1. DR. RAHUL
Antiadrenegics

2. Antiadrenegics
These are the drugs which
antagonize the actions of adrenaline
and related drugs.
They are both competitive
antagonist of alpha or beta or both.

3. ALHA 1 receptors
• Radial fibers – contraction –
mydriasisEye
• Contraction – can increase
peripheral resistance
Arterioles and
veins –.
• Contraction – urinary
retention
Bladder trigone
and sphincter –
• Glycogenolysis.Liver
• Ejaculation.Vas deferens

4. ALPHA 2
• Aggregation
Platelets
• Decrease release of
transmitter (NE)
Presynaptic
receptors
• Decrease insulin
release (predominant)Pancrease -

5. Alpha adrenergic blockers
• Ergot alkaloids : Ergotoxine, Ergotamine
• Hydrogenated ergot alkaloids: Dihydroergotoxine
• Imidazolines : Phentolamine, Tolazoline
Reversible type
• Prazosin, Terazosin, Doxazosin, Tamsulosin
Alpha1 selective-
Alpha2 selective- Yohimbine

6. Pharmacological Effects
Cardiovascular system: Fall in BP (alpha1 & 2 blockade)
Postural hypotension
Reflex tachycardia
Vasomotor reversal of Dale
Hypovolemia accentuates hypotension
• Na & water retention
• renin release BP
Hypotension-g.f.r reduced

7. Pharmacological Effects
Nasal stuffiness
Eye – miosis
• decreased tone in sphincter and prostate (alpha1a blockade)
Urinary bladder
Metabolic effects – increased insulin secretion
Reproductive system
Inhibition of contraction of Vas defrence and related
organs is blocked by alpha1 blockade…..inhibition of
ejaculation…impotence

8. Phenoxybenzamine
Alpha blockade develops gradually and lasts for 3-4
days. Fall in BP by Phenoxy. is mainly due to
venodilatation…postural hypotension.
Shifts blood from pulmonary to systemic circulation, extra
vascular to vascular compartments.
Lipid soluble drug can penetrate CNS may cause nausea &
vomiting on rapid iv administration
Management of pheochromocytoma.
Pheripheral vascular diseases.

9. Imidazoline derivatives -
Phentolamine
Congener of Tolazoline
Rapidly acting alpha blocker with short DOA
Many other effects including:
• Parasympathomimetic
• Increased gastric acid secretion
Cardiac stimulation
Increased secretion from exocrine glands, such as salivary, sweat, lacrimal,
pancreatic
Coronary artery disease and peptic ulcer relative contraindication to it.

10. Phentolamine : uses
Diagnostic and intraoperative management of
pheochromocytoma
For control of hypertension due to clonidine withdrawal.
Cheese reaction.
To counteract vasoconstriction due to extravasation of
noradrenaline / Dopamine given IV.

11. Ergot alkaloids
Ergotoxine, Ergotamine are partial agonist and
antagonist at adrenergic alpha, serotonergic and
dopaminergic receptors.
Ergotoxine, dihydroergotoxine are more potent alpha
blocker and less potent vasoconstrictor than ergotamine.
USE: Migraine

12. Alpha-1 selective blockers
Prazosin
Highly selective Alpha1 blocker, selectivity ratio 1000: 1
Less cardiac stimulation since it preserves alpha2 mediated
negative feedback + other mechanisms
Fall in BP with no/ minimal tachycardia.
Used in hypertension but tolerance develops with time, maybe
due to fluid retention.
Adverse effects: First dose phenomenon i.e postural
hypotension with initial doses.
Favorable effect on plasma lipids: increase HDL/LDL ratio

13. ADR
(µg/Kg)
1 10 100 5000.1
1 10 100 500
+PRAZOSIN
BP
HR
Effect of Adrenaline (ADR) on Blood Pressure and Heart Rate
Before and After Prazosin

14. Prazosin : uses
Antihypertensive
DOC: Benign prostatic hyperplagia ( BPH)
• Blocks alpha 1 in bladder trigone & prostate
• Decreases tone
• Improves urine flow
• Decreases residual urine
Dose :1-4 mg BD/ TDS
Terazosin : longer t1/2 , OD dosing

15. Tamsulosin
Dizziness and retrograde ejaculation are the only
AE.
No effect on BP and heart rate.
Alpha Ia are predominant in bladder base and
prostate. 30 times high affinity for alpha1a.
As effective as Terazosin in BPH
Uroselective alpha 1a/ alpha 1d blocker.

16. Alpha-2 selective blockers
Yohimbine
Cardiovascular effects – peripheral and
central effects
Blocks other receptors also – serotonin,
dopamine
Increases ADH release
Enhances sexual activity – aphrodisiac
Potential uses: depression, obesity, NIDDM

17. Alpha Blockade—Adverse Effects
Orthostatic hypotension
• Reduces blood flow to brain causing dizziness, lightheadedness and fainting
• Due to vasodilation of veins lowering blood flow to brain
Reflex tachycardia
• Increase heart rate by stimulating baroreceptor reflex which
causes and increased heart rate to compensate
Nasal Congestion
• Dilates vessels of nasal mucosa
Inhibition of ejaculation
• Alpha1, sympathetic reaction needed
Sodium retention
• Decreased blood pressure decreases filtering by kidneys and
causes retention of water and salt
MenuB F

