sympathetic nervous system Flashcards
adrenoceptor agonists: list the clinical uses, principal pharmacological features, mechanism of action and unwanted effects of selective and non-selective α and β adrenoceptor agonists
where are a1, a2, B1 and B2 (also B3) adrenoceptors located
SNS: post-ganglionic neurone to effector organ, adrenal medulla to effector organ
what do adrenoceptor agonists do
mimic actions of noradrenaline or adrenaline by binding to and stimulating adrenoceptors
what type of receptor are adrenoceptors
type 2 (G-protein coupled receptor)
secondary messengers of a1
PLC, IP3, DAG
secondary messengers of a2
downregulate cAMP so Gi (negative feedback receptor)
secondary messengers of B1
upregulate cAMP
secondary messengers of B2
upregulate cAMP
where are adrenoceptor agonists used principally
CVS, eyes, lungs
eye: adrenoceptor, importance and effect
a1, important, dilation; B, vaguely important, aqueous humour production by ciliary body
trachea and bronchioles: adrenoceptor, importance and effect
B2, vaguely important, dilation
liver: adrenoceptor, importance and effect
a1 and B2, very important, glycogenolysis and gluconeogenesis
adipose: adrenoceptor, importance and effect
a1 and B1, important, lipolysis
kidney: adrenoceptor, importance and effect
B1, important, increased renin secretion
ureters and bladder: adrenoceptor, importance and effect
B2, vaguely important, detrusor relaxation; a1, important, trigone and sphincter contraction
salivary glands: adrenoceptor and effect
a/B, thick and viscous secretions
skin: adrenoceptor, importance and effect
a1, very important, piloerection; increased sweating (cholinergic)
heart: adrenoceptor, importance and effect
B1, important, increased rate and contractility
GI: adrenoceptor and effect
a/B, decreased motility and tone, sphincter contraction
blood vessels to skeletal muscle: adrenoceptor, importance and effect
B2, important, dilation
blood vessels to skin, mucous membranes and splanchnic area: adrenoceptor, importance and effect
a1, very important, constriction
what endogenous agonists can activate all adrenoceptors
noradrenaline and adrenaline
relative selectivity for noradrenaline of adrenoceptors
a1 = a2 > B1 = B2; still selective to both
relative selectivity for adrenaline of adrenoceptors
B1 = B2 > a1 = a2; still selective to both
noradrenaline metabolism, release and uptake
tyrosine -> noradrenaline by enzymatic steps (incl. in vesicle) -> action potential promotes exocytosis -> has effect -> removed from synpase by transport proteins into tissue (a2 is presynpatic receptor and inhibits noradrenaline release, suppressing SNS) or nerve
5 directly acting SNS adrenoceptor agonsists and relevant adrenoceptor
adrenaline (non-selective), phenylephrine (a1), clonidine (a2), dobutamine (B1), salbutamol (B2)
why is adrenaline used in anaphylaxis treatment and relevant adrenoceptors
opens airways (B2 - bronchodilation); causes vasoconstriction (a1) and so increases TPR and blood pressure (as histamine acts as vasodilator); increases heart rate (B1 - tachycardia); suppresses mediator release from mast cells (B receptors present); stomach cramps prevented as SNS effect relaxes gut motility etc.
