Pharm.3

• – 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

• – 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

• – 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

• – 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

• - 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

• - 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

• - 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

• - sympatholytic indirect acting
• - a₂ receptor agonist
• - cns acting to reduce symp n.s. activity
• - act at N. Tractus Solitarius

• - VMAT inhibitor
• - indirect acting sympatholytic

• - Non-selective B Blocker
• - decrease CO
• - B₂ Activation...lungs, liver, skeletal vasculature

• - B₁ Selective blocker
• - dec CO

• - Non-selective B Blocker
• - decrease CO
• - B2 Activation...lungs, liver, skeletal vasculature

• SYMPATHOLYTIC DRUGS
• Block sympathetic n.s. induced contraction of arterial smooth muscle a₁ adrenergic receptor antagonists
• -OSIN

• SYMPATHOLYTIC DRUGS
• Block sympathetic n.s. induced contraction of arterial smooth muscle a1 adrenergic receptor antagonists
• -OSIN

• - direct vasodilator
• - oral drug: used for outpatient treatment of hypertension
• - selective arterial dilator

• - 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

• - 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

• - 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

• - 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

- CARDIOACTIVE CCBs: relax vascular smooth muscle andreduce cardiac output (decrease heart rate, AVconduction, and force of contraction)

• - DIPINE
• - NON-CARDIOACTIVE CCBs: relax vascular smooth muscle but have little effect on cardiac output
• - long-acting orsustained releaseformulations

- long-acting dihydropuridine

- Short-acting dihydropyridines CCBs = increased risk ofmyocardial infarction relative to patient taking diuretics or beta blockers

• 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

• - mixed beta-1 and alpha-1antagonist
• - B Blocker/Vasodilator
• - dec both CO and TPR

• - beta blocker that promotes nitric oxide (NO) production
• - dec both CO and TPR
• - B blocker/vasodilator

• - ACE Inhibitors: inhibit conversion of angiotensin to angiotensin II by angiotensin converting enzyme (ACE)
• - PRIL
• - no metabolism necessary

• - ACE Inhibitors: inhibit conversion of angiotensin to angiotensin II byangiotensin converting enzyme (ACE)
• - PRIL
• - pro-drug

• - Angiotensin Receptor Blockers (ARBs) inhibit binding of angiotensin IIto the AT1 receptor
• - ARTAN

• - Angiotensin Receptor Blockers (ARBs) inhibit binding of angiotensin IIto the AT1 receptor
• - ARTAN

- Renin Inhibitors: inhibit conversion of angiotensinogen to angiotensin I by the enzyme renin

• 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?)

• 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

• - Low molecular weight HEPARIN = less activity
• - anticoagulant
• - less risk for bleeding

• - 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

- combination of low and high molecular weights = more activity = more bleeding

- Direct Thrombin Inhibitors (DTI’s) Analogs of Hirudin – purifiedfrom medicinal leeches (Hirudo medicinalis); directly inhibit thrombin

• 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

- recombinant T-PA

• - tissue plasminogen activator drugs
• - destroy blood clots after they have formed
• - digests fibrin and breaks down fibrin-rich clots (red-thrombi)

- T-PA purified from bacteria

• - 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

• - 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

• - 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

• 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

• 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

• - 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

• - TREATMENT OF HYPERTRIGLYCERIDEMIA INVOLVES DECREASINGCIRCULATING VLDL LEVELS
• - no change in LDL

• - 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

• - 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

• 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)

• - Lipitor; most prescribed statin drug
• - High efficacy
• - no available generically

- statin drug

- statin drug

- low efficacy statin

• - high efficacy statin
• - Crestor
• - not available generically

• - Zocor
• - medium efficacy
• - available generically

• 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

• 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

• - inactivated through first pass metabolism and therefore are usually given sublingually as a tablet or spray or transdermally
• - organic nitrate
• - classic and variant angina

• - organic nitrate
• - admin orally
• - classic and variant angina

• -CCB
• - cardioactive: Block channels in vascular smooth muscle AND in the heart
• – Vasodilators AND cardiac inhibitors