ans Flashcards
What is the neurotransmitter at the preganglionic neuron of the sympathetic ns?
Acetylcholine
What is the neurotransmitter at the post ganglionic neuron of the sympathetic ns?
Noradrenaline
What are the target receptors for the sympathetic ns?
alpha and beta receptors
What is the neurotransmitter at the pre ganglionic neuron of the parasympathetic ns?
Acetylcholine
What is the neurotransmitter of the post ganglionic neuron of the parasympathetic ns?
Acetylcholine
What is the target receptor for the parasympathetic ns?
muscarinic acetylcholine receptors
What is the parasympathetic nerve effects of the heart?
Decrease rate (bradycardia)
Decrease force of contraction
What is the parasympathetic effect on the lungs?
Bronchoconstriction, secretion
What is the parasympathetic effect on the GI tract?
increase tone motility of small and large intestines
increase secretion of saliva and gastric acid
What is the parasympathetic effect on the glands?
increase sweating, salivation, lacrimation
What is the parasympathetic effect on the eye?
sphincter muscle contraction, ciliary muscle contraction
What is the parasympathetic effect on the blood vessels?
most blood not innervated
may be vasodilation in some
How is acetylcholine formed?
choline + acetyl-co-enzyme A = acetylcholine
What enzyme forms acetylcholine?
choline acetyltransferase
Does muscarine stimulate nicotinic receptors?
false
What is muscarine selective for?
muscarinic receptors
What is nicotine selective for?
nicotinic receptors
What is the uses of muscarinic agonists?
open angle glaucoma
urinary retention
paralytic ileus
How is open angle glaucoma treated with muscarinic agonists?
increases intraocular pressure
dilate pupil impairs aqueous humour drainage
cholinergic agonist constricts pupil
What is the mechanism of ACh-Est?
has two sites - anionic and esteratic to breakdown Acetylcholine
What are cholinesterase inhibitors?
inhibit the catalytic activity of cholinesterase enzymes
What do cholinesterase enzyme catalyse?
hydrolysis of acetylcholine
What are some short-acting reversible cholinesterase inhibitors?
edrophonium
What are some long-acting reversible cholinesterase inhibitors?
carbamylated intermediates, physostigmine; neostigmine
What are some therapeutic uses of cholinesterase inhibitors?
eye treatment
skeletal neuromuscular junction
gastrointestinal system
treatment of atropine poisoning
How is the eye treated by the use of cholinesterase inhibitors?
constriction of pupil
decreases intraocular pressure in open-angle glaucoma
What are some long-acting, irreversible cholinesterase inhibitors?
organophosphates
How does organophosphates work?
phosphorylation of acetylcholinesterase inhibits the acetyl site thus acetylcholine cannot be cleaved and accumulate
What are the risks of organophosphates?
insecticides
nerve gases
What is the risk of nerve gases?
deadly at low concentrations
toxicity due to increase acetylcholine at cholinergic synapses
persistent stimulation = neurotransmission paralysis
What are some signs of acute poisoning due to cholinesterase inhibitors?
bronchoconstriction, accumulation of respiratory secretions, weakened or paralysed respiratory muscles, central respiratory paralysis
bradycardia
sweating, salivation, lacrimation
constriction of the pupils
increase gastrointestinal activity
What are the treatments for cholinesterase inhibitor poisoning?
stop exposure
assist respiration
administer cholinergic antagonist, e.g. atropine
administer pralidoxime (organopshophate poisoning)
administer anticonvulsant
monitor for cardiac irregularities
administer diazepam (treat agitation + sedation)
Is atropine a muscarinic agonist or antagonist?
antagonist
What are the major pharmacological effects of atropine?
decrease sweating, salivation, lacrimation
decrease gastrointestinal motility
decrease gastric acid secretion
decrease production of bronchial mucus
bronchodilation
increase heart rate
What are some side-effects of atropine?
dry mouth + skin
urinary retention
cycloplegia
glaucoma
depression
hallucination
increase body temp.
What are catecholamines?
hormones made by the adrenal glands
What enzyme synthesises tyrosine into dihydroxyphenylalanine?
tyrosine hydroxylase
What enzyme synthesises dihydroxyphenylalanine into dopamine?
DOPA decarboxylase
What enzyme synthesises dopamine into noradrenaline?
dopamine β-hydroxylase
What enzyme synthesises noradrenaline into adrenaline?
phenylethanolamine N-methyltransferase
What happens to noradrenaline in the synapse?
