1

Adrenergic Receptors

α Subtype β Subtype

α1 α2 β1, β2 & β3
BV, GIT,
bladder,
bronch and
- Presynaptic adrenergic β1 (heart, kidney) ciliary body
smooth muscles nerve terminal β2 (smooth muscles, liver
(blood vessels/ -CNS and pancreas)
iris/ sphincters)
-β cells of pancreas β3 (lipocytes)

↑ Phospholipase C ↓ Adenylate cyclase ↑ Adenylate cyclase

(↑ calcium) (↓ cAMP) (↑ cAMP)
 Receptor blockers

Alpha blockers Beta blockers

Selective alpha 1 Selective beta 1
Non-selective
Non-selective Prazosin Atenolol
Propranolol
Phentolamine Terazosin Bisoprolol
Timolol
Phenoxybenzamine Doxazosin Betaxolol
Nadolol
Tamsulosin Nebivolol
Esmolol
Beta 1 blockers
Selective alpha 2 Alpha 1 betablockers with partial
Yohimbine Labetalol agonist activity
Carvedilol Pindolol
Acebutolol

Block the uptake: Reserpine

Block the release: Guanethidine

Blood vessels
• α1 (BV) →  PR (+++) …(1)

Heart
•  PR →  baroreceptors → Reflex tachycardia ( CO) … (2)
• α2 (presynaptic to heart) →  NA → β1 →  HR ( CO) .. (3)
From (1, 2, & 3)
GRF: Non-selective alpha blockers are NOT so useful as
antihypertensives because the decrease in PR is antagonized
by the elevation in cardiac output

4
• Block α receptors irreversibly → Long duration of action
• CVS effects similar to phentolamine

• Effect of alpha blockers and epinephrine on blood

pressure???

5
Therapeutic uses:
1- Raynaud’s disease is a
vasospastic disorder causing
discoloration of the fingers, toes, and
occasionally other areas.

2- Extravasation caused by
norepinephrine

3- Pheochromocytoma (together with

beta blockers)

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PRAZOSIN – TERAZOSIN – DOXAZOSIN - TAMSULOSIN

Blood vessels
• α1 (BV) →  PR (+++) …(1)
Heart
•  PR →  baroreceptors → Reflex tachycardia ( CO) … (2)
From (1 & 2)
selective alpha-1 blockers are useful as antihypertensives due
to minimal actions on CO
PRAZOSIN – TERAZOSIN – DOXAZOSIN - TAMSULOSIN

Therapeutic uses
1. Treatment of hypertension (prazosin, terazosin and
doxazosin)
2. TTT of congestive heart failure (prazosin): by veno- &
arteriodilation → resistance against heart pumping.
3. Symptomatic ttt of benign prostatic hypertrophy (BPH):
(Tamsulosin) by blocking α1A → relaxation of smooth
muscle of bladder neck → improved urinary flow.
4. Help the body clear or pass kidney stones, stuck in the
ureter. 9
PRAZOSIN – TERAZOSIN – DOXAZOSIN - TAMSULOSIN

Adverse effects
1. Syncope (1st dose effect): minimized by starting with 1/3rd or 1/4th
the full dose and giving the drug at bedtime.
2. Orthostatic (postural) hypotension
3. Minimal reflex tachycardia.
4. Na+/H2O retention: so used in combination with diuretics.

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YOHIMBINE
1. Sometimes used as a sexual stimulant.
2. It works at the level of the CNS to increase sympathetic
outflow to the periphery.
3. Yohimbine is contraindicated in CNS and CVS conditions
because it is a CNS and CVS stimulant.

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PROPRANOLOL

CVS effects
•  β1→  SAN/AVN → (-ve) ino- & chronotropic activity.
•  cardiac work and oxygen consumption → ttt of angina.

Peripheral vasoconstriction
•  β2 (BV)→ prevents β2-mediated vasodilation (α1 works
unopposed) → vasoconstriction.

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PROPRANOLOL
Bronchoconstriction
•  β2→ bronchoconstriction → respiratory crisis in asthmatic
patients or patients with COPD.

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PROPRANOLOL
Disturbances in glucose metabolism
•  β2→  glycogenolysis/gluconeogenesis →  bl. glucose.
G.R.: IDDM patients should NOT receive a non-selective beta
blocker. β1 Tachycardia
(hypoglycemia warning sign)

Take sweets

 Blood glucose
Adrenaline
β2

15 Glycogenolysis + gluconeogenesis
PROPRANOLOL
Pharmacokinetics
• Highly lipophilic (BBB).
• Subject to first-pass effect (25 % reaches the circulation).

