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306 Cards in this Set
- Front
- Back
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What is the first committed step in Cholesterol synthesis?
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HMG-Coa to Mevalonate via HMG-Coa reductase
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How do statins inhibit HMG-Coa reductase?
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Analogue of HMG-Coa intermediate during its reducxtion to Mevalonate
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Are statin's inhibition of HMG-Coa competitive or non-competitive?
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non-competitive
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How do statins affect LDL receptors?
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They increase them
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What does an increase in LDL receptors do for a patient?
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It increases LDL break down, and increases the extraction of LDL intermediates by the liver
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Apart from reducing LDL, what other affects do statins have?
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Small increase in HDL, and small decrease in plasma triglycerides
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Statins mainly act on which organ?
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The liver
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What toxicities do statins cause?
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Elevated aminotransferase activity, which may be associated with serious hepatotoxicity. Elevated creatine kinase, which causes muscle weakness. Myopathy (rhabdomyolysis) is rarely caused (only with high doses, and when mixed with other meds)
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What cholesterol does niacin affect?
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Lowers LDL, VLDL, and raises HDL
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What drug class is Niacin usually combined with?
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Statins
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What is the MOA of Niacin
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Stops VLDL secretion by hepatocytes.
Inhibits lipase of adipose tissue, which decreases VLDL in the liver. Decreases break down of HDL. Induces clearance of VLDL via LPL pathway, which decreases triglycerides |
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What is the toxicity for Niacin?
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Reversable elevation of aminotransferase activity, which may be associated with liver toxicity.
Hyperuricemia Induces prostoglandin production, which causes flushing |
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How can patients prevent flushing with Niacin
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Take asprin 30min prior, or take Niacin after meals
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How does Fibric acid Derivative affects cholesterol?
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Decreases VLDL.
Moderately decreases LDL |
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What patients would require use of Fibric acid derivatives
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Hypertriglyceridemia patients
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Fibric acid MOA
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Ligands for PPAR-alpha, which induce lipolysis of VLDL via LPL pathway.
Decrease lipolysis of lipids in adipose tissue, which decreases fatty acids in the liver, and decreases VLDL synthesis |
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Toxicity of Fibric acid derivatives
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Higher chance of myopathy when given with statins. (decrease metabolism of statins) Worst is gemfibrozil, best is fenofibrate
Cholesterol gallstones. Don't use in patients with liver or gallbladder disease, or with high risk groups such as women, obese patients, or native americans |
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Bile Acid Binding Resins are which drugs
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Colestipol, Cholestyramine, Colesevelam
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Bile acid binding resins affect cholesterol how?
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20% decrease in LDL
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What is the indication for bile acid binding resins?
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treats primary hyperlipidemia
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MOA of bile acid resins
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Bind to anionic bile acids
increase the excretion of bile acid up to 10 times liver increases the change of cholesterol to bile acid Low cholesterol increases LDL receptors Increase LDL receptors clear LDL from plasma |
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What is homozygous familial hypercholestoralemia
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Non functioning LDL receptors
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Toxicity of bile acid resins
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Absorption of digitalis glycosides, warfarin, thiazides, tetracyclines, iron salts, statins, folic acid, ascorbic acid, and aspirin
Colesevelam does not bind to digoxin, warfarin, or statins Take medications 1 hour before, or 2 hours after bile acid resins |
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ezetimibe MOA
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probably targets a transport protein NPC1L1 in the GI tract
inhibits the uptake of cholesterol and phytosterols inhibits reasborption of cholesterol in bile reduces LDL 18% small increase in HDL |
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ezetimibe is combined with what drug? What is the effect?
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Simvastatin. Reduction of LDL 60%
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Why is ezetimibe synergistic with simvastastin
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Simvastatin increases intestinal absorption of cholesterol, which ezetimibe inhibits.
Ezetimibe enhances cholesterol biosynthesis, which simvastatin inhibits |
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Which is better, ezetimibe/simvastatin or niacian/simvastatin?
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Niacin/simvastatin
lower total reduction in LDL, but increase diameter of corotid artery |
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Toxicity of ezetimibe
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reversable impared hepatic function
worse when used with simvastatin |
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Omega 3 fatty acid MOA
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reduces hepatic triglyceride production
increases triglyceride clearance long term use sees increase of HDL decrease LDL 20-50% |
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Omega 3 fatty acid is combined with which drug for which effect
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statin
reduces major coronary events |
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Toxicities of Lovaza
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Not much,
preferrable to fibrate/statin combination, because decrease risk of rhabdomyolysis |
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NSAIDS MOA and action
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antiinflammatory
antipyretic analgesic treats rheumatic disease symptoms Inhibits COX 1,2, which inhibits prosteglandins |
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COX 1 effects
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GIT, platlets, kidneys
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COX 2 effects
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inflamation
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additional action of some NSAIDS
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down regulation of interleukin 1
decreased free radical and oxidative species production |
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Do selective COX inhibitors affect platelet aggregation?
