Term
|
Definition
Complexes with AT III causes it to have a 1000x greater binding affinity to clotting factors --> inhibits activated Xa/IIa
At high conc, it also inhibits XIa and XIIa and platelet aggregation |
|
|
Term
| How do you monitor Heparin? |
|
Definition
| APTT (therapeutic range = 2-2.5x baseline) |
|
|
Term
| What is Heparin's indicated use? |
|
Definition
| surgical anticoagulation (bypass), therapeutic/prophylactic anticoagulation |
|
|
Term
|
Definition
| bleeding, Heparin-induced Thrombocytopenia (HIT), osteoporosis, alopecia |
|
|
Term
| What is the mechanism of HIT? |
|
Definition
| heparin combines with PF4. Abs are made against the complex. They also activate platelets and endothelial cells which leads to thrombosis. |
|
|
Term
| What part of Heparin binds to ATIII? |
|
Definition
|
|
Term
| Where is Heparin naturally found? |
|
Definition
| in granules of mast cells along with histamine and serotonin |
|
|
Term
| Where is the Heparin drug extracted from? |
|
Definition
| beef lung and porcine intestine |
|
|
Term
| What is the molecular structure of heparin? |
|
Definition
| highly ionized mucopolysaccharide composed of repeating units of sulfated glucuronic acid and sulfated glucosamine |
|
|
Term
| What is the only anticoagulant given in units vs grams? What is its conversion to grams? |
|
Definition
Heparin
12ug = 1 unit
1 mg Heparin = 120 USP |
|
|
Term
| What is Heparin's onset of action time? |
|
Definition
|
|
Term
| What are the pharmacokinetics of Heparin? |
|
Definition
|
|
Term
| What is the only anticoagulant that can be used for heart surgery? |
|
Definition
|
|
Term
| What is the antidote to Heparin overdose? How do you calculate the amount needed? |
|
Definition
protamine sulfate
1 USP of heparin is neutralized by 10ug of protamine (2500 units of heparin is neutralized by 25 ug of protamine) |
|
|
Term
|
Definition
| A low molecular weight heparin |
|
|
Term
| How are low molecular weight heparins produced? |
|
Definition
| depolymerization of native heparin |
|
|
Term
| How do low molecular weight heparins differ from Heparin? |
|
Definition
| LMW Heparins have 100% bioavailability, longer duration of action and are monitored by anti-Xa (instead of APTT), causes less bleeding and less thrombocytopenia |
|
|
Term
| What are the clinical uses of LMW heparins? |
|
Definition
| prophylaxis and treatment of DVT; management of ACS; They can also be used for anticoagulation for surgical and interventional cardiovascular procedures. |
|
|
Term
| What is Fondaparinux? What is it used for? |
|
Definition
| pentasaccharide of Heparin that complexes with ATIII and inhibits factor Xa; management of DVT |
|
|
Term
| What are the 3 Direct Thrombin Inhibitors? |
|
Definition
Argatroban, Bivalirudin, Hirudin (refludan)
DITz = A Birdbrained Hottie |
|
|
Term
| Where is Hirudin found naturally? |
|
Definition
| saliva of a medicinal leech |
|
|
Term
| What is the commercial preparation of Hirudin for clinical use? |
|
Definition
|
|
Term
How is Hirudin cleared?
