L1 and 2 - Autonomic drugs Flashcards
What are the 2 main fibres of neurone?
pre and post ganglionic
what are the 2 main NT?
cholinergic and adrenergic
what 2 systems is the nervous system split into?
- central
2. peripheral
2 branches of peripheral NS
somatic and autonomic
which NS is the sympathetic and parasympathetic a part of ?
autonomic
4 conditions where autonomic drugs are used?
- angina
- asthma
- anaphylactic shock
- hypertension
what does the parasympathetic system do?
rest and digest
what does the sympathetic system do?
fight or flight
where do parasympathetic neurones synapse?
cranial and sacral
where do sympathetic neurones synapse?
thoracic, lumbar, sacral
what type of synapse are ALL pre-ganglionic synapses in the ANS?
Cholinergic
what is the difference between the post-ganglionic synapses in the parasympathetic and sympathetic NS?
para - Ach
symp - ACh and NE
describe the difference in synapses in the symp NS
sweat glands - Ach
Cardiac +smooth muscle, gland cells, nerve terminals - NE
what synapses are the in somatic nervous system?
ACh
2 main types of autonomic receptors?
cholinoceptors
adrenoceptors
2 types of adrenoceptors
alpha and beta
2 types of cholinoceptors
nicotinic and muscarinic
what are the adrenoceptor alpha and beta subtypes?
a-1, a-2
b1 to b3
what are the cholinoceptor nicotinic subtypes?
muscle, ganglion and CNS
what are the cholinoceptor muscarinic subtypes?
M1 to M5
what type of receptors are in the heart for sympathetic stimulation?
B1
what type of receptors are in the heart for parasympathetic stimulation?
M2
which 2 tissues arterioles can both constrict and dialate (para and symp systems)?
erectile tissue and salivary glands
what type of transduction method is there in nicotinic receptors?
type 1 ionitropic
what type of transduction method is there in muscaranic receptors?
type 2 metabotropic
what does ionotropic mean?
ligand gated
what does metabotropic mean?
second messenger model
which is the only process which has an M1 parasympathetic receptr?
gastric acid secretion
which types of receptrs are present in the sympathetic system?
adrenonergic
which types of receptrs are present in the parasympathetic system?
cholinergic
what are the remaining organs parasympathetic receptors?
M3
what are all muscles sympathetic receptors?
b2
sympathetic receptor for BV arterioles; coronary, viscera, skin, brain, erectile tissue, salivary gland ?
a
sympathetic receptor for muscle arterioles and vein dilation?
b2
is there sympathetic stimulation for smooth muscle ? explain why
no - it is dilated by cirulating adrenaline
sympathetic receptor for smooth muscle which adrenaline acts on
b2
3 sympathetic receptor for smooth muscle GI tract
b2, a1, a2
2 sympathetic receptor for sphincters GI tract
b2, a2
what sympathetic receptor for uterine contraction for pregnant women?
a
what sympathetic receptor for uterine contraction for non-pregnant women?
b2
sympathetic receptor for bladder relaxation?
b2
sympathetic receptor for bladder sphincter contraction?
a1
which is the only process which uses b3 receptor - is this para or symapthetic?
adipose lipolysis - symp
sympathetic receptor for pupil dilation?
a
sympathetic receptor for ciliary eye muscle?
b
sympathetic receptor for sweat glands? why?
M3 - is it cholinergic
sympathetic receptor for piloerection in skin?
a
2 sympathetic receptor for salivary gland secretion?
a, b
sympathetic receptor for kidney renin secretion?
b1
sympathetic receptor for liver gluconeogeneis and glycogenolysis?
a, b2
6 types of cholinergic drugs
- muscarinic agonists
- muscarinic antagonists
- ganglion stimulating
- ganglion blocking
- neuro-muscular blockers
- anticholinesterases
what is another name for anticholinergic drugs?
muscarininc antagonsits
another name for muscarininc agonsits?
direct acting parasympatomimetic
4 naturally occuring muscarinic agonists
ACh
muscarine
arecoline
pilocarpine
2 clinically used muscarinic agonists
pilocarpine
betanechol
5 peripheral effects of muscarinic agonists
- exocrine secretion
- contraction of SM
- relaxation of sphincters
- eye; miosis (pupil constricion) + contraction of ciliary mucsle
- fall in arterial BP
what are pilocarpine drops useful in treating? explain how
glaucoma - allows fluid to drain out
equation for BP
BP = cardiac output x peripheral resistance
2 CV effects of muscarinic agonists
- reduction in cardiac output
2. vasodilation
how do muscarinic antagonists work?
