Download Adrenergic receptor antagonists

Adrenergic receptor
antagonists
Dr. Erika Pintér
2013
Alpha receptor antagonists
They antagonize the effects
of NA and adrenalin on 
adrenoceptors
-non selective: acting on 1
and 2
phentolamine
Short acting , reversible
Side effects: tachycardia
(baroreflex + 2 receptor
inhibition),
postural hypotension
phenoxybenzamine
• Mechanism. Binds covalently to alpha-1 and alpha-2
adrenergic receptors. i.e. non-selective, irreversible,
alpha blocker. Onset is slow requiring 10-20 minutes
for formation of covalent linkages. Offset is even
slower with a t1/2 of 24 hours. Terminated by
metabolism and new receptor synthesis. Called nonequilibrium or non-competitive blocker. New
receptors must be synthesized to overcome the
blockade. Several (2-5) days to regenerate.
• “Dirty” drug - also blocks histamine, acetylcholine, &
serotonin receptors
• Medical use: pheocromocytoma
Selective 1 receptor blockers:
They block 1 receptors in the arterioles
and venules
prazosin: t1/2: 3-4 h , remarkable first pass
effect
doxazosin
terazosin – longer lasting effect, ones a day
dose
They act on 1B subtype
Inhibit the TPR dilating arterioles and
venules. Antihypertensive effect.
Unwanted effects :orthostatic hypotension,
reflex tachycardia, no effect on 2
receptors
1A selective blocker:
tamsulosin, alfuzosin
Medical use: prostate
hypertrophy (relaxes the
urethral sphincter)
urapidil
• Urapidil is sympatholytic antihypertensive drug.
It acts as an α1-adrenoceptor antagonist and as
an 5-HT1A receptor agonist Unlike some
other α1-adrenoceptor antagonists, urapidil does
not elicit reflex tachycardia, and this may be
related to its weak β1-adrenoceptor antagonist
activity as well as its effect on cardiac vagal
drive. Urapidil is currently not approved by
the U.S. Food and Drug Administration
• but it is available in Europe.
• Medical use: hypertensive crisis
yohimbine
• Yohimbine blocks presynaptic alpha-2
adrenergic receptors. Yohimbine's
peripheral autonomic nervous system effect is to
increase parasympathetic (cholinergic) and
decrease sympathetic (adrenergic) activity. It is
to be noted that in male sexual performance,
erection is linked to cholinergic activity and to
alpha-2 adrenergic blockade which may
theoretically result in increased penile inflow,
decreased penile outflow or both. It is not used
anymore.
side effects
• Yohimbine readily penetrates the CNS and
produces a complex pattern of responses in lower
doses than required to produce peripheral (alpha)adrenergic blockage. These include anti-diuresis, a
general picture of central excitation including
elevated blood pressure and heart rate,
increased motor activity, irritability
and tremor. Sweating, nausea and vomiting are
common after parenteral administration of the
drug. Also dizziness, headache, and skin flushing
have been reported.
-receptor blockers
They antagonize the effects of
catecholamines on  receptors
Non-selective
propranolol: remarkable first pass
metabolism
Parcial agonists, with intrinsic
sympatomimetic activity
oxprenonol
pindolol
acebutolol
penbutolol
recommended for elderly people
(mild negative inotropic effect,
no tolerance)
Cardioselective  receptor blockers:
antagonist effect a 1 receptors
advantage: minimal 2 inhibition
metoprolol
atenolol
betaxolol - long lasting effect, ones a day
bisoprolol
nebivolol
Celiprolol
 +  blockers:
labetalol
medical use: pheocromocytoma, hypertensive crisis,
hypertension in pregnancy
Clinical uses of β-adrenoceptor antagonists
Cardiovascular
- angina pectoris
- myocardial infarction
- dysrhythmias
- heart failure
- hypertension
Other uses:
- glaucoma (e.g. timolol eye drops)
- thyrotoxicosis, as adjunct to definitive
treatment (e.g. preoperatively)
- anxiety to control somatic symptoms (e.g.
palpitations, tremor)
- migraine prophylaxis
- benign essential tremor (a familiar disorder)
Unwanted effects
The main side effects of β-receptor antagonists result from their
receptor-blocking action.
Bronchoconstriction
This is of little importance in the absence of airways disease,
but in asthmatic patients the effect can be dramatic and lifethreatening. It is also of clinical importance in patients with
other forms of obstructive lung disease (e.g. chronic bronchitis,
emphysema).
Cardiac depression
Cardiac depression can occur, leading to signs of heart failure,
particularly in elderly people. Patients suffering from heart
failure who are treated with β-receptor antagonists often
deteriorate in the first few weeks before the beneficial effect
develops.
Bradycardia
This side effect can lead to life-threatening heart block and can
occur in patients with coronary disease, particularly if they are
being treated with antiarrhythmic drugs that impair cardiac
conduction.
Hypoglycaemia
Glucose release in response to adrenaline is a safety device that
may be important to diabetic patients and to other individuals
prone to hypoglycaemic attacks. The sympathetic response to
hypoglycaemia produces symptoms (especially tachycardia) that
warn patients of the urgent need for carbohydrate (usually in the
form of a sugary drink). β-Receptor antagonists reduce these
symptoms, so incipient hypoglycaemia is more likely to go
unnoticed by the patient. The use of β-receptor antagonists is
generally to be avoided in patients with poorly controlled
diabetes. There is a theoretical advantage in using β1-selective
agents, because glucose release from the liver is controlled by β2
receptors.
Fatigue
This is probably due to reduced cardiac output and reduced
muscle perfusion in exercise. It is a frequent complaint of
patients taking β-receptor-blocking drugs.
Cold extremities
This is due to a loss of β-receptor-mediated vasodilatation in
cutaneous vessels, and is a common side effect. Theoretically,
β1-selective drugs are less likely to produce this effect, but it
is not clear that this is so in practice.
Other side effects associated with β-receptor antagonists are
not obviously the result of β-receptor blockade. One is the
occurrence of bad dreams, which occur mainly with highly
lipid-soluble drugs such as propranolol, which enter the brain
easily.