Adrenergic Signalling Flashcards
Adrenal Medulla Innervation
1 neuron
collection of post-ganglionic neurons
Chromaffin cells -> 80% A, 20% NA (neurohormones)
Tyramine
- natural occurring aa
- broken down by MAO in gut + liver
- found in flood (fermented, aged, processed meats, Kambutcha)
MAOi (used to tx depression - not 1st tx tho)
- don’t breakdown tyramine in gut + liver
- accumulation of tyramine = ends up in blood
- absorbed by axon terminals of NA neurons
- enters vesicles via VMAT
- kicks out NA into cytosol + cleft
- floods the system with NA
SYMPATHOMIMETIC
mimics what NA does
Symptoms = inc BP
-Not sure if bad b/c could eat proper servings
Pheochromocytoma
Tumour on adrenal medulla
- causes over-secretion of A + NA
- symptoms = inc BP
Tx. Metyrosine
-blocks TH completely (can’t convert Tyr to Dopa, etc.)
dec synthesis of NA + A 1st, then dec release
-often remove tumour thru surgery
Epi-Pens
Epi = epinephrine = A
- used for severe allergies (anaphylaxis)
- injected intramuscularly (no veins-hard to do, quick abs)
- major dec in BP, can’t breath b/c of constriction (d/t other chem mediators)
- not oral dose b/c takes lots of time + high metabolism by intestine (MAO + COMT)
A in Local Anaesthesia
Causes vasoconstriction
Dec BF = blood can’t wash away anaesthesia
Adrenergic Receptors
all GPCRs
- a = 1 + 2
- b = 1 + 2 + 3
- b3 drugs = now being developed
- drug outcomes depend on…
1) Affinity (a or b)
2) Tissue Expression
3) Routes of Admin
Agonist Affinity
a1: A, NA, phenylephrine
a2: A, NA, clonidine
b1: A, NA, isoproternol
b2: A, isoproternol, salbutamol
-salbutamol = low affinity for b1, but high doses = could bind
Phenylephrine
a1 receptors
in the lung + CV system
causes vasoconstriction
Eye
- mydriatic drug (LG pupil = mydriasis)
- dilate pupil by contracting radial muscles surrounding the pupil
- used historically for cosmetics (squeeze atropine juice in eye)
- other drugs causing dilation of pupil: NA, A, atropine (Anti-AChase, blocks constriction on M receptor)
- don’t tend to use atropine (less strong AChases often used)
CV System
- vasoconstriction of smooth muscle of arteries, arterioles, + veins
- Dec. r, Inc TPR, Inc BP
- heart = gen more P to push blood through system
- Phenylephrine = active ingredient in some nasal decongestants
- constricts nasal vasculature
- mucosa = 1st layer of nasal cavity
- Dec. BF = less inflamed + less mucus secretion
- adverse effects for patients with high BP (if taken orally = high systemic effects, not a problem if nasal spray (topical))
Salbutamol
“But a minute”
- short acting b2 agonist
- used to treat asthma
- causes bronchi dilation
Salmetrol
- long acting b2 agonist
- used to treat asthma (under poor control, >5 attacks/wk)
- causes bronchi dilation
Tiotropium
Anti-AChase
- can be used to also dilate bronchi
- treatment for COPD + asthma
a2 receptors in the CV system
- in some blood vessels = causes vasoconstriction
- OVERALL = DEC. BP
Clonidine: a2 agonist (Dec. BP)
- acts via CNS autoreceptors to dec NA release
- Dec. SNS activation (vasodilation)
- very lipophilic drug (can cross BBB)
- primary target = CNS, not peripheral
- brain effects > periphery effects (@ low doses)
- opp for @ high doses
b1 receptors in the CV system
Inc CO
Inc HR + F of contraction
Also present in kidneys
b2 receptors in the CV system
Inc. vasodilation
Dec. BP
In blood vessels (cardiac, skeletal muscles + liver)
Inc r, Dec R, Dec. BP
Baroreceptor Reflex
- receptors in carotid + aorta
- respond to stretch (affects firing rate to CV centre)
High BP
- Inc. stretch receptors
- Inc. firing of APs to CV centre
- Response: dec. SNS activation (vasomotor centre), inc. PSNS activation (vagal centre)
Low BP
- Dec. stretch responses
- Dec. AP firing
- Response: inc. SNS activation, dec. PSNS activation
- Inc. HR, CO, MAP, TPR
- Give IV drugs to get faster response
- goes to heart 1st
