Adrenergics

Question 1

What are the 5 types of adrenergic receptors?

Answer 1

A-1, A-2

B-1, B-2, B-3

Question 2

What are A-1 receptors coupled with, where are they found and what is their function?

Answer 2

Gaq coupled

Found in most smooth muscle tissue

Primarily effects phospholipase C which cleaves IP3 and DAG to increase intracellular calcium → causes muscle contraction

Question 3

What are A-2 receptors coupled with, where are they found and what is their function?

Answer 3

Gai

Primarily found in pre-synaptic neurons

Decreases SNS activity by reducing SNS activation in the CNS to cause hypotension, bradycardia, and sedation

Question 4

What are B-1 receptors coupled with, where are they found and what is their function?

Answer 4

Gas

Primarily expressed in the heart

Increase heart rate (tachycardia) and force of contraction

Question 5

What are B-2 receptors coupled with, where are they found and what is their function?

Answer 5

Gas

Primarily expressed in smooth muscle, including skeletal vascular smooth muscles, bronchioles and internal organs

Causes smooth muscle relaxation

Question 6

What are B-3 receptors coupled with and where are they found?

Answer 6

Gas

Found primarily in adipose tissue

Question 7

Describe catecholamine production

Answer 7

1. L-tyrosine → L-Dopa; tyrosine hydroxylase adds OH group to aromatic ring
2. L-Dopa → Dopamine; aromatic L-amino acid decarboxylase removes carboxylic acid from the end of the molecule
3. Dopamine → NE; Dopamine B-hydroxylase adds OH group in R3 position (happens inside storage vesicle)

***NE is converted to E by adding a methyl to the amine group

Question 8

Describe the metabolism of catecholamines

Answer 8

Can go through COMT only, MAO only or both

COMT → methylates one of the OH groups on the ring

MAO → converts the amine to an aldehyde

Question 9

What are the chemical differences between NE, E, and Isoproterenol (ISO) and how does this make them selective to certain receptors?

Answer 9

NE → most basic

E → same structure as NE but methyl group on the N

ISO → same structure as NE but isopropyl group on N

What that means:

• NE is not as potent at the B-2 receptors
• ISO is most potent at B-2, closely followed by E
• ISO is most potent at B-1, E + NE are almost equipotent

Question 10

What happens when small alkyl groups are added at the R2 position?

Answer 10

makes compounds more resistant to metabolism

Question 11

What happens when one OH is removed, or a larger OH group is present on the ring of a catecholamine?

Answer 11

OH removed → A1 selective

Larger OH → B-2 selective

Question 12

Predict what would happen after the administration of an adrenergic agonist (think in terms of each receptor)

Answer 12

A-1

• Vasoconstriction of vascular smooth muscle (not skeletal)
• Net effects affect reflex actions of heart
• Reflex bradycardia can happen from NE administration → when bp rises suddenly, the baroreceptors activate the PSNS to slow the HR

A-2

• Enlarged pupil
• Increase aqueous humor outflow

B-1

• Increase HR and force of contraction (tachycardia)

B-2

• Bronchodilation  important for treatment of asthma, COPD, allergic reactions
• Causes breakdown of glycogen

Question 13

Describe the actions of A adrenergic antagonists in the body

Answer 13

• A-1 Most common type used clinically
• Used to treat HTN by blocking these receptors in systemic vasculature to reduce peripheral resistance

Will inhibit the ability of vascular system to constrict if pressure suddenly needs to change (standing up quickly) → Drop in bp activates the SNS to release NE in vasculature and heart causing tachycardia

Most A-2 antagonists are reversible, competitive antagonists

Question 14

Describe the actions of B adrenergic antagonists in the body

Answer 14

• Can lower bp primarily by slowing AV node conduction; blocks chances of HCN channel opening
• Inhibit release of renin from kidneys; renin is released when someone has low bp, in HTN patients RAAS is over-activated and renin release is stopped by B-1 blockers
• Can cause bronchoconstriction at B-2 receptors; avoid non-selective in asthma or COPD patients
• Can prevent glycogenolysis in the liver; avoid in diabetic patients
• Can prevent migraines and anxiety associated with public speaking (must be soluble enough to enter the brain)

AEs: sedation, sleep disturbances, nightmares, causing or worsening depression

Question 15

What are some potential therapeutic uses for A adrenergic antagonists?

Answer 15

• HTN
• symptomatic benign prostatic hypertrophy

Question 16

What are some potential uses for B adrenergic antagonists/blockers?

Answer 16

CV: tachycardia, hypertension, myocardial infarction, congestive heart failure, cardiac arrhythmias, coronary artery disease

hyperthyroidism

glaucoma

migraine prophylaxis