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Hydrochlorothiazide
- – Inhibit sodium reabsorption from distal tubule; 10% Na+
- – Usually used for the long-term outpatient management of hypertension
- - deplete potassium = HYPOKALEMIA
- - inhibit uric acid elimination = promote gout
- - increase LDL levels
-
Chlorthalidone
- – Inhibit sodium reabsorption from distal tubule; 10% Na+
- – Usually used for the long-term outpatient management of hypertension
- - deplete potassium = HYPOKALEMIA
- - inhibit uric acid elimination = promote gout
- - increase LDL levels
-
Furosemide
- – Loop Diuretic: 35% filtered Na+
- -`Usually used for short-term management of more severe hypertension (morepowerful, high efficacy, shorter acting)
- – Inhibit sodium, reabsorption from the loop of Henle
- - deplete potassium = HYPOKALEMIA
- - inhibit uric acid elimination = promote gout
-
Ethacrynic acid
- – Loop Diuretic; 35% Na+
- -Usually used for short-term management of more severe hypertension (morepowerful, high efficacy, shorter acting)
- – Inhibit sodium, reabsorption from the loop of Henle
- - deplete potassium = HYPOKALEMIA
- - inhibit uric acid elimination = promote gout
-
Spironolactone
- - Potassium sparing diuretic; 5% Na+- Antagonist at mineralocorticoid receptor for aldosterone
- – Reduced Na+/K+ exchange in distal tubule and collecting duct results inreduced Na+ re-absorption and K+ retention
- – Commonly too weak to be used alone but counteract hypokalemia associated with other diuretics in high-risk patients
- - All diuretics have dehydration as a potential side effect
-
Triamterine
- - Potassium sparing diuretic; 5% Na+- Blocker of Na channel
- – Reduced Na+/K+ exchange in distal tubule and collecting duct results inreduced Na+ re-absorption and K+ retention
- – Commonly too weak to be used alone but counteract hypokalemia associated with other diuretics in high-risk patients
- - All diuretics have dehydration as a potential side effect
-
Amiloride
- - Potassium sparing diuretic; 5% Na+- Blocker of Na+ channel on apical membrane
- – Reduced Na+/K+ exchange in distal tubule and collecting duct results inreduced Na+ re-absorption and K+ retention
- – Commonly too weak to be used alone but counteract hypokalemia associated with other diuretics in high-risk patients
- - All diuretics have dehydration as a potential side effect
-
clonidine
- - sympatholytic indirect acting
- - a2 receptor agonist
- - cns acting to reduce symp n.s. activity
- - act at N. Tractus Solitarius
-
reserpine
- - VMAT inhibitor
- - indirect acting sympatholytic
-
propranolol
- - Non-selective B Blocker
- - decrease CO
- - B2 Activation...lungs, liver, skeletal vasculature
-
-
atenolol
- - B1 Selective blocker
- - dec CO
-
nadolol
- - Non-selective B Blocker
- - decrease CO
- - B2 Activation...lungs, liver, skeletal vasculature
-
prazosin
- SYMPATHOLYTIC DRUGS
- Block sympathetic n.s. induced contraction of arterial smooth muscle a1 adrenergic receptor antagonists
- -OSIN
-
terazosin
- SYMPATHOLYTIC DRUGS
- Block sympathetic n.s. induced contraction of arterial smooth muscle a1 adrenergic receptor antagonists
- -OSIN
-
hydralazine
- - direct vasodilator
- - oral drug: used for outpatient treatment of hypertension
- - selective arterial dilator
-
Calcium Channel Blockers
- - direct vasodilator
- - oral drug: used for outpatient treatment of hypertension
- - block voltage dep calcium channels (L-type) on vascular smooth muscle
- - tx for stable/classic angina when b blockers or nitrates unuseful
- - first choice for variant angina esp cardioactive ccb's
- -short acting should not be used w/ unstable angina or hx of MI
-
minoxidil
- - direct vasodilator
- - oral drug: used for outpatient treatment of hypertension
- - highly effective with lots of side effects (fyi: hypertrichosis); reserved for severehypertension that does not respond to other drugs
- - inc hair growth = rogaine
-
diazoxide
- - PARENTERAL DRUGS: used for emergency situations (hypertension crises)Too efficacious for outpatient use: too many side effects for outpatient use
- - highly effective and long-acting = not a first choice-drug
-
sodium nitroprusside
