Lesson 1.4. Pharmacologic Treatment for HTN

Diuretics

increase urine formation and excretion, decrease sodium reuptake

Sympatholytic Agents

reduce PVR and inhibit cardiac functions

Vasodilators

relax vascular smooth muscles. dilating vessels

Angiotensin Antagonists

reduce PVR and blood volume

sodium and water balance

Diuretics are drugs that alter _____________________________.

acetazolamide

DIURECTICS:

• Carbonic Anhydrase Inhibitors include:

mannitol

DIURECTICS:

• Osmotic Diuretics include:

Bumetanide, Furosemide, and Torasemide

DIURECTICS:

• Loop Diuretics include:

Bendroflumethiazide, Chlortalidone, Hydrochlorothiazide, Indapamide, and Metolazone

DIURECTICS:

• Thiazides and related Diuretics include:

Amiloride, Eplerenone, Spironolactone, and Triamterene

DIURECTICS:

• Potassium-Sparing Diuretics include:

Captopril

RAAS INHIBITORS:

ACE Inhibitors

• short-acting

Enalapril

RAAS INHIBITORS:

ACE Inhibitors

• prodrug

Lisinopril

RAAS INHIBITORS:

ACE Inhibitors

• derivative of enalapril

Ramipril, Benazepril, and Fosinopril

RAAS INHIBITORS:

ACE Inhibitors

• long-acting drugs

Perindopril and Quinapril

RAAS INHIBITORS:

ACE Inhibitors

• other

hypotension

RAAS INHIBITORS:

Adverse Effects of ACEi:

• Severe ___________ after initial doses, especially in hypovolemia as a result of diuretics, salt restriction, or gastrointestinal fluid loss.

Acute Renal Failure

RAAS INHIBITORS:

Adverse Effects of ACEi:

• _________________, particularly in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney

Hyperkalemia

RAAS INHIBITORS:

Adverse Effects of ACEi:

• other ADRs

dry cough, wheezing, angioedema

RAAS INHIBITORS:

Adverse Effects of ACEi:

• _____________________________ due to bradykinin or substance P

proteinuria and neutropenia

RAAS INHIBITORS:

Adverse Effects of ACEi:

• Captopril can cause ______________________ at high doses, especially in patients with renal insufficiency.

fetal malformations

RAAS INHIBITORS:

Adverse Effects of ACEi:

• It is contraindicated during pregnancy, it induces ____________________.

ARBs

RAAS INHIBITORS:

• may be used as first-line agents for treating HTN, especially in patients with a compelling indication of Diabetes Mellitus, Heart Failure, or Chronic Kidney Disease

• Same use as ACEIs

• Do not combine with ACEIs

• includes Losartan, Valsartan, Candesartan, Eprosartan, Irbesartan, Telmisartan, and Olmesartan

wheezing, coughing, and angioedema

RAAS INHIBITORS:

ARBs Adverse Effect

• like ACEIs, except _________________________________

Calcium Channel Blockers

• Management of HTN (as initial therapy or add-on therapy)

• Useful in HTN patients who also have asthma, diabetes, and/or peripheral vascular disease, because they do not have the potential to affect these conditions adversely, unlike β-blockers

• Useful in the treatment of angina

Diltiazem and Verapamil

Calcium Channel Blockers

• used in the treatment of atrial fibrillation

bradycardia, cardiac arrest, AV-block and congestive heart failure

ADVERSE DRUG REACTIONS OF CCBs:

• cardiac depression includes:

Flushing, dizziness, nausea, constipation, peripheral edema

ADVERSE DRUG REACTIONS OF CCBs:

• other ADRs

Methyldopa

CENTRALLY ANTI-ADRENERGIC DRUG:

• An a2-agonist converted centrally to methylnorepinephrine

• Reduces sympathetic outflow from CNS, decreases catecholamine release, reduces peripheral vascular resistance & cardiac output → decrease in blood pressure

• Used primarily for hypertension of pregnancy

sedation, drowsiness

CENTRALLY ANTI-ADRENERGIC DRUG:

Adverse Drug Reactions of Methyldopa

• CNS Effects

postural hypotension

CENTRALLY ANTI-ADRENERGIC DRUG:

Adverse Drug Reactions of Methyldopa

• little ____________________, may occur in volume-depleted patients

Guanabenz

CENTRALLY ANTI-ADRENERGIC DRUG:

• other

Clonidine

CENTRALLY ANTI-ADRENERGIC DRUG:

• A direct agonist at central α2-adrenoceptors, decreases circulating catecholamine levels & reduces blood pressure → reduction of the TPVR and reduction of the sympathetic & increases parasympathetic tone → blood pressure lowering & bradycardia

• Does not decrease renal blood flow or glomerular filtration → useful in the treatment of HTN complicated by renal disease

Dry mouth and Sedation

CENTRALLY ANTI-ADRENERGIC DRUG:

