ANTI-ADRENERGIC DRUGS PROF. A. K. SAKSENA

α ADRENOCEPTOR ANTAGONISTS Phenoxybenzamine, Phentolamine, Tolazoline, Ergotamine, DHE, Ergotoxine Yohimbine(α2) Non-selective older drugs; Block both α1 & α2 Prominent venodilation.

PHARMACOLOGICAL ACTIONS 1) Blood Vessels:- Severe dilation all over body. ↓ in t.p.r. and venous return Marked hypotension (+Postural hypot. also) Reflex tachycardia → d/t uninhibited release of NA → act on β1.

PHARMACOLOGICAL ACTIONS (contd.) 2) Kidney:- ↓ blood flow to kidneys Reflex ↑ in secretion of renin Activation of R-A-A system ↑ retention of Na/ water → ↑ blood volume Drawbacks in Tt of HT:- Intense vasodilation → ↑ Sym. Outflow Cardiac stimulation (palpitation), Miosis, Diarr Postural hypo, Nasal block, Impotence in male

NEWER DRUGS - Prazosin (a>v.), Doxazosin, Terazosin, Alfuzosin - Selective α1 block only → No marked S/E - First dose effect is +. - BP is ↓- less severe - Tamsulosin:- Most recent drug (α1A, α1D ) On prostate only - BHP

THERAPEUTIC USES Hypertensive crisis Pheochromocytoma Peripheral vascular disease BHP (newer selective drugs)

β-ADRENOCEPTOR ANTAGONISTS I. Non-selective:- Propranolol, Timolol, Labetalol (α also), Pindolol (Sym. mim.), Carvedilol (antioxidant). II. Cardio-selective:- Metoprolol, Atenolol, Betaxolol (α also), Celiprolol (β2 agonist)

PHARMACOLOGICAL ACTIONS 1) CVS:- A) Heart- ↓ in rate & force →↓ in cardiac work & O2 consumption Propanolol has Mem. Stabilizing action also. B) Bl. Vessels- Initially mild ↑ in PR. Later - ↓ in CO →↓ circulating volume V →↓PR Ultimately ↓ in BP– Sys./ Dias. (in HT mainly)

PHARMACOLOGICAL ACTIONS(contd.) 2) CNS:- Non specific β R in vasomotor area→ ↓ in sym. outflow. (Atenolol, Sotalol) 3) PNS:- Presynaptic β2 R at post gang. Sym. neuron terminals →↓ in release of NA.

PHARMACOLOGICAL ACTIONS(contd.) 4) Kidney:- β1 R at JG cells →↓ in release of renin → ↓ activity in R-A-A system. NOTE:- All the above 4 action contribute. 5) Respiratory sys:- β2 in bronchi – blocked → bronchospasm (esp. Asthmatics)

PHARMACOLOGICAL ACTIONS (contd.) 6) Metabolic:- β2 in liver/ muscle cells Block →↓ in glycogenolysis. 7) Skeletal Muscles:- Presynaptic β 2 at LMN →↓ release of ACh ↓ Blood flow to muscles → ↓ fatigue 8) Eye:- ↓ secretion of aqueous.

ADVERSE EFFECTS & CONTRAINDICATIONS CHF may be precipitated, Sick sinus syndrome Muscular weakness, fatigue Bronchial asthma may be precipitated, COPD Partial or complete heart block Peripheral vascular disease → worsened. Cold hands & feet. Sudden withdrawal → HT crisis Not in Diabetics

THERAPEUTIC USES Hypertension Angina Pectoris –Improve O2 supply/demand ratio Cardiac arrhythmias- Propranolol CHF Myocardial Infarction- Secondary prophylaxis ↓ O2 consumption Prevention of arrhythmias Thyrotoxicosis

THERAPEUTIC USES(contd.) Essential tremors Anxiety Glaucoma – Drops/ ocuserts Pheochromocytoma - along with α blocker Migraine