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198 Cards in this Set
- Front
- Back
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Evolution of atherosclerotic plaques
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accumulation of lipoproteins-->oxidative stress-->cytokines-->monocytes come in -->foam cells--> sm mm cells proliferate--> elab ECM = fibrofatty lesion --> calcification
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Anticoagulation in vascular endothelial cells
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Prostacyclin
Thrombomodulin Heparin sulfate Endogenous thromboplastin (t-PA) |
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Procoagulation in vascular endothelial cells
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Plasminogen activating factor
Tissue factor Von Willebrand factor |
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Typical vs Graft atherosclerosis
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typical = eccentric, lipids, focal
graft = concentric, no lipid core, diffuse |
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Effects of statins
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regression of atherosclerosis
reduce sudden death plaque stablization reduce fibrosis reduce AF |
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Statins MOA to improve coronary flow
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reduce ACh's vasoconstriction on diseased coronary aa's
(ACh vasodilates healthy ones) |
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Statins tox
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elevated liver enzymes
myopathy rhabdomyolysis |
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MI- ST elevation vs depression
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elevation = transmural ischemia
depression = subendocardial ischemia |
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Acute Plaque rupture therapy
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thrombolytics
angioplasty/stent inc coronary flow (nitro) beta blockers |
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prevent platelet thrombosis
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ASA, clopidogrel
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heparin
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prevent thrombosis
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6 statins in order of potency
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Fluvastatin
Lovastatin Pravastatin Simvastatin Atorvastatin Rosuvastatin |
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6 classes of diuretics and their prototype
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Carbonic anhydrase inhib-- acetazolamide
Osmotic agents - mannitol Loop - furosemide Thiazides - HCTZ Aldosterone antag (K sparing)- spironolactone ADH antagonist - conivaptan |
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Acetazolamide -- type, site, clinical use
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CA inhib, PCT
mountain sickness, urine alkalinization, glaucoma |
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Acetazolamide tox (4)
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CA inhib
hyperchloremic metabolic acidosis, dec diuretic action, renal stone, hepatic encephalopathy |
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Mannitol -type, site, clinical use
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osmotic, PCT and descending limb
kidney protection, reduce intracranial and intraocular P |
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Mannitol tox (3)
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exacerbate CHF edema
acute hyponatremia (dilutional) later hypernatremia (lose water>Na) |
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Furosemide-type, site, clinical use
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Loop, thick ascending limb (block Na/K/Cl)
get fluid off lungs in CHF! treat edema in hep and kid failure treat hyperkalemia treat anion overdose treat hypercalcemia |
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Furosemide tox (6)
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hypokalemic met acidosis
ototox hyperuricemia hypomagnesemia sulfur allergy dehydration |
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Other loop diuretics
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ethacryinic acid (ototox)
bumetanide |
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HCTZ-type, site, clinical use
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thiazide, block Na/Cl transport in DCT
treat htn and CHF prevent Ca kidney stones |
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HCTZ tox
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hypokalemia
hypokalemic metabolic acidosis hyperuricemia hyperglycemia inc LDL sulfonamide allergy |
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Other Thiazide diuretics
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Indapamide
Chlorthalidone Metolazone--- super potent w/ loop! |
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Sprinolactone MOA
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K sparing
antagonism of mineralcorticoid receptors |
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Amiloride MOA
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K sparing
inhibition of Na+ influx in luminal membrane |
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Primary and 2ary hyperaldosteronism
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Primary = Conn's syndrome - ectopic secretion, hypokalemia
2ary = CHF treat w/ K sparing (Aldost antag) diuretics |
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K sparing diuretics tox
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hyperkalemia (balance w/thiazide)
interact w/ ACE inhib, NSAIDs hyperchloremic met acidosis gynecomastia |
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Conivaptan (V1a and V2) and Tolvaptan (V2) -type, site, clinical use
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ADH receptor antag, medullary CD
treat SIADH, treat hyponatremia |
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ADH antag tox
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hypernatremia (+dehydration)
nephrogenic diabetes insipidus |
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classification of htn
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pre= up to 135/80s
mild = 140/90 Stage 1 mod = 140-159/90-99 Stage 2 severe= 160/100 and up |
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2ary htn
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pheochromocytoma
Cushing's (inc cortisol, Na retention) Primary aldosteronism - Lo K, inc Na coarctation of aorta renal aa constriction (renin) |
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Local regulation of BP
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endothelin 1 constricts
NO dilates BP= COxPVR |
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Which diuretic vasodilates?
