SNS Agonists Flashcards
Difference between adrenoceptors, nicotinic and muscarinic drugs?
Do NOT really have specific GBDs or MRAs
BUT
DO HAVE selective adrenoceptor drugs
How do Alpha-1 and 2 work?
Alpha-1:
x PLC, IP3 & DAG
Alpha-2:
x DOWNREGULATES cAMP
How do Beta-1 and 2 work?
BOTH:
UPREGULATE cAMP
How do SNS agonists work?
Mimic actions of NA/A by binding to and stimulating adrenoceptors (GPCRs)
Where do SNS agonists primarily work?
CVS
Eyes
Lungs
What are all adrenoceptors activated by?
Either by NA or A
What are the adrenoceptor selectivity for NA?
Alpha1/2 > Beta1/2
can act on ALL just slightly more selective for ALPHA
What are the adrenoceptor selectivity for A?
Beta1/2 > Alpha1/2
can act on ALL just slightly more selective for BETA
Where are NA and A synthesised?
NA - made in NERVE TERMINALS
A - made in ADRENAL MEDULLA
NA biosynthesis?
Tyr –> DOPA –> DA –> NA
What controls NA biosynthesis?
x Transport proteins (either into tissue or back into axon)
x Alpha 2!!
NA bind to these prejunctional receptors, negatively feedbacking on NA exocytosis
5 DIRECTLY acting SNS Agonists?
- Adrenaline (non-selective)
- Phenylephrine (alpha 1)
- Clonidine (alpha 2)
- Dobutamine (beta 1)
- Salbutamol (beta 2)
3 main areas that A acts on as a SNS agonist?
- Anaphylaxis
- COPD
- Glaucoma
Why is A used in the treatment of anaphylaxis (hint: adrenoceptors)?
Beta 2 = bronchoDILATION (airways, breathing)
o Histamine causes the blocking of airways so beta 2 just antagonises this = PHYSIOLOGICAL ANTAGONISM
Beta 1 = TACHYcardia (reduced chonotropic & ionotropic effect)
o Has massive HYPOTENSION so speeds it up
Alpha 1 = vasoCONSTRICTION (peripheral vasodilation)
o Combats HYPOTENSION caused by histamine
What other effects does A have on anaphylaxis?
o Suppresses mediator release - as also have beta-receptors on mast-cells
o Reduces stomach cramps - relaxing effect on the guy
Why is A more important than NA in anaphylaxis?
A has a GREATER SELECTIVITY for beta-receptors which are more important in being triggered for this
So in epi-pens have A!
A as a SNS agonist for COPD?
Used in asthma (emergency so I.M or S.C)
o Beta 2 - causes bronchoDILATION
o Suppresses mediator release
Is A the best choice as a SNS agonist for COPD?
NO - a selective beta-2 agonist is preferable
A as a SNS agonist for glaucoma?
Increases IOP - alpha 1 receptors (vasoconstriction)
Vasoconstriction of ocular blood vessels = restricts blood flow = limits production of aq. humour
Other uses of A as a SNS agonist?
o Cardiogenic shock - use beta-1
o Spinal anaesthesia - maintain BP keeps TPR & BP UP (maintaining it)
o Local anaesthesia - vasoconstricts = prolong action (as constrict b.v in region so anaesthesia cannot diffuse into blood and systemic and remains in desired region)
Unwanted effects of A as a SNS agonist?
o Secretions - reduced & thickened
o CNS - minimal
o CVS - tachycardia/palpitations/arrhythmias
cold extremities/hypertension
overdose - cerebral haemorrhage, pulmonary oedema
o GIT - minimal
o Skeletal muscle - tremor
Phenylephrine?
ALPHA 1 selective!!
Alpha 1»_space; alpha 2»_space;> beta 1/2
Property of Phenylephrine?
Chemically related to A
BUT
o MORE RESISTANT to COMT [peripheral enzyme] (more resistant to breakdown)
o BUT NOT to MAO [central enzyme]
So longer-lasting as a peripheral agent as not broken-down as easily
Clinical uses of Phenylephrine?
Decongestant! (as most alpha 1 action is ability to vasoconstrict)
o Vasoconstriction o Mydriatic (pupil dilation) o Nasal decongestant (vasoconstrict = less WBC accumulate = less mucous)