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No
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which NSAIDS binds covalently and non-reversably to COX
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Asprin
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toxicities of selective COX inhibitors
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increase occurances of edema and hypertension
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toxicities of all NSAIDS
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hepatotoxicity
nephrotoxicity |
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toxicities of non selective COX inhibitors
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gastric irritation
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Asprin toxicities
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gastric upset
ulcers high doses (vommiting, tinnitus, vertigo, decreased hearing) higher doses (cardiotoxitiy, metabolic acidosis, respiratory depression) |
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Is meloxicam selective, or non selective
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Somewhere in the middle
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ibuprofen is what at low doses, and what at high doses
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analgesic, anti inflammatory
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Tylenol MOA and action
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weak COX 1,2,3 inhibitor
analgesic, antipyretic no platelet effects no uric acid effects no GI effects doesn't antagonize uricosuric agents |
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Tylenol interactions
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increase effect of warfarin when used for 3 or so days at doses over 2g per day (a tylenol metabolite probably inhibits Vitamin-K reductase)
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Tylenol toxicity
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4 grams for 14 days, some hepatotoxicity (a metabolite from CytP450 is toxic)
7.5-10g is hepatotoxic (children 150mg/kg) 10-15g hepatic necrosis 15g and over hepatic necrosis and death |
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Tylenol toxicity for alcoholics
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More CYP enzymes in alcoholics = more dangerous metabolites
More liver damage with less glutathione (glutathione metabolizes tylenol's dangerous metabolite) even can be dangerous with moderate alcoholics |
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Gout psychophysiology
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Uric acid crystals collect in joints
crystals are phagocytized phagocytosis results in release of release of prostaglandins, lysosomal enzymes, and interleukin-1 release of those cause worse inflammatory response with release of polymorphonuclear leukocytes |
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Colchicine MOA and action
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treatment and prophylaxis of gout
binds to tubulin and prevents polymerization inhibits formation of leukotriene B4 |
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colchicine toxicity
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Caused by tubulin binding and ceased mitosis
diarrhea, nausea, vomiting myelosupression, neuromyopathy are rare |
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colchicine interactions
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substrate for CYP3A4, and eflux transporter P-glycoprotein, can't be used with inhibitors of CYP3A4 or P-glycoprotein
with statins or fibrates may cause rhabdomyolysis or myopathy |
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NSAID gout indication
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NSAIDS inhibit phagocytosis of uric acid. Prophilaxis or treatment (asprin increases uric acid)
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Uricosuric drugs
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Probenecid & Sulfinpyrazone
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MOA of uricosuric drugs
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competes for the reabsorption anion transporter
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What can low doses of uricosuric agents do?
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Can decrease excretion of uric acid in urine, because it decreases secretion
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Uricosuric interactions
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asprin antagonizes uricosuric agents, and decreases secretion. However low doses of asprin 81, or 162 per day are acceptable
decrease secretion of weak organic acids (beta-lactams, penicillins), so prolong duration of action |
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Toxicities of uricosuric (sulfinpyrazone, probenecid)
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GI irritation, skin rash, kidney stones (don't use in patients with kidney stones)
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Allopurinal action and MOA
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inhibits uric acid biosynthesis
long term treatment inhibits xanathine oxidase which converts xanathine and hypoxanathine into uric acid |
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allopurinal toxicities
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hypersensitivity
liver enzyme abnormalities leucopenia |
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allopurinal interactions
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xanathine oxidase catalyzes mercaptopurine, so allopurinal increases in levels
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xanathine oxidase inhibitor drug
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febuxostat Uloric
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febuxostate, Uloric xanathine oxidase inhibitor toxicities
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no allopurinal like hypersensitivity
increases in hepatic transaminase, arthralgias, and dizziness. cardiovascular events occur rarely, but more than with allopurinal don't have to reduce dose for mild liver and renal imparement, unlike allopurinal |
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febuxostate, Uloric xanathine oxidase inhibitor interactions
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azathioprine, mercaptopurine or theophylline, which are metabolized by xanthine oxidase.
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Pegloticase (Krystexxa®) action and MOA
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recombinant form of the uricase enzyme(not present in humans) that converts uric acid to allantoin.