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furosemide
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How much do diuretics lower BP?
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10-15mmHg
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What is the favored class of diuretic to treat htn?
When contraindicated? |
Thiazides
unless kidney disease |
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How do sympatholytics dec BP?
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dec PVR
dec HR and contractility |
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Methyldopa MOA
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sympatholytic
alpha-methyl NE central alpha agonist |
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Methyldopa tox
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sedation, CNS, Coombs +, hemolytic anemia, hepatitis
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Clonidine MOA
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sympatholytic
central alpha agonist alpha 2 --reduce NE release |
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Clonidine tox
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(central alpha agonist, antihtn)
dry mouth, sedation, depression, w/drawal, htn crises |
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Ganglionic blockers
list and MOA |
hexamethonium, trimethaphan, mecamylamine
block nicotinic cholinoreceptors on postganglionic neurons (block PANS and SANS and effects on BP) |
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Adrenergic neuronal blocking agents
list and MOA |
guanethidine
guanadrel reserpine - block uptake of biogenic amines DONT USE block NE release |
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Contraindications for Beta antagonists
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DM1, asthma/ COPD, PVD, acute cardiac decompensation, heart block, raynauds
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Hydralazine MOA and toxicity
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nonspecific vasodilator
NO mechanism slow acetylators= lupus-like syndrome tolerance inc HR = worse angina peripheral neuropathy and drug fever |
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Minoxidil MOA and toxicity
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nonspecific vasodilator
hyperpolarization of sm mm-- opening K channels depolarization is more difficult inc HR inc fluid and salt retention hypertrichosis |
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Sodium nitroprusside MOA
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nonspecific vasodilator
activate guanylyl cyclase dilate aa and vv |
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Nonspecific vasodilators
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hydralazine, minoxidil, sodium nitroprusside, diazoxide, fendolopam
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Sodium nitroprusside tox
|
-w/ rhodanese enzyme def= cyanide poisoning
-thiocyanate poison = diosriented, psychosis, mm spasm, convulsion -thyroid dysfun (thiocyanate mess w/ iodine) -methemoglobinemia |
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Diazoxide
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nonspecific vasodilator
hyperpolarizing agent like thiazide minus diuretic hypotension and hyperglycemia |
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Fendolopam
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nonspecific vasodilator
D1 agonist dilate aa's natriuresis inc intraocular pressure! |
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ACE inhibitor toxicities
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hyperkalemia
azotemia hypotension cough teratogen (2nd and 3rd trimester) cranial facial abnormalities drug fever angioedema -- esp lips |
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Clinical use for sympathomimetics
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septic shock
hemorrhagic shock hypovolemic shock cardiogenic shock severe HF |
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Epinephrine effects and uses
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alpha 1 = constriction
beta 2 = dilation beta 1 = inotropic/chronotropic asystole! anaphylaxis |
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NE effects and uses
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alpha = inc bp
beta 1 = inotropic and chronotropic (but baroreflex blunts HR response) use to inc sys and diastolic pressure |
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DA effects and uses
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dilate renal afferent arterioles
natriuretic (high dose = alpha agonist, inc BP and inotropy) use in hypotension w/ oliguria... |
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Direct acting sympathominetics
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phenylephrine (alpha ag)
methoxamine (alpha ag) isoproterenol (beta ag w/ lil alpha) dobutamine (b1 ag) ephedrine (beta ag) midodrine (a1 ag) |
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htn treatment in pt w/ hyperlipidemia
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ACE inhib and Ca channel blockers dont raise lipids or HR :)
Niacin lowers LDL and raises HDL diuretics raise HDL + reactive tachy beta blockers = inc lipids alpha blockers = reactive tachy |
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CHF pt w/ htn and fluid on lungs
How treat and what risks? |
Furosemide (cuz potent diuretic+ vasodilation)
tox = hypokalemic metabolic acidosis hyperuricemia hypomagnesia dehydration |
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What diuretic class would you give for hypercalcemia?
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Loop!
