Antihypertensive Drugs.pdf

Antihypertensive Drugs.pdf

• 1.
  ANTIHYPERTENSIVE DRUGS
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   Drugs usedin treatment of hypertension.  Persistant elevation of blood pressure from normal level is called hypertension.  Blood pressure is a pressure of the blood exerted against the blood vessels.  Normal BP: 120 (systolic) /80mm (diastolic) Hg.  Also known as SILENT KILLER as sometimes person is not having warning signs or symptoms initially.  Increased BP may lead to further complications like myocardial infarction and stroke.
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  Types of Hypertension(Based on Measurement of diastolic pressure) Mild Hypertension: If BP is between 90-110 Moderate Hypertension: If BP is between 110-130 Severe Hypertension: If BP is between 130-140. If BP exceeds above 140mm it leads to Hypertensive crisis (State of emergency) Based on cause Primary Hypertension (Essential/ Idiopathic): When cause or origin of disease is unknown. Secondary Hypertension: When cause is known i.e. it may be due to any disease like renal artery disease, pregnancy, pheochromocytoma etc.
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  CAUSES/ ETIOLOGY OFHYPERTENSION  Neural factors (Stress/ emotions)  Hormonal factors (Renin)  Electrolytic imbalance  Genetic factors  Environmental factors like smoking, obesity
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  Neural Factors  Increasein sympathetic outflow, increase release of Adrenaline and Nor-Adr So, there is increase in BP.  Drugs effective will be: Sympatholytic drugs like prazosin, propranolol
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  Renin (Juxtaglomerular cells ofkidney) Angiotensinogen (Liver) Angiotensin-I (Inactive) Angiotensin-II (Active) AT1 receptor Aldosterone release Vasoconstriction Increased sympathetic outflow Increased BP ACE Effective drugs ACE inhibitor AT1 receptor antagonist Renin inhibitor
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  Electrolytic factors Increase SodiumRetention Increase Blood volume Increase Peripheral resistance Increase BP/ Hypertension Drugs effective: Diuretics
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  MANAGEMENT OF HYPERTENSION Give up smoking.  Avoid sweets and coffee  Controlled salt intake  Diet control  Regular exercise  If still uncontrolled, antihypertensive drug therapy can be the treatment
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  CLASSIFICATION  Drugs effectingsympathetic nervous system  Alpha (α1)- adrenergic blocker: Prazosin, Terazosin, Phentolamine, Phenoxybenzamine  Beta (β)- adrenergic blocker: Propranolol, Metoprolol, Atenolol, Timolol  Non-selective (α + β) blocker: Labetolol, Carvedolol  Centrally acting drugs (α2-agonist): Clonidine, Methyl DOPA, Guanabenz  Adrenergic neuron blockers: Reserpine, Guanethidine
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   Drugs effectingRAAS system  Renin inhibitors: Alisekrin  ACE inhibitors: Captopril, Lisinopril, Enalapril, Benazepril, Quinapril  AT1 receptor antagonist:  Losartan, Candesartan (Non-peptide in nature)  Saralasin, Sarmesin (Peptide in nature) o Diuretics  Thiazide diuretics: Hydrochlorthiazide  Loop diuretics: Furosemide
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   Vasodialators  Hydralazine Diazoxide  Sodium nitroprusside  Minoxidil o Calcium channel blockers:  Verapamil, Amlodipine, Nifedipine  Drugs acting on Baroreceptors: Veratrum
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   ACE inhibitors •Contraindicated with Potassium sparing diuretics, NSAIDS, Gold sodium aurothiomalate • Common side effect is Cough. • Decreases excretion of potassium so leads to hyperkalemia. Captopril 1-[2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid First ACE inhibitor used for T/t of hypertension and CHF. Sulfhydryl-containing analog of proline. Side effects:  Cough due to increase in the plasma levels of bradykinin.  Postural Hypotension  Palpitation  Loss of Taste (dysgeusia)
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  Lisinopril 1-[6-amino-2-[1-carboxy-3-phenylpropyl] amino]hexanoyl]pyrrolidine-2-carboxylic acid Enalapril 1-[1-ethoxy-1-oxo-4-phenylbutan-2-yl aminopropanoyl]pyrrolidine-2 carboxylic acid Prodrugand is converted into enalaprilat (active drug )by enzyme esterase in liver Benazepril Prodrug and is converted into benazeprilat (active drug )by enzyme esterase in liver. Quinapril Prodrug and is converted into quinaprilat (active drug )by enzyme esterase in liver.