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Pegloticase (Krystexxa®) action and MOA continued
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Uricase catalyzes the oxidation of uric acid to allantoin
used for patients who don't respond to xanathine oxidase inhibitors IV infusion only |
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Pegloticase (Krystexxa®) toxicities
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anaphylaxis
infusion reactions (urticaria, dyspnea, chest pain, erythema, and pruritus) delayed-type hypersensitivity reactions premedicated with antihistamines and corticosteroids before receiving pegloticase to minimize the risk of anaphylaxis and infusion reactions. gout flares (during the first 3 months of therapy) (treat patients with NSAIDS or colchicine to help) nausea vomiting nasopharyngitis Don't take if you have glucose-6-phosphate dehydrogenase (G6PD) deficiency (mostly africans or mediteranians are at risk, screen before treatment) |
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Too much sodium does what in hypertension
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Increases vessel stiffness
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What is the initial and long term reactions to diuretics
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initial is lower blood volume, long term is lower perifial resistance
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How much do diaretics decrease blood pressure
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10-15mmHg
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why are diuretics used in combo with other antiHTN's
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other HTN's can increase sodium retension
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Central alpha-adrenergic agonist drugs
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methydopa
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Where do central alpha-adrenergic agonist's (methydopa) act
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central alpha recepters in the brain
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are central alpha-adrenergic agonists (methydopa) dependent on posture
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No, because they act centrally
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DO central alpha-adrenergic agonsts (methydopa) decrease CO or PVC
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Both
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toxicities of central alpha-adrenergic agosts (methydopa)
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sedation
depression nightmares |
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Adrenergic neuron-blocking agents drugs
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reserpine
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Adrenergic neuronal blocking agents MOA
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blocks uptake of biogenic amines in neurons
stops the creation of NE, dopamine, and seratonin decreases CO and PVR like centrally acting agents, lowers blood pressure standing and sitting |
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Reserpine toxicities
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depression in high doses
mild posterial hypotension Sedation nightmares mental depression rare parkinson disease symptoms from low dopamine |
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what are the 3 beta receptors, and what do they stimulate
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1heart, brain kidney
2 heart, smooth muscle, liver 3 heart, lipocytes |
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can low doses of cardioselective B-blockers cause broncho spasm
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Yes
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Which beta receptors contribute to decreasing blood pressure
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All of them, even in the kidneys, brain, etc.
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MOA of b-blockers
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decrease heart rate
contractility renin (mostly CO, but some PVR) |
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b-blockers used in conjuntion with what, and why
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vasodialators, to decrease reflex tachycardia
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What types of b-blockers are indicated from patients with bradycardia or postural HTN
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ones with intrinsic sympathomimetic activity (partial agonist to B-receptors)
pindolol, acebutolol, carteolol |
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b-blockers indicated for patients with angina or MI
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Non-sympathomimetic activity (antagonist, or non active partial agonists)
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which b-blocker has some vasodialation effect by stimulating NO
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nebivolol
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propranolol selective or nonselective
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nonselective
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propranolol affects mostly the heart or mostly the kidneys
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mostly the kidneys by inhibiting raas
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propranolol toxicities
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breathing depression
mental depression sleep disturbances |
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alpha blocker drugs
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prazosin
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what are the different alpha-receptors and what do they affect
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1 heart, smooth muscle, prostate
2 lipocytes, smooth muscle, platelets |
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postoral hypotension with a-blockers
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Yes, affects blood pressure in standing position more
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a-blockers toxicities
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reflex tachycardia(less than direct vasodialators) (non selective are worse, because they block both a1 and a2 whch cause release of adrenergic to act on b cells, if acting on a1 alone, than NE negative feedbacks itself)
retension of salt and water |
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when do you take a postural hypotension drug
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at bedtime
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CCB drugs
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verapamil
diltiazem nifedipine |
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CCB MOA and action
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Block Ca channels in the heart and smooth muscle of vessels
