1. Adrenergic agonists and antagonists
Hashem Mansour

2. 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.

3. Neurotransmission at adrenergic neurons

4. 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

5. Physiological effect of receptor activation

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

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

9. 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.

10. 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.

11. pharmacokinetics

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

13. 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).

14. 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.

15. 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.

16. 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

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

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

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

21. 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.

22. Adverse effects of alpha blockers

23. 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

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

25. 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.

26. 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.

27. 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.

28. 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.

29. 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

30. 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

31. 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

32. 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.

33. 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.

34. 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.

35. 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..