5 other clinical uses of adrenaline and relevant adrenoceptors
in asthma (B2: IM, SC; bronchodilation and mediator release); acute bronchospasm associated with chronic bronchitis or emphysema (B2); cardiogenic shock - sudden inability of heart to pump sufficient oxygen-rich blood (B1); spinal anaesthesia (a1: maintains blood pressure by vasoconstriction); local anaesthesia (a1: vasoconstricts - prolongs action to stop it getting into systemic circulation)
5 locations of unwanted actions of adrenaline (non-selective)
secretions, CNS (minimal), CVS, GIT (minimal), skeletal muscle
unwanted actions of adrenaline (non-selective) on secretions
reduced, thickened mucous
unwanted actions of adrenaline (non-selective) on CVS, including if overdose
tachycardia, palpitations, arrhythmias; cold extremities (vasoconstriction), hypertension; overdose - cerebral haemorrhage, pulmonary oedema
unwanted action of adrenaline (non-selective) on skeletal muscle
tremor (typically due to noradrenaline)
example of a selective a1 adrenoceptor agonist, and relevant adrenoceptor selectivity
phenylephrine: a1»a2»>B1/B2; chemically related to adrenaline
clinical uses of phenylephrine
nasal decongestant, vasoconstriction, mydriatic (pupil dilation)
why mght phenylephrine be used as a decongestant
vasoconstriction, so less white cell invasion and oedema into sinus (which is mucous)
phenylephrine relative duration in peripheral vs central
more resistant to COMT (peripheral enzyme) not MAO (central enzyme), so longer lasting in peripheral tissue
example of a selective a2 adrenoceptor agonist, and relevant adrenoceptor selectivity
clonidine: a2»a1»>B1/B2
how does clonidine work
a2 agonist so negative feedback, preventing noradrenaline release, looking like SNS antagonism
sympathomimetics treating glaucoma: cause and consequence
caused by increase in intraocular pressure due to poor drainage of aqueous humour produced by cilliary body by blocked venous drainage channels; if untreated, permanently damages optic nerve, causing blindness
sympathomimetics: which 2 areas are targeted by sympathomimetics to cause decreased glaucoma risk
in cilliary body, agonise a1 to cause vasoconstriction (restricts blood flow and thus aqueous humour production by limiting fluid loss), and agonise a2 to cause decreased humour formation; don’t activate B1 with agonist as this stimulates aqueous humour production
3 clinical uses of clonidine
treat glaucoma; treat hypertension and migraine (possible link); reduce sympathetic tone
how does clonidine reduce sympathetic tone and therefore blood pressure
stimulates a2 adrenoceptor of presynpatic neurone, inhibiting noradrenaline release; central action in brainstem within baroreceptor pathway to reduce symapthetic outflow
example of a selective B adrenoceptor agonist, and relevant adrenoceptor selectivity
isoprenaline: B1=B2»»a1/a2; chemically related to adrenaline
isoprenaline resistance to degradation and uptake and relevant location
more resistant to MAO and uptake 1 so used in brain not peripherally
clinical uses of isoprenaline
cardiogenic shock, acute heart failure, myocardial infarction
why might B2 receptor stimulation be a problem using isoprenaline
stimulates vasodilation in vascular smooth muscle in skeletal muscle, resulting in fall in venous blood pressure, triggering tachycardia via baroreceptor stimulation (reflex tachycardia)
example of a selective B1 adrenoceptor agonist, and relevant adrenoceptor selectivity
dobutamine: B1»B1»>a1/a2
clinical use of dobutamine
cardiogenic shock
why is dobutamine used to treat cardiogenic shock
lacks isoprenaline’s reflex tachycardia, and has a plasma half life of 2 minutes as rapidly metabolised by COMT so acute effect
example of a selective B2 adrenoceptor agonist, and relevant adrenoceptor selectivity
salbutamol (ventolin): B2»B1»>a1/a2
salbutamol resistance to degradation
synthetic catecholamine derivative with relative resistance to MAO and COMT
2 clinical uses of salbutamol
treatment of asthma, treatment of threatened premature labour
how does salbutamol treat asthma
B2 relaxation of bronchial smooth muscle; upregulates cAMP, leading to hyperpolarisation as K+ efflux so harder for action potential to be triggered, causing muscle relaxation; inhibition of release of bronchoconstritor substances from mast cells
how does salbutamol treat threatened premature labour
B2 relaxation of uterine smooth muscle
side effects of salbutamol use
reflex tachycardia, tremor, blood sugar dysregulation
