Muscarinic And Nicotinic Blockers Flashcards
Functions of nervous system
1) sensation
2) integration
3) response
What does somatic and ANS innervate
Somatic nervous system innervates skeletal muscles
ANS innervates Cardiac, smooth muscles and glandular epithelium
ACH is a neurotransmitter in
All motor fibers leaving CNS
Autonomic ganglia
Postganglionic parasympathetic fibers
Postganglionic sympathetic fibers in M, sweat glands
Adrenal medulla
Motor neurons running to striated muscles
Examples of Nicotinic receptor agonists
Nicotine, acetylcholine, choline, epibartidine, lobeline, varenicline and cytisine
Dominant receptor in ganglion is _______
List other receptors that can be found
Nicotinic NN receptors are the dominant
Others: M1,M2, adrenergic, dopaminergic, aminergic, peptidergic receptors
Selective Nicotinic agonist (Natural)
Nicotine( small doses)
Lobeline
Selective Nicotinic agonist (Synthetic)
DMPP Dimethyl phenyl piperazinium
TMA tetramethyl ammonium
Non selective muscarinic agonists
Acetylcholine, pilocarpine, Carbachol, anti cholinesterase
Excessive amounts of selective Nicotinic agonists leads to
Sustained depolarization and ganglion block
Clinical use of nicotine
Nicotine can be used as transdermal patches to treat nicotine dependence and can also aid smoking cessation
Clinical use of varenicline
As a partial agonist it can reduce both the craving and pleasurable effect of cigarettes and other tobacco products
Through this mechanism it helps some patients quit smoking
Cholinergic blocking drugs
Muscarinic antagonists, parasympatholytics, anticholinergics
Muscarinic receptor sites
Heart
Smooth muscles of GIT
Salivary glands
Genitourinary tract
Urinary bladder
List the cholinergic antagonists
Vesamicol
Hemicholinium
Botulinum toxins
Non depolarizing blocking agent e.g tubocurarine
Depolarizing blocking agents e.g suxamethonium
What does vesamicol inhibit
It inhibits VAT vesicular acetycholine transporter so acetylcholine won’t be transported into vescicles for storage
What does Hemicholinium inhibit
Inhibits choline transporter so choline can’t enter the neuron
Botulinum what does it do
It cleaves snare proteins and without snare proteins vescicles cannot fuse with membrane and then released
Example of non depolarizing blocking agent and function
Tubocurarine
Prevents acetylcholine from binding to post synaptic receptor
Example of depolarizing blocking agents and function
Suxamethonium
Blocks action of acetylcholine on post synaptic cleft and causes continuous depolarization until there is sensitivity of receptor
Where is M1 located
Primarily CNS ( cortex, hippocampus, corpus striatum), stomach
Function of M1 receptors on CNS
Improves learning , memory and motor function
Clinically selective anti cholinergic drugs on M1 receptors
Pirenzepine, telenzepine, dicyclomine, trihexyphenidyl
Clinical effects of M1 receptors
Hydrogen ion secretion
Clinical correlates of m2 receptors on CNS
Tremor, analgesia
Function of M2 receptors at presynaptic terminals/ cholinergic nerve endings of peripheral and central neurons
Reduces acetylcholine release
Clinically selective anti cholinergic drugs on M2 receptors
Tripitamine, methoctramine
Effect of M3 on vascular smooth muscle
It’s activity is mediated through the release of NO to produce vasodilation
Clinically selective M3 anticholinergics
Darifenacin, solifenacin, oxybutynin, tolterodine
Antagonist of M4 receptor
Himbacine
Function of M4 receptors
They function as inhibitory auto receptors for acetylcholine
When activated m4 receptors inhibit ACH release in striatum
List the anti muscarinic drugs
Natural
Atropine (DL hyoscyamine)
Scopolamine ( L hyoscine)
List the anti muscarinic drugs
Synthetic tertiary structural analogue of atropine
Homatropine
List the anti muscarinic drugs
Synthetic quaternary structural analogue of atropine
1) Atropine methyl nitrate
2) homatropine methyl bromide
3) methscopolamine bromide
4) Ipratropium
5) Tiotropium
List the anti muscarinic drugs
Synthetic tertiary structurally non related to atropine
Pirenzepine
Dicyclomine
Cyclopentolate
Oxyphenycyclimine
Tropicamide
List the anti muscarinic drugs
Synthetic quaternary structurally non related to atropine
Methantheline
Propantheline
Isopropamide
Glycopyrrolate
Natural alkaloids from antimuscarinic drugs
Atropine
Hyoscine (scopolamine)
Myadriatics semi synthetic derivatives
Homatropine
Antiasthmatics semi synthetic derivatives
Ipratropium
Tiotropium bromide
GI spasmolytics semi synthetic derivatives
Hyoscine butyl bromide
Myadriatics synthetic compounds
Tropicamide, cyclopentolate
Myadriatics synthetic compounds
Tropicamide, cyclopentolate
Myadriatics synthetic compounds
Tropicamide, cyclopentolate
Myadriatics synthetic compounds
Tropicamide, cyclopentolate
In the CNS atropine produces mainly _______ effects , low doses cause _________ higher doses cause __________ and ___________
Excitatory effects
mild restlessness
Agitation and disorientation
The central effects of atropine on CNS could be opposed by
Anticholinesterases e.g phsyostigmine (an effective antidote to atropine poisoning)
Hyoscine in low dose causes ______
Marked sedation similar to atropine at high doses
Atropine like drugs affect _______ reducing ________ and _________ in _______ disease
Extrapyramidal system
Involuntary movements and
Rigidity
In parkinston’s disease
Atropine produces a mild anaesthetic action on the _____
Cornea
How is atropine eliminated
50% metabolized in the liver and the remaining excreted unchanged in urine
Half life of atropine
Approx 4 hrs
Anti cholinergic toxicity mnemonics
Hot as a hare ( hyperthermia)
Dry as a bone (dry skin)
Red as a beet (flushed)
Blind as a bat (mydriasis)
Mad as a hatter (delirium)
Anticholinergic toxicity
1) altered level of consciousness (hallucinations, delirium, coma, slurred speech)
2) seizures
3) sinus tarchychardia
4) hypertension
5) Mydriasis
6) Dry eyes
7) Dry mouth
8) reduced bowel sounds
9) constipation
10) urinary retention
11) hyperthermia
Management of toxicity
1) control hyperthermia using cold sponging or ice bags
2) agitation might require physical constraints or chemical constraints ( benzodiazepines)
3) if ingested gastric labake
4) Antidote: physiostigmine 1-3 mg SC or IV for both central and pheripheral effects
Neostigmine ineffective for central effects
Management of anticholinergic toxicity is contraindicated in patients with
Bradychardia, intraventricular conduction delay, AV nodal block ,asthma,seizures and wheezing
Atropine delays gastric ________ and delays __________ of other drugs
Emptying
Absorption
Antacids interfere with absorption of _________
Anticholinergics
