Lecture 11 - Adrenergic effects

Question 1

Adrenergic synapse (5)

Answer 1

• AP down postganglionic fibre –> depolarise presynaptic terminal –> causes calcium to enter the cell –> releasing the neurotransmitter into the synaptic cleft –> producing a biological response.
• NA in synaptic cleft acts on its receptors.
• NA response is terminated by uptake into the presynaptic terminal where it is recycled OR it is broken down by monoamine oxidase (MAO).
• Feedback mechanism occurs on α2 receptors (presynaptic terminal) when you get the release of NA it acts here, if there is a high concentration it will feedback to α2 to switch of release -ve feedback so never too much noradrenaline released.
• If there was too much NA heart/blood vessels would contract too much, and blood pressure would be very high.

Question 2

Direct and indirect regulation of adrenergic transmission (4)

Answer 2

• Direct – Drugs that act at adrenoceptors.
• Indirect – Drugs that act at altering release/termination of transmission.
• Indirect might change storage/release/feedback mechanism, the SNS is either going to go up or down- it does not directly affect adrenergic receptors it does this through SNS.
• Cocaine – more people go to the hospital as – heart palpitations as there is a lot of NA around.

Question 3

Sympathomimetic - Adrenoreceptor agonists direct (1)

Answer 3

(of a drug) producing physiological effects characteristic of the sympathetic nervous system by promoting the stimulation of sympathetic nerves.

Question 4

Synthesis of NA/A (3) + Diagram

Answer 4

NA/A mediated at sympathetic post-ganglionic fibres/CNS/adrenal medulla.
Tyrosine hydroxylase -found in cathecholamine (type of MOA) containing cells. Des not accept indole precursors (e.g. DOPA).
Total turnover - 5 to 15 hours.

Question 5

Drug modulation (5)

Answer 5

• Reserpine will stop uptake of NA.
• Guanethidine will displace NA from the vesicle. Only used in research purposes not clinically.
• Clinical ones are cocaine, desipramine, imipramine (last 2 are antidepressants). Work by blocking NA uptake into the nerve.
• ATE is a stimulant as it works though modulating noradrenergic levels in the system it interacts with.
ATE - Amphetamine, Tyramine, Ephedrine
• MOA inhibitors inhibit MOA.

Question 6

Storage (5)

Answer 6

• Reserpine depletes NA within vesicles.
• NA in cytosol broken down by MAO.
• Reduces NA release.
• Less sympathetic actions, e.g. Less 1-mediated vasoconstriction.
• Early treatment for hypertension.

Question 7

Facilitation of release (2)

Answer 7

Tyramine
Dietary constituent (meats, cheeses, chocolate)
Enter terminal, displaces NA into synaptic cleft – sympathetic, BP
Normally tyramine broken down by MAO in GI tract – so it has little effect
But causes marked hypertension in patients treated with MAO inhibitors for depression – called the ‘cheese effect’

Amphetamine / Ephedrine
Reverses uptake transporters causing release of NA into cleft
Ephedrine (decongestant) – vasoconstriction of nasal blood vessels

Question 8

Inhibition of release (3)

Answer 8

Guanethidine
Compete with NA for inclusion into vesicles, reduces NA release

Clonidine / -methyl-DOPA
Stimulate pre-synaptic 2 receptors, reduces NA release

These drugs maybe used in for hypertensive emergencies (by reducing sympathetic activity) when other mediations are ineffective.

Question 9

CHRONOTROPIC effects (3)

Answer 9

Chronotropic drugs - Change the heart rate and rhythm by affecting the electrical conduction system of the heart and the nerves that influence it.
E.G. Changing the rhythm produced by the SAN.
Positive chronotropes increase heart rate; negative chronotropes decrease heart rate.

Question 10

IONOTROPIC effects (3)

Answer 10

Ionotropic state - drugs that affect the strength of contraction of heart muscle (myocardial contractility).
Positively inotropic agents increase the strength of muscular contraction. Negatively inotropic agents weaken the force of muscular contractions.

Question 11

Uses of Adrenergic Receptor Agonists (10)

Answer 11

ON OTHER FC SET

Question 12

Uses of Adrenergic Receptor Antagonists (8)

Answer 12

ON OTHER FC SET

Question 13

Termination inhibition (3)

Answer 13

NA is terminated by reuptake by ATE into presynaptic terminal. NA is then:

1) Recycled back into vesicles.
2) Metabolised by MAO in neurones or non-neuronal sites (Adrenal medulla).