(furosemide, bumetanide, torsemide) Def not a thiazide cuz holds on to Ca2+! |
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Active young guy with htn
How do you protect his heart? |
ACE inhib or Ca channel blocker
both cardioprotective and no effect on inotropy and chronotropy like B blocker could give pindolol cuz partial B agonist |
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Htn lady w/ 2+ proteinuria
how treat and protect kidneys? |
ACE inhibitors are nephroprotective!!
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Dialysis worsens lipid profile
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that sucks...
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Accelerated htn signs, workup, treatment
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eg: 190/120, pitting edema, disoriented, lil SOB, 3+ proteinuria
do workup for rheumatic fever dont lower BP too fast = CNS probs, lower ~25% give esmolol bc short action |
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Cushings w/ hypokalemia
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Gotta get rid of the tumor!
Don't give thiazide or loop diuretics bc worsen the hypokalemia |
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hypovolemic shock!
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give fluids if not overloaded
Dont give dobutamine!-- dilate = more hypotensive dont wana inc contracility if not HF Could give NE, but gotta get blood to renal so give DOPAMINE |
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Orthostatic hypotension treatment
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Drug of Choice = midodrine (a1 ag)
also can use ephedrine, yohimbine prazosin makes it worse! (alpha blocker) |
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What drug for htn used in pregnant ladies?
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methyldopa most widely used
verapamil and other Ca blockers not gonna hurt baby if u need to used those |
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Htn pt on furosemide and amiodarone....what else can I give?
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methyldopa and clonidine centrally acting alpha agonist
ganglionic blocking agent (side effects) |
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cardiac resting potential
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-80 to -95mV
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Ventricle cells permeable to...
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K+
Less to Na+ or Ca++ |
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Phases of action potential
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0- upstroke, Na channels open --> +25 to 35mV
1- early fast repolarization, Na close, K open 2- plateau, Ca++ open (K out = Ca in) 3- repolarization K open, Ca close 4- diastole, reestab concentrations |
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Threshold potential of SA node
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-40mV
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ACh vs NE in the SA node
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ACh inc K conductance = K out, makes depol harder
NE dec K conductance = K stays in, cell more positive= depolarization influence automaticity |
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altered automaticity
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1. increased Phase 4 slope= tachy – NE, amphetamines, hyperthyroid, atropine, hypokalemia, digoxin at purkinje.
2. Decreased slope of phase 4 bradycardia – BB, CCB. 3. Hyperpolarized diastolic potential, suppressed depol – Vagal/PANS activity, muscarinic, antiACHE, digoxin at SA/AV. 4. Elevated threshold bradycardia – sodium channel blocker, injury. |
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trigger arrhythmias
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Early afterdepolarizations-- phase 2 or 3 = Vtach and Torsades de Pointes
Delayed afterdepolarizations- phase 4- from inc intracellular Ca (too much digitalis, PDEinhib), hypoxia |
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effective refractory period
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0,1,2, most of 3
0 and1 = absolute 2 and 3 need super strong stimulus |
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pacemaker determined by
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whoever has fastest rise of phase 4 slope
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Automaticity increased by...
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SANS
hypokalemia |
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Hypokalemia and arrhythmia
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dec K+ conductance, dec the hyperpolarization effect of the ion during phase 4
potential remains "partly depolarized" it promotes automaticity. may be caused by chronic use of thiazide-diuretics |
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Automaticity decreased by...
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PANS
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Blocks in conduction
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Sinus exit block
AV block Bundle branch block His- purkinje block |
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re-entry requisites
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Bidirectional block exists
Anatomical substrate Unidirectional block Critically timed excitation (2 in a row) |
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Rate of atrial tachy, atrial fib, atrial flutter
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a tachy--150-250
a fib--250-350 a flutter--350-600 |
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reentrant arrhythmias
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atach, aflutter, afib, vtach
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Torsades de pointes
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form of polymorphic ventricular tachycardia (VT)
gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line |
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Class 1a sodium channel blockers
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Quinidine
Procainamide Disopyramide |
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Class 1b sodium channel blockers
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Lidocaine
Mexiletine Tocainide |
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Class 1c sodium channel blockers
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Flecainide
Propafenone |
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Class II antiarrhythmics
(Beta blockers) |
Propanolol
Atenolol Metoprolol |
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Class III antiarrhythmics
(K+ channel blockers) |
Amiodarone
Dronedarone Sotalol Ibutilide |
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Class IV antiarrhthymics (Ca2+ blockers)
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Dilitiazem
Verapamil |
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What antiarrhythmics Torsades as a side effect?