Adverse Effects of Clonidine

• dose-dependent

mental depression

CENTRALLY ANTI-ADRENERGIC DRUG:

Adverse Effects of Clonidine

• not be given to patients who are at risk for ____________________

hypertensive crisis

CENTRALLY ANTI-ADRENERGIC DRUG:

Adverse Effects of Clonidine

• withdrawal after prolonged use, at high doses it can cause _____________________

Beta-Blockers

• Bind to beta-adrenoceptors

• Inhibits normal sympathetic effects that act through beta-receptors

Bradycardia and Cardiac Block

MAJOR ADVERSE EFFECTS OF BETA-BLOCKERS:

1. due to B1-block

2. due to B2-block

3. masking signs and symptoms of __________________________

4. characterized by nervousness, tachycardia, increased intensity of angina, BP, and MI

1 = ?

Increased Peripheral Vascular Resistance and Bronchoconstriction

MAJOR ADVERSE EFFECTS OF BETA-BLOCKERS:

1. due to B1-block

2. due to B2-block

3. masking signs and symptoms of __________________________

4. characterized by nervousness, tachycardia, increased intensity of angina, BP, and MI

2 = ?

hypoglycemia

MAJOR ADVERSE EFFECTS OF BETA-BLOCKERS:

1. due to B1-block

2. due to B2-block

3. masking signs and symptoms of __________________________

4. characterized by nervousness, tachycardia, increased intensity of angina, BP, and MI

3 = ?

withdrawal syndrome

MAJOR ADVERSE EFFECTS OF BETA-BLOCKERS:

1. due to B1-block

2. due to B2-block

3. masking signs and symptoms of __________________________

4. characterized by nervousness, tachycardia, increased intensity of angina, BP, and MI

4 = ?

Alpha-blockers

• Reduce arterial pressure by dilating both resistance and capacitance vessels

• Α2-blockers → reflex activation of sympathetic neurons and greater release of norepinephrine and greater cardio-acceleration

• More effective, when given in combination, than alone

• Relax prostatic smooth muscle (HTN & BPH)

salt and water

Alpha-blockers Adverse Effects:

1. retention of ________________

2. selective alpha-blockers causes less _________________

1 = ?

reflex tachycardia

Alpha-blockers Adverse Effects:

1. retention of ________________

2. selective alpha-blockers causes less _________________

2 = ?

Direct Vasodilators

• Produce direct relaxation of vascular smooth muscle → vasodilation → decrease total peripheral vascular resistance

• Relax arterial smooth muscle more than venous smooth muscle → minimal postural hypotension

• Inadequate as monotherapy for hypertension because of tolerance, but more useful when combined with diuretics and/or β-blockers

Hydralazine

Direct Vasodilators

• Acts mainly by releasing nitric oxide (NO) and endotheliumderived relaxing factor (EDRF)

• Dilates arterioles, but not veins

headache, flushing, nasal congestion, palpitations, tachycardia, and thus, myocardial ischemia and precipitation of angina, skin rashes, and fever

Direct Vasodilators

Hydralazine Adverse Effects

1. other ADRs

2. lupus-like syndrome characterized by joint pain

3. muscle pain

4. no ______________ at higher doses

5. ADRs are _____________________ once the drug is stopped

1 = ?

athralgia

Direct Vasodilators

Hydralazine Adverse Effects

1. other ADRs

2. lupus-like syndrome characterized by joint pain

3. muscle pain

4. no ______________ at higher doses

5. ADRs are _____________________ once the drug is stopped

2 = ?

myalgia

Direct Vasodilators

Hydralazine Adverse Effects

1. other ADRs

2. lupus-like syndrome characterized by joint pain

3. muscle pain

4. no ______________ at higher doses

5. ADRs are _____________________ once the drug is stopped

3 = ?

renal damage

Direct Vasodilators

Hydralazine Adverse Effects

1. other ADRs

2. lupus-like syndrome characterized by joint pain

3. muscle pain

4. no ______________ at higher doses

5. ADRs are _____________________ once the drug is stopped

4 = ?

reversible

Direct Vasodilators

Hydralazine Adverse Effects

1. other ADRs

2. lupus-like syndrome characterized by joint pain

3. muscle pain

4. no ______________ at higher doses

5. ADRs are _____________________ once the drug is stopped

5 = ?

Minoxidil

Direct Vasodilators

• Metabolized in the liver to minoxidil sulfate, a K+ channel opener in smooth muscles → hyperpolarization and relaxation of smooth muscle

• Dilates arterioles, but not veins

headache, flushing, nasal congestion, palpitations, tachycardia, and thus, myocardial ischemia

Direct Vasodilators

Minoxidil Adverse Effects:

1. other ADRs

2. growth of body hair

1 = ?

hypertrichosis

Direct Vasodilators

Minoxidil Adverse Effects:

1. other ADRs

2. growth of body hair

2 = ?