Pharmacology Structures PDF

(Direct) Non-Selective a , β maintain blood pressure in acute hypotensive states not effective by the oral route...

(Direct) Non-Selective a , β maintain blood pressure in acute hypotensive states not effective by the oral route of administration, thus it given by Norepinephrine I.V R(-) 2-Amino-1-(3,4-dihydroxy-phenyl)- ethanol (Direct) non-Selective a ≤ β α agonist: peripheral decongestant β agonist: bronchodilation and cardiac stimulation Used by injection in anaphylactic reactions. Epinephrine Used by inhalation in asthma R(-) 1-(3,4-dihydroxy-phenyl)-2-N- Used in haemorrhage or nasal methylamino-ethanol congestion. (Direct) Selective a1 Vasoconstrictor given orally Used in ttt of hypotension, nasal congestion, glaucoma. No effect on β receptors, so don’t cause Phenylephrine increase in heart rate and cardiac 1-(3-Hydroxyphenyl)-2-methylamino-ethanol output Polar, so no CNS side effects (Direct) Selective a1 Used during surgery to maintain adequate arterial blood pressure It does not stimulate CNS. Methoxamine (Direct) Selective β (β1 & β2) Use for relief of bronchospasms, bronchial asthma dangerous adverse effect, sometimes made use in the treatment of heart block use by inhalation, injection, sublingual Isoproterenol Short duration 1-(3,4-Dihydroxyphenyl)-2-(isopropyl amino)- ethanol  (Direct) Selective β2 more effective than isoproterenol taken orally longer duration (Direct) Selective β2 very long acting (12 hours) due to lipophilic Phenyl alkyl substituent on nitrogen Salmeterol (Direct) Selective ß1 dopamine analogue used as a cardiac stimulant after surgery used in congestive heart failure Dobutamine a1-agonists vasoconstrictors used in Ophthalmic, nasal decongestants Xylometazoline Oxymetazoline Naphazoline Selective a2-agonist Stimulation of central a2, (I1) in the CNS causing inhibition of sympathetic output used for management of hypertension Clonidine hydrochloride  Selective a2-agonist (Centrally acting) inhibit sympathetic nervous system output Lower blood pressure no longer used due to its CNS side effects as depression, anxiety and Methyl dopa Parknsonism. Indirect Adrenergic agents The S-isomer is more potent than the R- isomer, so called “dextroamphetamine” Suppresses appetite Treatment of (ADHD) Amphetamine Treatment of narcolepsy Propylhexedrine(relief nasal congestion) the most active of the four isomers used orally, I.V., I.M., and topically nasal decongestant dilate the pupil or the bronchi. effective for asthma, hay fever, and urticaria D-(-)-Ephedrine It acts Indirect It is the (S,S) diastereomer of ephedrine used as nasal decongestant. L-(+)-Pseudo-ephedrine Nasal decongestants Non-selective (α1 and α2) irreversible inhibitor to α-adrenergic, forms a permanent covalent bond causes vasodilatation in blood vessels, due to antagonistic effect at the α-1 alleviating the sympathetic effects of Phenoxybenzamine pheochromocytoma  non-selective α-antagonist Reversible Its primary action is vasodilatation produces tachycardia Used in pheochromocytoma. Tolazoline Selective a1-antagonist causes peripheral vasodilation First dose phenomenon is characterized by dizziness, palpitation and syncope. Prazosin Selective a1-antagonist structure difference is reflected by alteration in rate of metabolism that results in improvement of bioavailability up to 90% compared to the 55% of prazosin Terazosin hydrochloride Selective ß1 -blockers Short duration of action CNS side effects Short duration of action Long duration of action Carvedilol Labetalol Mixed a/β-Blockers R(OH),R(CH3) is the active β-blocker S(-)enantiomer is both an a and nonselective β -blocker R(OH),S(CH3) diastereomer is predominantly an a1 R(+) enantiomer is an a1- blocker blocker. Effective in ischemic heart disease S(OH),S(CH3) , S(OH),R (CH3) are both inactive  antihypertensive agents Centrally Acting Sympatholytics inhibition of sympathetic output Stimulation of a2 , I1 receptor in CNS antihypertensive agents Centrally Acting Sympatholytics highly selective for the I1 receptor low affinity for a2 control blood pressure effectively without the adverse effects antihypertensive agents Guanethidine Adrenergic Neuron Blocking Agents at high doses >> prevent release of norepinephrine at usual doses>> "false Guanadrel neurotransmitters antihypertensive agents Vasodilators Arterial activating (opening) ATP-modulated potassium channel. Hydralazine hydrochloride antihypertensive agents Vasodilators Arterial The N-oxide function is integral to the drug's activity long-term therapy in patients with hypertension unresponsive to standard therapy shown some activity in alopecia  antihypertensive agents Vasodilators Arterial Parenteral , used in hypertensive emergencies Side effect: Hyperglycemia. Diazoxide antihypertensive agents Vasodilators due to release of NO-group Arterial and venous most powerful vasodilator given by IV infusion Toxicity due to accumulation of thiocyanate Sodium nitroprusside Renin Inhibitors peptidomimetics Aliskiren the first orally active inhibitor of ACE. Sulfhydryl-containing Inhibitors used in the treatment ofessential and renovascular hypertension side effects: Skin rashes, Dry cough, Taste disturbances ACE Inhibitors Dicarboxylate-containing Inhibitors 10-fold more potent than captopril excellent intravenous activity Enalaprilrate  ACE Inhibitors Phosphonate-containing Inhibitors more potent than captopril but less potent than enalaprilat inhibiting the conversion of angiotensin I to angiotensin II fosinoprilat non-peptide angiotensin II receptor antagonist show selectivity for this receptor subtype (A1) More binding affinity and lipid solubility than S-8308 Losartan Phenylalkylamines (e.g. verapamil). S(-) is more active than R(+) Benzothiazepines (e.g. diltiazem) SAR: Cis arrangement of acetyl ester and p-methoxyphenyl CCB 1,4-dihydropyridines