Adrenergics & Anti-adrenergics Flashcards
What are adrenergic drugs?
Sympathomimetic drugs – mimic the action of adrenaline or noradrenaline released by the nervous sytem
What are the two structural types of direct adrenergic drugs?
Catecholamines (similar structure to endogenous adrenaline) and non-catechol
What are the adrenergic receptors?
Alpha 1, 2 & Beta 1, 2 ,3
What is an alpha-1 selective adrenoreceptor agonist?
Phenylephrine
What is an alpha-2 selective adrenoreceptor agonist?
Brimonidine
What is a non-selective alpha receptor agonist?
Oxymetazoline
What is both an alpha 1 and beta 1 agonist?
Dopamine
What is a beta-1 selective adrenoreceptor agonist??
Dobutamine
What are two beta-2 selective adrenoreceptor agonists?
Salbutamol and Terbutaline
What is a beta-3 selective adrenoreceptor agonist?
mirabergon
What are two non-selective sympathomimetic drugs?
Epinephrine & norepinephrine
Is it possible to have complete selectivity for beta receptors? Why?
No - the receptors are structurally similar, so selectivity is dose-dependent
What is oxymetazoline used for and why?
Used topically to reduce mucus – causes vasoconstriction of nasal mucosa.
Has little systemic absorption so few side effects
Can phenylephrine be taken orally?
Yes, due to its selectivity – unlikely to have unwanted adverse effects due to activation of other receptors
Name the important receptors and the organs/functions they are specific to.
A2 receptors mediate secretions, B1 receptors mediate the heart and B2 receptors mediate the lungs
Why is isoprenaline not really used now?
It is non-selective. When used to treat asthma by activating beta 2 receptors, it causes unwanted tachycardia by activating beta 1 receptors
What is a drug used to treat urinary incontinence and what is its mechanism of action?
Mirabergon. It activates b3 receptors and causes bladder relaxation
What is dopamine used for and why?
Severe heart failure. Acts on alpha 1 receptors to cause peripheral vasoconstriction, shunting blood to the important organs. Acts on b1 receptors to stimulate the heart.
What is an adrenoreceptor agonist used to treat glaucoma?
Brimonidine. It is a selective a2 receptor activator. It induces vasoconstriction in the eye and reduces secretion of intraocular fluid, decreasing intraocular pressure. It also has a cytoprotective effect in the eye, slowing death of the retinal ganglia.
What are two drugs used for asthma and their MOA?
Salbutamol and terbutaline – by causing bronchodilation
What is the difference between salbutamol and terbutaline?
Salbutamol has a catechol structure while terbutaline does not – salbutamol thus has a short half life
Explain the idea of reflexive bradycardia:
When there is too much beta 1 stimulation, heart is too stimulated and blood pressure increases too quickly. This leads to a reflexive slowing down of the heart by the body
Indirect agonist adrenergic drugs act indirectly by….
increasing the extracellular levels of endogenous catecholamines
Explain the storage of noradrenaline
Stored in vesicles and replenished by the vesicular uptake of newly synthesized NA. It is also recycled by re-uptake via presynaptic uptake 1
Explain monoamine oxidases and their function
They are enzymes that catabolise catecholamines to aldehydes.
Found on the mitochondrial surface, mainly in nerve terminals, liver and intestines.
Has MAOA - breaks down NA - and MAOB - breaks down dopamine
Explain catechol - O - methyltransferase (COMT)
It is found in all tissues, and breaks down most catecholamines and by-products of MAO to methoxy derivatives
What are the three mechanisms of indirect adrenergic drugs (no need to go into detail)
- Inhibiting the breakdown of catecholamines
- Blocking presynaptic uptake 1
- Displacing endogenous NA from vesicles
Explain the mechanism of inhibition of the breakdown of catecholamines, as well as an example of an inhibitor.
Works by inhibiting monoamine oxidases – thus preventing the breaking down of the catecholamines –> increases availability.
An example is moclobemide –> used as an anti-depressant as it crosses the BBB to work on the CNS. The resultant increase in availability of catecholamines helps improve mood.
