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Pharmacology HTN

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List some causes of secondary hypertension
- chronic renal disease - renovascular disease - exogenous substances (steroids, NSAIDs, estrogens, alcohol)
Name some risk factors for hypertension
- age (males > 55, females > 65) - diabetes (#1 risk factor) - increased LDL, decreased HDL - GFR less than 60 - family history - obesity - tobacco - physical inactivity
Give examples of target organ damage due to hypertension
1. in the heart, such as revascularization, left ventricular hypertrophy (LVH), angina/MI, CHF 2. in the kidney, such as chronic kidney disease, nephropathy, retinopathy 3. in the brain, such as stroke, TIA, dementia
Give examples of lifestyle modifications to reduce hypertension
- weight loss (10 lb weight loss decreases BP 6-8 mm Hg) - limit alcohol intake - increase aerobic physical activity - reduce sodium intake - stop smoking - reduce intake of saturated fats and cholesterol
Generally, what do diuretics do?
decrease cardiac output and decrease fluid
What is the mechanism of action (MOA) of thiazide diuretics?
- inhibt Na/Cl symporter at the early distal convoluted tubule and cortical portion of the thick ascending limb of the loop of Henle - increased Na, Cl, and H20 excretion
Why are thiazide diuretics good for patients with osteoporosis?
thiazide diuretics reduce Ca++ excretion
What are some uses of thiazide diuretics?
- CHF - HTN - hepatic cirrhosis - renal disease - edma associated with corticosteroid and estrogen use - osteoporosis
What are side effects of thiazide diuretics?
- hyponatremia - hypokalemia - hypovolemia - hypomagnesemia - hyperuricemia
Name 4 thiazide diuretics and their dosages
1. HCTZ 12.5 - 25 mg daily 2. Chlorthalidone 12.5 - 50 mg daily 3. Indapamide 1.25 - 5 mg daily 4. Metolazone 2.5 - 10 mg daily (weakest of thiazide diuretics)
What is the mechanism of action of loop diuretics?
- acts primarily on the ascending loop of Henle by inhibiting the Na-K-Cl symporter - increases Na, Cl, K, and H20 excretion in large amounts
What are uses of loop diuretics?
- CHF - HTN - hepatic cirrhosis - renal disease - hypercalcemia
What are side effects of loop diuretics?
- hyponatremia - hypokalemia - hypovolemia (greatest with loop diuretics) - hypomagnesemia - hyperuricemia
Name 4 loop diuretics and their dosages
1. furosemide (Lasix) 40 - 240 mg bid - tid 2. Bumetanide (Bumex) 0.5 - 4 mg bid - tid 3. Torsemide (Demadex) 5 - 100 mg bid - tid 4. Ethacrynic Acid (Edecrin) 25 - 100 mg bid - tid
___ mg of Bumetadine = ___ mg of Furosemide
1 mg of Bumetadine = 20 mg of Furosemide
Which loop diuretic can be used to treat hypercalcemia?
Torsemide (Demadex)
Which loop diuretic is used for truely sulfa-allergic patients?
Ethacrynic Acid (Edecrin)
What are the 2 groups of potassium-sparing diuretics?
1. inhibitors of the renal epithelial Na channels; acts at the late distal tubule (Triametrene, Amiloride) 2. Aldosterone antagonist (spironalactone, elperelone)
When do you use potassium-sparing diuretics?
- used in adjunct treatment with thiazides and loop diuretics - to treat edema secondary to hyperaldosteronism
What are side-effects of potassium-sparing diuretics?
- gynecomastia (spironalactone) - hyperkalemia - hyponatremia
Name 4 potassium-sparing diuretics and their dosage
1. Amiloride 5-10 mg daily 2. Spironalactone 25 - 100 mg daily 3. Triameterene 25 - 100 mg daily 4. Elperelone 25 - 100 mg daily
What are general characteristics of Beta-Blockers?
1. reduce cardiac output through negative chronotropic and inotropic effectson the heart 2. blockade of beta receptors at the juxtaglomerular cells decrease release of renin 3. central action (crosses the blood brain barrier)
Which is the most potent beta-blocker that can cross the blood brain barrier?
propanolol
What are the 4 classifications of beta-blockers?
1. nonselective 2. selective 3. with ISA (intrinsic sympathetic activity) 4. without ISA
Which beta-blockers are nonselective?
