42)Adrenergic neurotransmission. Adrenomimetic drugs

Question 1

Adrenergic Neurotransmission

Answer 1

System of which A + B receptors to which noradrenaline + adrenaline bind to

These are key elements of SNS

NA ⇢ NT produced by nerve cells + work on a local level

AD ⇢ Hormone released by adrenal gland + works on a systemic level

Question 2

Adrenergic receptors

Answer 2

A1 ⇢ Smooth muscle constriction ⇢ Vasoconstriction ⇢ ⇡ BP

A2 ⇢ presynaptic protein ⇢ -ve feedback ⇢ ⇣ NA release

B1 ⇢ ⇡ HR, contractility + AV conduction + ⇡ Renin secretion = ⇡ BP

B2 ⇢ Smooth muscle relaxation in bronchi, GI tract , vessels = Vasodilation

B3

Question 3

Adrenergic NT process

Answer 3

1. Tyrosine transported into neuron via Na-dependant tyrosine transporter

• Tyrosine ⇢ hydroxylated ⇢ L-dopa in neurone
• L-dopa ⇢ Dopamine

2. Dopamine transported into vesicle ⇢ converted to NA
3. AP ⇢ opens Ca²⁺ channels ⇢ Ca²⁺ influx in neurone ⇢ synaptic vesicle fuses w/membrane + release contents into synapse
4. NA binds to postsynaptic receptor on effector organ ⇢ intracellular response
5. Na also binds to presyn receptor = ⇣ NA release
6. NA removed from synaptic space by diffusing into SS + Taken up by net protein

Question 4

Adrenergic antagonists

Answer 4

Catecholamine

• Ineffective oral usability
• Metabolised in gut, liver, CNS
• Short duration of action
• Poor CNS penetration

Non-catecholamine

• Effective orally
• Slower metabolism
• Longer duration of action
• Good CNS penetration ⇢ less polar

Question 5

Direct acting agonists - Non selective

Answer 5

Bind to A + B receptors ⇢ mimic action of AD, NA + Dopamine

They are Catecholamines ⇢ administered IV

Adrenaline

• Binds to all receptors ⇢ used for anaphylactic shock
• Leads to vasoconstriction ⇢ ⇣ mucosal oedema = Relieving airway construction + ⇡ BP

Activation of cardiac B1-receptors

• ⇡ cardiac output ⇢ can be used to restore cardiac function

Activation of B2 receptors in lungs

• Bronchodilation ⇢ used for respiratory conditions

Question 6

Direct acting antagonists - non selective p2

Answer 6

Noradrenaline

• Mainly A1 - receptors
• Vasoconstriction ⇢ ⇡ BP
• Almost no B2 activity
• Used for cardiac arrest + hypotensive shock

Dopamine

• Stimulates A, B + A-dopa receptors
• Low therapeutic doses ⇢ acts on dopamine receptors only
• As dose ⇡ ⇢ activates cardiac b1 receptors
• Higher doses activate a1 receptors
• Used for heart failure + hypotensive shock

Question 7

Selective direct acting agonists

Answer 7

a1 selective

• Oxymetazoline ⇢ in eye drops for eye redness
• Phenylephrine ⇢ can raise BP + both O + P in products for nasal congestion

a2 selective

• clonidine ⇢ hypertension

b1 selective

• Dobutamine ⇢ ⇡ Cardiac rate + output ⇢ acute heart failure

b2 selective

• Albuterol + Terbutaline ⇢ acute asthma symptoms
• Salmeterol + formeterol ⇢ prolonged bronchodilation

Question 8

Indirect acting agonists

Answer 8

Enhance effects of Na/AD ⇢ inhibits their reuptake/degradation

• Cocaine
• Amphetamine
• Simulate a1 + b1 receptors ⇢ ⇡ Sympathetic response
• ⇡ BP + HR

Question 9

Mixed action agonists

Answer 9

• Ephedrine
• Pseudoephedrine

Cause inactivation of adrenergic receptors via direct binding + release of stored NA

• Long duration of action
• Ephedrine ⇢ vasoconstriction + bronchodilation
• Pseudoephedrine ⇢ same effect bur activates receptors in nasal passages ⇢ ⇣ mucous production + inflammation