How is Argatroban cleared? |
|
Definition
Hirudin = kidney
Argatrobon = liver
*This is important for knowing how to treat HIT in pts with liver or renal failure. Give Hirudin for Hepatic failure and aRgatroban for Renal failure. |
|
|
Term
| What are Direct Thrombin Inhibitors used for? |
|
Definition
| to treat HIT (heparin and pentasaccharide cannot be used bc they have cross-reactivity to the Abs that form but DTIs do not) |
|
|
Term
| What is Antithrombin concentrate used for? |
|
Definition
| DIC, sepsis, thrombophilia, hypercoagulability, AT deficiency (congenital/acquired) |
|
|
Term
| How does protamine sulfate neutralize Heparin? |
|
Definition
| Protamine has a LMW and is highly basic protein so it combines with heparin (highly acidic) to form a stable salt that has no anticoagulant activity. |
|
|
Term
| How do you neutralize one USP unit of heparin? |
|
Definition
| One USP unit of heparin is neutralized by 10 ug of protamine (2500 units of heparin is neutralized by 25 mg of protamine). |
|
|
Term
|
Definition
| Inhibits epoxide reductase, inhibiting carboxylation of glutamic acid, thus CALCIUM cannot bind and Factors II, VII, IX, X are not functional. |
|
|
Term
| How do you monitor Warfarin? |
|
Definition
| PT/INR (needs to be monitored at the hospital every 2-4 wks because warfarin metabolism varies pt to pt) |
|
|
Term
| What is Warfarin used for? |
|
Definition
| prolonged treatment of DVT and Afib |
|
|
Term
| What are the side effects of Warfarin? |
|
Definition
| bleeding, Coumadin induced necrosis (happens 3-10 days after starting treatment when Protein C goes down before factor VII decreases and there is actually increased clotting), hypoprothrombinemia (ecchymosis, purpura, hematuria, hemorrhage), brain hemorrhage, Toxic to fetus – can cause bone malformation |
|
|
Term
| What coagulation factors require Vit K as a cofactor? |
|
Definition
| II, VII, IX, X, Proteins C and S |
|
|
Term
| What are the antidotes to oral anticoagulant overdose? |
|
Definition
| fresh frozen plasma to replace clotting factors; can also give recombinant Factor VIIa and Vit K |
|
|
Term
| What does Protein C do? How is it activated? |
|
Definition
endogenous anticoagulant -- digests factors 5 and 9
activated by thrombomodulin from the endothelial cells |
|
|
Term
| How many days is heparin given in the heparin-coumadin bridge? |
|
Definition
|
|
Term
| Why does Warfarin interact with many other drugs? |
|
Definition
It is highly protein bound (~97%) to plasma albumin. Fibrates are also strong protein binders and inc effects of Warfarin. In addition, Diuretics decrease warfarin effectiveness (dec PT)
Finally, Bile acid binding resins (Cholestyramine, Colestipol, Colesevelam) interfere with warfarin absorption. |
|
|
Term
|
Definition
INR = [PT in sec of the pt/PT in sec of control] x ISI
ISI = int'l sensitivity index |
|
|
Term
| What are the 3 main factors that affect the dose of warfarin? |
|
Definition
1. nutrition (diet high in vit K - green leafy veggies - could dec effectiveness)
2. liver disease (less production of coag factors leads to inc effectiveness of warfarin)
3. drugs (warfarin is 97% bound to plasma albumin) |
|
|
Term
| What are the newer oral anticoagulants? |
|
Definition
Anti-Xa agents = Rivaroxaban and Apixiban
Antithrombin agents = Dabigatran |
|
|
Term
| What benefits do the newer oral anticoagulants have over warfarin? |
|
Definition
| They do not require coagulation monitoring |
|
|
Term
| Which oral anticoagulants should not be given to pts in renal failure? |
|
Definition
Dabigatran (100% renally cleared)
Rivaroxaban (65% renally cleared) |
|
|
Term
| Which anti-coagulants interact with CYP3A4 inhibitors? |
|
Definition
|
|
Term
| What are the oral anticoagulants indicated for? |
|
Definition
stroke prevention in pts with A fib
Rivaroxiban is also indicated for prophylaxis and treatment of DVT |
|
|
Term
| If a pt has 4500 units of heparin in their blood, how much protamine is needed to neutralize the circulating heparin? |
|
Definition
|
|
Term
| How does aspirin prevent platelet aggregation? What are its indications? |
|
Definition
Aspirin inhibits arachidonic acid transformation into PGG2, PGH2 and TxA2;
it is indicated for ACS, stroke, and arterial thrombosis |
|
|
Term
| What drugs are used in every single pt who is stented? |
|
Definition
|
|
Term
| What are the ADP receptor inhibitors? |
|
Definition
| Clopidogrel (older), Prasugrel (less resistance due to polymorphism), Ticagrelor |
|
|
Term
