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68 Cards in this Set
- Front
- Back
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What is hemostasis?
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The spontaneous arrest of bleeding from a damaged blood vessel.
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What is ADP?
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A powerful inducer of platelet aggregation.
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What is synthesized within platelets and induces thrombogenesis and vasoconstriction?
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Thromboxane A2
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What is Prostacyclin?
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It is synthesized within vessel walls and inhibits thrombogenesis.
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Released from platelets, stimulating further aggregation and vasoconstriction.
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Serotonin
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Endogenous anticoagulants, diminish amplification in the blood clotting cascade by proteolysis of factors Va and VIIIa.
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Proteins C & S
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Remodels the thrombus and limits the extension of thrombis by proteolytic digestion of fibrin.
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Plasmin
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What are some substances that activate the fibrinolytic system?
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Tissue plasminogen activator, urokinase, and streptokinase.
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What are the indirect thrombin inhibitors?
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1. Unfactionated heparin
2. Low MW Heparin 3. Synthetic fondaparinux |
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Inhibits clotting factor protease, especially thrombin, IXa and Xa by forming equimolar stable complexes with them.
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Antithrombin
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True or False?
Once the antithrombin-protease complex is formed, that heparin is no longer active. |
False
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What is the difference in affinities between HMW and LMW Heparins?
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HMW fractions of heparin markedly inhibit all three factors especially thrombin and factor Xa.
LMW fractions inhibit factor Xa but have lower affinity for thrombin. |
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What are some LMW heparins?
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Enoxaparin, dalteparin, and tinzaparin
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What drug is given to reverse heparin action?
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Protamine sulfate
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What is the specific irreversible thrombin inhibitor from the leech that is now available in recombinant form as lepirudin?
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Hirudin
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What is the MOA of coumadin anticoagulants?
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The block the gamma carboxylation of several glutamate residues in the prothrombin and factors VII, IX, and X as well as the endogenous anticoagulants Proteins C and S
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How do fibrinolytic drugs work?
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They rapidly lyse thrombin by catalyzing the formation of the serine protease plasmin from its precursor zymogen, plasminogen.
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What are some fibrinolytic drugs?
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Streptokinase, altephase, antistreplase, tissue plasminogen activator, reteplase, tenecteplase, urokinase.
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What are the toxicities of heparin?
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Bleeding, Thrombocytopenia,
Thrombosis (Heparin-induced antibody complex bind to Fc receptors on adjacent platelets) Heparin does not cross the placenta |
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What is the difference between Hirudin and Bivalirudin?
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Hirudin binds irreversibly to both sides of thrombin.
Bivalirudin binds reversibly at one active site. |
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Why can direct thrombin inhibitors inactivate bound and circulating fibrin where heparin can only inactivate circulating fibrin?
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Heparin has too much steric hinderance to overcome.
Small DTIs have low MW. |
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What are some toxicities of warfarin?
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Bleeding, skin necrosis (purple toe syndrome, a deficiency of protein C and S)
Birth defects - 1st tri. nasal hypoplasia 2nd tri. CNS abnormalities (bleeding in brain) |
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What is the INR?
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International Normalized Ratio used to compare patient PT to control PT.
The usual goal is 2-3 times normal. |
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How do osmotic diuretics work?
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They sit in the solution and extract water adn electrolytes from intracellular fluid to increase ECF. It also increases renal blood flow in the medulla.
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Where does mannitol work?
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The proximal tubule and descending limb.
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When would you use osmotic diuretics?
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To increase urine volume with a crush damage.
To decrease intracranial and intraocular pressure Dialysis equilibrium |
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What are some carbonic anhydrase inhibitors?
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Sulfonamide derivatives, acetazolamide, dichlorphenamide, and methazolamide.
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Where do carbonic andydrase inhibitors work?
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Proximal tubules
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What are the 4 categories of regulating BP?
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1. Diuretics
2. Sympathoplegic agents 3. Direct vasodilators 4. ACE inhibitors |
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What are the 4 compensating actions the body can take against blood pressure?
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1. baroreflexes
2. shut down renin 3. vasopressin control 4. renal function - Increase secretion of Na |
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What drugs are the first choice for incomplicasted HTN?
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Diuretics
Reduce BP 10-15 mmHg |
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What pressure is considered HTN?
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140/90
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What are the 3 pathways that control renin release?
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Macula densa pathway
Intrarenal baroreceptor pathway B1 adrenergic receptor pathway |
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What are the effects of AII on altered peripheral resistence?
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1. Direct vaso-constriction, enhancement of noradrenergic neurotransmission (increase NE), and increase sympathetic discharge
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What are the effects of AII on altered renal function?
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Direct effect to increase Na reabsorption in proximal tubule, release of aldosterone from adrenal cortex, altered renal hemodynamics
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What are the rapid pressor responses of AII?
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increase total peripheral resistance
Increase cardiac contractility increase Heart rate |
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What are the slow pressor responses of AII?