dihydropyridine are more vasodialators, others (verapamil, diltiazem) affect the heart more verapamil is more cardiodepressing than diltiazem |
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Direct vasodialator drugs
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minoxidil (oral)
nitroprusside (IV) fenoldapan (IV) |
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which direct vasodialator affects arteries and veins
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nitroprusside
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direct vasodialator toxicities
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reflex tachycardia
sodium and water retension |
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do vasodialators cause orthostatic hypotension or sexual dysfunction
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no, because they have no sympathetic MOA
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minoxidil MOA and action
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activates ATP potasium channels in arteries to cause hyperpolarization
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drugs used in combo with minoxidil
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b-blocker
diaretic |
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minoxidil toxicities
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headache
sweating hirsutism (hair growth) |
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nitroprusside MOA and action
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combo of iron, cyanide, nitrosso groups
dialates arteries and veins activates Guanylyl cyclase via NO or directly |
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nitroprusside toxicities
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produces cyanide upon metabolism
Cyanide broken down with rhodanase in mitochrondria with sulfar to thiocyanate (treat with sodium thiosulfate (donates sulfur) or hydroxocobalamin (combines with cyanide to produce cyanocobalamin)) thiocyanate (metabolite of cyanide) cause disorientation, psychosis, muscle spasms, and convulsions. hypotension |
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fenoldapam MOA and action
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agonist of dopamine d1 receptor
vasodialates peripheral arteries |
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fenoldapam toxicities
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tachycardia
headache flushing increases intraocular pressure |
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Phosphodiesterase inhibitor drugs
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taldalafil
sildenafil |
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PDE inhibitors (taldalafil sildenafil) action and MOA
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pulmonary arterial hypertension
PDE-5 is main PDE in lungs increases cGMP levels vasodialates |
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is taldalafil or sildenafil more selective
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taldalafil, it increase pressure in the eyes
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PDE inhibitors interaction
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nitrates, and a-blockers cause hypotension
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PDE inhibitors (taldalafil, sildenafil) toxicities
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headache
flushing myalgia visual disterbances (sildenafil more than taldafil) |
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stimulants for raas system activation
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reduced renal artery pressure
hypotension sympathetic neural stimulations reduced renal perfusion reduced plasma volume reduced sodium delivory increased sodium concentration at distal tubule |
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angiotensin II MOA
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binds to angiotensin II type 1 receptor
vasoconstriction sodium reabsorption catecholamine release aldosterone secretion |
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angiotensin II negative feedback
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inhibit renin release
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renin inhibitor drugs
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aliskiren (tekturna)
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aliskiren (tekturna) action and MOA
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blocks renin, which blocks change of angiotensinogen to angiotensin I
don't cause compensitory increase in renin's activity unlike ACE I's and ARB's |
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aliskiren (tekturna) action and MOA
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dizziness
diarrhea nasopharyngitis (no increase in bradykinen, so no angioedema and cough) long half life, high affinity for binding, hard to stop tekturna if it causes hypotension |
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ACE inhibitor drug
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captopril
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ACE inhibitor action and MOA
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HTN
heart failure MI inhibit peptidyl dipeptidase (ACE) (ACE also is supposed to metabolism bradykinin) bradykinin and kallikrein increases also decrease blood pressure reduces PVR not CO produces positive feedback on renin making more angiotensin I other pathways can convert angiotensin 1 to angiotensin II |
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ACE I toxicity
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No reflex tachycardia due to downward resetting of baroreceptors, or increase parasympathetic activity
hypotension if you loose fluids or take diuretics hyperkalemia dry cough angioedema no use in 2nd and 3rd trimesters (fetal hypotension, renal failure, and death) |
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ACE I interactions
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Potassium, or K sparing diuretics cause hyperkalemia
NSAIDS block bradykinen, and so decrease anti HTN affects |
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ARB action and MOA
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block AT1 recptor
cause increase in renin levels and activity completely inhibit Ang II as affective as ACE I's |
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ARB toxicities
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hyperkalemia
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indirect thrombin inhibitors
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heparin
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herparin action and MOA
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activates antithrombin
antithrombin IIa, IXa, Xa made of mucopolysaccharides strongly acidic treats venous thrombosis treats pulmonary embolism |
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antidote for heparin, and MOA for the antidote
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protamine sulfate
highly basic forms salt with heparin |
