of thromboxane (platelet aggregation, release response, arterial constriction) associated with the prevention of an MI |
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block ADP receptors on platelets
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ticlopidine
clopidogrel |
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binds platelet surface receptors for cell-cell interaction
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abciximab
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prostacyclin's job
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stabilize cell against activation
arterial dilation inhibits platelet aggregation |
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lidocaine
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IV
used to treat ventricular arrhythmias class 1B Na channel blocker minimal toxicity |
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Amiodarone
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#1 drug for ventricular arrhytmias
class 3 (K blocker) increases APD and ERP many side effects |
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bradycardia due to MI
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acute MI invokes the vagus M2 receptor
treat with atropine (block ACH) |
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pulmonary congestion due to acute heart failure
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furosemide- rapid reduction of ECF volume
morphine- pain relief aminophylline: bronchodilation, vasodilation, cardiac stimulation |
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Pop quiz, hot shot.
low CO, low BP, high venous pressure, acute heart failure, shock What do you do? What do you do? |
vasodilate: arterioles and venules
increase CO: -dopamine, -dobutamine: beta 1 agonist -imarinone and milrinone: block phosphodiesterase, induce cAMP |
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sildenafil
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viagra
blocks phosphodiesterase to increase cGMP and to relax smooth muscle of corpora cavernosa cGMP is also activated by nitroprusside by NO therefore, sildenafil can potentiate nitrates to cause severe hypotension or a MI |
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right ventricular failure
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add volume
increase CO and BP increase Left venricular contractile force: dobutamine (beta 1 agonist), dopamine, imarinone and milrinone (phosphodiesterase inhibitors) |
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low dose aspirin
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80-160mg/day
block platelet thromboxane does not block vessel prostacyclin (unless dose is too high) stabilizes platelets effect lasts 7 days |
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ticlopidine and clopidogrel
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block ADP receptor on platelets
prevent expression of glycoprotein receptor that works in bridging suppresses platelet aggregation helps prevent TIA, CVA, MI always used in angioplasty and stents |
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Beta blockers use in MI
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propranolol and AMA
non ISA decrease heart work prevent arrhythmia, angina, ventricular events |
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Ca channel blockers in MI
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diltiazem and verapamil
relax heart and arteries delay attainment of angina where double product: HR x systolic BP= DP |
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What is double product
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HR x systolic BP
point of angina |
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risk factors for a MI
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smoking
weight diet stress |