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  DRUGS EFFECTING SYMPATHETIC NERVOUSSYSEM Beta BLOCKERS  Non-selective: Propranolol, Timolol  Selective beta 1 blocker: Atenolol, Metoprolol Timolol is a nonselective beta-adrenergic antagonist given in an eye drop solution to reduce intraocular pressure. It is also used in tablet form as a drug to treat hypertension Acts by Inhibiting renin release Reducing sympathetic outflow and cardiac output. Side effects include: Tiredness, slowhearbeat, cold hand and feet. 1-(tert-butylamino)-3-{[4-(morpholin-4-yl)- 1,2,5-thiadiazol-3-yl]oxy}propan-2-ol
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  CENTRALLY ACTING DRUGS α2 agonist.  Clonidine, Methyl Dopa, Guanabenz Methyl DOPA 2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid Having structural resemblance with DOPA so instead of DOPA, it will undergo decarboxylation to form methyl dopamine and then methyl nor-adr/adr, so no neurotransmitter release will be there, so no Increase BP.
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  Tyrosine Phenyl alanine DOPA Dopamine Adr/ NorAdr Hydroxylase Hydroxylase Decarboxylase Methyl-DOPA Methyl-Dopamine Methyl-Adr/Nor Adr (False neurotransmitter)
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  Uses  In treatmentof hypertension in conjugation with diuretics. Side Effects  Sedation  Dry mouth  Bradycardia  Constipation  Nausea and vomiting
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  Clonidine Clonidine is animidazole derivate that acts as an agonist of alpha-2 adrenoceptors. N-(2,6-dichlorophenyl)-4,5-dihydro- imidazol-2-amine 2-{[(2,6-dichlorophenyl) methylidene]amino}guanidine Guanabenz is an guanidine derivate that acts as an agonist of alpha-2 adrenoceptors Guanabenz
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  ADRENERGIC NEURON BLOCKERS Reserpine  Guanethidine An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines from peripheral sympathetic nerve endings. It has been used as an antihypertensive and an antipsychotic, but its adverse effects limit its clinical use. Side effects include nasal congestion, nausea, vomiting, weight gain, gastric intolerance, gastric ulceration
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  Guanethidine  Antihypertensive drug,act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues.  Side effects include postural hypotension and diarrhea. 2-[2-(azocan-1-yl)ethyl]guanidine
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  Vasodialators  Sodium nitroprusside Hydralazine  Minoxidil  Diazoxide
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  Sodium nitroprusside  Actsby vasodialation as organic nitrates  Very rapid mode of action so used to lower blood pressure in hypertensive crisis.  Side effects include: Skin rashes, stomachache, nausea, tinnitus, sweating and most important is cyanide toxicity.
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   Hydrazine derivativevasodilator used alone or as adjunct therapy in the treatment of hypertension.  Hydralazine may interfere with calcium transport in vascular smooth muscle to relax arteriolar smooth muscle and lower blood pressure.  Prevent influx of calcium into cells, preventing calcium release from intracellular compartments so no combination of actin and myosin, so no contraction.  Also act as antineoplastic by inhibiting enzyme DNA methyl transferase and thus inhibit cell replication.  Side effects: Headache, Anorexia, Nausea, vomiting, diarrhea. Hydralazine 1-hydrazinylphthalazine
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  Minoxidil  Mainly usedto treat alopecia.  Also used as an hypertensive due to its vasodialtion effect.  Act as potassium channel opener leading to hyperpolarisation effect.  Minoxidil is an example of prodrug and is converted into minoxidil sulfate (active form).  Side effects include chest pain, dry cough, nausea, sweating, rapid weight gain, facial hair. 6-(1-Piperidinyl)pyrimidine-2,4-diamine 3-oxide
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  Diazoxide 7-Chloro-3-methyl-1,2,4- benzothiadiazine 1,1-dioxide Potassium channelopener so increase membrane permeability to potassium ions causing vascular relaxation in smooth muscle. Also used to treat hypoglycemia Although belonging to thiazides but no diuretic action. Side effects: Nausea, loss of apetite, stomach upset.
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   Carbonic anhydraseinhibitors: Acetazolamide  Loop diuretics: Furosemide  Thiazide diuretics: Hydrochlorthiazide  Potassium sparing diuretics: Spironolactone