Anti HypertensiveAnti Hypertensive

Anti HypertensiveAnti Hypertensive

Types of HTN:Types of HTN:

1. Alternate HTN.2. Mild HTN (DBP 91 -104 MMHg).3. Moderate HTN (DBP 105 -114 MMHg).4. Severe HTN (DBP < 115 MMHg without End

organ damage).5. Malignant HTN (DBP < 115 MMHg with end

organ damage).6. Systolic HTN (syst BP < 160 MMHg(

ANTI HYPERTENSIVE THERAPYANTI HYPERTENSIVE THERAPY

Diuretics:- 4 major groups

1.1. Carbonic anhydrase inhibitors (prox. Tubules)Carbonic anhydrase inhibitors (prox. Tubules)

2. 2. Loop DiureticsLoop Diuretics Dose Dose

Bumetanide (Bumex) 0.5 – 5 mg Ethacrynic acid (Edecrin) 25 – 100

mg Furosemide (Lasix) 40 – 480 mg

Chlorothiazide (Diuril) 125 – 500 mg

Cyclothiazide (Anhydron) 0.5 – 2mg

Hydrochlorothiazide (Esidrix) 12.5 – 50 mg

Polythiazide (Renese) 1 – 4 mg

Methylclothiazide (Enduron) 2.5 – 5 mg

Bendroflumethiazide (Naturetin) 2.5 – 5 mg

Benzthiazide (Aquatag) 12.5 – 50 mg

Triclormethiazide (Metahydrin) 1 – 4 mg

3. 3. Thiazides and Related Sulfonamide CompThiazides and Related Sulfonamide Comp..

Sulfonamide CompoundsSulfonamide Compounds

Chlorthalidone (Hygroton) 12.5 -50 mls Indapamide (Lozol) 2 – 5 mg Metolazone (Zaroxolyn) 1 - 10 mg Quinethazone (Hydromox) 25 – 100 mg

4. Potassium – Sparing Agents

Spironolactone (Aldactone) 25 – 100 mg Amiloride (Midamor) 5 – 10 mg Triamterene (Dyrenium) 50 – 100 mg

MECHANISMS BY WHICH CHRONIC DIURETIC THERAPY MAY MECHANISMS BY WHICH CHRONIC DIURETIC THERAPY MAY LEAD TO VARIOUS COMPLICATIONSLEAD TO VARIOUS COMPLICATIONS

Diuretic therapy

Renal reabsorption of Na (and Mg) Hypomagnesemia

Hyponatremia Saluresis and dluresis

Plasma volume

Cardiac output Renal blood flow PRA

Postural hypotension GFR Aldosterone

Pre-renal Proximal Distal Ca++ Kaliuresis azotemia reabsorption reabsorption

uric acid calcium Hypokalemia Hyper – cholesterolemia

Hyperuricemia Hypercalcemia Glucose tolerance

Dosage and Choice of AgentDosage and Choice of Agent

Mild & Moderate HTN:Mild & Moderate HTN:

• With serum creatinine > 2 mg/dL• With serum creatinine < 2 mg/dL

Side Effects Side Effects

1.1. HypolemiaHypolemia

Use small dose of diuretics. Use moderately long acting (12–18 hours). Restrict Na+ intake. Increase dietary K+ intake. Restrict use of laxative. Combined Thiazide with K+ sparing agent.

Side Effects (cont.)Side Effects (cont.)

2. 2. HyponatremiaHyponatremia3. Hypomagnesemia3. Hypomagnesemia4. Hyperuricemia4. Hyperuricemia5. Hypercholesterolemia5. Hypercholesterolemia6. Hypercalcemia6. Hypercalcemia7. Hyperglycemia7. Hyperglycemia8. Impotence8. Impotence9. Use of NSAIDs9. Use of NSAIDs

Adrenergic InhibitorsAdrenergic Inhibitors:: Peripheral Inhibitors:Peripheral Inhibitors:

Reserphine Guanethidine (Ismelin) Guanadrel (Hylorel) Bethanidine (Tenathan)

Central Inhibitors:Central Inhibitors:

Methyldopa (Aldomet) Clonidine (Catapres)

* * A- Receptor Blockers:A- Receptor Blockers:

A.A. aa11- Receptor- Receptor

Doxazosin ( Cardura) Prazosin (Minipress)

B. aB. a11 and a and a22- Receptors- Receptors

Phentolamine (Regitine) Phenoxybenzamine (Dibenzyline)

* * B- Receptor BlockersB- Receptor Blockers

Acebutolol (Sectral) Atenolol (Ternomin) Betaxolol (Kerlone) Metoprolol (Lopressor) Nadolol (Corgard) Penbutolol (Levatol) Pindolol (Visken) Propranolol (Inderal)

Beta-adrenoceptor blocking drugsBeta-adrenoceptor blocking drugs

Nonselective selective with alpha-blocking activity

- + - + Labetalol ISA ISA ISA ISA Bucindolol CarvedilolNadolol Pindolol Atenolol AcebutololPropranolol Carteolol Esmolol (Practolol)Timolol Penbutolol Metoprolol CeliprololSotalol Alprenolol BevantololTertalolol Oxprenolol Bisoprolol Dilevalol Betaxolol

VASODILATORSVASODILATORS

DirectDirect::

Hydralazine A < V Minoxidil A < V Nitroproside A < v Diazoxide A < V Nitroglycerin V < A Calcium Blockers A < V Converting Enz. Inh. A < V Alpha Blockers A = V

