Lecture presentation

1. ADRENERGIC DRUGS
For BSN 1stYear
Dr. Pravin Prasad
2ndYear Resident, MD Clinical Pharmacology
Maharajgunj Medical Campus
14th March, 2017 (Chaitra 1, 2073),Tuesday

2. We will be discussing….
■ Overview of AdrenergicTransmission
■ 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
IP3/DAG (↑), cAMP (↓), K+
channel (↑)
cAMP (↑), Ca2+
channel (↑)

5. Alpha (α) adrenergic receptors
α1 α2
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
β1 β2 β3
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
sympathomimetic
s
Mixed action
sympathomimetics
Adr, NA, Iso,
Phenylephrine,
Xylometazoline,
Salbutamol
Tyramine,
Amphetamine
Ephedrine,
Mephentermine

11. Adrenergic drugs: overall actions
Heart
(β1)
• 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 (α1 and α2): cutaneous, mucous
membrane, renal beds
• Vasodilation (β2): 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 (β1 &β2)
• Adr: (slow i.v.) rise in systolic, fall in diastolic, mean BP
rises

13. Adrenergic drugs: overall actions
Respiration
• Adr & Iso: potent bronchodilator (β2)
• Adr: Bronchial mucosa decongestant
• Toxic dose of Adr: pulmonary edema
Eye
• Mydriasis (α1: 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 (D1 and D2) and adrenergic (α and β1)
agonist
■ Increases g.f.r. and exerts natriuretic effects (D1)
■ 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 β1 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 α1 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 α2 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!!