inhibiting responses of ACh
3 types of muscarinic antagonists
- non-selective receptor
- M1 selective
- M3 selective
example of non-selective muscarinic antagonists
atropine
example of M1 receptor muscarinic antagonists and use
pirenezipine - peptic ulcer
example of M3 receptor muscarinic antagonists and use
darifenacin - urinary incontinence
effects of muscarinic antagonists on the eye
mydriasis
paralysis of cilary muscle
pathological effects of atropine when trreating eye conditons
- blurred vision
- photophobia
- poor night vision
can alternative drug can be used instead of atropine to reduce side effects
tropicamide
when are cycloplegic drugs used?
treat squints
effect of muscarinic antagonists on CV
increases HR
clinical use of muscarinic antagonists on CV
treat bradycardia following MI
3 effects of muscarinic antagonists on resp system
- bronchodilation
- increased vital capacity
- decreased mucus secretion
example of 2 muscarinic antagonists drugs which are used to treat asthma/COPD
ipratropium
tiortropium
effects of muscarinic antagonists on urinary tract
contracts internal sphincter muscle
clinical use of muscarinic antagonists on urinary tract
treat urinary incontinence
5 clinical uses of muscarinic antagonists on CNS
- anti-emetic
- pre-med for anaethesia
- treat ridigitity parkinsons
- block cholingeric effects of antipsychotics
- antidote to parasympathomimetic drugs
1 muscarinic antagonists drug which is used to treat ridigitity in parkinsons
- Orphenadrine
- procyclidine
- trihexyphenidyl
naturally occuring ganglion stimulating drug
nicotine
clinical use of ganglion stimulating drug
smoking cessation
2 ways ganglion-blockign drugs work
- competitve inhibition of ACh at NICOTINIC receptors
2. block cation channels which are normally activated by ACh binding
what is hexomethonium used for ? what type of drug is it?
hypertension - ganglion blockign drug
clinical use of neuromuscular blocking drug
relaxation for surgery
2 sites where neuromuscular blocking drugs work
- pre synaptic
2. post synaptic
how do pre-synaptic neuromuscular blocking drug works
- block ACh release
2. block ACh synthesis
example of neuromuscular blocking drug which blocks Ach synthesis?
hemicholinium
how does botulinum work?
neuromuscular blocking - preventing exocytosis of ACh from pre-neurone
2 types of neuromuscular blocking drug post synatptic
- non-depolarising
2. depolarising
how do post-synaptic non-depolarising neuromuscular blocking drug work?
competitive ACh antagonist at receptor
how do post-synaptic depolarising neuromuscular blocking drug work?
decrease electrical excitability of end plate - cannot produce AP when ACh attaches
2 examples of post-synaptic non-depolarising neuromuscular blocking drug
tubocurarine
pancuronium
2 examples of post-synaptic depolarising neuromuscular blocking drug
decamethonium
suxamethonium
function of cholinesterases
hydrolyse and inactivate ACh
2 types of cholinesterases
- acetylcholinesterase (AChE)
2. Butyrylcholinesterase (BuChE)
which synapses are AChE found at?
cholinergic
which is more specific ; 1. acetylcholinesterase (AChE)
2. Butyrylcholinesterase (BuChE)
acetylcholinesterase (AChE)
AChE has 2 binding sites for its substrates. what are they - what do they do?
anionic = correct orientation esteric = hydrolysis reaction
function of anticholinesterases
inhibit ACh hydrolysis
what effect do anticholinesterases have on the synapse?
- build up of ACh
- prolonged + intensified effects
how are anticholinesterases classified?
nature of complex they form with ACh
3 types of anticholinesterases
- rapidly reversible
- slowly reversible
- irreversible
describe nature of rapidly reversible anticholinesterases
bind to anionic site
short duration
ionic bond
describe nature of slowly reversible anticholinesterases
- strongly bind to anionic site
- esteric site = slowly hydrolysed
describe nature of irreversible anticholinesterases
- binds to active/esteric site
- bond initially reversible but then irreversible
example of rapidly reversible anticholinesterase drug and clinical use
edrophonium - diagnosis of Myasthenia Gravis
2 examples of slowly reversible anticholinesterase drug and clinical use
physostigmine
neostigmine
miotic, alzheimers
which patients expeience milder SE when given anticholinesterases
dementia
2 side effects of anticholinesterases
- excessive peripheral muscarinic stimulation
2. CNS effects due to build up of excess ACh
Antagonistic drug to reduce SE of anticholinestarases
atropine
how to treat resp paralysis arising from progressive nicotinic peripheral excitation - how does the drug work?
pralidoxime - reactivates cholinesterase
what is the oxidative NE pathway metabolised by?
aldehyde dehydrogenase
what is the reductive NE pathway metabolised by?
aldehyde rectucase
which catecholamine is most potent in alpha receptors?