| What are the phosphodiesterase inhibitors of platelet aggregation? |
|
Definition
| Dipyridamole and Cilostazol |
|
|
Term
| What drug is used to treat intermittment claudication? |
|
Definition
|
|
Term
| What is a clinical use for Dipyridamole besides arterial thrombosis and stroke? |
|
Definition
|
|
Term
| What are the GPIIb/IIIa inhibitors? |
|
Definition
"EAT" your glycoPROTEIN so you don't need PCI (percutaneous coronary intervention to treat cholesterol-laden stenotic coronary arteries)
Eptifibitibe
Abciximab
Tirofiban |
|
|
Term
| What is the only antiplatelet drug for diabetics? |
|
Definition
|
|
Term
| What dose is aspirin given for antiplatelet actions? |
|
Definition
|
|
Term
| Why do some pts have aspirin resistance? |
|
Definition
|
|
Term
| What are antiplatelet drugs indicated for? |
|
Definition
| TIA, complete stroke, acute MI, unstable angina, PAOD, intermittment claudication, TTP |
|
|
Term
| What enzyme is responsible for the formation of arachidonic acid? |
|
Definition
|
|
Term
| Why are fish oils thought to be good for the heart? |
|
Definition
| Omega 3 fatty acids mimic AA. Instead of TXA formation, they become an antagonist, competing with arachidonic acid and blocking its vasoconstricting and platelet agg properties. |
|
|
Term
| What is arachidonic acid converted into in tissues? in platelets? in endothelial cells? how do their functions differ? |
|
Definition
tissues = prostaglandins (general class - many fxns, both vasodilatory and vasoconstrictive properties depending on tissue)
platelets = thromboxane (vasoconstriction + platelet agg)
endothelial cells = prostacyclin (vasodilator) |
|
|
Term
| What are the two major pathways of arachidonic acid metabolism? |
|
Definition
Cyclooxygenase pathway (prostaglandins)
Lipooxygenase pathway (leukotrienes) |
|
|
Term
| What are the physiologic inhibitors of fibrinolysis? |
|
Definition
PAI (plasminogen activator inhibitor)
a2-antiplasmin (inhibits plasmin)
C1-esterase inhibitor (blocks complement C1)
TAFI (thrombin activatable fibrinolytic inhibitor)
a2-macroglobulin (slow inhibitor of plasmin) |
|
|
Term
| What form of plasminogen binds the most tightly to the clot? |
|
Definition
|
|
Term
| What does the D-dimer test for? |
|
Definition
|
|
Term
|
Definition
| Fragments DDE,YD/DY and YYDD that are formed by the action of plasmin on polymerized fibrin monomers (clots). |
|
|
Term
| What are the clinically approved thrombolytics agents? |
|
Definition
| urokinase (UK), streptokinase (USA), recombinant tPA, Ancrod |
|
|
Term
| What are the 3 recombinant tPA and how do they differ? |
|
Definition
Alteplase - human tPA
Reteplase - more fibrin specific
Tenecteplase - longer half life |
|
|
Term
| What are thrombolytic agents used for? How are they administered? |
|
Definition
all given iv
used for thrombolysis, stroke, MI, PE |
|
|
Term
| What are the absolute contraindications for thrombolytic therapy? |
|
Definition
| intracranial bleeding and massive hemorrhage |
|
|
Term
| What are the pharmacologic antagonists for thrombolytic agents? aka what are the antidotes to fibrinolytic OD? |
|
Definition
EACA (Epsilon-amino caproic acid) = AMCAR
Tranexemic Acid = AMCHA
Aprotonin |
|
|
Term
| What is the side effect of tranexemic acid? |
|
Definition
|
|
Term
| What is the side effect of Aprotonin? |
|
Definition
|
|
Term
| What is the side effect of Ancrod? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What are the accepted values for desirable, borderline and high serum LDL, HDL and TG? |
|
Definition
Total cholesterol:
Optimal = <200 mg/dl*
Borderline = 200-239 mg/dl*
High = >240 mg/dl*
LDL:
Desirable = <100 mg/dl*
Borderline = 130-159
High = 160-189
VERY high = >190*
HDL:
Desirable = M >40 mg/dl, F >50*
TG:
Desirable = <150 mg/dl*
Borderline = 150-199 mg/dl
High = 200-499 mg/dl
Very high (risk of pancreatitis) = >500 mg/dl* |
|
|
Term
| What 3 main drugs treat hypercholesterolemia? |
|
Definition
1. STATINS
2. Bile acid binding resins
3. cholesterol uptake inhibitors |
|
|
Term
| What 3 main drugs treat hypertriglyceridemia? |
|
Definition
1. Niacin
2. Fibrates
3. Fish oil omega 3s |
|
|
Term
| What are lipoproteins comprised of? |
|
Definition
lipid membrane (phospholipids/cholesterol)
Hydrophobic core (TGs and cholesterol esters)
Apolipoproteins (structural proteins and ligands for particle uptake) |
|
|
Term
| What are the protective roles of HDL in the prevention of atherosclerosis? |
|
Definition
1. PON1 (paraoxonase enzyme)=enzyme on the surface of HDL has antioxidant activity to inhibit the oxidation of LDLs
