This document discusses antiadrenergic drugs, including their mechanisms of action and effects. It describes α and β adrenergic receptors, and different types of α and β receptor blockers. α blockers such as prazosin, terazosin, and doxazosin are selective for α1 receptors, causing vasodilation. Non-selective α blockers like phenoxybenzamine and phentolamine block both α1 and α2 receptors. β blockers include non-selective drugs like propranolol and timolol, as well as cardioselective drugs such as atenolol and metoprolol that mainly block β1 receptors. These drugs are used to treat hypertension, an

1. ANTIADRENERGIC
DRUGS
By: Darya Osman Hussein Daoud
Manal Bala Saeed

2. The
Adrenergic
Neuron
• Synthesis and release of
norepinephrine from the
adrenergic neuron
• MOA – Monoamine
Oxidase
• SNRI – Serotonin
norepinephrine
reuptake inhibitor

3. α Adrenergic Receptors
(α Adrenoreceptors):
Equally responsive to
naturally occurring
catecholamines (i.e. EP and
NE)
Classified as α1 and α2

4. α1 Receptors:
Present on postsynaptic membrane
Constrict smooth muscle
Activation initiates series of reaction through G protein
activation or phospholipase C
Ultimately results in generation of 2nd messengers IP3 (initiates
release of Ca2+ from ER into cytosol) and DAG (turns on other
proteins within the cell)

5. Present on sympathetic presynaptic nerve endings and
parasympathetic presynaptic neurons
Controls release of NE via feedback inhibition
Also inhibits Ach release
Binding is mediated by inhibition of adenyl cyclase and fall in
intracellular cAMP levels
α2 Receptors:

6. α Receptors
• DAG – diacylglycerol
• IP3 – Inositol 3
triphosphate
• ATP – Adenosine
triphosphate
• cAMP – cyclic adenosine
monophosphate

7. • Vasoconstriction
• Increased peripheral resistance
• Increase BP
• Mydriasis
• Increased closure of internal
sphincter of the bladder
α1
• Inhibition of NE release
• Inhibition of Ach release
• Inhibition of insulin release
α2

8. β Adrenergic Receptors
(β Adrenoreceptors):
Equally responsive to
naturally occurring
catecholamines (i.e. EP and
NE)
Classified as β1, β2 and β3

9. β Adrenergic Receptors
(β Adrenoreceptors):
β1 have equal affinities to EP and NE
β2 have higher affinity for EP than for NE
β3 are responsible for lipolysis and have effects on detrusor
muscle of the bladder
Binding results in activation of adenylyl cyclase and increased
cAMP concentration

10. • Tachycardia
• Increased lipolysis
• Increased myocardial contractility
• Increased release of renin
β1
• Vasodilation
• Decreased peripheral resistance
• Bronchodilation
• Increased muscle and liver
glycogenolysis
• Relaxed uterine smooth muscle
β2

11. Regulation:
Desensitization of receptors can occur after prolonged exposure to
catecholamines
Occurs via 1 of the following mechanisms:
1. Sequestration of receptors – become unavailable for interaction with ligand
2. Downregulation – disappearance of receptors by destruction or decreased
synthesis
3. Phosphorylation - an inability to couple to G protein because of
phosphorylation on cytoplasmic side

12. What are adrenergic antagonists?
Drugs which antagonize the action of EP and NE at the
receptor level
They occupy adrenergic receptors (α and β ) but do not
produce signal transduction.
Can be reversible or irreversible
Classified according to relative affinity for α or β receptors

14. α adrenergic blockers
PHENOXYBENZAMINE, PHENTOLAMINE, PRAZOSIN,
TERAZOSIN AND DOXAZOSIN

15. Phenoxybenzamine & Phentolamine

16. Non-selective α blockers
Actions:
 Block of α1 receptor
 vasodilation and postural hypotension.
 Block of α2 receptor
 reduced NE action on α2 receptors on the varicosity
 increases release of NE from varicosity which can cause
tachycardia and increased CO
Phenoxybenzamine & Phentolamine

17. Mechanism of action:
Binds covalently (and therefore
irreversibly) to α receptor and blocks
NA action.
Action is reversible in the case of
phentolamine.
Phenoxybenzamine & Phentolamine

18. Pharmacokinetics
Given orally, IV and SC injection.
T ½ for Phenoxybenzamine = 12 hours (because of irreversible binding
to receptor).
T ½ for Phentolamine = 3 hours.
Phenoxybenzamine & Phentolamine

