1. Adrenergics & Antiadrenergics Flashcards
What is the pre-cursor to norepinephrine
Dopamine
Rate-limiting enzyme for the biosynthesis of catecholamines
Tyrosine hydroxylase
Role of alpha 1 and alpha 2 adrenoceptors
- Vasoconstriction in visceral organs, mucous membranes and small blood vessels
- Shutting down GI and visceral functions
Role of beta 1 and beta 2 adrenoceptors
- Vasodilation of blood vessels supplying skeletal muscles
- Stimulation of the heart (mainly beta 1)
- Bronchodilation in the lungs (mainly beta 2)
Role of beta 3 adrenoceptors
- Lipolysis
- Thermogenesis
- Relax bladder
Types of direct adrenergic agents
alpha 1: phenylephrine alpha 2: brimonidine non-selective alpha: oxymetazoline beta 1: dobutamine beta 2: salbutamol, terbutaline beta 3: mirabegron non-selective beta: isoprenaline alpha 1 & beta 1: dopamine beta 3: mirabegron both alpha and beta: noradrenaline (more selective at alpha) & adrenaline (more selective at beta)
Uses for noradrenaline
severe hypotension
Uses for adrenaline
- anaphylactic shock
- cardiac resuscitation
- with local anaesthetics
Uses for dopamine
- cardiac resuscitation
2. severe hypotension
Major adverse effects of noradrenaline, adrenaline and dopamine
- hypertension
- tachycardia
- reflex bradycardia
- ventricular arrhythmias
- necrosis due to vasoconstriction at site of injection
Uses for oxymetazoline
nasal decongestant
Major adverse effect of oxymetazoline
rebound congestion
Uses for phenylephrine
- hypotension
2. nasal decongestant
Major adverse effect of phenylephrine
- hypertension
2. reflex bradycardia
Uses for brimonidine
open-angle glaucoma (topical to eye)
Major adverse effect of brimonidine
- hypotension (compare with systemic clonidine)
Uses for isoprenaline
- asthma
2. cardiac resuscitation
Major adverse effects of isoprenaline
- arrhythmias
2. tachycardias
Uses for dobutamine
congestive heart failure
Major advise effect of dobutamine
tachycardia
Uses for salbutamol/terbutaline
- asthma
2. premature labour
Major adverse effects of salbutamol/terbutaline
- arrhythmias
- tachycardia
- vasodilation
Uses for mirabegron
overactive bladder
Major adverse effects of mirabegron
- arrhythmias
2. tachycardias
Types of indirect adrenergic agents
- Inhibition of enzymatic breakdown of catecholamines: moclobemide
- Block of uptake 1: tricyclic antidepressants
- Displacement of endogenous noradrenaline: ephedrine and pseudoephedrine
MOA & uses of moclobemide
- MAO A inhibitor increases the biological availability of catecholamines
- Used as antidepressant
MOA & uses of tricyclic antidepressants
- Increases synaptic availability of NA but not adrenaline
- Mood enhancing effects in the CNS
- Used as antidepressant
MOA & uses of ephedrine and pseudoephedrine
- Taken up into the adrenergic terminals and compete with NA for vesicular compartment
- Ephedrine and pseudoephedrine are also competitive substrates for MAO
- Used as nasal decongestant
*ephedrine has additional alpha and beta-adrenoceptor agonist activity
Types of direct antiadrenergic agents
alpha 1: prazosin
non-selective alpha: phenoxybenzamine
beta 1: atenolol, betaxolol
non-selective beta: propranolol, sotalol, timolol
MOA & uses of phenoxybenzamine
- Irreversible and non-selective alpha-adrenoceptor antagonist
- Management of pheochromocytoma
Major adverse effects of phenoxybenzamine
- postural hypotension
- reflex tachycardia
- nasal congestion
- inhibition of ejaculation
- drowsiness
MOA & uses of prazosin
- alpha1-adrenoceptor antagonist
- block vasoconstriction (esp. visceral blood flow)
- used to treat chronic hypertension and urinary symptoms of BPH
Adverse effects of prazosin
- nasal congestion
- abnormal ejaculation
- drowsiness
- tachycardia (less common)
MOA and uses of propranolol
- beta-adrenoceptor antagonist
- used to treat hypertension, angina, arrhythmias, excessive catecholamine action in hyperthyroidism
- additional antihypertensive action due to block of renin by beta1 antagonism
MOA & uses of sotalol
- beta-adrenoceptor antagonist
- beta-blocker (class II antiarrhythmic)
- prolongation of cardiac action potential duration (class III antiarrhythmic)
- additional antihypertensive action due to block of renin by beta1 antagonism
Major adverse effects of propranolol and sotalol
- Bronchoconstriction: contraindicated in asthma
- Heart failure
- Propranolol has direct membrane effects (local anaesthetic-like actions) hence not used as topical application to the eye
MOA & uses of timolol
- beta-adrenoceptor antagonist
- used to treat glaucoma (reduces intraocular pressure by decreasing aqueous secretion from the ciliary epithelium)
- no local anaesthetic action therefore better for topical application to the eye as it does not block protective reflexes
Major adverse effects of timolol
topical application to eye limits systemic adverse effects
MOA & uses of atenolol
- beta1-adrenoceptor anatagonist
2. used to treat hypertension, angina, MI
Atenolol is contraindicated for use in?
Topical application to the eye as it has direct membrane effects at high concentration (local anaesthetic-like actions)
MOA & uses of betaxolol
- beta1-adrenoceptor antagonist
- used for treatment of glaucoma
- no local anaesthetic action
Major adverse effects of betaxolol
topical application to eye limits systemic adverse effects
Is there a need to exercise caution when using beta1-adrenoceptor antagonists in asthmatics?
YES! Although relatively selective for beta1-adrenoceptors, still have some level of beta2-adrenoceptor antagonism
Beta-blockers have to be used with caution in what medical condition
Diabetes! They can mask symptoms of hypoglycaemia (e.g. tremor, heart pounding)
Types of indirect antiadrenergic agents
- Agonists at presynaptic autoreceptors: dexmedetomidine, clonidine
- Decreasing noradrenaline synthesis: Methyldopa
MOA & uses of dexmedetomidine
- act as a presynaptic alpha2-adrenoceptor agonist which are autoreceptors involved in feedback inhibition of NA release, hence decreasing NA release
- decrease in NA reduces visceral vasoconstriction and in CNS causes sedation and hypotension
- used as a sedative
Adverse effects of dexmedetomidine
- hypotension
2. dry mouth
MOA & uses of methyldopa
- inhibits tyrosine hydroxylase, the rate limiting enzyme in adrenaline and noradrenaline synthesis
- results in the formation of false neurotransmitter methylnoradrenaline
- presynaptic alpha2-adrenoceptor agonist
- used in the treatment of hypertension
Adverse effects of methyldopa
- Haemolytic anemia
2. Hepatotoxicity