PHARMACOLOGY NOTES Your friendly paediatrician-in-making Dr.

r. SR mbbs1112 FOMS 2: DRUGS AFFECTING ANS ADRENERGIC AGONIST (SYMPATHO MIMETIC DRUG) increase sympathetic outflow or mimic sympathetic action Catecholamine Rapidly Epinephrine inactivated by Nor epinephrine Monoamine Dopamine Oxidase (MAO) Dobutamine and CatecholamineOmethyltransfera se (COMT) Not given orallyinactivation by gut Short duration of action Cant cross BBB Pharmacological Actions

Epinephrine cardiac arrest Anaphylactic shock Prolong duration of local anesthetic Nor epinephrine Not commonly used in therapy Dopamine Increase HR (beta-1) BV: renal and mesenteric vasodilation Cardiogenic shock: increase systolic BP + maintain renal blood flow (IV route) Dobutamine Increase myocardium contraction (beta-1) BV: vasoconstriction Acute cardiac failure : cardiogenic, septic shock Increase systolic BP with little change in HR (IV route) Alpha-1 selective agonist ephedrine, phenylephrine, methoxamine : vasoconstriction naphazoline, xylometazoline: local nasal decongestants pseudoephdrine, phenylpropanolamine- oral nose decongestant Alpha-2 selective baroreceptor action reduce sympathetic activity to heart and BV stimulate vagal effect on heart decrease BP Beta-2 selective agonist Salbutamol, Terbutaline Smooth muscle: bronchodilation Bronchial asthma

Non Catecholamine

1 selective agonists 2 selective agonists 2 selective agonists

can be given orally

Adrenergic Antagonist / Adrenergic receptor Blocker decrease sympathetic outflow/block sympathetic action Alpha 1 R 1 selective blocker: Receptor antagonist Prazosin Antagonist (selective) Terazosin 1,2 R Doxazosin antagonist Tamsulosin (non1,2 non selective blocker selective) Phenoxybenzamine Phentolamine Beta Receptor Antagonist 1 R antagonist 1,2 R antagonist 1,2 blocker (non selective) Propanolol Timolol Pindolol 1 selective blocker Atenolol Metoprolol } B.Asthma Esmolol Bisoprolol 1, blocker Labetolol Carvedilol -

Pharmocological Actions Alpha-1 selective blocker 1 agonist: vasoconstriction 1 blocker: vasodilation decrease BP: treat hypertension Adverse effect: Reflex tachycardia, postural hypertension Alpha-1,2 non selective blocker Phenoxybenzamine: block 2 - presynaptic Prozasin: block 1 Beta-1 Heart: decrease HR, decrease Cardiac Output Kidney: decrease rennin release AE: bradycardia Beta-2 Bronchial smooth muscle: bronchoconstriction PBV: Reflex vasoconstriction AE: worsen bronchial asthma

Hypertension decrease CO o -decrease rennin o -decrease sympathetic - Angina ,MI decrease myocardial O2 demand -Decrease HR Cardiac tachyarrythmias decrease HR

*Acetylcholine Nicotinic Receptor (somatic + Preganglionic parasympa), Muscarinic Receptor (parasympa postganglionic) Not used as drug Immediately metabolized by PChe found in liver, GIT , blood Prolonged the action of Ach : AchE inhibitor DRUGS Mechanism of Action

CHOLINERGIC RECEPTOR AGONIST Somatic and Parasympathetic ANS action M-receptor agonists

Bethanechol Pilocarpine Cevimeline

Bethanecol- Myasthenia Gravis Atropine- Block all the M receptors by using Atropine (IV injection) until sufficient amount of new AchE synthesized to metabolize accumulated Ach. REVERSIBLE Bind to AchE Inhibit Ach from binding to AchE Prolong action of Ach Few hours Reactivated AchE Carbamate + AchE Carbamylated AchE +Choline= hydrolysis (slow) = carbamate + AchE (reactivated) IRREVERSIBLE Bind to AchE Inhibit Ach from binding to AchE Last till 7 days Phosphorylated AchE is degraded very slowly but not reactivated Actioj remains until new AchE synthesised. HOW TO OVERCOME? Only at SKELETAL MUSCLE, not brain or ANS sites Pralidoxime (IV route)effective within 24 hours Atropine (IV): Block all the M receptors by using Atropine (IV injection) until sufficient amount of new AchE synthesized to metabolize accumulated Ach. -

AchE inhibitor Reversible Irreversible

Reversible Inhibitor Neostigmine- MG Pyridostigmine- MG Demecarium Rivastigmine Donepazil CI: AV Block Carbamate Irreversible Inhibitor Organophosphate Ecothiophate (therapeutic)

Cholinergic Antagonist Muscarinic Receptor Blocker/ Anti Muscarinic drugs/Anti cholinergic drugs

DRUGS Atropine Hyoscine *Oxybuthinin *Flavoxate *Valethemate ATROPINE

Block more selective at M receptor GU tract CI: Benign Prosthetic Hyperplasia

Uses OP Poisoning block Muscarinic Receptor Bradycardia/AV Block: Bradycardia is a result of excess vagal (parasympa) stimulation of myocardial where Ach is the NT at M receptor- block the M receptor by atropine Pre- Anesthetic: During anesthesia, respiratory secretions need to decreased to facilitate endotracheal intubation, block by atropine Biliary Colic: decrease the contraction of smooth muscle of biliary Opioids is also a pain reliever but it can contract the smooth muscle of biliary so use atropine Prevent motion sickness

Hyoscine

*Dicyclomine, Propantheline block selectively at M receptor of GI tract *Ipratropium Bromide- used in COPD and Bronchial Asthma (prevent release of chemical mediators)

AE of Atropine: Myadriasis, photophobia, hypotension, CNS toxicity, decrease bowel movement, difficulty in urination *use selective M receptor blocker *CNS toxicity treat by Benzodiazepines (Gnrl CNS depressant) Combined with Neostigmine- recovery of skeletal paralysis

*selective at specific sites

Nicotinic Receptor Blockers Ganglia Blockers Neuromuscular Receptor Blockers Neuromuscular Blockers Skeletal muscle relaxants

Trimethaphan

Vecuronium Tibocuararine Pancuronium *remember: Muscarinic Receptor Blocker is the important cholinergic antagonist action although there are other antagonist.*dr sabitha lecture notes pdf