drug names (L4-8) Flashcards
hemicholinium 3
cholinergic transmission at neuromuscular junction:
synthesis step is initiatied by the reuptake of choline. which is Na+ dependent
this is blocked by hemicholiniom 3 (blocks the pump - so twitches in the muscles will fade away since there is not ACh being synthesised)
(not used clinically)
vesicamol
cholinergic transmission at neuromuscular junction:
storage step - Uptake and storage of ACh in synaptic vesicles is inhibited by vesamicol
(not used clinically)
Pump can be inhibited by vesamicol. Slowly will develop a block of the muscle twitches because no ACh is pumped into vesicles
Tetrodotoxin (TTX)
cholinergic transmission at neuromuscular junction:
release step - Tetrodotoxin (TTX) blocks voltage-gated Na+ channels
(no action potential – no release)
conatoxins
cholinergic transmission at neuromuscular junction:
release step - P/Q & N-type voltage-gated
Ca2+ channels are blocked by conatoxins
(no Ca2+ influx – no release)
Botulinum toxin
cholinergic transmission at neuromuscular junction:
release step - Botulinum toxin blocks vesicle fusion – no release
inhibits the fusion process - toxin will destroy the proteins involved in the fusion of vesicles
Causes paralysis
Dendrotoxins
cholinergic transmission at neuromuscular junction:
release step - Dendrotoxins block voltage-gated K+ channels (more Ca2+ influx – more release)
AP doesn’t repolarise, prolonged depolarization, more CA influx, constant neurotransmitter release
Ziconotide
Ziconotide acts as a selective N-type voltage-gated calcium channel blocker.
Given via the intrathecal route for the management of severe pain (directly through the spinal cord)
clinical uses of Botulinum toxin
muscular spasms are resistant to other treatments
Give injection of botulinum toxin to prevent activity of neuromuscular junction there
children with cerebral palsy and this toxin can be used as treatment as well
overactivation of the neuromuscular junction could cause drooling or sweating
α-latrotoxin
black widow spider venom
With α-LTX - huge amount of release of neurotrans, muscles spams (black widow spider overcomes its prey like this)
After - stops the endocytosis process, so vesicle membranes are not taken back, no more vesicles produced, desensitisation of receptors of presynaptic membrane, paralysis
nerve gases or neostigmine (different drugs, same effect)
Drugs that inhibit AChE, anticholinesterases (eg nerve gases, neostigmine) increase the concentration and effects of ACh -can lead to muscle spasms
Tubocurarine
found in vines of amazons, effective antagonist of receptors at neuromuscular junction, competitive antagonist
so if you increase the conc of ACh by inhibiting the enzyme that breaks it down, you can overcome the effect of tubocurarine
arrow poison – kills prey by respiratory paralysis
clinical side effects – decreased BP due to ganglion block & resultant vasodilatation
alpha bungarotoxin
Non depolarising because they are antagonists and block the receptors (like alpha bungarotoxin, found in the taiwanese snake, it binds to the same place as acetylcholine so should be competitive with tubocurarine, but it sticks covalently to the binding site so it cannot come off)
Vecuronium and rocuronium
used clinically because during an operation, we dont want muscle twitches. used for anaesthetics (safer because used at low doses)
Very rapid onsets, so for urgent surgeries
Reversed by anticholinesterases by poisoning it
suxamethonium
depolarising blocker - agonist
used clinically
rapid onset of paralysis
short duration – broken down by plasmacholinesterases
tracheal intubation, electroconvulsive therapy
BUT
side effects include:
bradycardia (decreased heart rate) due to M2 mAChR activation in heart
K+ release in trauma (eg burns) – cardiac dysrhythmias & cardiac arrest
prolonged paralysis (2hr+) in 1:3500 people
κ-bungarotoxin
irreversible (like α-bungarotoxin at NMJ)
trimethaphan
competitive antagonist
occasionally used in surgery for controlled hypotension & hypertensive crises
hexamethonium & tubocurarine
non competitive-open channel blockers
(drug sits in channel like plug in a bottle)
(compare with tubocurarine at NMJ-competitive)
hexamethonium used to reduce blood pressure
tubocurarine blocks the binding site of ach
nicotine & lobeline
ACh nicotinic receptor (nAChR) agonists
Lobeline - selective for ganglionic & chromaffin cell nAChR
repeatedly stimulate receptors
inactivate voltage-gated Na+ channels
desensitise nAChR receptors
not broken down by AChE
not used clinically as ganglion blockers – but nicotine (and varenicline - α4β2 nAChR) for tobacco addiction…
Ganglionic non-depolarising blockers (antagonists)
κ-bungarotoxin
trimethaphan
hexamethonium
tubocurarine
Depolarising blockers (agonists)
nicotine
lobeline
suxamethonium
parasympathomimetics
called parasympathomimetics because they mimic the physiological effects of the parasympathetic nervous system
carbachol
pilocarpine
cevimeline
bethanechol
parasympatholytics
called parasympatholytic because they oppose the effects of the parasympathetic nervous system
physotigmine
From the Calabar Bean aka “The Ordeal Bean”
First anticholinesterases found
1st clinical use:
1877 for glaucoma
clinical uses of neostigmine
reversal of neuromuscular paralysis
clinical uses of Edrophonium
diagnosis of myasthenia gravis
clinical uses of Neostigmine & pyridostigmine
treatment of myasthenia gravis
clinical uses of Physostigmine & ecothiopate
treatment of glaucoma (previously)
clinical uses of Donepezil (Aricept), Galantamine, Rivastigmine
Alzheimer’s Disease
physiological effects of neostigmine, edrophonium, neostigmine, pyridostigmine, phsostigmine, ecotigmine, ecothiopate, donepezil, galantamine and rivastimine
due to ↑↑↑ACh activity at autonomic NEJ, NMJ & CNS
↑ secretion: salivary, lacrimal,
bronchial, GI glands
↑ peristaltic activity
(stimulant laxatives)
🕆 NMJ: depolarisation block
🕆 bronchoconstriction
🕆 bradycardia and hypotension
🕆 CNS - convulsions, respiratory failure, unconsciousness, death
atropine
counteract effects of excessive ACh M stimulation
it is a possible treatment for nerve agent intoxication
M3 receptors are found on the lumen of blood vessels, circulation of acetylcholine is stimulating M3, leads to vasodilation
increasing heart rate
also counteracts effects of excessive mach stimulation
reversal of organophosphate nerve agent effects (name the 3 compounds for this)
ATROPINE
counteract effects of excessive mACh stimulation
OXIMES eg pralidoxime (2-PAM) antidote to nerve agent reactivate the AChE But…ageing….
