symptomatic medications

1. Adrenergic Antagonist
Laith J. Al-Asadi

2. Adrenergic Antagonist
• An adrenergic antagonist is a drug that
inhibits the function of adrenergic
receptors.
• There are five adrenergic receptors, which
are divided into two groups :

3. Adrenergic Receptors
• The first group of receptors are the alpha
(α) adrenergic receptors.
There are α1 and α2 receptors.
• The second group contains the beta (β)
adrenoceptors.
There are only β1, β2, and β3 receptors

4. Classification of
Adrenoceptors Blockers
1- alpha vs. beta
• Adrenoceptors are classified as α, β, or
dopamine receptors
• These groups are further subdivided into
subgroups.

6. Classification of
Adrenoceptors Blockers
2- competitive vs. non competitive
2-A: Competitive
• While only a few α-adrenergic
antagonists are competitive, all β-
adrenergic antagonists are competitive
(reversible) antagonists

7. Classification of
Adrenoceptors Blockers
• Adrenergic competitive antagonists are
shorter lasting than the other types of
antagonists
2-B: non-competitive antagonists
• can either bind to the ligand site or other
site called the allosteric site

8. Classification of Adrenoceptors
Blockers
• The binding of a non-competitive
antagonist is irreversible.
• If the non-competitive antagonist binds to
the allosteric site and an agonist binds to
the ligand site, the receptor will remain
inactive ex: phenoxybenzamine

9. Classification of
Adrenoceptors Blockers
3- selective vs. non selective
Alpha1-selective Prazosin
Alpha2-selective Yohimbine
Beta1 – selective metoprolol

11. Mechanism of Action
• Phenoxybenzamine binds covalently to the
α receptor, thereby producing an
irreversible blockade.
• The other agents are competitive
antagonists, and their effects can be
surmounted by increased concentrations
of agonist

12. Pharmacological effects
 cardiovascular system:
• a reduction in vascular tone with a
reduction of both arterial and venous
pressures.

13. Pharmacological effects
 Epinephrine reversal
• is a predictable effect in a patient who has
received an α blocker. The term refers to a
reversal of the blood pressure effect of
large doses of epinephrine

14. Pharmacological effects
Urinary system
• α1 blockers (selective), tamsulosin,
prazocin and silodosin are also used to
reduce urinary hesitancy and prevent
urinary retention in men with benign
prostatic hyperplasia.

15. Clinical uses
pheochromocytoma
Overdose with drugs of abuse such as
amphetamine, cocaine.
Hypertension.
Congestive heart failure.
urinary retention in men with benign prostatic
hyperplasia.

16. Pharmacokinetics
• Phentolamine has a duration of action of
2–4 h when used orally and 20–40 min
when given parenterally. Prazosin and the
other α1
• selective blockers act for 8–24 h.

17. Pharmacokinetics
• Phenoxybenzamine has a short
elimination half-life but a long duration of
action about 48 hr. because it binds
covalently to its receptor.

18. Adverse effects
The most important adverse effects are :
• orthostatic hypotension.
• marked reflex tachycardia. (non selective)
• In patients with coronary disease, angina may
be precipitated by the tachycardia.
• Inhibition of ejaculation.
• Oral administration of some of these drugs can
cause nausea and vomiting.

19. α1 blockers
Phentolamine
phenoxybenzamine
Tamsulosin
Prazocin
Alfazocin
Doxazocin
Tolazolin
Terazocin

20. Beta adrenergic blockers
• All of the β blockers used clinically are
competitive pharmacologic antagonists.
• β blockers usually classified into subgroups
on the basis of
 β1 selectivity
 partial agonist activity
 local anesthetic action
 lipid-solubility

21. Receptor selectivity—Beta1
• (β1 block > β2 ) acebutolol, atenolol, esmolol,
metoprolol.
• This property may be an advantage when
treating patients with asthma.
• Nadolol, propranolol, and timolol are typical
nonselective β blockers.
• Labetalol and carvedilol have combined α- and
β-blocking actions.

22. Partial agonist activity
• Have (intrinsic sympathomimetic activity”)
• an advantage in treating patients with asthma
because these drugs (eg, pindolol, acebutolol)
less likely to cause bronchospasm.
• In contrast, full antagonists such as propranolol
are more likely to cause severe bronchospasm
in patients with airway disease.

23. Local anesthetic activity
• (membrane-stabilizing activity) is a disadvantage
when β blockers are used topically in the eye
because it decreases protective reflexes and
increases the risk of corneal ulceration.
• Local anesthetic effects are absent from timolol
and several other β blockers that are useful in
glaucoma.
• Acebutolol and betaxolol

24. Pharmacokinetics
• Most of the systemic agents have been
developed for chronic oral use, but
bioavailability and duration of action vary
widely .

25. Pharmacokinetics
• Esmolol is a short-acting ester β blocker that is
used only parenterally.
• Nadolol is the longest-acting β blocker.
• Acebutolol, atenolol, and nadolol are less
lipid-soluble than other β blockers and probably
enter the central nervous system (CNS) to a
lesser extent

26. Clinical uses
• The treatment of open-angle glaucoma
involves the use of several groups of
autonomic drugs as well as other agents
• The cardiovascular applications of β
adrenergic blockers—especially in
hypertension, angina, and arrhythmias
are extremely important

27. Clinical uses
• Some, but not all, β blockers can reduce
morbidity and mortality when used
properly in heart failure like labetalol,
carvedilol, and metoprolol
• Pheochromocytoma is sometimes
treated with combined α- and β-blocking
agents (eg, labetalol), especially if the
tumor is producing large amounts of
epinephrine as well as norepinephrine.

28. Adverse effects
• Bradycardia.
• Atrioventricular blockade.
• Heart failure.
• Asthma attacks.
• Masking symptoms of hypoglycemia.
• Cold extremities.
• CNS adverse effects include sedation.
fatigue, and sleep alterations.

29. β blockers
Propranolol Nebivilol
Atenolol Oxprenolol
Metoprolol Timolol
Pindolol Nadolol
Esmolol Acebutolol
Sotalol Talinolol
Betaxolol Labetalol Carvedilol

30. Thank you