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Quinidine, Sotalol
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What sodium channel blocker causes a lupus-like syndrome and hypotension as side effects?
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Procainamide
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What anti-arrhthymics cause CNS side effects?
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-1b sodium channel blockers (lidocaine, mexiletine, tocainide)
-amiodarone (Kchannel blocker) -Propanolol |
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What K+ channel blocker affects the thyroid?
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Amiodarone
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What sodium channel blocker causes agranulocytosis?
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Tocainide
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Which antiarrhythmics can be proarrythmic?
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Quinidine (1a... cause Torsade)
Sotalol (3 -- torsade) Propafenone (1c) Ibutilide (K blocker) |
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Which antiarrhythmics cause dec LV function?
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Verapamil
Atenolol Sotalol (K blocker) |
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Kinetics of 1a, 1b, 1c
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1a intermediate
1b rapid 1c very slow |
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Which antiarrhythmics cause hypotension?
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Procainamide
Diltiazem Verapamil |
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What does procainamide break down into and what is that metabolite's effect?
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NAPA --- class III (K+channel blocker)
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Which sodium channel blockers have class III action?
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Quinidine and Procainamide
(prolong QT) |
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What drug treats HOCM, A and V arrhythmias, and causes atropine like side effects (urinary retention, dry mouth, warmth, blurry vision)?
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Disopyramide
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What inactivates lidocaine?
|
Alpha 1 acid glyocprotein (acute phase reactant)
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Which antiarrhythmic only acts on ventricle?
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Lidocaine
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Relationship b/w lidocaine and mexiletine?
|
Mexiletine = orally active form of lidocaine
(1b sodium channel blockers) |
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Which drug is fluorinated procainamide?
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Flecainide (1a --> 1c)
^treat atrial arrhythmias |
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Propafenone
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weak beta blocker and Ca channel blocker
treat supraventricular arrhythmias negatively inotropic |
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Which beta blocker is polar and which is nonpolar?
|
polar = atenolol
nonpolar = metoprolol |
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Propanolol has some ___ action
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1a sodium channel blocker
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Which is the most effective anti-arrhythmic and only one that reduces sudden death?
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Amiodarone
K channel blocker but also weak Na and Ca channel blocker increases effective refractory period |
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Amiodarone toxicity
|
thyroid (cuz 2 iodine molecules)
liver blood skin optic neuropathy pulm fibrosis |
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Dronedarone
|
amiodarone minus iodine
treat sinus vtach |
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Vernakalant use and toxicity
|
convert afib
tox = dysgeusia (taste), sneezing, parasthesias |
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What K channel blocker do you have to adjust the dosing for kidney disease?
|
Dofetilide (cleared renally)
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What class 3 drug is also a strong beta blocker?
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Sotalol
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What Ca channel blocker suppresses automaticity (treat EADs and DADs)?
|
Verapamil
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Adenosine effects
|
activate inward K current
inhibit Ca outward current = hyperpolarization stop SA and AV node conduction (inc refractory period) |
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What blocks adenosine?
|
theophylline
caffeine dipyridamole |
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Magnesium
|
deficiency = Torsades de pointes
treats digitialis arrhythmia Block Ca and K channels |
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Bretylium
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anti adrenergic (block release and uptake of NE)
hyperpolarizes cell |
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high output heart failure
|
shunts
PE Beriberi severe anemia septicemia hyperthyroidism Paget's disease valve disease |
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Levosimendan
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Ca sensitizer
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Ryanodine
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plant alkaloid that blocks Ca release
|
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2 problems you need to address to treat heart failure
|
decrease in stroke work and increase in pressure
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neurohormones that make HF worse
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NE, angII, endothelin, aldosterone, ADH
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INOTROPES
|
digitalis (digoxin)
inamrinone milrinone dobutamine |
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DIURETICS used in HF
|
acute - furosemide
chronic = other loop ones (furos, torsemide, bumetanide) metolazone (if resistant to loop) spironolactone and eplerenone |
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ACE INHIBITORS
|
captopril
enalapril lisinopril ramipril (lipophilic) |
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Name the lipophilic ACE inhibitor
|
Ramipril
|
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ARB prototype
|
Losartan
acts on AT1 receptor don't use w/ ACE inhibitors! |
|
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Aliskiren
|
Renin inhibitor
|
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VASODILATORS
|
Hydralazine/ ISDN
Nitroprusside Bosentan (pulm htn only) Carvediol + metoprolol (reduce afterload) |
|
|
Systolic dysfunction treatment
|
remove sodium -- diuretic + diet
antagonize RAAS-- ACE, ARB, renin inhibitor ^inotropy -- low dose digoxin Beta blockers - carvediol+metaprolol vasodilate-- ISDN/hydralazine cardiac resynchronization LVAD transplant antagonize aldosterone (eplerenone) |
|
|
Diastolic dysfunction treatment
|
Beta blockers
ACE inhibitors Aldosterone antagonist (Epelerenone) |
|
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Nesiritide
|
synthetic brain natriuretic peptide
natriuresis and diuresis treat acute HF |
|
|
Bosentan
|
inhibit endothelin
vasodilator treat pulmonary htn -- NOT HF |
|
|
Acute HF treatment
|
IV furosemide (or metolazone)
Vasodilators/ intotropes ACE or ARB intra-aortic balloon counterpulsation LVADN |
|
|
Digoxin in acute HF
|
NOT RECOMMENDED
ineffective + arrhythmogenic |
|
|
Hyponatremic pt in acute HF...