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how does heparin bond to antithrombin
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ionic bonds
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what does heparin have that allows it to bind
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pentasaccharide sequence
consists of repeating sulfated disaccharide units of D-glucosamine-L-iduronic acid and D-glucosamine-D-glucuronic acid |
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what does the binding of heparin do
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exposes antithrombins active site
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what does heparin do after it binds
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it is released and binds to another antithrombin
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unfractionated heparin affects what through antithrombin
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IIa, IXa, Xa
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Low MW heparin affects what through antithrombin
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Xa
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why is Low MW heparin used
|
increased bioavailability
sc injection long half-life |
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Low MW heparin drugs
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Enoxaparin (Lovenox®), dalteparin (Fragmin®), and tinzaparin (Innohep®)
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heparin toxicity
|
bleeding
thrombocytopenia allergy, since it is an animal product |
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warfarin interactions
|
aprin increases affact
heparin increases affect third gen cephalosporins increase affect (inhibit bacteria vit K production) hepatic disease increase (inhibits clotting factors) hyperthyroidism increases (increases clotting factor turnover) hypotheyroidism (opposit) Vit K decreases Diruetics decrease (increase clotting factor concentration) |
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warfarin overdose drugs
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vitamin K1 (phytonadione)
fresh-frozen plasma prothrombin complex concentrates (PCC) recombinant clotting factor VIIa |
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fibrinolytic drugs
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streptokinase
alteplase anistreplase tissue plasminogen activator (t-PA) reteplase tenecteplase urokinase. |
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fibrinolytic action and MOA
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catalyze plasminogen to serine protease plasmin
this lyses thrombi lyse fibrin |
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fibrinolytic indications
|
deep vein throbosis
peripheral vascular disease |
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antifibrinolytic drugs general
|
Aminocaproic Acid (Amicar®)
Tranexamic Acid (Lysteda®) inhibit plasmin from plasminogen indicated for bleeding disorders |
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streptokinase action and MOA
|
catalyzes plasminogen to plasmin
protects plasmin from anti plasmin agents, so can dissolve the center of the clot |
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Urokinase action and MOA
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Human enzyme
directly converts plasminogen to plasmin protects plasmin inside thrombin from anti plasmin agents, and so plasmin can dissolve the thrombus from within |
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tissue plasminogen activator drugs
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Alteplase
Reteplase Tenecteplase |
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tpa drugs (alteplase, reteplase, tenecteplase) action and MOA
|
selectively activates plasminogen bound to plasmin
altaplase is human form reteplase is human, except missing a group, which makes it less selective tenecteplase is mutated for with longer half life |
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asprin (anti-platelet) MOA and action
|
inhibits thromboxin a-2 (a platelet aggregater)
inhibits txa-2 by inhibiting COX 1 |
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asprin drug interactions
|
NSAIDS use with asprin competes and antagonizes the the anti platelet agg affect of asprin
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asprin toxicities
|
bleeding
hemorragic stroke |
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theinopryadines drugs
|
Clopidogrel, Prasugrel, Ticlopidine
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theinopryadines (clopidogrel, prasurgrel, ticlopidine) action and MOA
|
bind to and irreversibly block the P2Y12 ADP receptor, which inhibits ADP, which inhibits platelet aggregation
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theinopryadines (clopidogrel) interactions
|
clopidogrel activated by cyp2c19
PPI's inhibit cyp2c19 (nexium most, protonix least) PPI's are commonly used with clopidogrel/asprin therapy to reduce GI bleed possibilities east asians are more likely to have mutated cyp2c19 h2-blockers are best choice for those on clopidogrel/asprin therapy |
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Blockers of Platelet GP IIb/IIIa Receptor Complex drugs
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Abciximab, Eptifibatide, Tirofiban
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blockers of platelet gp iib/iiia receptor complex (abiciximab, iptifibatide, tirofiban) action and MOA
|
block platelet gp iib/iiia receptor complex, which activates fibrenogen, vibronectin, and other clotting factors
|
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patients without platelet gp iib/iiia receptor have what problem
|
bleeding disorder called glanzmann thromblasthenia
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abiciximab moa
|
monoclonal human antibody against platelet gp iib/iiia receptor
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Eptifibatide and Tirofiban MOA and action
|
analogues of fibrinogen amino acids, which mediate fibrinogen binding to platelet iia/iiib receptor binding
do not block vibronectin binding site |
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dipyridamole MOA and action
|
inhibits platelet uptake of adenosine
blocks ADP-induced platelet aggregation |
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dipyridamole combos
|
w/ asprin to preven ischemia
w/ warfarin to prevent thromboemboli |
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angina pectoris
|
chest pain from ischemia
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angina pectoris initial drug therapy
|
nitrates, ccb's, b-blockers
|
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nitrate drugs
|
nitroglycerin
|
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nitrate relax arteries or veins
|
both
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nitroglycerin MOA
|
denitrated by glutathione s transferase
nitrate ion release nitrate ion convered to NO |
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nitroglycerin toxicities
|
headache
