Metabolic responses to adrenaline Flashcards
Adrenaline generally helps prepare ?
The body for increased activity/action by mobilising fuels and improving delivery of oxygen to the tissues
What can adrenaline be a response to ?
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)
Adrenaline and noradrenaline are Catecholamine hormones. Explain this ?
- 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
What are the different Adrenergic receptor classifications ?
- 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
Explain the Adrenergic receptor second messengers?
- Different receptors have different sensitivity to hormones (and to levels of hormones)
- Note that alpha2 and beta2 are directly antagonistic
Explain β2 adrenergic receptors ?
- 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
E.g. what would mild stress cause ?
Mild stress will cause you to blush – vasodilation but extreme stress will cause you to turn very pale – vasoconstriction
Which response to GPCR stimulation would be most rapid?
Activation of a G protein that regulates the opening of an ion channel
Drugs can potentially either ?
Stimulate or inhibit GPCR signalling
Adrenaline as a drug: treatment of anaphylaxis
- 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
What do agonists do to receptors ?
Agonists stimulate the receptors
Explain the clinical uses of adrenoceptor agonists: Cardiovascular system ?
- cardiac arrest: adrenaline
- cardiogenic shock: dobutamine(β1-agonist)
Explain the clinical uses of adrenoceptor agonists: Anaphylactic shock (acute hypersensitivity) ?
shock (acute hypersensitivity)
Explain the clinical uses of adrenoceptor agonists: Respiratory system ?
- 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
What is Clonidine ?
- Clonidine: alpha2 agonist, treats hypertension & anxiety, ADHD (affects receptors primarily in the brain)
Explain the clinical uses of adrenoceptors antagonists ?
- These are drugs which antagonise the receptor action of adrenaline and related drugs
- They are competitive antagonists at α or β or both
Name non-selective alpha antagonists ?
- Ergot alkaloids: Ergotamine (migraine)
- Imidazolines: Phentolamine (hypertensive emergency)
Name selective alpha antagonists ?
- α1 selective- Prazosin, Doxazosin (high blood pressure, anxiety)
- α2 selective- Yohimbine (reverses sedation in animals)
What are Beta adrenergic antagonists ?
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
Give examples of non-selective, beta1 selective and with additional alpha blocking property ?
- Non-selective, e.g. propranolol, sotalol
- Beta1 selective, e.g. atenolol, metoprolol
- With additional alpha blocking property, e.g. labetalol, carvedilol
What is the cardiovascular use of beta adrenergic antagonists?
Cardiovascular use: Hypertension, Congestive heart failure, Angina pectoris, cardiac arrhythmias, myocardial infarction
Use of Anti-anxiolytic ?
Anti-anxiolytic: Used in treatment of anxiety (reduces physical manifestations), stress
What is metoprolol ?
Metoprolol, a beta blocker, is used to treat hypertension by acting as an antagonist to the β1-adrenergic receptor
What determines the effectiveness of metoprolol ?
The types of alleles for the β1-adrenergic receptor that an individual possesses determine the effectiveness of metoprolol
