Adrenergic drugs

Adrenergic drugs

1. Adrenergic drugs S. Parasuraman, M.Pharm ., Ph.D., Senior Lecturer, Faculty of Pharmacy, AIMST University.

2. Overall actions of Adrenaline and Noradrenaline The actions of a sympathomimetic amine depend on its relative activity at different types of adrenergic receptors. Heart: Adrenaline ( Adr ) increases heart rate by increasing the slope of slow diastolic depolarization of cells in the SA node. Adr also increase the force of contraction and reduce refractory period (RP) of all types of cardiac cells acting through β 1 receptor. In higher dose Adr produce a rrhythmias and increases blood pressure (BP).

3. Overall actions of Adrenaline and Noradrenaline Blood vessels: Adrenergic drug produces both vasoconstriction (mediated through α ) and, vasodilatation (mediated through β 2) and these effect depends on drug and its dose. The direct effect of Adr / NA on cerebral vessels is not prominent .

4. Overall actions of Adrenaline and Noradrenaline Blood pressure: The effect is depends on the amine, its dose and rate of administration. NA causes rise in systolic, diastolic and mean blood pressure and it dose not cause vasodilation. NA: more specific to alpha ARs than beta ARs Adr : alpha ARs and beta ARs equal action Isoprenaline : More specific to beta ARs than alpha ARs

5. Overall actions of Adrenaline and Noradrenaline Blood pressure: Norepinephrine Heart Rate - Decreases due to reflex increase in vagal tone on SA and AV nodes. Contractile Force - Increases due to effects on beta1-ARs on myocardial cells. Total Peripheral Vascular Resistance - Increases due to activation of alpha1-ARs on vascular smooth muscle cells. Blood Pressure - Increases due to effects on total peripheral vascular resistance Isoproterenol Heart rate - increases due to activation of beta1 receptors in SA and AV nodes. Contractile force - increases due to activation of beta 1 receptors on myocardial cells. Total peripheral vascular resistance - decreases due to activation of beta 2 receptors. Blood pressure = cardiac output x total peripheral vascular resistance

6. Overall actions of Adrenaline and Noradrenaline Blood pressure: Low dose of Epinephrine Heart Rate - Increases due to beta1-ARs on SA and AV nodal tissues Contractile Force - Increases due to activation of beta1-ARs on myocardial cells Total Peripheral Vascular Resistance - Decreases due to preferential activation of beta 2 -ARs, at these doses there would be little activation of alpha 1 -ARs Blood Pressure - Similar to isoproterenol High dose of Epinephrine Heart Rate - Similar to the effects of norepinepherine Contractile Force - Increases due to beta1-ARs on myocardial cells Total Peripheral Vascular Resistance - Increases due to activation of alpha1-ARs on vascular smooth muscle cells. Blood Pressure - Increases due to activation of alpha1-ARs on vascular smooth muscle cells

7. Overall actions of Adrenaline and Noradrenaline Respiration: Adr and isoprenaline are potent bronchodilators ( β 2) but not NA. In therapeutic dose Adr can directly stimulate respiratory centre (RC) and in toxic dose it causes pulmonary edema by shifting blood from systemic to pulmonary circuit.

8. Overall actions of Adrenaline and Noradrenaline Eye: Mydriasis occurs due to contraction of radial muscles of iris (α1). Adr has complex effects on aqueous humor dynamics. Adrenaline Aqueous secretion ↓ Trabecular outflow ↑ Uveoscleral outflow ↑

9. Overall actions of Adrenaline and Noradrenaline Gastrointestinal tract: Muscle relaxation occurs through both α and β receptors. Bladder: Detrusor is relaxed (β) and trigone is constricted (α): both actions tend to hinder Uterus: Adr can contract and relax uterine muscle through both α and β receptors. Human uterus is relaxed by Adr at term of pregnancy, but at other times, its concentrations are enhanced.

10. Overall actions of Adrenaline and Noradrenaline Splenic capsule: No evident on human systemic effect. Skeletal muscle: Neuromuscular transmission is facilitated. Action on autonomic nerve endings, is mediated through α ( α1 subtype ) receptor activation on motor nerve endings augments ACh release. The direct effect on muscle fibres is exerted through β2 receptors.

11. Overall actions of Adrenaline and Noradrenaline Central nervous system: Activation of α2 receptors in the brainstem (by selective α2 agonists ) results in decreased sympathetic outflow → fall in BP and bradycardia . Clinically does not produce any marked CNS effects because of poor penetration in brain, but restlessness, apprehension and tremor may occur.