- diffuses and has no role
- bind to pre-junction α2 receptors = inhibition of noradrenaline
- diffuse and stimulate post-junctional α and β receptors
- taken up by NET
- taken up by ENT at post-junctional cell
What synthesises adrenaline?
adrenal medulla
What are some modifications of noradrenaline?
increase bulkiness of substituents on the N-atom = resistance to monoamine oxidase (MAO)
modification of catechol -OH groups = resistance to catechol-O-methyl transferase (COMT)
What are the function of α1-receptors?
blood vessel = vasoconstriction
lung = decrease secretion
GI tract = decrease smooth muscle motility and tone
eye = radial muscle contraction
What are the functions of β-receptors?
heart = increase rate and force of contraction
blood vessels = vasodilation
GI tract = decrease smooth muscle motility and tone
lung = bronchodilation, increase secretion
eye = ciliary muscle relaxation
What are the different types of adrenergic drugs?
adrenoceptor agonists
adrenoceptor antagonists
adrenergic neurone blockers
monoamine oxidase inhibitors
What classifies adrenoceptors?
molecular cloning of distinct protein moieties
functional characteristics
potencies of various stimulatory catecholamines
What is potencies of α-receptors to stimulatory catecholamines?
noradrenaline > adrenaline > isoprenaline
What is the potencies of β-receptors to various stimulatory catecholamines?
isoprenaline > adrenaline > noradrenaline
Where are α1 receptors found?
post-junctional sites
Where are most α2 receptors found?
pre-junctional sympathetic nerve endings
What does the activation of α2 receptors do?
inhibit noradrenaline release
Where are β1 receptors found in abundance?
heart and intestinal tract
Where are β2 receptors found in abundance?
respiratory tract, blood vessels and liver
What does β1 receptors trigger?
increase in heart rate and force
What does β2 receptors trigger?
relaxation of airway and vascular smooth muscle
glycogenolysis/gluconeogenesis in the liver
What does the effect of adrenoceptor agonist depend on?
receptor selectivity of the drug
adrenoceptor profile of the cell
cellular response to receptor activation
What are the clinical uses of adrenaline?
anaphylactic reactions (β-adrenoceptors)
cardiac arrest (β1-adrenoceptors)
local anaesthetic solutions (α1-adrenoceptors)
How can adrenaline help during cardiac arrest?
helps restore cardiac rhythm
Why can adrenaline be used as a local anaesthetic?
vasoconstrictor effect
increase duration of action
decrease risk of systemic toxicity
What are sympathomimetic drugs?
stimulant compounds which mimic the effects of endogenous agonists of the SNS
What do indirect-acting sympathomimetics do?
no direct agonist activity but cause
- release of noradrenaline
- block noradrenaline uptake
- inhibit noradrenaline metabolism
What is a mixed-acting sympathomimetics?
Ephedrine
What is the action of Ephedrine?
direct actions on adrenergic receptors
releases noradrenaline from sympathetic nerves
Is Ephedrine a substrate for COMT or MAO?
no
What is Ephedrine used clinically for?
relieve nasal congestion (vasoconstrictor)
What are adrenoceptor antagonists?
prevent endogenous adrenoceptor agonists from binding to and stimulating adrenoceptors
α1-adrenoceptors antagonism can help treat?
hypertension
β1-adrenoceptor antagonism can help treat?
angina, arrhythmia, hypertension, post-myocardial infarcation
β-adrenoceptor antagonists are used to?
prevent endogenous adrenoceptor agonists from binding to and activating β-adrenoceptors
Most β-adrenoceptor antagonists end in?
-olol
What is an example of a β-adrenoceptor antagonists?
propranolol
What are the properties of propranolol?
non-selective antagonist
oxymethylene bridge improves antagonists potency
similar structure to β-agonists and local anaesthetics
What are the adverse effects of non-selective β-adrenoceptor antagonists?
may precipitate congestive heart failure (β1-blockade)
may induce bronchoconstriction in asthmatics (β2-blockade)
may potentiate hypoglyceamia in diabetics (β1-blockade)
What are adrenergic neurone blockers?
primarily block the release of noradrenaline from sympathetic neurones by inhibiting excitation-release coupling
What other major pharmacological actions contribute to sympathetic neuronal blockade?
taken up into sympathetic neurones via NET
stored in vesicles
released as false neurotransmitters
What is an example of an adrenergic neurone blocker?
Guanethidine
