Pharmacology in english class 9th, Cheat Sheet of Pharmacology

Download Pharmacology in english class 9th and more Cheat Sheet Pharmacology in PDF only on Docsity! SYMPATHOMIMETIC SYSTEM Nehal V. Trambadiya Asst. Professor Smt. N. M. Padalia Pharmacy College CATECHOLAMINES • Norepinephrine and dopamine are synthesized in axonal terminals • Epinephrine is released by the adrenal medulla Release of Catecholamine: • Release of catecholamine take place by exocytosis and all the vesicular content are poured out. • Indirect acting sympathomimetic amines for example tyramine also induce the release of NA. Uptake of Catecholamines: • NA release from nerve terminal is recapture. • Axonal uptake: • Active amine pump (NET) is present at the neuronal membrane which transport NA by Na+ coupled mechanism. • Take up NA at a higher rate than adrenaline and known as uptake 1. • This uptake is important for terminating post junctional action of NA. • This pump is inhibited by cocaine, desipramine. • Vesicular uptake: • The membrane of intracellular vesicles has another amine pump Vesicular monoamine transporter (VMAT-2) transports CAs from cytoplasm to storage vesicle. • Transport monoamine by exchanging with H+ ion. • Vesicular NA is constantly leaking out into axoplasm and is recapture by this mechanism. • This carrier also take Dopamine for further synthesis to NA. • Important in maintaining NA content of the neuron. • This uptake is inhibited by reserpine. • Adrenergic receptor : • G protein couple receptor, • Increase or decrease cAMP or IP3 / DAG. • Adrenergic receptor are of two type α and  • An α receptor again classified into α1 and α2.   receptor again classified into 1 , 2, , 3 Table 9.3: Differences between a, and 02 receptors Oh a Location Function subserved Selective agonist Selective antagonist Effector pathway Postjunctional on effector organs GU Smooth muscle-contraction Vasoconstriction Gland—secretion Gut—telaxation Liver—glycogenolysis Heart—arrhythmia Phenylephrine, Methoxamine Prazosin IP;/DAG T Phospholipase A; T—PG release Prejunctional on nerve ending (04), also postjunctional in brain, pancreatic B cells and extrajunctional in certain blood vessels, platelets Inhibition of transmitter release Vasoconstriction Decreased central sympathetic flow Decreased insulin release Platelet aggregation Clonidine Yohimbine, Rauwolscine cAMP | K* channel T Ca channel J or T IP,/DAG t GU: Genitourinary Table 9.2: Differences between B,, 8, and B; receptors by by Bs _ Location Heart, Bronchi, blood Adipose tissue JG cells in kidney vessels, uterus, liver, gi.t,, urinary tract, eye . Selective agonist Dobutamine Salbutamol, terbufalin BRL 37344 3. Selective antagonist Metoprolol, 11118551 CGP 20712A (also B,) Atenolol a-methyl propranolol ICT 118551 (also 8;) Potency of NA as Moderate Weak Strong agonist  Nasal decongestant : Naphazoline, Phenyl propanolamine, Xylometazoline, oxymetazoline, pseudoephedrine, phenylephrine  CNS stimulant : Amphetamine, Dexamphetamine, methamphetamine  Anorectics: Fenfluramine, dexfenfluramine, sibutramine  Uterine relaxant and vasodilators: Ritodrine, Salbutamol, Terbutaline, isoxsuprine • (c) According to mechanism of action : • 1 Directly acting :  Specific α adrenoceptor agonist : Noraderaline, Phenylephrine  Specific  adrenoceptor agonist : Isoprenaline  Mixed agonist : Adrenaline  α1 agonist : Mithoxamine, Phenylephrine  α2 agonist : Clonidine, Guanabenz  1 agonist : Dobutamine, xamoterol  2 agonist : Salbutamol, Terbutaline, salmeterol  3 agonist : BRL – 37344, AD - 9677 • 2 Indirectly acting : • These drugs do not act directly on the receptors but affect adrenergic transmission to produce noradrenaline at the site or increase availability of noradrenaline at the site of action. I. Drugs that release the transmitter : tyramine, Amphetamine, Methamphetamine, Methyphenidate, Pemoline II. Uptake blockers : cocaine, desipramine (blocking uptake 1 ) corticosteroid (blocking uptake 2) Reserpine (blocking granular uptake) III.Enzyme inhibitors : tranylcypromine (MAOI) tolcapone and entacapone (COMTI) • Blood pressure : • NA increase systolic ,diastolic and mean BP • Respiratory System: • Adrenaline and isoprenaline produce a powerful relaxation of smooth muscle of bronchi, through stimulation of 2 adrenoceptors. • Adrenaline produce transient apnoea due to inhibition of respiratory centre. • High dose of Adrenaline cause pulmonary edema by shifting blood from systemic to pulmonary circuit. • Noradrenaline does not produce any significant action. • GIT: • Both α and  adrenoceptor are inhibitory in nature. • Produce relaxation of smooth muscle. • Thus decrease in tone and motility. • Eye: • Mydriasis occur due to contraction of radial muscle of iris (α1). • This effect is minimum after topical application because Adrenaline penetrate cornea poorly. • Intraocular tension tends to fall in wide angle glaucoma PHARMACOKINETICS • Adrenaline, Noradrenaline, isoprenaline are not absorbed from GIT. • So, it is not given orally. • Isoprenaline sometimes given by sublingual route, I.V. • Metabolized by MAO or COMT. • Final product is 3-methoxy 4-hydroxy mandelic acid which is excreted in urine. Contraindication • Not given during anaesthesia with halothane because risk of arrythmias. • Not given patient receiving  blocker because increase in blood pressure. • Adrenaline is contraindicated in hypertensive, hyperthyroid, angina patient. Therapeutic uses 1. Vascular uses Hypotensive state Along with local anaesthetics, action prolonged Control of local bleeding (hemostatic) . Nasal decongestant 2 Cardiac uses Cardiac arrest (Cardiac resuscitation) Partial or complete A-V block CCF 3. Bronchial asthma • Synthetic Catecholamines • Dobutamine : • Act on 1 adrenoceptor in the heart. • Little or no action on 2 or alpha receptor. • Does not release noradrenaline. • Increase the contractile force of the heart raising the stroke volume and cardiac output. • Without increase in heart rate. • Increase oxygen demand to the heart to a lesser extent. • Produce vasodilation of renal and mesenteric vessels. • Systemic vascular resistance is decreased • Has short duration of action. THERAPEUTIC USES • Management of acute cardiac decompensation due depressed contractility resulting from organic heart disease on cardiac surgery. • Cardiac shock Adverse effect and contraindication : • Premature ventricular beat • Less frequently headache, palpitation , nausea, anginal pain. • Contraindication include idiopathic hypertrophic subaortic stenosis, pre existing hypertension, cardiac valvular disease. Non-catecholamines 1 agonists • Phenylephrine 1 agonist Increases BP and peripheral resistance uses:- nasal decongestant, mydriatic, hypotension or shock. • Naphazoline, Oxymetazoline, Xylometazoline nasal decongestants in rhinorrhoea, in epistaxis Non-catecholamines beta2 agonists Salbutamol, Pirbuterol • Beta2 agonist • Relaxes Bronchi, uterus, minimal cardiac effects • Being non-catecholamines, not degraded by COMT, thus longer action • Uses:- asthma, to arrest premature labour • S/e:- tremors in hands, palpitations • Pirbuterol – same as salbutamol Terbutaline • Beta2 selective bronchodilator • Not metabolised by COMT, longer acting • Relieves bronchospasm • Also in COPD, premature labour, urticaria(used along with ketotifen) • Inhaled powder may harm tooth enamel, cause tooth erosion Non – catecholamine beta3 agonists BRL-37344 and AD-9677 • Beta3 agonist • Anti obesity drugs Sympathomimetics having mixed actions Ephedrine • Non-catecholamine alkaloid obtd from Ephedra Vulgaris • Directly acts on receptors and releases NE from neurns. Not destroyed by MAO and COMT< therefore longer acting than E and NE • Crosses BBB, powerful CNS stimulant action • Used to treat hypotension that may occur with spinal anesthesia. • S/e:- Hypertension, insomnia, tachycardia • Pseudoephedrine is stereo isomer of ephedrine, used as nasal decongestant in oral formulations • Orlistat : • Pancreatic and gastric lipase inhibitor. • Inhibit digestion and absorption of triglycerides. • Absorption of cholesterol, fat soluble vitamin is impaired. • Weight loss seen in clinical trial. • Use in management of obesity and type II diabetes • Contraindication include chronic malabsorption syndrome, pregnancy, breast-feeding. • Side effect include nasal