2. inhibits expression of adhesion molecules on edothelium (prevents recruitment of monocytes to plaque)
3. inhibit formation of FOAM cells
4. promote REVERSE CHOLESTEROL TRANSPORT back to the liver where it can be secreted as bile |
|
|
Term
| 54% of pts with premature CHD and 70% of pts with abnormal lipid profile have what? |
|
Definition
| Familial Hypercholesterolemia (monogenic) or Familial Combined Hyperlipoproteinemia (polygenic) |
|
|
Term
| What is the DOC to treat severe hypercholesterolemia (LDL >190 mg/dl) or above optimal LDL (>100) with high CV risk (previous CHD, diabetes, >2 risk factors)? |
|
Definition
|
|
Term
| What is the most prescribed class of drug in the US (~10% of adults >20)? |
|
Definition
|
|
Term
| What is the order of most potent to least potent statins? |
|
Definition
RASP LF
Rosuvastatin
Atorvastatin
Simvastatin
Pravastatin
Lovastatin
Fluvastatin |
|
|
Term
|
Definition
| they are analogs of HMG-CoA so they competitively inhibit endogenous cholesterol synthesis |
|
|
Term
| What TF is activated during reduced hepatic cholesterol synthesis? |
|
Definition
| SREBP TG which leads to inc expression of the LDL-R at the plasma membrane = inc clearance of serum LDL |
|
|
Term
| What is the most serious (but rare) SE of statins? What types of drugs inc the potential of this SE? |
|
Definition
rhabdomyolysis - pt present with fever, malaise, myalgia, elevated serum CK and myoglobin in urine
CYP3A4 inhibitors (eg. cyclosporin*, macrolides, diltiazem, verapamil, amiodarone, ketaconazole, ritonavir, itraconazole, gemfibrozil*, warfarin, grapefruit juice) |
|
|
Term
| Which statin has fewer adverse muscle effects? Why? |
|
Definition
| Pravastatin (only statin that does not have CYP450 metabolism) |
|
|
Term
| Which statins undergo metabolism by CYP3A4 in the intestine? |
|
Definition
Lovastatin
Simvastatin
Atorvastatin |
|
|
Term
| What anion transporter transports statins into the liver? |
|
Definition
|
|
Term
| Which statins undergo metabolism by CYP2C9? |
|
Definition
|
|
Term
| How does Gemfibrozil increase the bioavailability of statins (leading to inc risk of rhabdomyolysis)? |
|
Definition
1. it inhibits the OATP2 transporter-mediated uptake of statins into the liver
2. it inhibits the gluronidation of ALL statins (inc pravastatin) which can cause an inc in system levels |
|
|
Term
| When are statins contraindicated? |
|
Definition
pregnant, nursing and expectant mothers
liver disease (pravastatin may be ok)
gemfibrozil |
|
|
Term
| What are the 3 Bile Acid Binding Resins? |
|
Definition
| Cholestyramine, Colestipol, Colesevelam |
|
|
Term
| What is the main effect of a Bile Acid Binding Resin? |
|
Definition
| modest reduction in LDL (10-25%) |
|
|
Term
| What is a major side effect of Bile Acid Binding Resins? |
|
Definition
|
|
Term
| What do Bile Acid Binding Resins work? |
|
Definition
| resins are cationic polymers that bind to negatively charged bile acids and prevents their reabsorption in the small intestine and the resin/bile acids are excreted in the feces (~10x inc). Thin in turn increases bile acid production by upregulating cholesterol 7a-hydroxylase leading to a dec in hepatic cholesterol conc and triggers upregulation of LDL-R. |
|
|
Term
| What drugs are used with statins to lower the dose of statin used and therefore dec chance of SE? |
|
Definition
Bile Acid Binding Resins (#1)
Ezetimibe |
|
|
Term
| What drugs is used to treat hypercholesterolemia in pregnant or breastfeeding women? |
|
Definition
|
|
Term
| Which Bile Acid Binding Resin has the fewest SE? |
|
Definition
| Colesevelam (does not impair absorbtion of fat soluble vitamins or other drugs) |
|
|
Term
| When are Bile Acid Binding Resins contraindicated? |
|
Definition
| Type III Dysbetalipoproteinemia and raised TGs (>400) due to risk of further increasing VLDL levels (caused by inc HMG-CoA reductase) |
|
|
Term
| What drug can be used to prevent pruritus in a patient with liver failure? |
|
Definition
| Bile Acid Binding Resins (Cholestyramine and Colestipol) -- promotes excretion of bile acids causing itching |
|
|
Term
| What drug can be used to prevent diarrhea in Crohn's disease pts? |
|
Definition
|
|
Term
| What drug is effective at preventing diarrhea in C diff pts? |
|
Definition
| Bile Acid Binding Resins (absorbs toxins A and B) |
|
|
Term
| What drug treats an OD of digoxin, leflunomide or levothyroxine? |
|
Definition
|
|
Term
| What is the MOA of Ezetimibe? |
|
Definition
Inhibitor of cholesterol absorption.
