Adrenergic drugs 2017

Lecture presentation

1. Adrenergic Drugs For BSN 1 st Year Dr. Pravin Prasad 2 nd Year Resident, MD Clinical Pharmacology Maharajgunj Medical Campus 14 th March, 2017 (Chaitra 1, 2073), Tuesday

2. We will be discussing…. Overview of Adrenergic Transmission Adrenergic receptors Adrenergic Drugs

3. Adrenergic Transmission

4. Adrenergic Receptors Alpha ( α ) receptors Beta( β ) receptors Relative potency of agonists Adrenaline ( Adr ) ≥ Noradrenaline (NA )> Isoprenaline ( Iso ) Iso > Adr > NA Antagonists Phenoxybenzamine Propanolol Coupling Protein Go/ Gq / Gi Gs Effector Pathway IP 3 /DAG ( ↑), cAMP ( ↓ ), K + channel ( ↑) cAMP ( ↑ ), Ca 2+ channel ( ↑ )

5. Alpha ( α ) adrenergic receptors α 1 α 2 Location Post-junctional on effector organs Prejunctional Post-junctional Extra-junctional Functions GU smooth muscle contraction Vasoconstriction ↑ glandular secretion Relaxation of gut Glycogenolysis in liver Arrhythmia in heart Inhibitor of transmitter release Vasoconstriction Decreased sympathetic flow Decreased insulin release Platelet aggregation

6. Beta( β ) adrenergic receptors β 1 β 2 β 3 Location Heart JG cells in kidney Bronchi Blood vessels Uterus Liver Gastro-intestinal tract Urinary tract Eye Adipose tissue

7. Adrenergic responses Alpha ( α ) receptors Beta ( β ) receptors Rise in BP Fall in BP Little action on heart, arrhythmia at high doses ↑ rate, force and conduction velocity of heart - Bronchodilation Mydriasis, decreased aqueous secretion No effect on iris, relaxation of ciliary muscles, enhanced aqueous secretion

8. Adrenergic responses Alpha ( α ) receptors Beta ( β ) receptors Intestinal relaxation, contraction of sphincters Intestinal relaxation Bladder trigone contraction Detrusor relaxation Uterus contraction Relaxation

9. Adrenergic responses Alpha ( α ) receptors Beta ( β ) receptors Splenic capsule contraction Relaxation NM transmission facilitated Active state prolonged in fast contracting fibres, abbreviated in slow contracting fibres Decreased insulin secretion Augmented insulin and glucagon secretion

10. Adrenergic Drugs: Types Direct Acting Sympathomimetics Indirect acting sympathomimetics Mixed action sympathomimetics Adr , NA, Iso , Phenylephrine, Xylometazoline, Salbutamol Tyramine, Amphetamine Ephedrine, Mephentermine

11. Adrenergic drugs: overall actions Heart ( β 1 ) Increases HR Activates latent pacemakers – arrhythmia at higher doses Force of contraction, cardiac output and oxygen consumption- increased Increased conduction velocity – may overcome partial heart block

12. Adrenergic drugs: overall actions Blood vessels Vasoconstriction ( α 1 and α 2 ): cutaneous, mucous membrane, renal beds Vasodilation ( β 2 ): skeletal muscles, liver, coronaries Action more marked in arterioles and precapillary sphincters Blood Pressure NA: rise in systolic, diastolic and mean BP ( α ) Iso : rise in systolic BP, marked fall in diastolic BP ( β 1 & β 2 ) Adr : (slow i.v. ) rise in systolic, fall in diastolic, mean BP rises

13. Adrenergic drugs: overall actions Respiration Adr & Iso : potent bronchodilator ( β 2 ) Adr : Bronchial mucosa decongestant Toxic dose of Adr : pulmonary edema Eye Mydriasis ( α 1 : radial muscle contraction; poor with Adr ) Reduced aqueous formation and outflow facilitated