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PROPRANOLOL
Therapeutic effects
A. Hypertension
1. Block β1 (heart)→  CO
2. Block β1 (kidney)→  RAAS
3. Decreased central sympathetic flow

B. Migraine: Prophylactic ( incidence of attacks)

C. Hyperthyroidism
Thyroid storm up-regulates β1 (heart) → severe tachycardia →

17 arrhythmias (blocked by β -blockers).

PROPRANOLOL
Therapeutic effects
D. Angina pectoris and Myocardial infarction
1. Angina (reduced O2 supply versus increased O2 demand).
2. MI (damaged heart muscle due to diminished blood supply i.e.:
ischemia)
β -blockers  cardiac work →  O2 demand →  anginal pain/ size of MI.

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PROPRANOLOL Adverse effects
A. Bronchoconstriction: C.I. in asthma & COPD
B. Arrhythmias: why?
1. Continuous use → up-regulation of β1 (heart).
2. Sudden withdrawal →    β1 → arrhythmia.
3. Therefore, should be gradually withdrawn.
C. Metabolic disturbances:
1. Prevents counter-regulatory effects of catecholamines during
hypoglycemia (use cardioselective blockers).
2.  LDL (bad cholesterol),  TG,  HDL (good cholesterol) → bad
lipid profile (use cardioselective blockers).
D. CNS effects: Depression, weakness and memory impairment.
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Timolol - Nadolol
• More potent than propranolol.
• Nadolol has a very long duration of action.
• Timolol reduces the production of aqueous humor in the
eye (used topically for open-angle glaucoma). Advantage on
pilocarpine ???

• For acute attacks ??

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Atenolol, metoprolol, bisoprolol, betaxolol, nebivolol, and
esmolol:
• Selectivity appears at low doses & lost at high doses.
• Useful for diabetic patients and asthmatics.
• Actions:
1. Esmolol (very short lifetime)→ only given IV in surgery.
2. Nebivolol also has vasodilator properties mediated by
nitric oxide (NO).

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Pindolol (non-selective) – Acebutolol (β1-selective):
• Actions:
1. Not pure antagonists.
2. Weakly stimulate β1 & β2 (Intrinsic sympathomimetic
activity -ISA-).
3. Partial agonists → weakly stimulate the β receptors but
inhibit their stimulation by the more potent endogenous
catecholamines, E & NE → lower effect on HR and CO
compared to that of β blockers without ISA.

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Pindolol (non-selective) – Acebutolol (β1-selective):
• Advantages:
1. Less tendency to cause metabolic disturbances (glucose
& lipid alterations).
2. Suitable for diabetic patients
3. Suitable for hypertensive patients with moderate
bradycardia
4. NOT suitable as antiarrhythmics

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Labetalol – Carvedilol:
• Actions:
1. They produce peripheral vasodilation (c.f.: other non
selective β blockers that produce peripheral
vasoconstriction)
2. Useful in treating hypertensive patients for whom
increased PR is undesirable.
3. They do not alter serum lipid or blood glucose levels.
4. Carvedilol decreases lipid peroxidation and vascular
wall thickening → beneficial in heart failure.
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Labetalol – Carvedilol:
• Uses in hypertension & heart failure:
1. Labetalol:
• Treating elderly or black hypertensive patient in whom
increased PR is undesirable.
• Alternative to methyldopa in the treatment of pregnancy-
induced hypertension.
• In hypertensive emergencies, because it can rapidly lower
blood pressure.
2. Carvedilol: prevents cardiovascular mortalities in patients with
heart failure.
Adverse effects: orthostatic hypotension (α1 blockade).
Reflex tachycardia???
 Adrenal
Medulla

80% of NA
methylation

Adrenaline

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• Blocks the transport of biogenic amines (NE, DA, and
serotonin) from the cytoplasm into storage vesicles →
ultimate depletion of biogenic amines → release of NE.
• The drug has a slow onset, a long duration of action, and
effects that persist for many days after discontinuation.
• Antihypertensive

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• It blocks the release of stored NE
• Antihypertensive

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 Drug Receptors
Phentolamine and Non-selective α blockers
Phenoxybenzamine
Terazosin- Doxazosin- α1 blockers
Prazosin- Tamsulosin
Yohimbine α2 blockers
Propranolol- Nadolol – Non-selective β blockers
Sympatholytics

Timolol
Atenolol- Metoprolol, β1 blockers
Bisoprolol- Betaxolol,
Nebivolol - Esmolol
Pindolol – Acebutolol Partial agonist on β receptors
Labetalol – Carvedilol α1 – β Blockers

Reserpine Inhibit reuptake 3

Guanethedine Block NE release

 Glad to
teach you
Glad to
teach you
Good
Luck
Good Luck 31