orthostatic hypotention reflex tachycardia |
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nitroglycerin contraindications
|
Intracranial pressure is high
|
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nitroglycerin tolerance
|
there is tolerance, and salt and water retension
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CCB's block what type of calcium channels
|
L-type, vascular smooth muscle, and cardiac muscle
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CCB's drugs
|
nifedipine (dihydropyridine), diltiazem, and verapamil
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CCB's MOA
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Depolarize vascular smooth muscle, and cardiac cells
dihydropyridines, and verapamil and diltizem have different binding sites vasodialation in arteries reduction in contractility and heart rate |
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CCB's arteries or veins
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arteries
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dihydropyridines or dilt/verap more vasodialators
|
dihydropyridines
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CCB's toxicity
|
cardiac arrest, bradycardia, av block, heart failure, all are rare however
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CCB's interactions
|
B-blockers increase cardiac depression toxcities
|
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b-blockers used for angina?
|
Yes
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b-blockers increase or decrease diastolic volume?
|
increase
|
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b-blockers angina contraindications
|
ashma
brochospatic conditions bradycardia av block left ventricular failure |
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ranolazine indication
|
chronic angina, when other angina drugs aren't working
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ranolazine drug interactions
|
don't use with dilt/verap
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heart failure
|
can't get O2 to the body
|
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signs and symptoms of heart failure
|
tachycardia
peripheral and pulmonary edema shortness of breath cardiomegaly |
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heart failure drug classes
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Digoxin
Bipyridines Diuretics ACE Inhibitors b-Blockers b-Agonists Vasodilators Angiotensin Receptor Blockers |
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positive inotrop drug
|
digoxin
|
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digoxin therapeutic and toxic levels
|
therapeuric .5 - 1.5 ng/ml
toxic >2ng/ml |
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digoxin moa
|
inhibits Na/K atpase
more Na in cell this inhibits Na/Ca exchanger more Ca in cell More Ca in SR for stronger heart contractions |
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digoxin affects
|
decrease in length of action potential
decrease in refractory periods |
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digoxin toxcitiy heart
|
hyperpolarization by exit of K from cell
oscillatory depolarizing afterpotentials results in overloaded Ca, and oscillatory Ca premature depolarization (etopic beats) with preceeding regular action potentials called bigeminal beats goes to self-sustaining tachycardia into fibrillation either ventricular or atrial |
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digoxin toxicity outside heart
|
excitability in neurons and smooth muscle cells
annorexia nausia vomitting diarreah dissorientations hallucinations convulsions visual disterbances gynocomastia |
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digoxin interactions
|
hypokalemia
hypomagnecemia hypercalcemia must evaluate serum levels before treatment with digoxin |
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dipyridine drugs
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inamrinone
milrinone |
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dipyridine drugs (inamrinone, milrinone) indications
|
acute heart failure
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dipyridines (inamrinone, milrinone) MOA
|
PDE inhibitors
selective for PDE-3 isozyme (found in cardiac and smooth muscle) increases cAMP increases cadiac influx into heart vasodialation and contractility |
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dipyridines (inamrinone, milrinone) toxicity
|
arrythmia
bone marrow toxicity liver enzyme changes milrinon is less likely to cause bone marrow and liver toxities, more likely to cause arrythmias |
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b-adrenergic agonists drugs
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dobutamine
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b-agonists (dobuamine) drugs
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increases intracellular cAMP
increase CO decrease ventricular filling pressure |
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b-agonists (dobutamine) toxities
|
tachycardia (so arrithmias)
angina |
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non-positive inotropic heart failure drugs
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diuretics
aceis vasodialators b-blockers |
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aceis in heart failure
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reduce arterial resistance, and so after load
reduce remodeling decrease sympathetic activity by decreasing angiotensin |
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diuretics in heart failure
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reduce edema
reduce heart size improve pump effeciency |
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ARB's in heart failure
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same as aceis
reduce remodeling |
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vasodialators in heart failure
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reduce preload and after load
so reduce heart remodeling |
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b-blockers in heart failure
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not good for acute HF, but good for long term treatment
bisoprolol, metaprolol, carvedilol are ones used reduces catecholamines effects up-regulates b-receptors decreases heart rate reduces remodeling |
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what are common conditions and drugs that cause arrithmias
|
digitalis 25%
anesthesia 50% acute MI 80% |
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are arrythmias often treated
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only if symptomatic
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what makes arrythmias worse
|
ischemia
hypoxia acidosis or alkalosis electrolyte abnormalities excessive catecholamine exposure drug toxicity (e.g., digitalis or antiarrhythmic drugs) overstretching of cardiac fibers and the presence of scarred or otherwise diseased tissue |
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all arythmias result from what three things