Ezetimibe inhibits the action of the NPC1L1 protein involved in the absorption of dietary and biliary cholesterol in the small intestine. |
|
|
Term
| Which lipoprotein are serums TGs associated with? |
|
Definition
| decreased HDLs increases serum TGs |
|
|
Term
| What is the range for borderline high serum TG in which only lifestyle changes are indicated? |
|
Definition
|
|
Term
| What is the most effective drug at raising HDLs? |
|
Definition
|
|
Term
| What drug lowers both plasma cholesterol and TGs (and thus is useful in Familial Dysbetalipoproteinemia)? |
|
Definition
|
|
Term
| What clinical effects does niacin have? |
|
Definition
30-80% reduction in TGs*
10-20% reduction in LDLs
10-30% reduction in HDLs* |
|
|
Term
| What antihyperlipidemia drug is given post-MI to prevent reinfarction, cerebrovascular events and mortality? |
|
Definition
|
|
Term
| What anti-hyperlipidemia drug decreases thrombosis? |
|
Definition
| Niacin -- it reduces the level of Lp(a) lipoprotein which normally inhibits the action of plasminogen. Therefore, plasmin can become activated and lyse clots. |
|
|
Term
| What are the major adverse effects of niacin? |
|
Definition
Skin flushing (prostaglandin-mediated -- can be diminished with NSAID)
Gout
Peptic ulcer disease
hyperglycemia
hepatic toxicity |
|
|
Term
| What are the primary clinical effects of fibrates (Fenofibrate and Gemfibrozil)? |
|
Definition
40-60% reduction in TGs
10-20% reduction in LDL
10-20% inc in HDL |
|
|
Term
| What is the MOA for fibrates? |
|
Definition
Fibrates act as ligands for the nuclear hormone TF PPARa. They activate PPARa which expresses genes involved in lipoprotein structure, fxn and metabolism.