- - PARENTERAL DRUGS: used for emergency situations (hypertension crises)Too efficacious for outpatient use: too many side effects for outpatient use
- - nitrate drug
- - dinitrated to NO = vasodilator
-
verapamil
- CARDIOACTIVE CCBs: relax vascular smooth muscle andreduce cardiac output (decrease heart rate, AVconduction, and force of contraction)
-
dihydropyridines
- - DIPINE
- - NON-CARDIOACTIVE CCBs: relax vascular smooth muscle but have little effect on cardiac output
- - long-acting orsustained releaseformulations
-
amlodipine
- long-acting dihydropuridine
-
nifedipine
- Short-acting dihydropyridines CCBs = increased risk ofmyocardial infarction relative to patient taking diuretics or beta blockers
-
Vasodilator Side Effects
- Postural hypotension
- flushing, sweating
- headache
- reflex tachycardia: prevented w/ coadmin B Blocker
- reflex fluid ret: coadmin w/ diuretic
- - Vasodilators are almost always coadmin w/ either to prevent reflexes
-
Carvedilol
- - mixed beta-1 and alpha-1antagonist
- - B Blocker/Vasodilator
- - dec both CO and TPR
-
Nebivolol
- - beta blocker that promotes nitric oxide (NO) production
- - dec both CO and TPR
- - B blocker/vasodilator
-
captopril
- - ACE Inhibitors: inhibit conversion of angiotensin to angiotensin II by angiotensin converting enzyme (ACE)
- - PRIL
- - no metabolism necessary
-
enalapril
- - ACE Inhibitors: inhibit conversion of angiotensin to angiotensin II byangiotensin converting enzyme (ACE)
- - PRIL
- - pro-drug
-
losartan
- - Angiotensin Receptor Blockers (ARBs) inhibit binding of angiotensin IIto the AT1 receptor
- - ARTAN
-
valsartan
- - Angiotensin Receptor Blockers (ARBs) inhibit binding of angiotensin IIto the AT1 receptor
- - ARTAN
-
aliskiren
- Renin Inhibitors: inhibit conversion of angiotensinogen to angiotensin I by the enzyme renin
-
Angiotensin related Agents
- Block effects of the renin-angiotensin system, thereby reducing blood pressure primarily by inhibiting angiotensin II induced…
- • Vasoconstriction
- • Increases in aldosterone production
- • Increases in vasopressin release
- • No reflex sympathetic activation (resetting of baroreceptors?)
-
ACE Inhibitor Side Effects
- SIDE EFFECTS:
- • Dry cough (bradykinin effect due to ACE inhibition)
- • Angioedema (rapid non-allergic swelling of skin and mucosa; also dueto bradykinin)
- • Hyperkalemia (reduced sodium potassium exchange in kidney)
- • Reduced kidney function (use with caution if kidney function is alreadyimpaired)
- • TERATOGENIC: DO NOT USE DURING PREGNANCY
-
Enoxaparin
- - Low molecular weight HEPARIN = less activity
- - anticoagulant
- - less risk for bleeding
-
Heparins
- - parenteral anticoagulants
- - Binds to and stimulates ANTITHROMBIN III, an endogenousinhibitor of clotting factors.
- • Given as mixture of different sizemolecules purified from animal sources biological units)
- • Molecular weight determines activity
- - Polysaccharide = very hydrophilic & susceptible to digestion so must be given IV or SC
- - reversed by PROTAMINE
-
Unfractionated Heparin
- combination of low and high molecular weights = more activity = more bleeding
-
Lepirudin
- Direct Thrombin Inhibitors (DTI’s) Analogs of Hirudin – purifiedfrom medicinal leeches (Hirudo medicinalis); directly inhibit thrombin
-
Warfarin
- ORAL ANTICOAGULANT
- • PREVENTS VITAMIN K RE-ACTIVATION by inhibiting Vit K epoxidereductase
- • Active Vitamin K is required for synthesis of clotting factors in both theintrinsic and extrinsic systems
- • Delayed onset of action
- • Teratogenic: avoid during pregnancy; Has many drug interactions
- - • Genetic variation in CYP2C9 reduceswarfarin metabolism = increased bleedingrisk
- • variation in the VKORC1 subunit reduces warfarin sensitivity = increased clotting risk
-
Alteplase
- recombinant T-PA
-
T-PA
- - tissue plasminogen activator drugs
- - destroy blood clots after they have formed
- - digests fibrin and breaks down fibrin-rich clots (red-thrombi)
-
Streptokinase
- T-PA purified from bacteria
-
Aspirin
- - acetylates and inhibits COX-1 to reduce TXA2 sythesis
- - anti-thrombotic
- -75-81 mg (one baby aspirin/day) is sufficient to protect against acute MI in moderate tohigh risk individuals