12. Overall actions of Adrenaline and Noradrenaline Metabolic effects: Adr causes glycogenolysis → hyperglycaemia , hyperlactacidaemia ( β2 ) Lipolysis → rise in plasma free fatty acid (FFA) and calorigenesis ( β2 + β3 ).

13. Therapeutic classification of adrenergic drugs Pressor agents Noradrenaline, Ephedrine, Dopamine, Phenylephrine, Methoxamine Cardiac stimulants Adrenaline, Dobutamine , Isoprenaline Bronchodilators Isoprenaline , Salbutamol (Albuterol) , Salmeterol, Formoterol, Bambuterol , Terbutaline Nasal decongestants Phenylephrine, Pseudoephedrine, Phenyl propanolamine CNS stimulants Amphetamine, Methamphetamine, Dexamphetamine Anorectics (is a dietary supplement or drug which reduces appetite) Fenfluramine , Sibutramine , Dexfenfluramine Uterine relaxant and vasodilators Ritodrine , Isoxsuprine , Salbutamol, Terbutaline

14. Therapeutic uses Vascular uses: Hypotensive states : Adrenergic drugs are one of the pressor agents used along with volume replacement for neurogenic and haemorrhagic shock. It is used in in the management of cardiogenic shock to raise BP may also increase cardiac work . Slow i.v. infusion of dopamine/ dobutamine is more appropriate in this situation. Dopamine increases cardiac contactility without causing significant tachycardia. Dobutamine has relatively more selective inotropic effect . Use of NA is practically outdated.

15. Therapeutic uses Vascular uses: Along with local anaesthetics : Adr may be enhancing spinal anaesthesia by reducing spinal cord blood flow or by its own analgesic effect exerted through spinal α2 adrenoceptors. Duration of anaesthesia is prolonged and systemic toxicity of local anaesthetic is reduced ( addition of adrenaline may increase safe limit by upto 40% ).

16. Therapeutic uses Vascular uses: Control of local bleeding Nasal decongestant: α- agonists are used as nasal decongestant. Nasal decongestants should be used very cautiously in hypertensive patients and in elderly males .

17. Therapeutic uses Vascular uses: Control of local bleeding Nasal decongestant: α- agonists are used as nasal decongestant. Nasal decongestants should be used very cautiously in hypertensive patients and in elderly males .

18. Therapeutic uses Vascular uses: Peripheral vascular diseases: Isoxsuprine (a β2 adrenoreceptor agonist that causes direct relaxation of uterine and vascular smooth muscle) is used in the management of Buerger’s disease , Raynaud’s phenomena, diabetic vascular insufficiency , gangrene , frost bite, ischaemic ulcers, night leg cramps and cerebral vascular inadequacy .

19. Therapeutic uses Cardiac uses: Cardiac arrest: Adr may be used to stimulate the heart. Partial or complete A-V block: Isoprenaline may be used as temporary measure to maintain sufficient ventricular rate. Congestive heart failure (CHF): Adrenergic inotropic drugs are not useful in the routine treatment of CHF. Controlled short term i.v. infusion of DA/ dobutamine used in acute cardiac decompensation during myocardial infarction, cardiac surgery and in resistant CHF .

20. Therapeutic uses Bronchial asthma and COPD: β2 stimulants are the primary drugs for treatment of reversible airway obstruction. Allergic disorders: Adr is a physiological antagonist of histamine which is an important mediator of many acute hypersensitivity reactions .

21. Therapeutic uses Mydriatic : Phenylephrine is used to facilitate fundus examination. It tends to reduce intraocular tension in wide angle glaucoma .

22. Therapeutic uses Central uses: Attention deficit hyperkinetic disorder (ADHD): Amphetamines have an apparently paradoxical effect to calm down hyperkinetic children . Narcolepsy: Narcolepsy is sleep occurring in fits and is adequately controlled by amphetamines . Epilepsy: Amphetamines are occasionally used as adjuvants and to counteract sedation caused by antiepileptics .

23. Therapeutic uses Central uses: Parkinsonism: Amphetamines improve mood and reduce rigidity (slightly) but do not benefit tremor. They are occasionally used as adjuvants in parkinsonism . Obesity: The anorectic drugs can help the obese to tolerate a reducing diet for short periods, but do not improve the long-term outlook .

24. Therapeutic uses Uterine relaxant : Isoxsuprine , β 2 adrenoreceptor agonist has been used in threatened abortion and dysmenorrhoea .