SNS agonists Flashcards
how do directly acting sympathomimetics work?
- mimic actions of NA/A by binidng to and stimulating adrenoreceptors
- used principally for their actions in CVS, eyes, lungs
what do the adrenoreceptors in the eye do?
- ALPHA 1: contraction of iris radial muscle
- BETA: aqueous humour proudction by ciliary body
what do the adrenoreceptors do in the trachea and bronchioles?
- BETA 2: dilate
what do the adrenoreceptors in the liver do?
- ALPHA 1: glycogenolysis
- BETA 2: gluconeogenesis
what do the adrenoreceptors in the adipose tissue do?
- ALPHA 1, BETA 1: lipoylsis
what do adrenoreceptors do in the kidney?
- BETA 1: inc. renin release
what do adrenoreceptors do in the urinary bladder?
- BETA 2: relaxes detrusor
- ALPHA 1: constricts trigone and sphincter
what do adrenoreceptors do in the ureter?
- ALPHA 1: inc. motility and tone
what do adrenoreceptors do in male genitalia?
- ALPHA 1: stimulates ejaculation
what do adrenoreceptors do in the lacrimal glands?
- ALPHA 1: stimulates tears
what do adrenoreceptors do in salivary glands?
ALPHA/BETA: thick viscid secretion
what do adrenoreceptors do in heart?
BETA 1: inc. rate and contractility
what do adrenoreceptors do in GIT?
ALPHA/BETA: dec. muscle motility and tone, contraction of sphincters
what do adrenoreceptors do in female genitalia?
- BETA 2: relaxation of uterus
what do adrenoreceptors do in blood vessels?
- BETA 2: skeletal muscle blood vessel dilation
- ALPHA 1: skin, mucus membranes, splanchnic are, abdo viscera, salivary gland bloos vessels construction
what is the noradrenaline selectivity?
- sensitive to alpha
- alpha 1 = alpha 2 > beta 1 = beta 2
what is the adrenaline selectivity?
- sensitive to beta
- beta 1 = beta 2 > alpha 1 = alpha 2
where is NA synthesised? A?
NA in nerve terminals
A in adrenal medulla
what is the -ve feedback on NE?
NE binding to prejunctional alpha 2 adrenoceptors negatively feedbacks on NE exosytosis
name 6 directly acting SNS agonists and what they are selective for?
- adrenaline: non selective
- phenylephrine: alpha 1 selective
- clonidine: alpha 2 selective
- isoprenaline: beta selective
- dobutamine: beta 1 selective
- salbutamol: beta 2 selective
how is adrenaline used in the treatment of anaphylaxis?
- Adrenaline non selective
management of: - airways: beta 2 = bronchodilation
- tachycardia: beta 1 = reduced chronotropic and ionotropic effect
- peripheral vasodilation: alpha 1 = vasoconstriction
- suppression of mediator reelease
why is adrenaline used in COPD management?
- asthma management of: - airways, breathing: beta 2 = bronchodilation - suppression of mediator release - selective beta 2 agonsist preferable
why is adrenaline used in glaucoma management?
- inc. IOP
- vasoconstriction of ocular blood vessels restricts blood flow so production of aqueous humour
- ALPHA 1: vasoconstriction, dec. in IOP
what are some other uses of adrenaline?
- cardiogenic shock (beta 1 actions)
- spinal anaesthesia (maintain BP)
- local anaesthesia (prolong duration of action using alpha 1)
what are the unwanted actions of adrenaline?
- secretions: reduced and thickened
- CVS: tachycardia, palpitations, arrhythmia, cold extremities, hypertension
- skeletal muscle: tremor
what is the selectivity of phenylephrine?
most selective to least selective
alpha 1
alpha 2
beta 1/2
what is the difference between adrenaline and phenylephrine?
- molecularly similar to adrenaline
- but resistance to COMT (but not MAO)
what are the clinical uses of phenylephrine?
- vasoconstriction
- mydriasis - dilation
- nasal decongestant via vasoconstriction
what is the selectivity of clonidine?
most selective to least selective
alpha 2
alpha 1
beta 1/2
where does clonidine act?
mainly on prejunctional neuronal alpha2-receptor to inhibits NA release
what are the clinical uses of clonidine?
- treatment of hypertension and migraine
- reduces sympathetic tone (alpha 2 mediated presynaptic inhibition of NA release, central brainstem action within baroreceptor to reduce sympathetic outflow)
what is the selectivity of isoprenaline?
beta 1/2»_space; alpha 1/2
what is the structure of isoprenaline?
- molecularly similar to adrenaline
- less susceptible to uptake 1 and MAO breakdown
- fast plasms half life of 2 hrs
what are the clinical uses of isoprenaline?
- cardiogenic shock
- acute HF
- MI
- CAUTION: beta 2 stimulaiton in VSM in skeletal muscle triggers a fall in venous BP, trigger reflex tachycardia via BR stimulation
what is the selectivity of dobutamine?
beta 1» beta 2»_space;> alpha 1/2
describe the pharmacokinetics of dobutamine?
admin by IV infusion
very short half life of 2 mins
rapidly metabolsied by COMT
what are the uses of dobutamine?
- cardiogenic shock
- lacks isoprenaline’s reflec tachycardia
what is the selectivity of salbutamol?
beta 2»_space; beta 1»_space;> alpha 1/2
what is the structure of salbutamol?
synthetic catecholamine
resistance to COMT and MAO
what are the clinical uses?
- treatment of asthma (beta 2 relaxation of SM, inhibition of release of bronchoconstriction substances)
- treatment of threatened premature labour (beta 2 relaxation of SM)
what are the side effects of salbutamol?
- reflex tachycardia
- tremor
- blood sugar dysregulation
name an indirectly acting SNS agonist. what is it’s MoA?
- cocaine
- uptake 1 blocker
what are the CNS effects of cocaine?
low doses: euphoria, excitement, inc, motor activity
high doses: activation of CTZ, CNS depression, resp failure, convulsions, death
what are the CVS effects of cocaine?
low doses: tachycardia, vasoconstriction, raised BP
high doses: VF and cardiac arrest
what is tyramine? what is the problem with it?
- false neurotransmitter
- usually not a problem when the normal mechanisms for degradation are in place
what happens when there is inhibited MAO?
- tyramine admin can compete with any MAO left
- lead to a massive hypertensive crisis when NA build up is more than usual
describe the actions of tyramine
- weak action at the receptors for NA
- weak inhibitory effect on the uptake 1
- displaces NA form vesicles
- competes for MAO breakdown so less breakdown of NA
- leakage of NA out of vesicles
