1. ADRENERGIC ANTAGONITS
SAMUEL AGUAZIM ( MD)

2. Organization of Class
The effect of the SNS can be blocked either by decreasing sympathetic outflow from the brain, suppressing release of NE from terminals or by blocking postsynaptic receptors.
Adrenergic antagonists reduce the effectiveness of sympathetic nerve stimulation and effects of exogenously applied agonists, such as Isoproterenol.

3. What are adrenergic antagonists
They are drugs that bind to adrenergic receptors but do not initiate the usual intracellular response
They are divided into 2 main subdivisions
1. alpha blockers
2. beta blockers
In this chapter we will discuss alpha 2 agonist because it reduce sympathetic nerve activity and are used to treat hypertension

4. ADRENERGIC BLOCKERS ALPHA BLOCKERS Alpha 1 Blockers Nonselective Alpha
Doxazosin Phenoxybenzamine
Prazosin Phentolamine
Terazosin
Most alpha antagonists allow vasodilatation and thus, decrease blood pressure( remember a-receptor activation results in vasoconstriction)

5. DRUGS AFFECTING NEUROTRANSMITTER UPTAKE OR RELEASE
Cocaine
Guanethidine
Reserpine

6. Phenoxybenzamine Blocks alpha 1 and 2, irreversible blockade MOSTLY
Noncompetitive inhibitor
Actions - prevents Vaso-Constriction, induces a reflex tachycardia
Epinephrine reversal
Therapeutic uses :
Opposing catecholamines --pheochromocytoma
Causes vasodilation
Benign prostatic hypertrophy
Spinal cord injuries

7. SE:
Postural hypotension
Sexual dysfunction ( inhibit ejaculation)
Tachycardia
Contraindicated in ↓ coronary perfusion.

8. Phentolamine Alpha 1 and 2 blocker Competitive inhibitor
Duration of action less
Uses & SE – mostly same as Phenoxybenzamine.

9. Alpha 1 specific blockers
Prazosin
Terazosin
Doxazosin – long acting
Blockade of alpha 1 adrenergic receptors on vascular smooth muscle inhibits constriction of arterioles and veins. This results in decreased peripheral vascular resistance and lower blood pressure.
Blockade in bladder ( relaxation and decreased resistance to urine flow)

10. Actions
Dose
Uses
Side effects
CVS
Avoid high doses
HTN and prevention of urinary retention in patients who have benign prostatic hypertrophy
Orthostatic hypotension
Nasal stuffiness
Fatigue
Sexual dysfunction (less)

11. Non Selective Beta 1 selective Blockers Blockers
BETA BLOCKERS
Non Selective Beta 1 selective Blockers Blockers
Propranolol Metoprolol
Timolol Atenolol
Nadolol Esmolol
Acebutolol
Betaxolol
Labetalol - Both Alpha and Beta Blocker
Beta 1receptors found in the heart and their activation leads to an increase in HR and contractility .
Beta 2 receptor are found in SM of the respiratory tract, the uterus and blood vessels. Their activation leads to relaxation of SM

12. Non selective beta antagonists
Propranolol
Timolol
Nadolol

13. Propranolol CVS – HR ↓ , CO ↓ PERIPHERAL VESSELS – NO ALPHA ACTION
BRONCHI - ↑ CONTRACTION
SODIUM LEVELS - ↑
GLYCOGENOLYSIS -↓ GLUCAGON - ↓
BLOCKS DRUGS – Isoproterenol , &
β actions of epinephrine

14. USES HTN ---- decreases CO ANGINA---decreases oxygen demand
MI---- protects myocardium
GLAUCOMA-- Timolol
MIGRAINE
HYPERTHYROIDISM– blunts sympathetic stimulation

15. SIDE EFFECTS BRONCHOCONSTRICTION CONTRAINDICATION –ASTHMA, COPD
ARRHYTHMIAS – gradual reduction in dose
SEXUAL IMPAIREMENT

16. NON SELECTIVE BETA ANTAGONISTS
TIMOLOL
NADOLOL → very long duration of action
Considered more potent than propranolol.
Same effects and SE as propranolol.

17. SELECTIVE BETA 1 ANTAGONISTS (Cardioselective)
ATENOLOL
METOPROLOL
ESMOLOL
USES – HTN,ANGINA
CAN BE USED IN COPD, Diabetics CASES

18. ANTAGONISTS AND PARTIAL AGONISTS
PINDOLOL
ACEBUTOLOL
They very mildly stimulate both beta 1 and beta 2 adrenergic receptors.
USES : HTN with moderate bradycardia

19. ALPHA AND BETA BLOCKER LABETALOL( non-selective)
Peripheral vasodilation -- ↓ B.P
No vasoconstrictive effect
USES : OLD AGE HTN, congestive heart failure
SE: Orthostatic hypotension and dizziness.

20. NT AFFECTING DRUGS RESERPINE
It blocks Norepinephrine transport from CYTOPLASM TO STORAGE VESICLE
USES -- ↓B.P. ↓ H.R

21. NT AFFECTING DRUGS GUANETHIDINE
–BLOCKS RELEASE OF stored NE IN VESICLE TO MEMBRANE
USES—gradual lowering of B.P and H.R. in hypertensives
SE: orthostatic hypotension and sexual dysfunction

22. NT AFFECTING DRUGS COCAINE Block Na-K ATPase REUPTAKE DECREASED (NE)
USES ----local anesthetic???

23. General use of beta blockers
Angina, hypertension, post MI ( ALL DRUGS)
ANTIARRTHYMICS( CLASS 2 PROPRANOL,ACETABUTOLOL,ESMOLOL,)
GLAUCOMA: TIMOLOL
MIGRAINE, THYROTOXICOSIS, PERFORMANCE ANXIETY, ESSENTIAL TREMOL: PROPRANOLOL

24. COMBINED ALPHA 1 AND BETA BLOCKING ACTIVITY
LABETALOL AND CARVEDILOR: USED IN CONGESTIVE HEART FAILURE
POTASSIUM CHANNEL BLOACKADE AND BETA BLOCKING ACTIVITIY
SOTALOL: USED IN ANTIARRTHYMIC (CLASS 3)