1. increased ApoA1 = inc plasma HDL
2. decreased apoCIII = inc LPL expression in the muscle = inc FFA uptake = FA oxidation = inc peripheral VLDL clearance = dec plasma TG
3. increased hepatic expression of genes involved in FA transport/metabolism = dec hepatic TG synthesis and dec VLDL secretion = dec plasma TG |
|
|
Term
| What is the DOC of Familial dysbetalipoproteinemia? |
|
Definition
|
|
Term
| What are the major adverse effects of fibrates? |
|
Definition
| gallstones, rhabdomyolsis (Gemfibrozil), hepatitis, myopathy |
|
|
Term
| What are fibrates contraindicated with? |
|
Definition
| Warfarin, statins (Fenofibrate can be used with statins), T2DM, pregnant/lactating women, renal dysfunction, gallbladder dx |
|
|
Term
| What hyperlipidemia drug can increase VLDL? |
|
Definition
|
|
Term
| How is endogenous NO formed? When is it released? |
|
Definition
| • Endogenous NO is generated from the oxidation of the guanidine group of arginine. It is released from vascular endothelium upon stimulation with Ach and carbochol. |
|
|
Term
| What are the nitric oxide synathases? |
|
Definition
| nNOS and eNOS are constitutive wherease iNOS is inducible and is BAD. iNOS (NOS-2) is produced by MACs, smooth muscle cell damage in sepsis, cancer, stroke. iNOS is activated by LPS. |
|
|
Term
| What are inhibitors of NO synthesis? |
|
Definition
| L-arginine derivatives (L-NMMA, L-NAME) which inhibit action of NOS converting Arg to citrulline, superoxide (SOD would prolong duration of NO action), 7-nitroindazole, scavengers of NO like heme. |
|
|
Term
| What vasoactive substance promotes graft rejection at high levels? |
|
Definition
|
|
Term
| What neurons release NO in an erectile response? |
|
Definition
|
|
Term
| When is NO most often administered? |
|
Definition
|
|
Term
|
Definition
| NO donor, vasodilator - acts more on arterioles |
|
|
Term
| Which nitrates act more on veins than arteries? |
|
Definition
Nitroglycerine (most widely used) - can be sublingual (10-30min) or patch (8-10 hrs)
isosorbide dinitrate - sublingual or oral
amyl nitrates - volatile 3-5 min |
|
|
Term
| What type of nitrate is a phosphodiesterase inhibitor? |
|
Definition
|
|
Term
| What are other names for ACE enzymes? |
|
Definition
| peptidyl dipeptidase or kininase II |
|
|
Term
|
Definition
| catalyzes the cleavage of a dipeptide from the carboxyl terminal of AT I into AT II (octapeptide). It also blocks the degradation of other vasopeptides such as bradykinin*, substance P and enkephalin |
|
|
Term
| What drug reduces remodeling of the heart, preventing LV dysfunction after MI? |
|
Definition
|
|
Term
|
Definition
captopril - short half life
Enalopril - converted to active metabolite, longer onset of action, longer half life
lisinopril - water soluble, excreted unchanged by the kidney, longer half life |
|
|
Term
| Which ACEI is good for HTN along with diuretics? |
|
Definition
|
|
Term
| What are ACEIs contraindicated with? |
|
Definition
| pregnancy, K sparing drugs |
|
|
Term
| What HTN drug is good for diabetic pts? |
|
Definition
| ACEI (they delay loss of renal fxn) |
|
|
Term
| What combo of drugs would you give for HF? |
|
Definition
|
|
Term
| What diuretics would you NOT give with ACEIs? |
|
Definition
| K+ sparing diuretics would exacerbate hyperkalemia |
|
|
Term
| What antihypertensive is good for a hypertensive pt with sepsis? |
|
Definition
| ARBs (Losartan, Valsartan) |
|
|
Term
|
Definition
| Bradykinin B2 receptor inhibitor - still in clinical trials. |
|
|
Term
| What drug is approved for angio-neurotic edema in EU? |
|
Definition
|
|
Term
| What is desmopressin (dDAVP) indicated for? |
|
Definition
| increase the factor VIII activity in pts with mild hemophilia and VWD; control bleeding in mild surgeries |
|
|
Term
| What activates plasma kallikrein? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| like ADH, it increases water resorption in the kidney |
|
|
Term
| What does atrial natriutetic peptide do? |
|
Definition
| enhance vasodilation, reduce vasoconstriction and increase sodium excretion |
|
|
Term
|
Definition
| non-selective endothelin receptor inhibitor, used to treat pulmonary arterial HTN |
|
|
Term
| What drugs are given to combat mountain sickness? |
|
