SNS agonist Flashcards
Outline the signalling mechanisms at each adrenergic recetor
a1- PLC, IP3, DAG
a2- decrease cAMP (inhibitory)
B1- increase cAMP
B2- increase cAMP
Outline the difference adrenergic receptors present on blood vessels
In skeletal muscle blood vessels, lots of B2++ receptors to cause dilation, but in blood vessels to skin, mucous membranes etc. have a1 effects to constrict (learn receptors for all major sites)
Outline the selectivity of adrenoceptors for adrenalin and NA
noradrnaline more alpha, adrenaline more beta 2
Effect of a2 receptors on presynaptic membrane
NE can bind and then reduce synpatic transmission
Why is adrenaline used in anaphylaxis
- act on a1 receptors of blood vessels to cause vasoconstriction to increase BP
- acts on b1 reeptors on the heart to cause tachycardia
- b2 receptor binding cause bronchodilation
- beta receptors on mast cells which suppresses mediator release
What is the effect of anaphylactic shock
-histamine causes increased permeability of capillary so more fluid loss and vasodilation
Contraction of smooth mscle in resp tract
Contraction of smooth muscle in the GI tract eading to vomiting
Other use of adrenaline other than anaphylaxis
asthma,
acute bronchospasm due to chronic bronchitis,
cardiogenic shock- b1 inotropic (inability of heart to pump sufficient oxygen rich blood),
spinal anaesthesia a1 (to maintain BP), as lidocaine causes fall due to Na+ blockade
local anaesthesia- vasoconstrict to ensure the LA stays local for longer. A1. (infiltration anaesthesia and nerve block anaesthesia)
Side effects of adrenaline
Secretions (reduced and thickened mucous)
Minimal CNS
Minimal GIT
Skeletal muscle temor (adrenergic receptors on skeletal muscle)
CVS: PATCH! palipitations,arrhythmias, tachycardia,
COLD EXTREMITIES, hypertension
Outline selectivity of phenylephrine
a1»a2»>b1/b2
Difference between phenylephrine and adrenaline
Use of phenylephrine
phenylephrine chemically related to adrenaline but more resistant to COMT breakdown (post-synaptic membrane) but not MAO (mitochondria of the presynaptic)
used as nasal degongestant
Why is phenylephrine used as decongestant
Congestion due to capillary leakage in vessels travelling around nasal sinus…. stimulate a1 receptors increase vasocnstriction and reduces leakage
Other phenylephrine uses
Mydriatic (causes pupul dilation)
Anti-glaucoma (as it stimutes constriction of capillaries in the ciliary body, thus preventing movement of substrates from capillaries to ciliary body to make aqeous humour)
(pheNEYElephrine)
N for nose (decongestant)
sounds like EYE for mydriatic
Selectivity of clonidine
a2»a1»>b1/b2
Clonidine mimics sympthetic effects t/f
F! Because you get increased stimulation of a2 prejunctional receptor which causes inhibition of synaptic transmission at sympathetic synapse!
Which receptors would you need to stimulate to reduce glaucoma
a2 receptor agonist- stimulate a2 receptors on epithelium to decrease production of aqueous humour
a1 receptor agonist on the blood vessel so vasoconstrction
Clinical uses of clonidine
treatment of hypertension and migraine (reverse vasoconstriction)
Mechanism of action of clonidine
a2 receptors prejunctionally and also in the CNS,
clonidine has a central action in the brainstem within baroreceptor pathway to reduce sympathetic outflow
AND
a2 adrenoceptor mediated
presynaptic inhibition of NA release
will reduce CO, cause vasodilation etc
…
……
Selectivity of isoprenaline
b1=b2»»a1/2
Compare isoprenaline to adrenaline
chemically related but more resistant to MAO and uptake 1
Clincal uses of isoprenaline
cardiogenic shock, acute heart failure, myocardial infarction
Normally with heart failure you want to reduce myocardial oxygen demand
but HF is associated with low CO, so this is aimed at increasing CO if the HF gets really bad and the CO is dangerously low
Why is the b2 stimulation of isoprenaline a problem
b2 stimulation in VSMC in skeletal muscle blood vessels results in fall in venous BP causing reflex tachycardia via stimulation of baroreceptors. So you want less of the beta 2 effects
State the selectivity of dobutamine
b1»b2»>a1/2
Clincal use of dobutamine
cardiogenic shock, no relfex tachycadia and also short plasma half life (2 mins due to rapid breakdown by COMT, which is a good thing in this case)
T/F dobutamine and salbutamol are both rapidly broken down by COMT
F… dobutamine is, but salbutamol is a wynthetic catecholamine derivate with relative resistance to MAO and COMT
Action of salbutamol
You get increased stimulation of b2 receptors in the lungs, as you get increased cAMP and increased PKA causing bronchodilation due to:
- opening of K+ channels
- Increased Na/Ca2+ exchange to reduce Ca2+ in cell
inhibition of release of brochoconstrictor substances from mast cells.
Clinical use of ventolin
asthma ( b2 relaxation of bronchial smooth muscle, inhibtion of release of bronchoconstrictors from mast cells )
Treatment of threatened premature labour (b2 relaxation of uterine smooth muscle
Side effects of ventoiln
reflex tachycardia (less than isprenaline but still a bit), tremor and blood sugar dysregulation
Outline what happens in anaphylactic shock
Upon secondary exposure to antigen, mast cells degranulate, releasing inflammagtory mediarors:
Heart and CVS:
-Capillaries leak in response to histamine, tissues swell (incl. tongue), blood volume decreses, irregular heartbeat, loss of oxygen to tissue
Respiratory tract:
Constriction of smooth muscle and muscles in throat
Difficulty swallowing and breathing
GI tract:
Contraction of smooth muscle, stomach cramps, vomiting
Consequences of adrenaline overdose
Cerebral haemorrhage
Pulmonary oedema
Why do isoprenaline and phenylephrine AND SALBUTAMOLlast longer in the body than endogenous catcholamines
Name a drug that does not share this property
Because isoprenaline is more resistant to COMT breakdown
Phenylephrine more resistant to MAO and uptake 1
Salbuatmol has relative resistancew to MAO and COMT
so broken down less quickly than adrenaline
Dobutamine has half life of 2 minutes (RAPIDLY metabolised by COMT!)
Why is dobutamine a good drug in emergecny situations
In cardiogenic shock emergency
Lacks reflex tachy
Plasma half life just 2 mins (rapidly metabolised by COMT)
Mast cells contain which adrenergic receptors
b2