18. Alpha Blockade—Uses
• Essential hypertension
• Benign prostatic
hyperplasia
• Pheochromocytoma
• Overdose of alpha1
agonist
Therapeutic
Applications

19. Therapeutic Uses of
Alpha-Adrenergic Blockers
Hypertension - alpha-1 selective
Conditions associated with increased sympathetic activity – e.g.
pheochromocytoma
Hemodynamic shock
Peripheral vascular disease – Raynaud’s
Congestive heart failure
Benign prostatic hyperplasia-prazosin
Pulmonary hypertension – tolazoline
Yohimbine or intracavernous Phentolamine+ papaverine for
impotence

20. BETA BLOCKERS
DR. RAHUL

21. Beta blockers
 These drugs inhibit adrenergic responses
mediated through beta receptors.
 All beta blockers are competitive antagonists.
 History: Dichloroisoproterenol- 1958
Propranolol-1963

22. Classification
 NONSELECTIVE: (BETA 1 & 2)
A) Without intrinsic symphathomimetic activity
 Propranolol
 Sotalol : Class III antiarrhythmic
 Timolol : topical use in eye
B) With intrinsic symphathomimetic activity
 Pindolol
C) With alpha blockade activity (alpha + beta
blockade)
 Labetalol
 carvedilol

23. CARDIOSELECTIVE (BETA 1 )
 Metoprolol
 Atenolol
 Bisoprolol
 Esmolol
 Acebutolol (intrinsic symphathomimetic and membrane stabilizing activity)
 Celiprolol (Beta 1 blocker + beta 2 agonism)
 Nebivolol

25. Pharmacological actions : CVS:
 Heart:
 Propranolol decreases heart rate, force of contraction,
COP. Decreases cardiac work and oxygen
consumption.
 Blood vessels: Fall in BP both diastolic and
systolic after continuous treatment.
 Decrease in COP
 Initial increase followed by decrease in TPR
 Decrease renin release from kidney
 Central action decreasing symphathetic outflow

26. OTHER SYSTEMS
 Respiratory system : Bronchoconstriction
 CNS: Decreases anxiety, tremors, other actions.
 Metabolic :
 Increases LDL, triglycerides, decreases HDL
by inhibiting lipolysis.
 Adversely effects recovery from insulin
induced hypoglycemia.
 Skeletal muscles : Pnl inhibits adrenegically
evoked tremors.
 Eye : synthesis and releases of aqueous humour
… iop

27. Contraindication
 CHF
 Bradycardia
 COPD
 Bronchial asthma
 Diabetis mellitus
 Hypertriglygeridemia

28. Adverse effects
 Adverse Effects of beta1 blockade
 Bradycardia
 Reduced cardiac output
 Heart failure
 AV block
 COPD, Bronchial asthma
 Tiredness , reduced exercise capacity.
 Rebound hypertension on abrupt withdrawl.
 Cold hands and feets
 Hypoglycemia
 Others: gi upset, lack of drive, lightheadedness,
forgetfulness, nightmares, rarely hallucinations

29. CARDIOSELECTIVE (BETA 1 )
 Metoprolol
 Atenolol
 Acebutolol
 Bisoprolol
 Esmolol
 No effect on bronchus, carbohydrate
metabolism, lipids.
 Lower incidences of Cold hands and feets.
 Less liable to impair essential tremors.

30. CARDIOSELECTIVE (BETA 1 )
DRUG FEATURES USE
Metoprolol Preferred in diabetics on insulin
or oral hypoglycemics.
AMI without bradycardia
Atenolol Low lipid solubility.
Longer duration action. (OD)
Hypertention
Angina
Acebutolol Cardioselective with intrinsic
symphathomimetic and
membrane stabilizing activity
Preferred in severe bradycardia
and low cardiac reserve
Esmolol Ultra short acting cardioselective
beta blocker.
DOA 15-20mins after iv infusion
To terminate supraventricular
tachycardia
Atrial fibrillation or flutter
Early treatment of AMI
Celiprolol
Nebivolol
Beta 1 blocker + beta 2 agonism
Acts as NO donor
(vasodilatation)
Hypertension
CHF

31. Without intrinsic symphathomimetic
activity
 Sotalol : Class III antiarrhythmic
 Timolol : topical use in eye

32. Uses of Beta blockers
 Hypertension
 Angina pectoris
 Cardiac arryhythmias
 AMI
 Secondary prophylaxis of AMI
 Myocardial salvage
 CHF
 Pheochromocytoma
 Thyrotoxicosis
 Migraine
 Essential tremors.
 Glaucoma
 Anxiety

33. Carvedilol
 β 1 + β2+ α1 blocker, calcium channel blocker.
 Antioxidant property.
 Use:
 Hypertension
 CHF
 Angina.

34. With alpha blockade activity (alpha
+ beta blockade)
 Labetalol
 β 1 + β2+ α1 blocking aswellas β2 agonism.
 5 times more potent β blocker than α.
 Effects at low dose resembles propranolol while at
high dose ppn + prazosin
 Fall in BP is due to decrease in COP and TPR
 Uses : pheochromocytoma, clonidine withdrawl,
essential hypertention.
 A/E: postural hypotension, impotence.