- carvedilol - labetalol - nadolol - pindolol - propanolol
Which beta-blockers are selective?
- atenolol - metoprolol - acetobutolol - bisoprolol
Which beta-blockers are approved to use for CHF?
- carvedilol - metoprolol succinate (Toprol XL) - bisoprolol (approved in Europe)
What are the effects of beta-blockers with ISA? Give 2 examples.
- beta-blockers with ISA lower blood pressure without reducing resting heart rate - examples are Pindolol (nonselective) and Acetobutolol (selective)
Beta-blockers are used for what conditions?
- hypertension - angina pectoris - arrhythmias - myocardial infarction - stable CHF (not acute CHF)
What are side effects of beta-blockers?
- bradycardia - bronchodilation - cold extremities - hypotension - increase serum lipids - mask symptoms of hypoglycemia
What are contraindications for using beta-blockers?
- second and third degree heart block - bradycardia (HR less than 50) - COPD with nonselective beta-blocker - beta blockers without ISA in PVD
What can occur if beta blockers are withdrawled abruptly?
- can get rebound angina and tachycardia - should reduce beta-blocker by 50% everyday to avoid withdrawl symptoms
Name 6 beta blockers and their dosage ranges
1. Acebutolol 200 - 800 mg daily 2. Atenolol 25 - 100 mg daily (or BID) 3. Carvedilol 6.25 - 50 mg BID 4. Metoprolol 50 - 300 BID 5. Pindolol 10 - 60 mg BID 6. Propanolol 40 - 480 BID
What is MOA of calcium channel blockers?
inhibit calcium entry through voltage dependant channels
Describe how calcium channel blockers affect smooth muscle, cardiac muscle, and the cardiac conduction system
1. smooth muscle - decreases muscle contraction (decreases total peripheral resistance through arteriolar relaxation) 2. cardiac muscle - decreases depolarization and reduces myocardial contractility (inhibits action potential) 3. cardiac conduction system - inhibition of pacemaker potential and slows AV conduction
What are the 2 classifications of calcium channel blockers?
- nondihydropyridines (used for rate control as antiarrhythmics) - dihydropyridines (used for HTN)
Name some examples of nondihydropyridines
- diltiazem - verapamil - nifedipine
Name examples of dihydropyridines
- amlodipine (Norvasc) - felodipine - nicardipine - nisoldipine
What are indications for use of Nicardipine?
- used in patients with a bleed - used for post-operative HTN
What are indications for using Nisoldipine?
- used with acute hemmorhagic stroke - must be given with 8 hrs of stroke
What are the dosages for Diltiazem?
- comes in immediate-release (IR) or sustained-release (SR) Diltiazem IR (Cardizem): 30, 60, 90 mg Q 8hrs Diltiazem SR (aka Cardizem CD, Tiazac): 120, 240, 320, 360, 480 mg Q 24
What is the dosage for Verapamil?
IR: 40, 80 mg Q 8-12 hr SR: 80, 160, 240, 320 mg Q 24 hr
What is the dosage of Nifedipine?
IR: 10 mg PRN SR (Procardia): 30, 60, 90 mg Q 12-24 hrs
What are the dosages for the dihydropyridines?
Amlodipine: 5-10 mg Q 24 Felodipine: 5-10 mg Q 24 Nicardipine: 30, 60, 90 mg Q 24 (90 mg is IV formulation) Nisoldipine: 10 mg Q 6 hrs
What are clinical indications for using calcium channel blockers?
- HTN - effort induced angina - arrhythmias - esophageal spasm
What are side effects of calcium channel blockers?
- constipation - flushing - headaches - palpitations - peripheral edema (seen in non-DHPs)
What is the MOA for ACE inhibitors?
- blocks the conversion of angiotensin I to angiotensin II - leads to a decrease in total peripheral resistance (TPR) and causes vasodilation - inhibts the breakdown of bradykinin (causes vasodilation)
List 7 examples of ACE inhibitors
- Benazepril (Lotensin) - Captopril - Enalapril (Vasotec) - Lisinopril (Zestril) - Quinapril (Accupril) - Ramipril (Altace) - Trandolapril
Which is the only ACE inhibitor to come IV?
Enalapril 1.25 mg IV
What are the dosages of Ramipril (Altace)?