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Disturbances in impulse formation
Disturbances in impulse conduction Disturbances in both impulse formation and conduction |
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what are disterbances in impulse conduction
|
blocks (av node block, bundle branch block, etc.)
reentry (a few extra heart beats, or sustained tachycardia) |
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what are the 4 classes of arrythmia therapy drugs
|
sodium channel blockers
b-blockers potasium blockers calcium channel blockers |
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chronically depolarized cells respond in what way to channel blocking
|
blocking drugs dissasociate more slowly, and so cause more affect than on regular cells
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do antiarrythmic drugs affect both chronically depolarized cells, and other cells in the heart at the same time
|
at therapeutic concentrations, they only affect chronically depolarized cells (which are cells that create arrythmias)
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what conditions cause arrythmias for people on anti-arrythmic drugs
|
tachycardia
hyperkalemia acidosis ischemia |
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are antiarrythmic drugs bases or acids
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weak basis
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how does acidosis affect antiarrythmic drugs
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promotes cationic form of drug, which delays release from channel, which increases affect
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how does alkylosis affecxt antiarythmic drugs
|
creats uncharged for of drug
decreases affect |
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class 1a antiarythmic drugs
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Quinidine
Procainamide Disopyramide. |
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which class 1a (quinidine, procainamide, disopyramide) effects
|
prolong AP
prolong refractory period |
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Class 1b drugs
|
Lidocain
mexilitine |
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Class 1b (lidocane, mexilitine) effects
|
prolong refractory period
|
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class 1c drugs and action
|
Flecainide
Propafenone Moricizine |
|
|
do antiarrythmic drugs affect both chronically depolarized cells, and other cells in the heart at the same time
|
at therapeutic concentrations, they only affect chronically depolarized cells (which are cells that create arrythmias)
|
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what conditions cause arrythmias for people on anti-arrythmic drugs
|
tachycardia
hyperkalemia acidosis ischemia |
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are antiarrythmic drugs bases or acids
|
weak basis
|
|
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how does acidosis affect antiarrythmic drugs
|
promotes cationic form of drug, which delays release from channel, which increases affect
|
|
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how does alkylosis affecxt antiarythmic drugs
|
creats uncharged for of drug
decreases affect |
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class 1a antiarythmic drugs
|
Quinidine
Procainamide Disopyramide. |
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which class 1a (quinidine, procainamide, disopyramide) effects
|
prolong AP
prolong refractory period |
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Class 1b drugs
|
Lidocain
mexilitine |
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Class 1b (lidocane, mexilitine) effects
|
prolong refractory period
|
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class 1c drugs and action
|
Flecainide
Propafenone Moricizine prolongs refractory period minimally affects AP |
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class 2 drugs and action
|
b-blockers
some prolong action potential |
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class 3 drugs and action
|
potasium channel blockers
Amiodarone prolong action potential duration prolong effective refractory period block Ikr potasium channel |
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class 3 drugs (potasium channel blockers, amioderone) toxities
|
reverse use dependence (high affinity for resting channels)
arrythmias like toseds de points |
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class 4 drugs and action
|
CCB's diltiazem, verapamil, bepridil
slow conduction in SA and AV nodes, which are calcium dependent |
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lidocane indications
|
arrythmias associated with acute MI
ventricular tachycardia ventricular fibrilation class 1b not used for prophylaxis |
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lidocaine MOA
|
blocks resting and active sodium channels
slows conduction |
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lidocaine toxicity
|
least cadiotoxic sodium channel blocker
high doses can cause hypotension as an anesthetic, has neurologic toxities (dose related and short lived) tremer nausea hearing disterbances convlusions |
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amiodarone class 3 indications and MOA
|
ventricular arrythmias
aterial fibrillation |
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amiodarone moa
|
blocks potasium channels
blocks sodium channels prolongs duration of action potential attatches to resting and open channel conformations weak adrenergic and calcium channel blocking (slow heart rate and av node conduction) high efficacy and low toxicity because of its equal affinity for resting, open, and closed conformations |
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amiodarone toxicity
|
bradycardia and heart blocks in pt with sinus or av node disease
dose related pulmonary toxicity prevents t4 changing to t3 (changes thyroid hormone levels) |
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verapamil is in what class
|
4
|
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verapamil arrythmia indications
|
arrythmic supraventricular tachycardia
|
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verapamil moa
|
blocks active and inactive l-type calcium channels
use dependent only works on cells that fire alot and are less polarized at rest prolongs av node conduction and refractory period slows sa node directly, but reflex tacycardia ends up slightly increase sa node causes peripheral vasodialation |
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verapamil toxicity
|
dose related and avoidable
causes hypotension and ventricular fibrillation if use in patients with ventricular tachycardia causes av block if patients have av disease (atropine or b-agonists can reverse it) cause sinus arrest in pt with sinus node disease constipation nervousness peripheral edema |
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diuresis
|
increase in urine volume
|
|
|
naturesis
|
increase in renal sodium
|
|
|
naturetic drugs are also called
|
diuretics
|
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|