congestion , headache, abdominal pain, fluid motions, steatorrhoea, vitamin deficiency Sibutramine • Inhibits reuptake of NE and 5-HT at hypothalamic sites that regulate food intake. • Reduces food intake • Cause dose-dependant weight loss. • Increases thermogenesis mediated by sympathetic nervous system. • S/e:- drug interactions, CVR effects. Pharmacological action Propanolol • Cardiovascular system : Cause decrease in heart rate, myocardial contractility, conduction velocity and cardiac output • Because of decrease in workload by heart , so decrease in oxygen demand. • Automaticity of heart is suppressed because of inhibition of latent pacemaker. • Produce fall in BP. • Postural hypotension is least troublesome as is seen with α blocker. 2. Respiratory system : • Propranolol increase bronchial resistance by blocking 2 receptor. • Hence it is contraindicated in asthmatic patient. • Specific 1 adrenoceptor blockers are prefer in patient with bronchial asthma in the treatment of hypertensinon 3. Local anesthetics : • Is potent local anesthetics as lignocaine. • It is not use because of its irritant property. 4. Eye : • Reduce formation of aqueous humour. • Thus reduce intraocular pressure in patient with glaucoma. 5. Uterus : • Relaxation of uterus by 2 agonist is blocked by propranolol. • Normal uterus activity is not altered. 6. CNS : • Produce sedation , disturbing in sleep after long term use. • Propranolol supress anxiety in short term stressful states. Interaction : 1. Due to Pharmacokinetic reasons : • Al3+ salt, cholestyramine, cholestipol decrease the absorption of  blocker. • Enzyme inducer decrease its plasma concentration. • Cimetidine and hydralazine may increase its bioavailability.   – blocker impair the clearance of lignocaine and thus increase its bioavailability. 2. Due to pharmacodynamic reasons : • Digitalis and verapamil cause additive depression of SA node, AV conduction and lead to cardiac arrest. • Indomethacin and aspirin can oppose the antihypertensive effect of  blocker. • Adverse effect and contraindication ; • Bronchoconstriction • Cardiac failure • Hypoglycemia • Bradycardia • Cold extremities • Rebound hypertension and anginal attacks after sudden withdrawal • Adverse serum lipid profile • CNS effect such as fatigue, depression Pindolol and Oxyprenolol • Possess inherent intrinsic sympathomimetic activity on beta1 and beta2 receptors. • Benefits of this property are:- 1. Lesser bradycardia and myocardial depression. Can be used in patients prone to bradycardia and in those with low cardiac reserve as in CHF. Because of beta agonistic action, less troublesome to asthamatics. 2. Less likely rebound hypertension. Beta action prevents supersensitivity of upregulated beta receptors. 3. Lipid profile less worsened, compared to propranolol • Disadvantage of intrinsic sympathomimetic activity • Can not be used in migraine as intrinsic 2 agonist activity dilate cerebral blood vessel. • Less suitable for secondary prophylaxis of MI. • Membrane stabilising activity in Propranolol, oxprenolol, acebutolol contributes to antiarrhythmic action • Lipid insolubility ( atenolol, sotalol) • Less likely to produce central effects. • Are incompletely absorbed orally. • Selective Beta1 blockers( cardioselective beta blockers) • Metaprolol, Atenolol, Esmolol, Betaxolol Advantage of cardioselective 1 blocker over non selective : • Safe in asthmatic patient. • Safe in diabetes , cause less inhibition of glycogenolysis during hypoglycaemia. Safe in patient with peripheral vascular disease. • Less deleterious effect on lipid profile. Disadvantage of cardioselective : • Rebound hypertension after abrupt withdrawal. • Ineffective in controlling essential tremors. • Nebivolol:- highly selective beta1 blocker plus NO donor, produces vasodilatation and has a potential to improve endothelial function which may delay atherosclerosis • Has rapid hypotensive action. Used in Hypertension and CHF. Selective B2- blocker • Butoxamine and ICI-118551 • Experimental tools Mixed alpha beta blocker eg. Labetalol, Carvedilol • Labetalol blocks 1, 1, 2, partial agonist at 2 ( causes peripheral vasodilatation and