1. -ADRENOCEPTOR ANTAGONISTS
( -BLOCKERS )

2. CLASSIFICATION I. ACCORDING TO SELECTIVITY
A) NON-SELECTIVE (1, 2) BLOCKERS
1. PURE BLOCKES
v SOTALOL
v TIMOLOL
v NADOLOL
2. WITH MEMBRANE STABILIZING ACTIVITY (MSA)
v PROPANOLOL
3. WITH INTRINSIC SYMPATHETIC ACTIVITY (ISA)
v PENBUTOLOL
v CARTEOLOL
4. WITH ISA & MSA
v OXPRENOLOL
v ALPRENOLOL
v PINDOLOL (MSA )

3. B) CARDIOSELECTIVE (1) BLOCKERES
1. PURE BLOCKERS
v ATENOLOL
v BISOPROLOL
2. WITH MSA
v METOPROLOL
v TOLAMOLOL
v BETAXOLOL
3. WITH ISA
v PRACTALOL
4. WITH ISA & MSA
v ACEBUTALOL
C) BOTH  &  BLOCKERS
v LABETALOL
v CARVEDILOL
D) 1 BLOCKER WITH PARTIAL 2 AGONIST ACTIVITY
v CELIPROLOL
E) 2 selective blocker Butoxamine, used only in research.

4. CLASSIFICATION II. ACCORDING TO SOLUBILITY
LIPID SOLUBLE
PROPRANOLOL
TIMOLOL
METOPROLOL
WATER SOLUBLE
NADOLOL
ATENOLOL

5. CLASSIFICATION III. ACCORDING TO DURATION OF ACTION
ULTRA SHORT ACTING
ESMOLOL t ½ 9min
INTERMEDIATE ACTING
PROPRANOLOL 3-5 hours
PINDOLOL hours
METOPROLOL 3-4 hours
LONG ACTING
NADOLOL hours
ATENOLOL hours
BISOPROLOL

7. PHARMACOKINETICS

8. Absorption:
well absorbed orally, peak concentration 1-3 hrs
Sustained release preparations are available
Bioavailability:
Propranolol extensive hepatic (first pass metabolism)
Rapidly distributed and have large volume of distribution.
Can cross blood brain barrier

9. Nadolol is excreted unchanged in urine and has longest half life of 24 hrs.

11. EFFECT OF BINDING OF ADRENALINE TO  RECEPTORS.
-Receptor are G Protein Mediated
Binding Adrenaline to  Receptors (Extracellular)
Stimulation of Adenyl cyclase (intracellular)
Increase Conversion of ATP to cAMP
Stimulation of Protein Kinase C.
Phosphorylation of Enzymes (Enzyme-PO4)
Response

12. PHARMACOLOGICAL ACTIONS
1.      CVS

13. Suppression of renin release and effects in the central nervous system.
Prominent effect on heart
Negative inotropic and chronotropic effects.
In vascular system, β2 mediated vasodilatation

14. 3. Eye (reduce aqueous humor production)
2.  Respiratory System (increase in airway resistance)
3.  Eye (reduce aqueous humor production)
4.   Metabolism (increase VLDL and decrease HDL
5.   Intrinsic Sympathomimetic Activity (ISA)
Precipitation of asthma, excessive bradycardia is prevented
6. Membrane stabilizing Activity (MSA)
Local anesthetic action (Na+ channel blockade)

15. THERAPEUTIC USES ANTI-HYPERTENSIVE
ANTI-ANGINAL (reduce the frequency of anginal episode)
ANTI-ARRHYTHMIC
Prophylaxis after myocardial infarction, Treatment of other Cardiac Arrhythmias, Supraventricular and ventricular arrhythmias.
Sotalol
Metoprolol
Timolol
Propranolol
Esmolol
Acebutolol

16. Slowing of ventricular ejection and decrease outflow resistance.
MYOCARDIAL INFARACTION (MI) (prolong survival)
HYPERTROPHIC SUBAORTIC STENOSIS
HYPERTROPHIC CARDIOMYOPATHY: Propranolol
Slowing of ventricular ejection and decrease outflow resistance.

17. THYRO TOXICOSIS, Thyroid storm: Inhibition of peripheral conversion of thyroxine to triiodothyronine
GLAUCOMA:
TIMOLOL BETAXOLOL
Reduce production of aqueous humor by ciliary body

18. MIGRAINE (frequency and intensity of migraine attacks)
PHEOCHROMOCYTOMA: LABETALOL
TREATMENT OF CHRONIC (NOT ACUTE) CCF:
LABETALOL CARVEDILOL

19. FAMILAL TREMORS, OTHER TYPES OF TREMORS
(sympathetic activity may enhance skeletal muscle tremor)

20. ANXIETY Alcohol WITHDRAWAL SYNDROME (symptomatic treatment)
PORTAL HYPERTENSION
ACUTE PANIC SYMPTOMS – stage fright, viva-voce examination, public appearance etc. (PROPAYLACTIC USE)

21. ADVERSE EFFECTS 1. CNS (bad dreams, lassitude, depression).
2. CVS (Congestive Cardiac failure, Bradycardia, Atrioventricular blockade).
3. METABOLIC EFFECTS
HYPOGLYCEMIA – exercise induced, insulin induced.
Slow recovery from hypoglycemia and masking the manifestations of sympathetic activity due to exercise / insulin induced hypoglycemia in diabetic patients, resulting in loss of warning signal and the patient may land into hypoglycemic coma.

22. 4. RESPIRATORY EFFECTS
Bronchoconstriction
Worsening of preexisting asthma

23. 5. COLDNESS OF EXTREMITIES
6. FATIGUE
7. Aggravation of diabetes mellitus, hyperlipidemic states, peripheral vascular spastic diseases by the use of Non selective beta blockers.
ADVERSE EFFECTS ON SUDDEN WITHDRAWAL (up regulation of receptors)

24. ANTIDOTE OVER DOSAGE a. PRENALTEROL: SELECTIVE 1 AGONIST,
MAY BE USED IN -BLOCKERS’ TOXICITY CAUSED BY HIGH DOSES.
b. Pressor agents
c. Atropine
d. Glucagon

25. CONTRA-INDICATIONS 1. ASTHMA 2. DIABETESE MELLITUS
3. HYPER LIPIDAEMIC STATES
4. DEPRESSION
5. PERIPHERAL VASCULAR DISEASES
6. 2ND OR 3RD DEGREE HEART BLOCK
7. HEART FAILURE
INTERMITTENT CLAUDICATIONS

26. DRUG INTERACTIONS Enzyme inducers & Inhibitors Lignocaine & GAs
Oral anti-diabetic drugs

27. Esmolol
ultra short acting ester linkage Esterases in RBC rapidly metabolize esmolol.
Useful supraventricular arrhythmias, arrhythmias associated with thyrotoxicosis, perioperative hypertension and myocardial ischemia.

28. Thank you