What are the adverse effects of indirect adrenergic activators?
Adverse effects: increases HR, chronotropic (increases hr and rhythm) and inotropic (increases force of heartbeat). Also causes GI slowing and constipation.
Basically overstimulation of the sympathetic system
Explain the mechanism of blocking presynaptic uptake 1, and an example.
By blocking the presynaptic uptake 1, synaptic availability of NE is increased. However, it doesn’t increase availability of epinephrine bc the affinity of uptake is much greater for NE. This also has mood-enhancing effects – mainly used as anti-depressants.
An example is tricyclic antidepressants.
Explain the mechanism of displacement of endogenous NE, and two examples.
The drugs are taken into synaptic terminals, where they compete with NE for vesicles. This reduces the amount of NE that can be stored, increasing availability.
They also compete for MAO, preventing breakdown of catecholamines.
Two examples are ephedrine and pseudoephedrine
What are anti-adrenergic drugs?
Drugs that block the action of NE or epinephrine
What is an adrenoreceptor antagonist used as an anti-arrhythmic agent? What is its MOA?
Sotalol
It prolongs cardiac action potential duration.
Why are there no beta 3 antagonists?
Beta 3 mediates urinary continence and lipolysis,
What is phenoxybenzamine used for?
It is an irreversible, non-selective alpha adrenoreceptor antagonist.
used to treat the symptoms of pheochromocytomas (which produces excess NE and epinephrine). It covalently binds to provide a 14-48h block
it also has actions on histamine, acetylcholine and serotonin receptors
What are the adverse effects of alpha adrenoreceptor antagonists?
Postural hypotension and reflex tachycardia (due to blood pooling in the peripheries)
Nasal congestion
Inhibition of ejaculation and drowsiness (CNS effects)
What do the alpha-1 antagonists and what are they used to treat?
Prazosin, azosin. They are used to treat hypertension by blocking vasoconstriction.
They are also used to treat benign prostatic hyperplasia, by relaxing the bladder and inhibiting urination.
What are some beta-blockers/beta adrenoreceptor antagonists?
Non-selective: propanolol, sotalol and timolol
beta 1 selective (somewhat): atenolol and betaxolol
What is propanolol used for?
It is a non-selective beta blocker.
Quite general. Used for hypertension, agina, arrythmias, excessive catecholamine action, and hyperthyroidism.
To note: it has local anaesthetic effects
Explain how b1 antagonism is anti-hypertensive
Blocks renin secretion
What are some adverse effects of non-selective beta-blockers?
Bronchoconstriction (no go if has asthma), heart failure
What is timolol used for and why?
Used to treat glaucoma. Reduces secretion of intraocular fluid so decreased IOP.
Has no local anaesthetic effects so doesn’t affect blinking (blinking affects the clearance of the fluid and thus increases IOP).
Topical application of timolol ensures fewer systemic effects
What is atenolol used for?
Mainly cardiac: hypertension, angina, MI.
Has local anaesthetic effects and so cannot be administered topically
What is betaxolol used for?
Honestly q similar to timolol. For glaucoma, no local anaesthetic action.
Topical application so few systemic effects
Has some B2 antagonism so cannot use for asthmatic patients
What are the two mechanisms of indirect antiadrenergic agents?
Agonists at presynaptic uptake receptors
Decreasing NE synthesis
Explain agonists at presynaptic uptake receptors, with examples.
Presynaptic alpha 2 adrenoreceptors are involved in feedback inhibition of NE release
Agonists decrease NE release. This results in reduced visceral vasoconstriction and CNS sedation – hypotension
For eg. dexmedetomidine as a sedative –> hypotension and dry mouth
Explain the mechanism of decreasing NE synthesis, with examples.
For example, methyldopa.
It mimics L-DOPA, which is an alpha 2 adrenergic angonist.
It thus inhibits tyrosine hydroxylase, which is essential in the rate-limiting step in catecholamine synthesis.
Used to treat hypertension.
What are possible side effects of methyldopa?
Haemolytic anaemia
Can cause hepatotoxicity. Contraindicated if past history of methyldopa-induced liver dysfunction)