- -At time of heart attack: four baby aspirin (325 mg; chewed) to protect against re-occlusionand subsequent heart attack
- -Maintain on higher-dose (325 mg) aspirin after acute MI to protect against another heartattac
-
Clopidogrel
- - anti-thrombotic
- - Prodrug activated by the CYP system
- - prevent ADP from binding to platelet purinergic receptors
- - Higher-risk individuals for MI; post-MI; post PCI surgery
-
Ticlopidine
- - ADP receptor blocker
- - anti-thrombotic
- - More side effects than clopidogrel : GI effects, greater bleeding risk
- - Higher-risk individuals for MI; post-MI; post PCI surgery
-
Abciximab
- PLATELET RECEPTOR ANTAGONISTS
- • Antagonize receptors on platelet cell membranes to prevent physicalinteraction of platelets with fibinogen and therefore platelet aggregation
- • Administered parenterally for Percutaneous Coronary Interventions (PCIs;new term for angioplasty) to prevent reocclusion of coronary vessel
- - anti-GPIIb/IIIa antibody
- - given during PCI surgery
-
Tirofiban
- PLATELET RECEPTOR ANTAGONISTS
- • Antagonize receptors on platelet cell membranes to prevent physicalinteraction of platelets with fibinogen and therefore platelet aggregation
- • Administered parenterally for Percutaneous Coronary Interventions (PCIs;new term for angioplasty) to prevent reocclusion of coronary vessel
- - GPIIb/IIa Antagonists
- - given during PCI surgery
-
Niacin
- - TREATMENT OF HYPERTRIGLYCERIDEMIA INVOLVES DECREASINGCIRCULATING VLDL LEVELS
- - increases HDL levels
- - does have net dec in LDL due to mainly acting on dec vldl syn in liver
-
Gemfibrozil
- - TREATMENT OF HYPERTRIGLYCERIDEMIA INVOLVES DECREASINGCIRCULATING VLDL LEVELS
- - no change in LDL
-
Colestipol
- - tx hypercholestolemia hyperlipidemia
- - bile acid-binding resin
- - less bile available for reabsorption
- - dec liver bile, lower live cholesterol, increase in ldl receptors, inc ldl uptake into liver
-
Cholestyramine
- - tx hypercholestolemia hyperlipidemia
- - bile acid-binding resin
- - less bile available for reabsorption
- - dec liver bile, lower live cholesterol, increase in ldl receptors, inc ldl uptake into liver
-
Statins
- HMG-CoA Reductase Inhibitors
- – HMG-CoA reductase is a key liver enzyme for the synthesis of cholesterol
- – By inhibiting cholesterol synthesis in the liver, cellular concentrations are reduced andLDL receptors are up-regulated resulting in increased removal of LDL from the blood.
- - Also produce modest increases in HDL (less than niacin) and decreases in VLDL (lessthan niacin/fibric acid drugs)
-
atorvastatin
- - Lipitor; most prescribed statin drug
- - High efficacy
- - no available generically
-
fluvastatin
- statin drug
-
-
pravastatin
- low efficacy statin
-
rosuvastatin
- - high efficacy statin
- - Crestor
- - not available generically
-
simvastatin
- - Zocor
- - medium efficacy
- - available generically
-
Ezetimibe
- Binds to protein on GI epithelial cells that promotes cholesterol absorption in the small intestine.
- • Inhibits of intestinal absorption of dietary cholesterol
- • Reduces LDL levels (tx. hypercholestolemia)
- • GI side effects
-
Vytorin
- Ezetimibe (Zetia) + simvastatin
- •ENHANCE study (fyi: Merck and Schering-Plough): although Vytorin produced greaterreductions in LDL than simvastatin alone,coronary atherosclerotic plaque formationwas no different
- Implications:
- 1. Vytorin is no more protective against coronary heart disease than statinmonotherapy; potentially questions the effectiveness of ezetimibe
- 2. Suggests that effectiveness of statins versus coronary heart diseasemay not only involve reductions in LDL; potential anti-inflammatoryeffects
-
Nitroglycerin
- - inactivated through first pass metabolism and therefore are usually given sublingually as a tablet or spray or transdermally
- - organic nitrate
- - classic and variant angina
-
isosorbide di-/mono-nitrate
- - organic nitrate
- - admin orally
- - classic and variant angina
-
diltiazem
- -CCB
- - cardioactive: Block channels in vascular smooth muscle AND in the heart
- – Vasodilators AND cardiac inhibitors
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