alpha & beta- adrenergic receptor blockers adrenoceptor blockers adrenolytics adrenergic neuron...
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Alpha & beta- adrenergic receptor blockersForm False TransmittersDeplete StorageInhibit Release & Enhance Uptake
TyrosineTyrosineDopaDANENaCOMTNETNorepinephrine (NE)2. RESERPINEDepletes Stores3. Gaunthidine Adrenergic Neuron Blockers [SYMPATHOLYTICS]a-methyl tyrosineFalse Transmitters1. METHYLDOPAAntihypertensive in PREGNANCY Enhance Uptake Inhibit ReleaseAdrenoceptor Blockers [ADRENOLYTICS]
AdrenolyticsAdrenergic Receptor Blockers
Long acting a ADRENOCEPTOR BLOCKERSPhenoxybenzaminePhentolamineIrreversibleReversibleBlocks a1& a2 Blocks a12. Before removal of Pheochromocytoma to prevent Hypertensive crisis Short acting 1. In Irreversible shockonlya1 blockerPrazosin & DoxazosinShort acting Long acting Raynauds disease: induce peripheral vasodilatationBenign prostatic hypertrophy (BPH) Rarely in hypertension & HFIndications ADRs hypotension, syncope, fluid retention, head-ache, nasal stuffiness, ejaculation & impotence.TamsulosinuroselectiveContracts bladder wall Relaxes bladder neck & sphincters
b ADRENOCEPTOR BLOCKERSSelectiveNon-SelectiveBlock b1& b2 Propranolol, TimololBlock b1>> b2 Atenolol, BisoprololAccording to extent of blocked of each type they are eitherPharmacodynamic Classification Block b & a1 Labetalol, CarvedilolPropranolol, Timolol, Atenolol, Bisoprolol, LabetalolCarvedilol2According to presence of agonistic/antagonistic action (ISA) = PARTIAL AGONISTS or only antagonistic action1
b ADRENOCEPTOR BLOCKERSAccording to their lipid solubilityPharmacokinetic Classification
LipophylicHydrophilicOral absorptionCompleteIrregularLiver metabolismYesNot 1/2 ShortLongCNS side effectsHighlowPropranolol, Timolol Labetalol > Carvedilol Atenolol, Bisoprolol
PROPRANOLOL1. Non-Selective Blocker of b1 & b2 2. Has membrane stabilizing action3. Has sedative action Actions Heart; by block b1 Inhibit heart properties cardiac outputHas antianginal effects cardiac work + O2 consumptionHas anti-arrhythmic effects excitability, automaticity & conductivity + by membrane stabilizing activityBlood Vessels [BV]; by block b2Vasoconstriction blood flow to all organs except brain cold extremities + intermittent claudications BP; by block b1 & b2 Has antihypertensive action by Inhibiting heart properties cardiac output Vasoconstriction to kidney BV: renin & aldosterone secretion Presynaptic inhibition of NE release from adrenergic nerves Inhibiting sympathetic outflow in CNS Completely absorbed70% destroyed during 1st pass hepatic metabolism, 90-95% protein bound,cross BBB Kinetics Dynamics
Bronchi: by block b2 Bronchospasm specially in susceptible patientsIntestine: by block b2 Intestinal motilityPROPRANOLOLMetabolism: by block mainly b2 In liver; Glycogenolysis HypoglycaemiaIn pancreas; Glucagon secretionIn adipocytes; Lipolysis In skeletal muscles; glycolysisOn peripheral & central nervous systems:Has local anesthetic effect tremors & anxiety Actions Cont.
PROPRANOLOLINDICATIONS Hypertension Arrhythmias; Ventricular > atrial Angina Myocardial infarction Cardioprotective death Migraine [Prophylaxis] Pheochromocytoma; used with -blockers (never alone)Chronic glaucoma Tremors Anxiety Hyperthyroidism; * Controls symptoms; tachycardia, tremors, sweating * Protects heart against sympathetic over-stimulation.* Lowers conversion rate of T4 into T3
PROPRANOLOLADRDue to block of cardiac 1-receptors: Heart failure Bradycardia HypotensionDue to blockade of 2- receptor: (only with non-selective b-blockers) Asthma, emphysema, chronic bronchitis Cold extremities & intermittent claudication Erectile dysfunction & impotence Hypoglycemia & triglycerides All b-blockers mask hypo-glycaemic manifestations devlop COMA Depression, nightmares, vivid dreams and hallucinations. Gastrointestinal disturbances. Sodium retention Hypersensitivity reactions: skin rash and fever.
PROPRANOLOL Sudden stoppage will give rise to a withdrawal manifestations: Rebound angina, arrhythmia, myocardial infarction & hypertension So drug must be withdrawn gradually to prevent its happening Contraindications Depressed myocardial function as in; Uncompensated Heart Failure, Massive Myocardial Infarction, Heart Block. Hypotension Bronchial Asthma (safer with cardio-selective -blockers). Peripheral vascular disease (safer with cardio-selective -blockers). Diabetic patients > (Type I) (specially on Insulin) for fear of hypoglycaemia)With ISA
InteractionsPROPRANOLOLPharmacodynamic Interactions Bradycardia / heart block with verapamil both induce A.V block Rebound hypertension & impaired tissue perfusion if used with cocaine, amphetamine or a-blocker overdose Attenuation of hypertensive effect with NSAIDs because they formation of vasodilating prostaglandins. HF with other cardiac depressants as quinidine. Claudications, parasthesia, etc with ergot alkaloids in migraine. Enhanced neuromuscular blockade Tubocurarine Hypoglycaemia with anti-diabetic drugs ( insulin > sulfonylureas) > Non selective -blockers
LABETALOLCARVEDILOLBlocks & 1 Rapid acting, non-selective with little ISA & local anesthetic effectDo not alter serum lipids or blood glucoseUsed in Severe hypertension in pheochromocytoma & hypertensive crisis during abrupt withdraw of clonidineMay be used pregnancy-induced hypertension but better alpha-methyldopa ADR; Orthostatic hypotension, sedation & dizziness Blocks > 1 (so more vasodialating)Non-selective with no ISA & no local anesthetic effect. Has antioxidantFavorable metabolic profile.Used effective in congestive heart failure reverses its patho- physiological changes ADR; Edema
Agents specifically indicated for hypertensionAtenolol, BisoprololAgents specifically indicated for cardiac arrhythmia PropranololAgents specifically indicated for congestive heart failure Carvedilol, BisoprololAgents specifically indicated for myocardial infarction Atenolol, PropranololAgents specifically indicated for glaucoma Timolol Agents specifically indicated for migraine prophylaxis Timolol, Propranolol