14. Adrenergic drugs: overall actions Metabolic Causes glycogenolysis : hyperglycaemia, hyperlactacidemia Lipolysis: rise in plasma free fatty acids, calorigenesis Transient hyperkalemia followed by hypokalemia

15. Adrenaline: Adverse Effects s.c. / i.m . injection: Transient restlessness, headache, palpitation, anxiety, tremor and pallor Marked rise in BP leading to CVA, VT/VF, angina Large doses or inadvertent i.v. injection of Adr  myocardial infarction

16. Adrenaline: Contraindications Should not be given: During general anaesthesia (halothane): risk of arrhythmia Patients receiving β blockers : marked rise in BP Contraindications: Hypertension Hyperthyroid Angina patients

17. Therapeutic Classification: Adrenergic Drugs Therapeutic Class Examples Pressor agents Noradrenaline, Phenylephrine, Ephedrine, Methoxamine, Dopamine, Mephentermine Cardiac stimulants Adrenaline, Dobutamine , Isoprenaline Bronchodilators Isoprenaline , Salmeterol, Salbutamol, Formeterol , Bambuterol , Terbutaline Nasal decongestants Phenylephrine, Naphazoline , Xylometazoline , Pseudoephedrine, Oxymetazoline , Phenylpropanolamine CNS stimulants Amphetamine, Methamphetamine, Dexamphetamine Anorectics Fenfluramine , Sibutramine , Dexfenfluramine Uterine relaxant Ritodrine , salbutamol, Isosuxprine , Terubtaline

18. Dopamine Dopaminergic (D 1 and D 2 ) and adrenergic ( α and β 1 ) agonist Increases g.f.r. and exerts natriuretic effects (D 1 ) Normal doses: raises cardiac output and systolic BP Moderately High Doses: Positive inotropic effect Uses Cardiogenic or septic shock Severe CHF

19. Dobutamine Derivative of Dopamine Selective β 1 agonist Uses- As an inotropic agent in pump failure accompanying: Myocardial Infarction Cardiac surgery Short term management of severe congestive heart failure

20. Ephedrine Mixed sympathomimetic drug; mainly acts indirectly Shows tachyphylaxis Effective orally Uses Mild bronchial asthma Hypotension during spinal anesthesia Occasionally for postural hypotension

21. Phenylephrine Selective α 1 agonist: raises BP due to vasoconstriction Reduces intra-ocular pressure Can be given orally as nasal decongestants Topical uses: Nasal decongestants Mydriasis without Cycloplegia Side effects:- After congestion seen

22. Nasal Decongestants α agonist- topically produces local vasoconstriction Selective α 2 agonists ( naphazoline , xylometazoline , oxymetazoline ): longer duration of action Lesser after congestion Side Effects: Initial stinging, Impairs mucosal ciliary function on prolonged use: atrophic rhinitis and anosmia; Systemic side effects: CNS depression, fall in BP

23. Indications: Vascular Uses Hypotensive states (shock, spinal anaesthesia, hypotensive drugs) Along with local anaesthetics Control of local bleeding Nasal Decongestants

24. Indications: Cardiac Use Cardiac arrest (drowning, electrocution, etc.) In combination with external cardiac massage Partial or complete A-V block Isoprenaline as temporary measure Congestive Heart Failure

25. Indications Bronchial asthma Allergic disorders (histamine mediated) Mydriatic Fundus examination Wide angle glaucoma

26. Indications Insulin Hypoglycaemia Nocturnal enuresis in children and urinary incontinence Amphetamine Uterine relaxant Ritoridine : to postpone labour Isosuxprine : threatened abortion and dysmenorrhoea

27. Indications: Central Uses Attention Deficit Hyperkinetic Disorders Amphetamine Narcolepsy Amphetamine, Modafinil Imipramine like drugs Epilepsy Amphetamines Parkinsonism Amphetamine Obesity Considered in severe obesity

28. Any queries?? Next Topic: Overview of Anti-adrenergic drugs Drugs used in Glaucoma Thank you!!