VALIUM
for seizures
organophosphate working as insecticides
Organophosphate insecticides can give rise to some bad symptoms
Because sulfur group replaces the oxygen group in malathion insecticides
Very effective against insects because they have oxidase that converts S to O which kills them (we are less efficient at that process)
monoamine oxidase
MAO
inhibitors used for depression
catechol-o-methyl transferase (COMT)
inhibitors used for parkinsons disease to increase the dopamine levels in the brain
aldehyde dehydrogenase (ADH)
??
α-methylparatyrosine
was used in treating pheochromocytoma, a tumour of chromaffin cells in adrenal medulla. This will release a lot of adrenaline or noradrenaline, heart beats fast, high blood pressure etc
antabuse effects (2)
- Dopamine b hydroxylase affected by antabuse. so antabuse inhibits the conversion of dopamine into noradrenaline
- Primary target of it is another enzyme that degrades alcohol (acetyldehydrogenase), so it causes accumulation of toxic compounds in our body after taking alcohol.
tyramine
(it’s an indirectly acting sympathomimetics)
stimulates NA release
Competes with NA for NET
Displaces NA from vesicle
CHEESE REACTION
Tyramine in food (red wine, cheese, yogurt) metabolised by MAO
Some antidepressants (Phenelzine) inhibit MAO
Combining both can lead to “Cheese Reaction” & hypertensive crisis
noradrenaline (NA)
Arousal/wakefulness/alertness - forebrain
Mood - amygdala/hippocampus
Control of pain – spinal cord
Blood pressure/autonomic function - hypothalamus & NTS
dopamine (DA)
Nigrostriatal system - motor control
Mesolimbic/mesocortical systems - behaviour / mood
Tuberohypophyseal system - endocrine control
serotonin (5-HT)
- sleep, wakefulness and mood
- feeding behaviour
- control of sensory transmission (especially pain pathways)
MDMA effect on monoamine uptake
COMPETES WITH SEROTONIN
MDMA has preferential action on serotonin both at the level of the transporter (MDMA is taken up by the serotonin transporter) and interferes with VMAT
this results in an efflux of serotonin from the inside to outside of the cell - you get an accumulation of serotonin outside of the cell
cocaine effect on monoamine uptake
Cocaine has a preferential action at the dopamine transporter, which results in the accumulation of dopamine in the extracellular space (affects dopamine transporter and others too)
it blocks the transporter and doesn’t allow anything through
amphetamine effect on monoamine uptake
Amphetamine targets noradrenaline/norepinephrine transporter. it enters the cell using it. Can also affect the vesicular monoamine transporter.
It also inhibits MAO, monoamine oxidase (enzyme that breaks down the monoamine) so inhibiting s MAO will allow the release of more monoamine in the synaptic cleft to prolong the effects of amphetamine
stimulant properties of amphetamines
MAIN EFFECTS increased motor activity euphoria and excitement insomnia anorexia
- Effects are due mainly to increased levels of monoamines in the synaptic cleft.
- Amphetamines induce strong psychological dependence.
- Amphetamine psychosis can occur with prolonged use and resembles symptoms of schizophrenia
clinical uses of amphetamines
- Attention deficit hyperactivity disorder (ADHD)
Adderall- 2.5 or 5 mg once or twice per day
Ritalin - < 60 mg /day - Narcolepsy
Adderall- 5 mg to 60 mg per day in divided doses
Ritalin - < 60 mg /day - Obesity
Methedrine - 5 mg tablet before each meal as it suppresses the appetite
stimulant properties of cocaine
MAIN EFFECTS
Increased motor activity
Euphoria, excitement and garrulousness
Increased peripheral sympathetic NS activity (↑BP, ↑HR)
- Effects are due mainly to increased levels of monoamines (especially dopamine) in the synaptic cleft.
- Shorter lasting effects compared to amph.
- Causes strong psychological dependence.
modafinil effects
MAIN EFFECTS
Increased wakefulness and vigilance
Suggested to improve cognitive performance (likely through increased wakefulness)
- Binds with low affinity to DAT and to NET
- Has additional actions at a variety of NT systems (5-HT, glutamate)
- Low abuse potential (no high or euphoria)