Definition
|
|
Term
| What is the MOA for CA inhibitors? |
|
Definition
| acts on the PCT -- reversibly splits H2CO2 to water and CO2. It can inhibit reabsorption of 85% of NaHCO3. In the distal nephron, Na+ is largely reabsorbed (unlike HCO3-) and is exchanged for K+. |
|
|
Term
| What are the CA inhibitors? |
|
Definition
Acetazolamide
Dichlorphenamide - 30x more potent
Methazolamide - 5x more potent
Dorzolamide - not used as a diuretic |
|
|
Term
| What drug is used as a topical preparation in glaucoma? |
|
Definition
|
|
Term
| What diuretics are contraindicated in cirrhosis? |
|
Definition
| CA inhibitors - reduced urine pH reduces NH3 secretion into lumen |
|
|
Term
| What is a side effect of chronic use of CA inhibitors? |
|
Definition
| HCO3- depletion can cause metabolic acidosis |
|
|
Term
| What is an acute side effect of CA inhibitors? |
|
Definition
| increased HCO3- in tubles leads to lumen negative potential and increased risk for calcium phosphate stones; hypersensitivity (sulfa drug) |
|
|
Term
| How do most diuretics reach the urine? which does not? |
|
Definition
via secretion
mannitol is filtered at the glomerulus |
|
|
Term
| Where do most diuretics exert their effects in the nephron? which do not? |
|
Definition
most diuretics work from the luminal side of the nephron
spironolactone and ADH antagonists do not |
|
|
Term
| which diuretic must be administered iv? |
|
Definition
|
|
Term
| What are the 2 main indications for mannitol? |
|
Definition
treat/prevent ACUTE renal Failure
reduce intracranial pressure |
|
|
Term
| What are the two major SE of mannitol? |
|
Definition
inc plasma osmolality
pulmonary edema
hyponatremia (with impaired renal fxn)
hypernatremia (with prolonged use) |
|
|
Term
| When is mannitol contraindicated? |
|
Definition
CHRONIC renal failure (actually a treatment for acute RF)
CHF, pulmonary edema |
|
|
Term
| What is the most efficacious diuretic? |
|
Definition
| loop diuretics excrete up to 20% filtered Na |
|
|
Term
| How/where do loop diuretics work? |
|
Definition
| Na/K/Cl cotransporter in the thick ascending limb. increases urinary water, Na, K, Ca and Mg excretion. They also cause dilation of the venous system and RENAL VASODILATION |
|
|
Term
| Which diuretics have a renal vasodilatory effect? |
|
Definition
| loops diuretics (prostaglandin effect) |
|
|
Term
| Which loop diuretic does not have a sulfonamide structure? |
|
Definition
|
|
Term
| What are the side effects of ethacrynic acid? |
|
Definition
| nephrotoxicity and ototoxicity |
|
|
Term
| How are loop diuretics administered in chronic right HF? acute left HF? |
|
Definition
chronic right HF= oral
acute left HF = iv |
|
|
Term
| What diuretic is given in ACUTE pulmonary edema? |
|
Definition
|
|
Term
| what diuretics can cause metabolic alkalosis? |
|
Definition
|
|
Term
| What diuretics are given to reduce edema assoc with CHF in the presence of renal insufficiency? |
|
Definition
|
|
Term
| What are the 4 loop diuretics? |
|
Definition
Furosemide
Bumetanide -40x more potent
Torsemide - longer half life
ethacrynic acid - only used for hypersensitivity |
|
|
Term
| What is the MOA for thiazides? |
|
Definition
| inhibit Na/Cl co-transport in the DCT - mild diuresis |
|
|
Term
| What is the DOC to treat uncomplicated HTN? |
|
Definition
|
|
Term
| Which diuretic is used to treat hypercalciuria? |
|
Definition
|
|
Term
| What are the 5 thiazides? |
|
Definition
hydrochlorothiazide
chlorothiazide - 1/10 potency
metolazone - 10x potency - good for reduced GFR
indapamide - 20x potency
chlorthalidone |
|
|
Term
| what is the only drug effective in pts with reduced GFR? |
|
Definition
|
|
Term
| Which diuretic has a side effect of hyperlipidemia (inc LDL)? |
|
Definition
|
|
Term
| What are the side effects of thiazides? |
|
Definition
| “hyper GLUC” (glycemia, lipidemia, urecemia, calcemia) |
|
|
Term
| How do potassium-sparing diuretics work? |
|
Definition
| act on the CT by inhibition of aldosterone actions or by directly blocking Na channels. sodium entry exceeds potassium ext. The net neg charge repels Cl- and attracts K+ |
|
|
Term
| What are the main indications of K-sparing diuretics? |
|
Definition