|
can use Conivaptan
V1a antagonist effective against dilutional hyponatremia |
|
|
Nitroprusside vs Nitroglycerine
|
Nitroprusside = afterload
Nitroglycerine= preload |
|
|
Dobutamine vs Dopamine
|
Dobutamine = afterload + inotropic
Dopamine= natriuretic at low dose |
|
|
Digitalis MOA
|
inhibit Na/K pump
slows Na/Ca exchanger Ca builds = stronger contraction |
|
|
Digitalis electrical effects
|
shortens APD
inc DADs increase vagal tone = decrease HR |
|
|
Digitalis toxicity
|
nausea, arrhythmias (VT) and coronary constriction (sympathetic outflow), visual disturbances (blue scotoma)
|
|
|
Digitalis PK
|
cleared renally
Very low TI! 1ng/mL therpeutic vs 2ng/mL toxic! |
|
|
Reverse digitalis toxicity
|
Mg ++ or Digibind
Ca++ inc digitalis toxicity! |
|
|
Inamrinone
|
PDE inhibitor = inc Ca
treat acute decompensation myelosuppression and liver tox |
|
|
Milrinone
|
PDE inhibitor = inc Ca
treat acute decompensation vasodilator+ inotrope |
|
|
Dobutamine
|
B1 stimulator
vasodilate + inotropic |
|
|
Dopamine
|
B1 stimulator
D1 inc renal perfusion, natriuresis @ low dose |
|
|
Spironolactone and eplerenone role in HF
|
reduce aldosterone = reduce preload
also antifibrotic |
|
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ACE inhibitors' role in HF
|
dec afterload (stop angII's vasoconstriction)
inc bradykinin (vasodilator) prevent remodeling post MI |
|
|
What drug produces thiocynate and cyanide toxicity?
|
Nitroprusside
|
|
|
Effort angina treatment
|
nitrates
dihydropyridines w/ beta blockers nondihydropyridines beta blockers |
|
|
Vasospastic/variant angina treatment
|
nitrates
dihydropyridines beta blockers make it worse!!! give w/nitrates |
|
|
Unstable angina treatment
|
nitrates
beta blockers make it worse!!! give w/nitrates |
|
|
therapeutic effects of nitrates
|
coronary dilation
arterial dilator venodilator dec platelet aggregation |
|
|
adverse effects of nitrates
|
tolerance
reflex tachycardia (block w/betablockers) methemoglobinemia |
|
|
Oral and inhaled nitrates
|
oral= isosorbide dinitrate
inhaled= amyl nitrate |
|
|
Nicroandil
|
anti-anginal
NO release K channel opener |
|
|
Dihydropyridines
|
treat variant and effort agina and htn
nifedipine (short acting) amlodipine (long acting) isradipine (long acting) nimodipine (cerebral bv's) |
|
|
Non-dihydropyridine
MOA |
Verapamil/Diltiazem
bind alpha1 subunit on Ca channel on smooth mm, SA and AV nodes, and myocardial cells can worsen HF (but still used in acute HF to treat AF decompensating mitral stenosis) |
|
|
Verapamil
|
nondihydropyridine
strong effect on SA and AV node negatively inotropic treat SVT (AV block)-- slows ventricular response |
|
|
Diltiazem
|
nondihydropyridine
more vasodilator strong SA and AV node block |
|
|
Nebivolol
|
treat htn
vasodilate, NO release |
|
|
Ranolazine
|
anti anginal
late Na channel blocker dec Ca++ = reduce contractility also dec FA oxidation (change metabolsm of myocardium) |
|
|
Ivabradine
|
Na channel blocker
inhibit hyperpolarization-activated Na channel in the SA node slows HR |
|
|
non pharamacological treatment of angina
|
angioplasty + stent
surgical revascularization intra-aortic balloon counterpulsation for unstable |
|
|
Why give beta blockers and nitrates together?
