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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