NA
which catecholamine is most potent in beta receptors?
isoprenaline
peripheral location of a1 receptor and function
BV, smooth muscle; contract
peripheral location of a2 receptor and function
nerve endings - inhibit release
peripheral location of b1 receptor and function
heart; increase rate and force
peripheral location of b2 receptor and function
smooth muscles ; relax
peripheral location of b3 receptor and function
fat cells; lipolysis
detrusor muscle; relax
transduction method of all alpha and beta receptors
type 2 - metabotropic
2 main drug categories of adrenergic transmission
sympathomimetic
sympatholytic
2 types of sympathomimetic drugs
- direct acting - adrenoceptor agonists
2. indirect acting
2 types of sympatholytic drugs
- direct acting - adrenoceptor antagonists
2. indirect acting
2 ways in which sympathomimetic indirect acting drugs work?
1) Ca2+ independent release of NA from vesicles into synapse
2) block reuptake of NA at nerve terminals
how do sympatholytic indirect acting drugs work?
inhibit NE release
3 examples of direct acting sympathomimetic drugs
- Epinephrine
- salbutamol
- terbutaline
3 examples of indirect acting sympathomimetic drugs
- tyramine
- TCA
- amphetamine
2 types of direct acting symaptholytic drugs
alpha and beta blockers
3 examples of direct acting symaptholytic drugs
- doxazosin
- propanolol
- atenolol
2 examples of indirect acting symaptholytic drugs
- methyldopa
2. resperine
side effect of tyramine
cheese effect
effects of isoprenaline and adrenaline on
i) HR
ii) peripheral resistance
iii) BP
i) increase
ii) decrease
iii) increase systolic, decreases diastolic
effects of NA
i) HR
ii) peripheral resistance
iii) BP
i) dec
ii) incre
iii) increase
how do catecholamines regulate energy metabolism
mobilise glygogen and fat stores to meet energy req
2 effect of sympathomimetics on the eye
- mydriasis
2. dec intraocular pressure in glaucoma
effect of sympathomimetic drugs on vasculature
vasoconstriction
in terms of the CVD effects, what can sympathomimetic drugs be used to treat?
- hypertension
- cardiac arrest
- circ shock
- anaphylactic shock
effect of sympathomimetic drugs on smooth muscle
relaxation
what is mirabegron used for
treatment of overactive bladder
3 examples of alpha blockers
- phentolamine
- prazosin
- yahimbine
3 clinical uses of alpha blockers
- raynauds syndrome
- hypertension
- benign hypertrophy prostate
what type of drug is doxazocin and what is it used for?
alpha blocker - hypertension
main beta blocker
propanaolol
what condition are beta blockers contraindiacted in?
asthma
5 use of beta blockers in CV
- MI
- angina
- hypertension
- heart failure
- cardiac arrythmias
4 uses (not CV) of beta blockers
- reduce formation of aq fluid in glaucoma
- migraine headaches
- overactive thyroud
- anxiety
2 functions of indirect acting sympatholytic drugs
- blocks NA stores
2. inhibits NA release
indirect acting sympatholytic drug which blocks NA stores
reserpine
indirect acting sympatholytic drug which inhibits NA release
Guanethidine
clinical use of indirect acting sympatholytic drugs
treat hypertension during pregnancy
nerve terminal of nerves supplying sympathetic innveration to adrenal medulla
cholinergic
nerve terminal of somatic nerves to voluntary/skeletal muscles
cholingerfic
all organs supplied by this division can be stimulated simultaenously
sympathetic
which nerve supplies the parasymp autonomic innervations to most organs in abdo and thorax
vagus nerve
receptor subtype of neuro-effector junction of all parasymp nerves
muscarinic
receptor subtype of neuro-effector junction of all symp nerves (except sweat glands)
adrenergic - alpha or beta
receptor subtype of neuro-effector junction of all symp nerves supplyin sweat glands
M3
location of M1 receptors
stomach
location of M2 receptors
heart
location of M3 receptors
glands + smooth muscle
what is organophosphase poisoning ?
organophosphates irreversibly inhibit cholinesterases - build up of ACh
2 drug used to treat organophosphase poisoning ?
atropine (antimuscarinic) - inhibits effects of ACh
pralaxidome - reactivates cholinesterase enzymes