diuretics basic moa
|
block na reabsorption at 4 sites in the nephron
|
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|
site 1 location
|
proximal tubule
|
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site 2 location
|
thick ascending loop of henle
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site 3 location
|
distal convulted tubule
|
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|
site 4 location
|
connecting tubule (end of the distal convulted tuble), and collecting ducts
|
|
|
site 1 reabsorbs
|
65% nacl, water, k
85% bicarbonate, phosphate, urate 100% glucose, amino acid, low MW proteins |
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|
site 1 diuretics moa
|
blocks carbonic anhydrase, which blocks na/bicarb reabsorption
|
|
|
site 2 reabsorbs
|
25% na
25% ca |
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|
diuretics that act on site 1 have what affects further down the nephron
|
more na reabsorption in site 2
|
|
|
site 2 moa
|
inhibit luminal membrane bound na/k/2cl symport
|
|
|
site 2 drugs (loop diuretics)
|
furosemide
ethacrynic acid |
|
|
site 3 reabsorbs
|
5% na
|
|
|
site 3 moa
|
anti luminal na/k atpase supplied by luminal na/cl co transporter
|
|
|
thiazide moa
|
inhibits site 3 luminal na/cl cotransporter
|
|
|
site 4 reabsorbs
|
3% na
|
|
|
site 4 moa
|
exchange luminal na for principle k and intercalated h
|
|
|
aldosterone kidney moa
|
increases na reabsorption, h and k secretion at site 4
|
|
|
does flow rate affect na reabsorption
|
yes, increases it
|
|
|
acidosis causes what change at site 4
|
na reabsorption
h secretion |
|
|
alkalosis at site 4 causes
|
increases na/k pump
|
|
|
spironolactone moa
|
antagonizes aldosterone at site 4
decreases na reabsorption decreases h and k secretion |
|
|
triamterine, amiloride moa
|
blocks na pump in luminal membrane of principle cells
thereby prevents na reaborption, k and h secretion |
|
|
site 1, 2, and 3 cause _kalemia
|
hypokalemia
|
|
|
which sites and drugs have to have high intracellular concentrations to produce an affect
|
site 1 CA inhibitors
site 4 sprinolactone |
|
|
what causes diuretics to be less effective
|
drugs or diseases that decrease gfr
|
|
|
2 structural groups of CA inhibitors
|
heterocyclic sulfanamides
meta-disulfamoylbenzene derivitives |
|
|
inhibition of intracellular CA decreases what
|
na reabsorption
h secretion |
|
|
inhibition of luminal CA decreases what
|
CO2 secretion
bicarb reabsorption |
|
|
how does site 1 diuretics cause hypokalemia
|
increases na flow to the rest of the sites which change na reabsorption for k secretion
|
|
|
side effects of CA inhibitors
|
increase na in urine
increase water increase flow decrease H secretion decreases cl |
|
|
what causes resistance to CA inhibitor therapy
|
reduction in filtered bicarbonate caused by CA inhibitor decreases bicarbonate reabsorption
|
|
|
2nd cause for CA inhibitor resistance after 1 week of use
|
metabolic acidosis provides more H to exchange with Na
|
|
|
CA inhibitor toxicity
|
metabolic acidosis
hypokalemia sulfonamide hypersensitivity exacerbate symptoms associated with cirrhosis of the liver (causes urinary alkalosis, which causes less amonium ion secretion, causes more ammonia in blood, contributes to hepatic encephalopathy) |
|
|
CA inhibitor indications
|
glaucoma (inhibits ocular CA which decreases secretion of ocular humor)
|
|
|
site 3 diuretic drugs
|
hydrochlorothiazide
indapamide metalazone |
|
|
site 3 diuretic drugs are similar in what respects and differ in what respects
|
same effectiveness
different potency and duration of action |
|
|
why are site 3 diuretics different in potency
|
moiety attatched to the 3-position of the benzothiadiazine nucleus, which changes lipophilicity
|
|
|
differences in duration of action by site 3 diuretics
|
degree of protein plasma binding
lipid water partition coeffecient |
|
|
what determines the reabsorption of site 3 diuretics in the distal convuluted tubule
|
PH, PKA, and lipid water particition coeffecient
|
|
|
do site 3 diuretics have long or short half lives
|
typically long because they are reabsorbed well
|
|
|
why does site 3 diuretics cause hypokalemia
|
more na for site 4 to change with K
|
|
|
what do thiazides have to do with CA inhibitors
|
thiazides have can inhibit CA a little bit which helps with bicarbonate reabsorption
|
|
|
long term use of thiazides cause
|
increase in CA secretion
|
|
|
site 3 diuretics moa
|
prevent luminal Na/Cl co transport
|
|
|
site 3 diuretics toxicity
|
sulfonamide allergies
hypokalemia some tolerance develops hypercalcemia, hyperuricemia (after chronic use, because of compensitory reabsorption) thiazides cause reduction in GFR (except metalozone and indapamide) |
|
|
site 3 (thiazide) interactions
|
increases reabsorption of lithium
calcium supplements NSAIDS (inhibit prostiglanden synthesis, which antagonize thiazides) NSAIDS also reduce GFR cardiac glycosides (shouldn't be used under hypokalemic levels) |
|
|
site 3 thiazide indications
|
edema caused by CHF, liver necrosis, nephrotic syndrome
htn hypercalceuria mixed with K-spring diuretics |
|
|
site 2 diuretics are also called
|
loop diuretics
|
|
|
site 2 (loop) diuretic drugs
|
furosemide
bumetanide ethacrynic acid |
|
|
site 2 (loop) diuretics moa
|
inihibit na/k/2cl cotransport on luminal side
affects 20-25% of filtered Na don't decrease GFR because they don't trigger the GFR feedback mechanism increase renal blood flow by increasing release of prostiglandins |
|
|
how do site 2 (loop) diuretics affect K an H secretion
|
they increase it
K by blocking Na/K/Cl reabsorption H by K by sending more Na to site 4 to be exchanged with H and K secretion |
|
|
site 2 (loop) diuretic toxicity
|
hypokalemia
alkalosis (secretion of H) sulfonamide hypersensitivity (except ethacrynic acid) ototoxicity (especially in the renal impared and those taking aminoglycocides which also cause ototoxicity) ethacrinic acid has worse ototoxicity and GI effects than the others NSAIDS increase risk of renal failure by inhibiting prostiglandins |
|
|
site 2 (loop) diuretic indications
|
edema
too much loop diuretics can decrease bp enough to exacerbate HF used for hypercalcemia furosemide and bumetanide is more preferred over ethacrynic acid (more effective, less GI toxicity, less ototoxicity) |
|
|
site 4 (K sparing) diuretics drugs
|
spironolactone (aldosterone antagonist)
amilioride, triamterine (Na channel blockers) |
|
|
spironolactone moa
|
changed to active metabolite, canrenon
inhibits aldosterone which usually exchanges Na for K and H |
|
|
sprinolactone toxicity
|
hyperkalemia
acidosis hormone activity can cause gynocomastia in men and menstral disturbances in women |
|
|
triamterine moa
|
blocks na reabsorption which inhibits secretion of K and H
|
|
|
triamterine toxcitiy
|
hyperkalemia and renal stone formation
don't give to those with renal toxicity don't use it alone as a diuretic (low efficacy) |
|
|
amiloride moa
|
basic guanidine moiety PKA of 8.7
mostly charged, so GI tract which mostly only absorbs uncharged drugs allows much of amiloride to pass through the system inhibits na reabsorption, which prohibits exchange of K and H |
|
|
amiloride toxicity
|
hyperkalemia
NVD headache |