2.5, 5, 10 mg Q 24 hr
What is the dosage for Enalapril?
2.5, 5, 10, 20 mg Q 12-24 hrs
What are the dosages for Lisinopril (Zestril)?
2.5, 5, 10, 20 mg Q 12-24 hrs
What are the dosages for Benazepril (Lotensin)?
5, 10, 20, 40 mg Q 12-24 hrs
What is the dosage for Quinapril (Accupril)?
2.5, 5, 10 mg Q 24hrs
What is the dosage for Captopril?
6.25, 12.5, 25, 50 mg Q 8hrs - drug is a TID drug which is not good for patient compliance
What are indications for using ACE inhibitors?
- HTN - proteinuria - CHF - myocardial infarction - diabetic nephropathy
What are side effects of ACE inhibitors?
- angioedema (due to increase of bradykinin, which causes vasodilation) - cough (due to increase of bradykinin, which causes vasodilation) - hyperkalemia - hypotension - increased serum creatinine (stop if SCR doubles or triples in 2 days) - taste disturbances
What are contraindications of ACE inhibitors?
- acute renal failure - bilateral renal stenosis - pregnancy
What is the MOA of angiotensin receptor blockers?
- blocks angiotensin II from binding to receptor - leads to a decrease in afterload and preload
Why is there a lower incidence in cough with ARBs?
ARBs do not affect bradykinin
Name 4 ARBs
- Losartan (Cozaar) - Valsartan (Diovan) - Candesartan (Atacand) - Irbesartan (Avapro)
What is the dosing for Losartan (Cozaar)?
25-100 mg Q24 hr
What is the dosing for Valsartan (Diovan)?
40, 80, 120 mg Q24
What is the dosing for Candesartan (Atacand?
6, 8, 12, 24, 32 mg Q24
What is the dosing for Irbesartan (Avapro)?
75, 150, 30 mg Q24
What are clinical indications are ARBs?
- CHF - diabetic nephropathy - HTN - myocardial infarction - proteinuria
What are side effects of ARBs?
- angioedema - hyperkalemia - hypotension - increase Scr
What are contraindications for ARBs?
- same as ACE inhibitors - patients with bilateral renal stenosis - acute renal failure - pregnancy
What is the MOA of alpha 1 receptor blockers?
dilate both resistance and capacitance vessels, reducing total peripheral resistance and venous return
Why do you administer alpha 1 receptor blockers at night?
to prevent orthostatic hypotension
Name 3 alpha 1 receptor antagonists and their dosing
Prazosin 2-30 mg BID Doxazosin (Cardura) 1-16 mg Q24 Terazosin 1-20 mg Q24
What are clinical indications for using alpha 1 receptor antagonists?
- HTN - benign prostatic hyperplasia (BPH)
What are side effects of alpha 1 receptor antagonists?
- hypotension - orthostatic hypotension
What are contraindications for alpha 1 receptor antagonist?
decreased heart rate
What is the MOA for alpha 2 agonist?
- firing of the sympathetic nerve decreases - decreases the amount of norepinephrine found at the nerve terminals - works on catecholamines
Name 2 alpha 2 agonists and their dosing
Clonidine 0.2-1.2 mg po BID Methyldopa 125-500 mg po BID
What are side effects of alpha 2 agonist?
- drowsiness - dry mouth - hypotension - sedation
What is the indication for using methlydopa?
methlydopa is the drug of choice for pregnant women with HTN
What is the first line drug for a patient with diabetes type 1 and HTN?
ACE inhibitor or ARB
What drug should you use with a diabetic type 1 patient with HTN and a contraindication to ACE inhibitors?
- calcium channel blockers - hydralazine with a nitrate
What are first line drugs for treatment of heart failure?
- ACE inhibitor or ARBs - diuretics used with an ACE inhibitor or ARBs
What are first line drugs for acute myocardial infarction?
- Beta - blockers (non-ISA) such as pindolol or acebutolol - ACE inhibitor or ARB in conjunction with a beta-blocker (ACE-I prevents myocardial remodeling)
What drugs are contraindicated with COPD?
beta-blockers unless there are compelling indications like MI
Which drugs should be avoided in patients with gout?
thiazide and loop diuretics
Which drugs are contraindicated with 2nd and 3rd degree heart block?
avoid beta-blockers and calcium channel blockers

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