| to prevent the hypokalemic effects of other diuretics; spironolactone is used to treat secondary hyperaldosteronism due to hepatic cirrhosis complicated by ascites |
|
|
Term
| What are SE of spironolactone? |
|
Definition
| hyperkalemia, metabolic acidosis, gynecomastia, hirsutism, testicular atrophy |
|
|
Term
| What is the SE of Amiloride besides hyperkalemia? |
|
Definition
| glucose intolerance in diabetic pts |
|
|
Term
| What is the SE of Triamterene besides hyperkalemia? |
|
Definition
| megaloblastic anemia in pts with liver cirrhosis |
|
|
Term
| What are the 4-K sparing diuretics? |
|
Definition
Save Karen a "SEAT"
Spironolactone - inhibits aldosterone receptor
Eplerenone - inhibits aldosterone receptor
Amiloride - blocks Na channels in principal cells
Triamterene - blocks Na channels in principal cells |
|
|
Term
| Which diuretics are contraindicated with ACEI? |
|
Definition
|
|
Term
| Which drug would you give to prevent kidney stones? |
|
Definition
|
|
Term
| What diuretic is used to treat hepatic cirrhosis? |
|
Definition
|
|
Term
| What are the ADH antagonists? |
|
Definition
Demeclocyline - antibiotic
Lithium - psych drug
Tolvaptan, Mozavaptan - selective antagonist of V2 (blocks diuretic action of ADH)
Conivaptan - V1a and V2 receptor antagonist |
|
|
Term
| How do ADH antagonists work? |
|
Definition
| prevent the ADH-stimulated reabsorption of H2O in the CT by decreasing aquaporin insrtion so the pt excretes more water |
|
|
Term
| Which diuretics are indicated in HTN? |
|
Definition
thiazides (hydrochlorothiazide, chlorthalidone)
Loop (furosemide)
K sparing (spironolactone, eplerenone) |
|
|
Term
| What calcium channel blockers are used in HTN? |
|
Definition
dihydropyridines (Nifedipine) = reduce Ca influx in VSM
nondihydropyridines (Diltiazem, Verapamil) - reduce Ca influx in VSM AND reduce pacemaker potentials, AV node conduction and contractility |
|
|
Term
| What antihypertensive is used in pregnancy? |
|
Definition
|
|
Term
| What centrally acting agents are used to treat HTN? |
|
Definition
Clonidine (a2 receptor agonist in medullary CV)
Guanfacine (same as clonidine, less chance of rebound)
Methyldopa (used in pregnancy)
Reserpine (blocks VMAT vesicular transporter), not used as monotherapy |
|
|
Term
| What alpha adrenergic receptors are used in HTN? |
|
Definition
phenoxybenzamine- nonselective, pheochromochromocytoma, can cause tachy
prazosin -a1, less tachy
terazosin, doxazosin - a1, dec LDL
terazosin |
|
|
Term
| Which class of drugs can be used at antihypertensive monotherapy except in African American pts? |
|
Definition
| B-blockers (must be combined with diuretics in AA pts) |
|
|
Term
| What antihypertensive can mask the side effects of hyperglycemia? |
|
Definition
|
|
Term
| What are the nonselective B blockers? |
|
Definition
propanolol
nadolol
pindolol |
|
|
Term
| What are the B1 selective blockers? |
|
Definition
AME
atenolol
metoprolol
esmolol |
|
|
Term
| When are B blockers contraindicated? |
|
Definition
| pregnancy, obstructive airway disease, hyperlipidemia, with CCBs |
|
|
Term
| Which B blockers have a-blocker activity? |
|
Definition
|
|
Term
| What vasodilator can cause hypertrichosis? |
|
Definition
|
|
Term
| Which nitrate is good for controlling HTN in pregnancy? |
|
Definition
|
|
Term
| what drug would you give to control a HTN emergency? |
|
Definition
|
|
Term
| What is the major SE of nitroprusside? |
|
Definition
|
|
Term
| What are the four classes of antianginal drugs? |
|
Definition
nitrates = nitroglycerin, isosorbide dinitrate
CCBs = best to use diltiazem
B-blockers
Ranazoline (pFOX inhbitor that inhibits beta oxidation of FAs - glucose can be used for energy) |
|
|
Term
| How do nitrates cause reflex tachy? |
|
Definition
| dropping venous return sets of baroreceptors |
|
|
Term
| Which CCB has the greatest vasodilatory effects? |
|
Definition
|
|
Term
| Which CCB has the greatest negative inotropic effect? |
|
Definition
|
|
Term
| Which CCB has the greatest negative chronotropic effect? |
|
Definition
|
|
Term
| What is a side effect of Ranolazine? |
|
Definition
|
|
Term
| What is the first line of drugs to treat chronic CHF? |
|
Definition
beta blockers
*used in addition to digoxin, diuretic, ACEI |
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