Peripheral Nervous System, Adrenoreceptors and Ocular Pharmacology Flashcards
2 regions of the Peripheral Nervous System
Somatic and Autonomic
3 regions of the Autonomic Nervous System
Enteric, Parasympathetic and Sympathetic
3 places nicotinic receptors can be found
Muscle, neuronal (CNS) and neuronal (autonomic ganglia)
what are nicotinic receptors in the autonomic ganglia regulated by?
Muscarinic receptors
Effect of M1 receptor
Slow EPSP
Effect of M2 receptor
Slow IPSP
Effect of M3 receptor
late/slow EPSP
Most postsynaptic SYMPATHETIC fibres release…
NA
Most postsynaptic PARASYMPATHETIC fibres release…
ACh
What NT acts on Muscarinic Receptors?
ACh
2 exceptions for NA release in the sympathetic nervous system
Sweat glands and Renal vessels (dopamine)
3 types of pre-synaptic modulation
homo/heterotropic inhibition, tissue/plasma derived substances and co-trasnporters
name 3 examples of tissue/plasma derived substances that help modulate pre-synaptically
prostaglandins, histamine, adenosine and bradykinin
name 3 examples of cotransporters that help modulate pre-synaptically
ATP, neuropeptides and NO
What NT is associated with the Sympathetic NS
Noradrenaline
What amino acid does NA derive from
Tyrosine
Pathway from Tyrosine –> Adrenaline
Tyrosine –> DOPA –> Dopamine –> NA –> A
α-methyl-p-tyrosine
tyrosine hydroxylase inhibitor (reduce amount of NA)
carbidopa
DOPA decarboxylase inhibitor (reduce amount of NA)
methyldopa
α2 agonist (reduce amount of NA, via negative feedback)
guanethidine
substrate for NET and VMAT, blocking the effect of adrenergic receptors
reserpine
inhibits VMAT, blocking the effect of adrenergic receptors
What effects would the drugs decreasing the amount of NA have?
anti-sympathetic: hypotension, bradycardia, sexual dysfunction
How do β1 adrenoreceptors work?
Activate adenylyl cyclase via Gs, increasing cAMP, increasing kinase activity, increasing cell response - found predominantly in the heart, when activated increase the HR
How do β2 adrenoreceptors work?
Activate adenylyl cyclase via Gs, increasing cAMP, increasing kinase activity, increasing cell response - when activated in the lungs, causes relaxation/dilation of the bronchioles.
How do β3 adrenoreceptors work?
Activate adenylyl cyclase via Gs, increasing cAMP, increasing kinase activity, increasing cell response
How do α2 adrenoreceptors work?
INHIBIT adenylyl cyclase via Gi, decreasing cAMP, reduced kinase activity, reduced cell response = decreased release at adrenergic and cholinergic.
How do α1 adrenoreceptors work?
Activate PLC which increases IP3, increasing Ca release, increasing cell response also increases DAG.
What effect do active α1 have?
constrict/contract (except in the GI tract)
phenylephrine
α1 agonist (vasoconstrictor)
clonidine
α2 agonist (prevents NA release, decreasing the BP)
dobutamine
β1 agonist (increase cardiac contractility)
salbutamol
β2 agonist (bronchodilation)
prazosin
α1 antagonist (vasodilator)
yohimbine
α2 antagonist
phenoxybenzamine
non-selective α antagonist
phentolamine
non-selective α antagonist
labetalol
α/β antagonist
carvediol
α/β antagonist
propranolol
non-selective β antagonist
atenolol
β1 antagonist
timolol
β1 antagonist
β blocker most important desired effect is where
heart/cardiovascular system
unwanted effects of β blockers
bronchoconstriction, bradycardia, hypoglycaemia
what type of receptors are muscarinic receptors?
GPCR
which nervous system do muscarinic receptors work on?
parasympathetic
M1, M3, M5 all work through which reaction
activated Gq, which activates IP3
M2 works through
Gi, which decreases cAMP, reducing [Ca]
when muscarinic receptors are activated, what is a side effect?
SLUDGE, lots of liquid released
What is the main NT in the parasympathetic NS
ACh
ACh is a…
cholinergic AGONIST
Pilocarpine
cholinergic AGONIST
Bethanachol
cholinergic AGONIST
3 side effects of muscarinic antagonists
inhibit secretions, tachycardia, mydriasis
atropine
non-selective muscarinic antagonist
hyoscine
non-selective muscarinic antagonist
pirenzepine
M1 selective antagonist (peptide ulcers)
darifenacin
M3 selective antagonist
side effects of non-selective muscarinic antagonists
urinary retention, dry mouth, blurred vision
Nerve impulses are controlled by…
presynaptic M2 receptors
which muscarinic receptors predominantly work in the airways
M3
normal cholinergic signalling pathway in airways
nerve impulse –> ACh released –> M3 receptor –> Gq –> PLC –> Ca release –> contraction
ipratropium
muscarinic antagonist
how does ipratropium work?
relax SM in airways, dilating them and treating asthma/bronchitis
problem with non-specific muscarinic receptors
block both M2 and M3, removing the negative feedback, so more ACh released, which could overcome the M3 block!
M3 selective antagonist
tiotropium
why is tiotropium good?
does not get inhibit the negative feedback loop at M2 presynaptically
3 things muscarinic agonists help with
emptying bladder, glaucoma, slowing HR, secretion
3 things muscarinic antagonists help with
prevent parasympathetic responses, inhibit secretion, tachycardia
3 muscles in the eye
Radial, sphincter and ciliary muscles
pupil dilation, contraction of radial SM, sympathetic innervation
mydriasis
pupil gets smaller, contraction of sphincter SM, parasympathetic innervation
miosis
NT and receptor for mydriasis
NA on α1
NT and receptor for miosis
ACh on M3
what would an α1 adrenoreceptor ANTAGONIST cause
miosis
what would a M3 muscarinic receptor ANTAGONIST cause?
mydriasis
pilocarpine
muscarinic agonist
how would a muscarinic agonist act on the eye
miosis, contraction of constrictor, parasympathetic response, block constrictor muscle
how would a muscarinic antagonist act on the eye
mydriasis, contraction of radial muscle, sympathetic response
atropine
muscarinic antagonist
dominant effect on the eye
PARA
glaucoma is caused by
increase intra-ocular pressure
what can cause open-angled glaucoma
obstruction in drainage through the TRABECULAR NETWORK and CANAL OF SCHLEMM
what is the formation of aqueous humour stimulated by
β agonists
what is the formation of aqueous humour inhibited by
α agonists (α1 agonists, vasoconstrictors decrease blood flow to ciliary body, β antagonists and α2 agonists decrease cAMP)
β antagonist that would reduce AH formation
Timolol
another drug group that could reduce AH formation
carbonic anhydrase inhibitors
example of a carbonic anhydrase inhibitor
acetazolamide
where is aqueous humour produced?
ciliary body
what targets the trabecular meshwork?
Miotics
example of a muscarinic agonist
pilocarpine
2 ways the AH can flow out of the eye
trabecular meshwork (90%), uveoscleral pathway (10%)
3 main drug targets for glaucoma and an example
trabecular meshwork outflow (PILOCARPINE), uveoscleral pathway (LATANOPROST), AH formation (β adrenoreceptor antagonist, TIMOLOL, α adrenoreceptor agonist, CLONIDINE, carbonic anhydrase inhibitor, ACETAZOLAMIDE).
Wet Macular Degeneration drugs
VEGF inhibitors (VERTEPORFORIN)