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Decrease in renal excretory function, endothelin-1, aldosterone
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How does AII affect cardiovascular structure?
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Increase expression of proto-oncogenese, Increase growth factors, Increase collagen, chronic HTN damage (Increased afterload, increase wall tension)
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What suffix refers to converting enzyme inhibitors?
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~pril (~prilat for prodrug)
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What suffix refers to AII receptor antagonists?
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~sartan
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What diuretic does not work from the luminal side?
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Spironolactone
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What role does Ca++ play in the kidneys?
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It is a NKCC cotransporter in the thick ascending limb. When the lumen-positive electric potential is inhibited, Ca++ secretion increases.
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What transporters are in the distal tubule?
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Na/Cl- cotransporter
Apical Ca++ channel Basolateral Na+/Ca++ exchanger |
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What is the mechanism of action of osmotic diuretics?
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Increase in osmotic pressure in tubular fluid. Increase in renal blood flow (renin turned off)
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What are the pharmacodynamics of osmotic diuretics?
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Water excretion is greater than Na+ excretion.
ECF expansion Decrease in blood viscosity Suppress renin release to decrease constriction |
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What are the adverse effects of osmotic diuretics?
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Acute ECF expansion (congestive HF and pulmonary edema)
Dehydration |
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What are the pharmacodynamics of carbonic anhydrase inhibitors?
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Increase in bicarb excretion, increase in NaCl reabsorption, increase in K+ secretion, decrease in RBF and GFR because the macula densa sees more fluid and constricts AA.
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What are the adverse effects of CA inhibitors?
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Hyperchloremia, metabolic acidosis, renal stones, hypokalemia, allergic reactions
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What are the clinical indications for CA inhibitors?
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Glaucoma, urinary alkaliniation, metabolic alkalosis, acute mountain sickness, epilepsy
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Where is the site of action for loop diuretics?
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The thick ascending limb of the loop of henle.
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What is the mechanism of action of loop diuretics?
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1. Inhibit NKCC symport
-stop (+) potential and Ca++ and Mg++ reabsorption decreases -increase GFR and increase renin release |
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What are some drug interactions with loop diuretics?
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NSAIDS and probenacid
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What are the pharmacodynamics of loop diuretics?
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Decrease NaCl reabsorption
decrease ECF volume Decrease Ca+, Mg+ reabsorption ---> hypomagnesia stimulate renal prostaglandin synthesis increase K+ and H+ secretion |
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What are adverse effects of loop diuretics?
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Hypokalemia, hyperuricemia, hyperchloremia, ototoxicity
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What are the indications for loop diuretics?
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Chronic CHF, acute renal failure, pulmonary edema, anion overdose
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What is the prototype thiazide?
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HCTZ
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Where is the site of action for thiazide diuretics?
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Early distal tubule, past the macula densa
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What is the mechanism of action of thiazide diuretics?
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Inhibition of Na+-Cl cotransport.
Theory: If Na+ reabsorption is inhibited, Na+/Ca+ is upregulated and Ca+ is increased to regulate ICF levels |
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What are the pharmacodynamics of HCTZ?
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Weak carbonic anhydrase inhibition.
Increase Ca+ reabsorption, decrease Mg+ reabsorption Increase K+ and H+ secretion, renal prostaglandin synthesis |
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True or False?
Thiazides cause Ca+ precipitation in urine? |
False.
Thiazides cause a decrease in Ca+ secretion and decrease pH so Ca+ is poorly soluble |
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What are some adverse effects of thiazides?
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Hypokalemia, hypochloremia, metabolic alkalosis, hypomagnesemia, hyperuricemia, carbohydrate intolerance. Increase serum lipid and lipoprotein conc.
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What are the clinical indications of thiazides?
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HTN, edema, nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus.
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What are the potassium sparing diuretics?
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Organic bases - amiloride, triamterene
Mineralocorticoids - Spironolactone |
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Where is the site of action for potassium sparing diuretics?
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Late distal tubule
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What is the mechanism of action for potassium sparing diuretics?
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Inhibition of Na+ channels in luminal membrane (amiloride)
Competitive antagonist at mineralocorticoid receptor (prevents aldosterone from creating proteins necessary for Na+ reabsorption) |
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What are the dynamics of K+ sparing diuretics?
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Decrease Na+ reabsorption
Decrease K+ secretion - hyperkalemis Decrease H+secretion - metabolic acidosis |
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What are some adverse effects of spirolactone and amiloride?
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Hyperkalemia, hyperchloremic metabolic acidosis
Spironolactone - gynecomastia and hirusitism Triamterene - weak folate antagonist (megaloblastic anemia and folate deficiency) |
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What are the clinical indications for K+ sparing diuretics?
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Primary hyperaldosteronism - (Conn's syndrome, ectopic ACTH)
Secondary hyperaldosteronism - (heart failure, hepatic cirrohsis, nephrotic syndrome) |
