Lectures 10, 11, 12: Adrenergic System 1, 2 and 3 (Adrenergic Agonists & Antagonists) Flashcards
- Blocks transport of NA into the vesicles, thus depleting noradrenaline stores.
- Not used clinically.
Reserpine
Bronchoconstriction (due to the blockade of β2-adrenergic receptors on bronchial smooth muscle)
Propranolol
- Non-catecholamine (First, they lack the catechol group, therefore they are not substrates for COMT and are metabolized slowly by MAO.
- As a result, the half-lives of non-catecholamines are much longer than those of catecholamines.
- Second, because they do not undergo rapid degradation by MAO and COMT, non- catecholamines can be given Orally.
- Third, non-catecholamines are considerably less polar than catecholamines, and hence are more able to cross the blood-brain barrier.)
Phenylephrine
Direct-acting agonists act directly on adrenoceptors (α and/or β) by activating them, and are said to be sympathomimetic (Drugs that produce an effect similar to the effect that is produced by stimulation of the sympathetic nervous system).
Noradrenaline (Norepinephrine), Phenylephrine, Clonidine, Isoprenaline (Isoproterenol), Dobutamine, Salbutamol
-Promotion of NA Release. By acting on terminals of sympathetic nerves to cause NA release.
-These agents don’t act directly on postsynaptic receptors.
-They cause NA release from the nerve terminals by displacing NA from vesicles.
-Found in fermented foods such as cheese and is metabolized by MAO.
-The effect of indirect acting adrenergic agonists is much enhanced by
monoamine oxidase (MAO) inhibition, which can lead to severe hypertension following ingestion of tyramine-rich foods by patients treated with MAO inhibitors.
-The patient is taking MAO inhibitors, tyramine- containing diet can
cause serious vasopressor effects (hypertensive crisis).
-Promotion of NA release
Amphetamine and Tyramine
β-Blockers (Propranolol, and Atenolol)
- β-Blockers are used to treat multiple diseases of the heart. They interfere with the effects of endogenous catecholamines.
- When β-blocking drugs are given, they block the access of catecholamines to their receptors, so that the heart will pump with less intensity.
- Therefore, beta-blockers cause: a decrease in heart rate (-ve chronotropic effect) & decreased contractility (-ve inotropic effect).
Therapeutic uses of: Propranolol & Atenolol (β- Antagonist)
Therapeutic Uses of β- Antagonists:
-Reduction of blood pressure in hypertension:
● Can be used alone or in combination with other blood pressure-lowering drugs to maximize effect.
● Mechanism of action: Lower blood pressure by decreasing cardiac output & inhibiting the release of renin.
-Angina: Chest pain due to an inadequate supply of oxygen to the heart muscle.
● Blockade of β1-receptors in the myocardium reduces the influence of endogenous catecholamines.
● Result in decreased cardiac output & decreased blood pressure.
-Myocardial infarction:
● β-blockers have protective effect on the myocardium.
● Patients who have had one myocardial infarction appear to be protected against a second attack by prophylactic use of β blockers.
-Hyperthyroidism: There is increased sympathetic activity.
● Some of the symptoms of hyperthyroidism (such as tachycardia and anxiety) can be improved by beta-blockers.
What does Isoprenaline (Isoproterenol) cause?
Causes: bronchodilation, peripheral vasodilation, and increased cardiac output.
Used as nasal decongestants.
Phenylephrine
Adverse effects of α-adrenergic blockers are:
- Orthostatic hypotension (the change in the BP due to changing posture)
- Nasal congestion (due to dilation of nasal mucosal arterioles)
- Reflex tachycardia
Phentolamine, Prazosin, and Yohimbine (adverse effects of α-adrenergic blockers are for both selective and non selective α blockers)
Stimulates adrenergic receptors directly and also causes the release of noradrenaline from the adrenergic neuron.
Ephedrine
_____ acts on adrenergic receptors: α and β adrenergic receptors
Noradrenaline (Norepinephrine)
Selective α1-adrenoceptor agonists (vasoconstrictors)
Phenylephrine
Block the release of NA into the synaptic space.
Guanethidine
Selective β1 agonists (produce increased cardiac contractility, clinically useful to increase cardiac output in congestive heart failure.
Dobutamine
Selective α2 agonists (centrally-acting)
Clonidine
Mixed-action adrenergic agonists
Ephedrine
Selective α1 antagonists
Prazosin
Adverse effects of: Propranolol & Atenolol (β- Antagonist)
adverse effects:
- Bronchoconstriction can occur, especially when non-selective beta-blockers are administered to asthmatic patients.
- Cardio-selective beta-1 blockers should be used for asthmatic patients.
- Non-selective beta-blockers are contraindicated in patients with asthma.
Selective β1 antagonist
Atenolol
Non selective α blockers (block both α1 & α2 receptors)
Phentolamine
Tyrosine, is the substrate for the syntheses of _____
Noradrenaline (Norepinephrine)
________, an indirect acting adrenergic agonist, is found in fermented foods such as cheese. It is metabolized by MAO.
Tyramine
Non selective β receptor antagonist (blocks both β1 & β2)
Propranolol
- By blocking neuronal NA reuptake (uptake 1), drugs can cause NA to accumulate within the synaptic gap, and can thereby increase receptor activation.
- Inhibition of NA reuptake
Cocaine, Tricyclic antidepressants
Selective α2 antagonist
Yohimbine
Indirect acting adrenergic agonists
Amphetamine
Treatment of hypertension
Clonidine, Prazosin
Selective β2 agonists used mainly for their bronchodilator action in asthma and in the treatment of premature labor.
Salbutamol
_____ is released at the postganglionic sympathetic nerve terminals (e.g. Cardiac muscle, smooth muscle, glands) & also at the adrenal medulla where the hormone adrenaline is formed.
Noradrenaline (Norepinephrine)
Treatment of shock.
Noradrenaline (Norepinephrine)
If the patient is taking MAO inhibitors, _______- containing diet can cause serious vasopressor effects (hypertensive crisis).
tyramine
The effect of indirect acting adrenergic agonists is much enhanced by monoamine oxidase (MAO) inhibition, which can lead to severe hypertension following ingestion of __________ foods by patients treated with MAO inhibitors.
tyramine-rich
Neurotransmitter
Noradrenaline (Norepinephrine)
Treatment of hypertensive emergencies caused by pheochromocytoma
Phentolamine
Non selective β-agonist, it stimulates both β-1 and β-2 adrenergic receptors.
Isoprenaline (Isoproterenol)
