8 - SNS Agonists Flashcards
What is a main difference between cholinergic and adrenergic drugs?
Adrenergic drugs are much more selective for the alpha and beta subtypes, which means that the side effect profile is not as bad
What do adrenergic agonists do?
They mimic the effects of A or NorA; used in the CVSm eyes and lungs
What are the 4 different adrenergic receptor transducer systems?
They are G coupled protein receptors
a1 - PLC, IP3, DAG
a2 - decreased cAMP
b1 - increased cAMP
b2 - increased cAMP
Why is the a2 receptor unique?
It is prejunctional and inhibitory
Inhibits NorA release, negative feedback
Therefore an a2 agonist will decrease sympathetic function
What are the relative selectivities of NorA and A between the a and b receptors
NorA more a but some b
A more b but some a
N.B. However compared to drugs, both can act on all receptors
How does cocaine work?
It blocks the neuronal reuptake of NorA
Give an example of an SNS agonist for each adrenoceptor subtype
Adrenaline (non-selective)
Phenylephrine (a1) Clonidine (a2) Isoprenaline (b1=b2) Dobutamine (b1) Salbutamol (b2)
Outline the properties, 4 uses and effects of adrenaline
Non-selective
Allergic reactions and anaphylactic shock
Slightly more selective for b receptors so b effects will be more powerful
b2 bronchodilation (via physiological antagonism)
b1 tachycardia
a1 vasoconstriction
+ suppression of mediator release
b2 Asthma (emergencies) and bronchospasm (chronic bronchitis/emphysema)
b1 Cardiogenic shock (inotropic effect, increases FOC)
a1 spinal and local anaesthesia (keeps TPR and BP up, also prolongs action by keeping blood in area)
What are some side effects of adrenaline?
Reduced and thickened secretions
Tachycardia, palpitations, arrhythmias
Cold extremities, hypertension
Overdose - cerebral haemorrhage, pulmonary oedema
Tremor
Outline the properties, uses and effects of phenylephrine
a1 selective - modified adrenaline (extra hydroxyl group); more resistant to breakdown by COMT not MAO (COMT is peripheral, MAO is central) - longer lasting than adrenaline in peripheral tissues
Decongestant* (e.g. sudafed) via a1 vasoconstriction
Mydriatic (pupil dilation)
*Congestion is caused by white cell infiltration, vasoconstriction reduces infiltration and fluid exudation, reduces mucus buildup
Outline the properties, uses and effects of clonidine
a2 selective - works like an antagonist
Glaucoma - a2 agonist at ciliary body (prevents aqueous humour formation), more powerful a1 agonist (vasoconstriction as aqueous humour is produced from blood)
Hypotension and migraine (vasodilation causes migraine?) - reduces sympathetic tone via a2 adrenoceptor mediated presynaptic inhibition of NorA release and central action in brainstem within baroreceptor firing pathway
Outline the properties, uses and effects of isoprenaline
b1=b2 selective - similar to adrenaline (more resistant to MAO and uptake 1
cardiogenic shock
acute heart failure
myocardial infarction
asthma (historically)*
*b2 stimulation causes vasodilation in vascular smooth muscle - the profound drop in BP causes reflex tachycardia via stimulation of baroreceptors when isoprenaline is being used to treat asthma
Outline the properties, uses and effects of dobutamine
b1 selective
Cardiogenic shock
- lacks isoprenaline’s reflex tachycardia\
- plasma half-life is 2 mins (rapidly metabolised by COMT)
Outline the properties, uses and effects of salbutamol (Ventolin)
b2 selective - synthetic catecholamine derivative w/ relative resistance to COMT and MAO
Asthma - relaxation of bronchial smooth muscle and inhibition of release of bronchoconstrictor substances from mast cells
Threatened premature labour - b2 relation of uterine smooth muscle
b2 receptor - cAMP - PKA - potassium efflux - muscle relaxation
Outline the side effects of salbutamol (Ventolin)
Reflex tachycardia
Tremor
Blood sugar dysregulation