bronchodilation), inhibits NE uptake, has vasodilator capacity, cause fall in BP, s/e:- postural hypotension , hepatotoxicity Uses:- hypertension in elderly, pheochromocytoma, to control rebound hypertension after clonidine withdrawal. Reversible non selective a blockers : • Phentolamine and Tolazoline • Similar affinity for α1 as well as α2 receptor. • Pharmacological effect : 1. CVS : • Produce vasodilation, decrease in peripheral vascular resistance. • Resultant fall in BP stimulate baroreceptor reflex causing sympathetic discharge. • Block presynaptic α2 receptor which promote neuronal release of NE to produce more tachycardia and palpitation. • Pretreatment with α1 blocker prevent pressor response of adrenaline. 2. Other effect : • Miosis means loss of tone of radial muscle of iris • Nasal stuffiness due to vasodilation and congestion of nasal mucosa. • Improve urine flow rate due to smooth muscle relaxation of bladder neck and prostate. • Failure of ejaculation due to inhibition of contraction of vas deference and ejaculation duct. • Therapeutic uses : • For diagnosis and management of Pheochromocytoma • For peripheral vascular disease. • Prevent dermal necrosis • Treatment of hypertension • Adverse effect • Orthostatic hypotention, • Tachycardia • Nasal stuffiness • Contraindicated in CAD and angina pectoris. • Thymoxamine (opilon) • Competitive alpha adrenoceptor antagonist • Has weak antihistaminic property. • Use to treat peripheral vasospastic disorders like ACROCYANOSIS and RAYNAUD’S DISEASE. • Given orally or intravenously. • Overdose cause palpitation, hypotension, headache. Irreversible Non-selective : • Phenoxybenzamine bind covalently to α1 and α2 receptor causing irreversible blockage of this receptor. • Pharmacological action : • Cause vasodilation, decrease in peripheral resistance and tachycardia. • Causing marked postural hypotension. • Therapeutic uses : • Treatment of pheochromocytoma • Treatment of benign prostatic hyperplasia • Treat haemorrhagic and endotoxic shock • To control manifestations of autonomic hyperreflexia in patients with spinal cord transection. • Terazosin and Doxazosin have longer duration of action. • Used in Hypertension and BPH( Terazosin more effective than Finasteride- drug which inhibits conversion of testosterone to dihydrotestosterone, arrests growth and reduce size of prostrate gland) • Tamsulosin: • Uroselective α1A and α1D blocker. • Does not cause significant change in BP or HR. No CVR s/e • Dizziness and retrograde ejaculation (failure of ejaculation) are side effects. • Plasma half life is 6-9 hr. α2 adrenergic blockers : • Yohimbine , Mianserine and Idazoxan • Yohimbine can cross BBB. • Also has 5-HT antagonist action. • Use to treat autonomic insufficiency (by blocking α2 presynaptic receptors), Sexual dysfunction, diabetic neuropathy and postural hypotension • Reverses action of Clonidine • Idazoxan has membrane stabilising action • Mianserine used as antidepressant 2. Alpha adrenergic agonist : • Adrenaline, dipivefrine, apraclonidine, brimonidine 3. Prostaglandin analogues : • PGF2 lower i.o.t without inducing ocular inflammation. • Increase out flow of aqueous humor . • For eg. Latanoprost • Needs only once dosing, has replaced beta blocker. 4. Carbonic anhydrous inhibitor : • Reducing aqueous formation by generation of bicarbonate ion in the ciliary epithelium. • For eg. Dorzolamide, acetazolamide 5. Miotics : • Topical pilocarpine and/or antiChEs • Lower i.o.t by increasing ciliary muscle tone. • Levobunolol:- Used for open angle glaucoma. • Introduced as once daily alternative to Timolol . Ocular and systemic effects are similar, only duration of action is longer. (B) Angle closure (narrow angle, acute congestive ) glaucoma : • Occur with narrow iridocorneal angle and shallow anterior chamber. • i.o.t remain normal until an attack is precipitated. • i.o.t rises to very high value (40-60 mmHg) • Following drugs may be used : 1. Hypertonic mannitol (20%) or glycerol (10%) 2. Acetazolamide 3. Miotic 4. Topical beta blocker 5. Apraclonidine • Drugs only terminate the attack of angle closure glaucoma. • Definitive treatment is surgical or laser iridotomy.