|
Bblockers may worsen vasospasm and dec coronary flow, but reduce O2 demand
betablockers stop the reflex tachy from nitrates |
|
|
Peripheral aa disease and claudication treatment
|
pentoxifylline
cilostazol venoplasty |
|
|
Pentoxifylline
|
treat PAD and claudication
xanthine derivative makes RBCs more pliable, venodilation |
|
|
Cilostazol
|
treat PAD and claudication
PDE3 inhibitor= venodilation |
|
|
Why be careful w/ ED treatment and angina treatment?
|
PDE-5 inhibitors (inc cGMP) potentiate nitrates = hypotension --- need 6hr nitrate free interval
|
|
|
Alprostadil
|
PGE1 analog
inject into cavernosa or urethral suppository worked if PDE5 inhibitors don't |
|
|
treatment for ACS
|
nitro
beta blocker heparin anti-platelet |
|
|
treatment for nonSTEMI
|
ASA
clopidogrel heparin (thrombolytics don't work) |
|
|
treatment for STEMI
|
nitro
beta blockers nondihydro Ca channel blockers ACE inhibits Antiplatelet Heparin Bivalirudin |
|
|
Heparin action and adverse effects
|
action- potentiates antithrombin III
adverse- thrombocytopenia |
|
|
How reverse heparin?
|
protamine
|
|
|
Low-molecular heparin
|
Enoxaparin
(less bleeding, easier dosing) |
|
|
Rivaroxiban
|
oral factor 10 inhibitor
prevent emboli in AF pt's |
|
|
Direct thrombin inhibitors
|
Hirudin
Bivalirudin Argatroban Dabigatran |
|
|
Primary action of warfarin
|
inhibits factors 7,9,10
|
|
|
genetic polymorphisms that determines how warfarin affects pt
|
VKORC1 - determine degree of effect
CYP2C9*2 or CYP2C9*3 *2 = 17% lower dose *3 = 37% lower dose |
|
|
What should INR be in a pt on warfarin?
|
2-3.5
|
|
|
MOA of fibrinolytic agents
|
lyse thrombi by catalyzing formation of plasmin from plasminogen
|
|
|
when to use fibrinolytic agents
|
MI
PE DVT ascending thrombophlebitis stroke |
|
|
Fibrinolytic agents
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Streptokinase-- faciliates plasmin formation
Urokinase-- faciliates plasmin formation Alteplase--human tPA Reteplase--recombinant tPA Tenecteplase-- mutant tPA |
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Antiplatelet drugs
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ASA
Clopidogrel Ticlopidine Prasugrel Ticagrelor Abciximab Dipyridamole Cilostazol |
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Antidotes for warfarin and heparin
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Vitamin K1
antagonizes warfarin's effects on 7,9,10 Protamine combines w/ heparin 1mg/100units heparin |
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Clopidogrel
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antiplatelet
inhibits ADP (adenosine diphosphate) |
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Ticlopidine
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like clopidogrel (inhibit ADP)
leukopenia and blood dyscrasias :( |
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Prasugrel
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like clopidogrel (inhibit ADP)
activated faster less drug interaction more bleeding |
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Ticagrelor
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Newest clopidogrel-like agent
structure like adenosine |
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Abiciximab
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ab against IIb/IIa receptor on platelet
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Dipyridamole MOA
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inhibits adenosine uptake by platelet
inhibits cGMP PDE activity use w/ ASA in pt's w/ prosthetic heart valves |
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Cilostazol MOA
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PDE inhibitor
promotes vasodilation inhibits platelet aggregation treat claudication (for pts who fail ASA and clopidogrel) |