19. Clinical Use:
Used in treatment of phaeochromocytoma
Adverse effects:
Postural hypotension
Tachycardia
Dizziness and headache
Sexual disfunction
Phenoxybenzamine & Phentolamine

20. Prazosin, terazosin and doxazosin

21. Selective α1 antagonist
Action:
Vasodilatation and reduction in BP.
Increase HR (a reflex β1 receptor resonse to the decrease in BP)
Decrease bladder sphincter tone.
Inhibition of hypertrophy on smooth muscle of bladder neck and prostate
capsule.
Prazosin, terazosin and doxazosin

22. Mechanism of Action:
Block the action of endogenous and exogenous agonists on the α1
receptor.
Decrease peripheral vascular resistance
Relaxes arterial and venous smooth muscle
Causes minimal changes in CO, renal blood flow and GFR
Prazosin, terazosin and doxazosin

23. Pharmacokinetics:
Prazosin and Terazosin
absorbed orally
T ½ = 3 – 4 hours
Metabolised by liver
Extensive 1st pass metabolism
Doxazosin
T ½ = 22 hours
Prazosin, terazosin and doxazosin

24. Examples of uses of α1 selective blocker

25. Clinical use:
◦ Severe hypertension.
◦ Benign prostatic hypertrophy.
Adverse effects:
◦ Orthostatic hypotension
◦ Dizziness
◦ Hypersensitivity reactions
◦ Insomnia
◦ Priapism
Prazosin, terazosin and doxazosin

26. Caution -
Syncope
First dose of α1 receptor
blocker may produce an
orthostatic hypotensive
response and result in
fainting

27. β adrenergic blockers
PROPRANOLOL, TIMOLOL, NADOLOL,
ACEBUTOLOL, ATENOLOL, METOPROLOL AND
ESMOLOL

28. NON SELECTIVE
Propranolol
Timolol
Nadolol
Β1 SELECTIVE
(CARDIOSELECTIVE)
Acebutolol
Atenolol
Metoprolol
Esmolol
β adrenergic blockers

29. Propranolol
Non – Selective β blocker
Action:
CVS
decreases CO (-ve inotropic and chronotropic effects)
Decreased SA and AV node activity
Peripheral vasoconstriction via increased peripheral resistance
Bronchoconstriction
Reduces renin release
Decreased glycogenolysis and glucagon secretion

30. Mechanism of Action:
Block sympathetic drive
Reducing pacemaker activity and increases AV conduction time
Reduces the slow inward Ca2+ current
Propranolol

31. Pharmacokinetics:
Orally administered
Almost completely absorbed
Extensive 1st pass metabolism (only 0.25 bioavailability)
Large volume of distribution
Readily crosses blood-brain barrier
Metabolites excreted in urine
Propranolol

32. Therapeutic uses:
Class II antiarrhythmic
Hypertension
Angina pectoris
Migraine
Hyperthyroidism
Prevention of death by dysrhythima following myocardial infarction
Paroxymal atrial fibrillation
Propranolol

33. Propranolol
Adverse effects:
Bronchoconstriction
Arrhythmias (if stopped abruptly)
Sexual impairment
Metabolic disturbances (fasting
hypoglycemia)
CNS effects
Dissiness
Lethargy
Fatigue
Weakness
Visual disturbances
Hallucinations
Short term memory loss
Emotiaonal lability
Vivide dreams
Depression

34. Nadolol and Timolol
Non selective beta antagonists
Nadolol has very long duration of action
Action:
Drecrease intraocular pressure
More potent than propranolol

35. Nadolol and Timolol
Mechanism of action:
Reduce production of aqueous humor in the eye
Decrease secretion of aqueous humor by ciliary body
Do not cause cycloplesia

36. Nadolol and Timolol
Pharmacokinetics:
Onset is about 30 minutes when administered intraocularly
D.O.A. = 12 to 24 hrs
Clinical Use:
Chronic management of glaucoma

37. Acebutolol, Atenolol, Bisoprolol,
Esmolol, and Metoprolol
Slective beta blockers – known as cardioselective
Selectivity is lost at high doses
Action:
Decrease BP in hypertension
Inrease exorcise tolerane in angina

38. Pharmacokinetics:
Orally administered
T ½
Atenolol = 6 hours
Esmolol = 10 hours
Acebutolol, Atenolol, Bisoprolol,
Esmolol, and Metoprolol

39. Clinical Use:
Emergency treatment of supraventricular dysrhythmias (Esmolol)
Antianginal
Antihypertensive in diabetic patients reviecing insulin or oral
hypoglycemic agents
Acebutolol, Atenolol, Bisoprolol,
Esmolol, and Metoprolol