Pharmacological Effects of CaPharmacological Effects of Ca++ Blockers Blockers

DeltiazemDeltiazem VerapamilVerapamil NefidipineNefidipine NicardipineNicardipine

Heart rate

- -

Myocardial

Contractility - -

Nodal Conduction - -

Peripheral Vasodilation

ACE INHIBITORSACE INHIBITORS Captopril Enalipril Lisinopril Fosinopril Ramipril Quinapril Benazepril

ANGIOTENSION II ANTAGONISTANGIOTENSION II ANTAGONIST

losartan Olmesartan

DRUGS COMMONLY USEDDRUGS COMMONLY USED

B-Blockers In-patient with angina pectoris

Or Ca + Channel Blockers + Peripheral Vascular Disease

ACE Inhibitor In-patient with DM

Or Ca + Blocker ++ In patient with hyperlipidemia

Diuretics In CHF

Or ACE Inhibitors

Diuretics In CRF

Or Ca + Blockers

Diuretics

Or Ca + Blockers In Asthma + COPD

TABLE 29-12 PARENTERAL DRUGS FOR TREATMENT OF TABLE 29-12 PARENTERAL DRUGS FOR TREATMENT OF HYPERTENSIVE EMERGENCY (IN ORDER OF RAPIDITY OF HYPERTENSIVE EMERGENCY (IN ORDER OF RAPIDITY OF ACTION)ACTION)

DRUGDRUG DOSAGEDOSAGE ONSET OF ONSET OF ACTIONACTION

ADVERSE EFFECTSADVERSE EFFECTS

VASODILATORS

Nitroprusside (Nipride,Nitropress)

0.25 -10 ug/kg/min as I.V. infusion Instantaneous Nausea, vaomiting, muscle twitching sweating, thiocyanate intoxication

Nitroglycerin 5 -100 ug/min as I.V. Infusion 2 – 5 min Tachycardia, flushing, headache, vomiting, methemoglobinemia

Diazoxide (Hyperstat) 50 – 100 mg/IV bolus, repeated or 15 – 30 mg/min by I.V infusion

2 – 4 min Nausea, hypotension, flushing, tachycardia, chest pain

Hydralazine (Apresoline)

10 – 20 mg I.V

10 – 50 mg I.M

10 – 20 min

20 – 30 min

Tachycardia, flushing, headache, vomiting, aggravation of angina

Enalapril (Vasotec IV) 1.25 – 5 mg q 6 hr 15 min Precipitous fall in BP in high renin states; response variable

Nicardiprine 5 – 15 mg/hr I.V 10 min Tachycardia, headache, flushing, local phlebitis

TABLE 29-12 PARENTERAL DRUGS FOR TREATMENT OF TABLE 29-12 PARENTERAL DRUGS FOR TREATMENT OF HYPERTENSIVE EMERGENCY (IN ORDER RAPIDITY OF ACTION)HYPERTENSIVE EMERGENCY (IN ORDER RAPIDITY OF ACTION)

(Cont.)(Cont.)

DRUG DOSAGE ONSET OF ACTION

ADVERSE EFFECTS

ADRENERGIC INHIBITORS

Phentolamine (Regitine) 5 – 15 mg I.V. 1 – 2 min Tachycardia, flushing

Trimethaphan (Arfonad) 0.5 – 5 mg/min as I.V. infusion 1 – 5 min Paresis of bowel and bladder, orthostatic hypotension, blurred vision, dry mouth

Esmolol ( Brevibloc) 500 ug/kg/min for 4 min, then 150 -300 ug/kg/min I.V.

1 – 2 min Hypotension

Propranolol (Inderal) 1 – 10 mg load; 3ng/hr 1 – 2 min Beta blocker side effects, e.g., bronchospasm, decreased cardiac output

Laberalol (Normodyne, Trandate)

20–80 mg I.V. bolus every 10 min

2 mg/min I.V. infusion

5 – 10 min Vomiting, scalp tingling, burning in throat, postural hypotension, dizziness, nausea

Table 9 – 35 Adverse Effects of Antihypertensive AgentsTable 9 – 35 Adverse Effects of Antihypertensive Agents

Diuretics Nausea, muscle cramps, hypovolemia, hypokalemia, hyponatremia, hyperurcemia, hyperglycemia, rash.

Potassium-sparing diuretics

Hyperkalemia, gynecomastia

Adrenergic inhibitors

Methyldopa Drowsiness, dry mouth, impotence, hepatitis, postural hypotension, hemolytic anemia, fever

Reserpine Somnolence, nasal congestion, nightmares, mental depression

Gunethidine Postural hypotension, diarrhea, retrograde ejaculation, weakness on exertion

Propranolol Bradycardia, left ventricular failure, asthma, Raynaud’s syndrome, central nervous system symptoms, sodium retention

Mecamylamine and trimethaphan

Postural hypotension, parasympathetic blockade with constipation and paralytic ileus, loss of visual accommodation.

Clonidine Dry mouth, drowsiness, rebound hypertension if drug stopped abruptly

Table 9 – 35 Adverse Effects of Antihypertensive AgentsTable 9 – 35 Adverse Effects of Antihypertensive Agents(Cont.)(Cont.)

vasodilator agentsPrazosin Tachycardia, headache, postural weakness and

hypotension

Hydralazine Lupuslike syndrome, headache, tachycardia, angina

Minoxidil Tachycardia, hirsutism, headache, sodium retention

Diazoxide Hyperglycemia, tachycardia, angina, sodium retention

Sodium nitroprusside Excess hypotension, acute tubular necrosis, thiocyanate toxicity