Metabolic responses to adrenaline

Question 1

Adrenaline generally helps prepare ?

Answer 1

The body for increased activity/action by mobilising fuels and improving delivery of oxygen to the tissues

Question 2

What can adrenaline be a response to ?

Answer 2

It can be a response to low blood sugar, activity (e.g. exercise), or a more serious situation, as part of the fight or flight response (with noradrenaline and other hormones)

Question 3

Adrenaline and noradrenaline are Catecholamine hormones. Explain this ?

Answer 3

• Synthesised in chromaffin cells of adrenal medulla
• Made from the amino acid L-tyrosine
• Concentrated in storage vesicles and released
  Released via sympathetic innervation in response to stress or low blood glucose
• Effects in muscle through beta-adrenergic receptors and increased cAMP
• Response may also be through α1 and α2-adrenergic receptors

Question 4

What are the different Adrenergic receptor classifications ?

Answer 4

• There are two main classes: alpha and beta receptors, discovered by Alquist in 1948
• These are further subdivided into alpha1, alpha2 and beta1, beta2 and now beta3

Question 5

Explain the Adrenergic receptor second messengers?

Answer 5

• Different receptors have different sensitivity to hormones (and to levels of hormones)
• Note that alpha2 and beta2 are directly antagonistic

Question 6

Explain β2 adrenergic receptors ?

Answer 6

• Activates adenylate cyclase and makes cAMP where as α2 inhibits adenylate cyclase and blocks cAMP production: these are always directly antagonistic
• High levels of hormone will activate α2 receptors and override the β2 signalling

Question 7

E.g. what would mild stress cause ?

Answer 7

Mild stress will cause you to blush – vasodilation but extreme stress will cause you to turn very pale – vasoconstriction

Question 8

Which response to GPCR stimulation would be most rapid?

Answer 8

Activation of a G protein that regulates the opening of an ion channel

Question 9

Drugs can potentially either ?

Answer 9

Stimulate or inhibit GPCR signalling

Question 10

Adrenaline as a drug: treatment of anaphylaxis

Answer 10

• Anaphylaxis is an extreme allergic reaction
• Inflammatory mediators such as histamine cause low blood pressure, constriction of the airways, and oedema
• Injection of adrenaline (“Epipen”) is the treatment of choice to reverse effects

Question 11

What do agonists do to receptors ?

Answer 11

Agonists stimulate the receptors

Question 12

Explain the clinical uses of adrenoceptor agonists: Cardiovascular system ?

Answer 12

• cardiac arrest: adrenaline

- cardiogenic shock: dobutamine(β1-agonist)

Question 13

Explain the clinical uses of adrenoceptor agonists: Anaphylactic shock (acute hypersensitivity) ?

Answer 13

shock (acute hypersensitivity)

Question 14

Explain the clinical uses of adrenoceptor agonists: Respiratory system ?

Answer 14

• Asthma : selective β2-receptor agonists: salbutamol, terbutaline, salmeterol, formoterol. Bronchodilators: open up airways
• nasal decongestion: drops containing oxymetazoline (α1) for short-term use. Cause vasoconstriction in the mucous membranes

Question 15

What is Clonidine ?

Answer 15

• Clonidine: alpha2 agonist, treats hypertension & anxiety, ADHD (affects receptors primarily in the brain)

Question 16

Explain the clinical uses of adrenoceptors antagonists ?

Answer 16

• These are drugs which antagonise the receptor action of adrenaline and related drugs
• They are competitive antagonists at α or β or both

Question 17

Name non-selective alpha antagonists ?

Answer 17

• Ergot alkaloids: Ergotamine (migraine)

- Imidazolines: Phentolamine (hypertensive emergency)

Question 18

Name selective alpha antagonists ?

Answer 18

• α1 selective- Prazosin, Doxazosin (high blood pressure, anxiety)
• α2 selective- Yohimbine (reverses sedation in animals)

Question 19

What are Beta adrenergic antagonists ?

Answer 19

Commonly called “Beta blockers”: first generation were non-selective; second generation are specific for beta1 receptors; third generation may have additional alpha blocking effects for vasodilation

Question 20

Give examples of non-selective, beta1 selective and with additional alpha blocking property ?

Answer 20

• Non-selective, e.g. propranolol, sotalol
• Beta1 selective, e.g. atenolol, metoprolol
• With additional alpha blocking property, e.g. labetalol, carvedilol

Question 21

What is the cardiovascular use of beta adrenergic antagonists?

Answer 21

Cardiovascular use: Hypertension, Congestive heart failure, Angina pectoris, cardiac arrhythmias, myocardial infarction

Question 22

Use of Anti-anxiolytic ?

Answer 22

Anti-anxiolytic: Used in treatment of anxiety (reduces physical manifestations), stress

Question 23

What is metoprolol ?

Answer 23

Metoprolol, a beta blocker, is used to treat hypertension by acting as an antagonist to the β1-adrenergic receptor

Question 24

What determines the effectiveness of metoprolol ?

Answer 24

The types of alleles for the β1-adrenergic receptor that an individual possesses determine the effectiveness of metoprolol