Lectures 10, 11, 12: Adrenergic System 1, 2 and 3 (Adrenergic Agonists & Antagonists)

Question 1

• Blocks transport of NA into the vesicles, thus depleting noradrenaline stores.
• Not used clinically.

Answer 1

Reserpine

Question 2

Bronchoconstriction (due to the blockade of β2-adrenergic receptors on bronchial smooth muscle)

Answer 2

Propranolol

Question 3

• 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.)

Answer 3

Phenylephrine

Question 4

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).

Answer 4

Noradrenaline (Norepinephrine), Phenylephrine, Clonidine, Isoprenaline (Isoproterenol), Dobutamine, Salbutamol

Question 5

-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

Answer 5

Amphetamine and Tyramine

Question 6

β-Blockers (Propranolol, and Atenolol)

Answer 6

• 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).

Question 7

Therapeutic uses of: Propranolol & Atenolol (β- Antagonist)

Answer 7

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.

Question 8

What does Isoprenaline (Isoproterenol) cause?

Answer 8

Causes: bronchodilation, peripheral vasodilation, and increased cardiac output.

Question 9

Used as nasal decongestants.

Answer 9

Phenylephrine

Question 10

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

Answer 10

Phentolamine, Prazosin, and Yohimbine (adverse effects of α-adrenergic blockers are for both selective and non selective α blockers)

Question 11

Stimulates adrenergic receptors directly and also causes the release of noradrenaline from the adrenergic neuron.

Answer 11

Ephedrine

Question 12

_____ acts on adrenergic receptors: α and β adrenergic receptors

Answer 12

Noradrenaline (Norepinephrine)

Question 13

Selective α1-adrenoceptor agonists (vasoconstrictors)

Answer 13

Phenylephrine

Question 14

Block the release of NA into the synaptic space.

Answer 14

Guanethidine

Question 15

Selective β1 agonists (produce increased cardiac contractility, clinically useful to increase cardiac output in congestive heart failure.

Answer 15

Dobutamine

Question 16

Selective α2 agonists (centrally-acting)

Answer 16

Clonidine

Question 17

Mixed-action adrenergic agonists

Answer 17

Ephedrine

Question 18

Selective α1 antagonists

Answer 18

Prazosin

Question 19

Adverse effects of: Propranolol & Atenolol (β- Antagonist)

Answer 19

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.

Question 20

Selective β1 antagonist

Answer 20

Atenolol

Question 21

Non selective α blockers (block both α1 & α2 receptors)

Answer 21

Phentolamine

Question 22

Tyrosine, is the substrate for the syntheses of _____

Answer 22

Noradrenaline (Norepinephrine)

Question 23

________, an indirect acting adrenergic agonist, is found in fermented foods such as cheese. It is metabolized by MAO.

Answer 23

Tyramine

Question 24

Non selective β receptor antagonist (blocks both β1 & β2)

Answer 24

Propranolol

Question 25

• 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

Answer 25

Cocaine, Tricyclic antidepressants

Question 26

Selective α2 antagonist

Answer 26

Yohimbine

Question 27

Indirect acting adrenergic agonists

Answer 27

Amphetamine

Question 28

Treatment of hypertension

Answer 28

Clonidine, Prazosin

Question 29

Selective β2 agonists used mainly for their bronchodilator action in asthma and in the treatment of premature labor.

Answer 29

Salbutamol

Question 30

_____ 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.

Answer 30

Noradrenaline (Norepinephrine)

Question 31

Treatment of shock.

Answer 31

Noradrenaline (Norepinephrine)

Question 32

If the patient is taking MAO inhibitors, _______- containing diet can cause serious vasopressor effects (hypertensive crisis).

Answer 32

tyramine

Question 33

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.

Answer 33

tyramine-rich

Question 34

Neurotransmitter

Answer 34

Noradrenaline (Norepinephrine)

Question 35

Treatment of hypertensive emergencies caused by pheochromocytoma

Answer 35

Phentolamine

Question 36

Non selective β-agonist, it stimulates both β-1 and β-2 adrenergic receptors.

Answer 36

Isoprenaline (Isoproterenol)