Adrenergic agonists and antagonists Hashem Mansour

THE ADRENERGIC NEURON Adrenergic neurons release norepinephrine as the primary neurotransmitter. These neurons are found in the central nervous system (CNS) and in the sympathetic nervous system. Drugs that activate adrenergic receptors are termed sympathomimetics.

Neurotransmission at adrenergic neurons

Adrenergic receptors (adrenoceptors) The receptors are divided into two groups alpha (α) and beta (β) receptors. These are further subdivided to α1, α2, β1 and β2 This depend on the responses to epinephrine, norepinephrine, and isoproterenol

Physiological effect of receptor activation

Mechanism of action of adrenergic agonists (sympathomimetics) Direct : epinephrin Indirect : cocain Mixed : pseudoephedrin

ADRENERGIC AGONISTS A. Catecholamines: such as epinephrine, norepinephrine, and dopamine B. Noncatecholamines : phenylephrine, ephedrine .

DIRECT-ACTING ADRENERGIC AGONISTS epinephrin and Norepinephrine At low doses, β effects (vasodilation) on the vascular system predominate, whereas at high doses, α effects (vasoconstriction) are the strongest. 1. Actions: a. Cardiovascular: positive inotrope and chronotrope Kidney cause renin release. increase systolic blood pressure.

DIRECT-ACTING ADRENERGIC AGONISTS epinephrin and Norepinephrine Respiratory: bronchodilation (β2 action). Hyperglycemia: Epinephrine has a significant hyperglycemic effect because of increased glycogenolysis in the liver and decrease insulin release. Lipolysis: Epinephrine initiates lipolysis.

pharmacokinetics

Adverse effects Restlessness, palpitation, anxiety, tremor. Rise in BP leading to cerebral haemorrhage, ventricular tachycardia/fibrillation, angina, myocardial infarction.

Contra indication Adrenalin is contraindicated in hypertensive, hyperthyroid and angina patients. Adrenalin should be used very cautiously in patients with heart disease. It should not be given to patients receiving β blockers (marked rise in BP can occur).

Oxymetazoline Stimulates α adrenergic receptors. Over-the-counter short-term nasal spray decongestants, as well as in ophthalmic drops. Rebound congestion and dependence are observed with long-term use.

Albuterol and terbutaline Are short-acting β2 agonists used primarily as bronchodilators. Albuterol is the β2 agonist of choice for the management of acute asthma symptoms. Side effects: tremor, restlessness, and anxiety, tachycardia or arrhythmia especially in patients with underlying cardiac disease.

THERAPEUTIC USES Hypotensive states (shock NA) Adrenalin is the drug of choice for anaphylactic life-saving. Control of local bleeding from skin, mucous membranes, tooth socket, epistaxis

Therapeutic uses Nasal decongestant In colds, rhinitis, sinusitis Cardiac arrest Bronchial asthma ( β2 stimulants). Uterine relaxant Selective β2 stimulants, used to postpone labour.

ADRENERGIC RECEPTOR ANTAGONISTS These are drugs which antagonize the receptor action of adrenaline and related drugs.

α ADRENERGIC BLOCKING DRUGS Phenoxybenzamine, Chlorpromazine, Prazosin, Tamsulosin, Alfuzosin.

GENERAL EFFECTS OF α BLOCKERS Reduces peripheral resistance and cardiac output → fall in BP. Nasal stuffiness and miosis. Intestinal motility is increased Reduce renal blood flow → increase in blood volume. Tone of smooth muscle in bladder trigone, sphincter and prostate is reduced → urine flow in patients with benign hypertrophy of prostate (BHP) is improved.

Adverse effects of alpha blockers

USES OF α BLOCKERS Hypertension : Prazosin is primarily used as an antihypertensive. Pheochromocytoma Benign hypertrophy of prostate (BHP) doxazosin and tamsulosin Raynaud’s phenomenon: symptomatic relief when vasoconstriction is prominent

β ADRENERGIC BLOCKING DRUGS CLASSIFICATION Nonselective (β1 and β2) Propranolol, Sotalol, Timolol, Labetalol, Carvedilol. Cardioselective (β1) Atenolol, Bisoprolol.

PHARMACOLOGICAL ACTIONS 1. Heart decreases heart rate, force of contraction and output (c.o.). 2. Blood vessels: vasodilatation 3. Respiratory tract Increases bronchial resistance . 4. Metabolic Increase in plasma free fatty acid levels. It also inhibits glycogenolysis 5. Eye Reduces secretion of aqueous humor: i.o.t. is lowered.

ADVERSE EFFECTS AND CONTRAINDICATIONS Bradycardia, worsen CHF. Can precipitate life-threatening attack of bronchial asthma: contraindicated in asthmatics. Worsening of angina and even sudden death can occur. Propranolol is contraindicated in partial and complete heart block: arrest may occur. Sleep disturbances, nightmares.

Cardioselective β1 BLOCKERS Atenolol and bisoprolol. More selective in blocking (β1) than (β2) receptors. Have lower propensity (tendency) to cause bronchoconstriction. Bradycardia and depression of contractility at rest are not prominent.

Uses of beta blockers Timolol: used topically in the eye for glaucoma. Hypertension: β blockers for mild antihypertensives. Angina pectoris All β blockers benefit angina of effort Cardiac arrhythmias β blockers suppress extrasystoles and tachycardias.

Uses of beta blockers Secondary prophylaxis of MI: bisoprolol Congestive heart failure: bisoprolol. Thyrotoxicosis: Propranolol rapidly controls symptoms. Migraine Propranolol is the most effective drug for chronic prophylaxis of migraine

α + β ADRENERGIC BLOCKERS Labetalol It is the first adrenergic antagonist capable of blocking both α and β receptors. Used in treatment of emergency hypertension

Impact in physiotherapy Sympathomimetic drugs are prescribed in the treatment of upper and lower respiratory dysfunctions Sympatholytic drugs are prescribed in the treatment of various cardiovascular disorders

CLINICAL RELEVANCE FOR REHABILITATION Adverse Drug Reactions Central nervous system: restlessness and insomnia. Alpha agonists may increase blood pressure and precipitate angina pectoris in patients during aerobic rehabilitation activities. Beta2 agonists may increase heart rate and precipitate angina pectoris or cardiac dysrhythmias. Orthostatic hypotension is a problem with many of the sympatholytic drugs. Bronchoconstriction is a problem with the β-receptor antagonists.

Effects Interfering with Rehabilitation Orthostatic hypotension may cause patients to faint when transferring from sitting or supine positions to standing, exiting from a warm aqua therapy area, or if aerobic exercise is terminated without an appropriate cool-down period. Dyspnea may decrease the aerobic capacity of patients. Heart rate cannot be used as a marker of exertion for patients taking β-receptor antagonists.

Possible Therapy Solutions To prevent fainting associated with orthostatic hypotension, assist patients with positional changes and when exiting a warm pool. Always provide a cool-d own period following a period of exercise. Allow increased time to complete aerobic tasks to prevent dyspnea and account for depressed cardiac activity.

Possible Therapy Solutions Check blood pressure and heart rate prior to and following aerobic activities. Monitor heart rate during aerobic activities. Potentiation of Functional Outcomes Secondary to Drug Therapy Patients with asthma or other respiratory dysfunction may benefit from the use of β2 agonists prior to aerobic activities..