drug names (L4-8)

Question 1

hemicholinium 3

Answer 1

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)

Question 2

vesicamol

Answer 2

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

Question 3

Tetrodotoxin (TTX)

Answer 3

cholinergic transmission at neuromuscular junction:
release step - Tetrodotoxin (TTX) blocks voltage-gated Na+ channels
(no action potential – no release)

Question 4

conatoxins

Answer 4

cholinergic transmission at neuromuscular junction:
release step - P/Q & N-type voltage-gated
Ca2+ channels are blocked by conatoxins
(no Ca2+ influx – no release)

Question 5

Botulinum toxin

Answer 5

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

Question 6

Dendrotoxins

Answer 6

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

Question 7

Ziconotide

Answer 7

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)

Question 8

clinical uses of Botulinum toxin

Answer 8

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

Question 9

α-latrotoxin

Answer 9

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

Question 10

nerve gases or neostigmine (different drugs, same effect)

Answer 10

Drugs that inhibit AChE, anticholinesterases (eg nerve gases, neostigmine) increase the concentration and effects of ACh -can lead to muscle spasms

Question 11

Tubocurarine

Answer 11

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

Question 12

alpha bungarotoxin

Answer 12

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)

Question 13

Vecuronium and rocuronium

Answer 13

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

Question 14

suxamethonium

Answer 14

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

Question 15

κ-bungarotoxin

Answer 15

irreversible (like α-bungarotoxin at NMJ)

Question 16

trimethaphan

Answer 16

competitive antagonist

occasionally used in surgery for controlled hypotension & hypertensive crises

Question 17

hexamethonium & tubocurarine

Answer 17

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

Question 18

nicotine & lobeline

Answer 18

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…

Question 19

Ganglionic non-depolarising blockers (antagonists)

Answer 19

κ-bungarotoxin
trimethaphan
hexamethonium
tubocurarine

Question 20

Depolarising blockers (agonists)

Answer 20

nicotine
lobeline
suxamethonium

Question 21

parasympathomimetics

Answer 21

called parasympathomimetics because they mimic the physiological effects of the parasympathetic nervous system

carbachol
pilocarpine
cevimeline
bethanechol

Question 22

parasympatholytics

Answer 22

called parasympatholytic because they oppose the effects of the parasympathetic nervous system

Question 23

physotigmine

Answer 23

From the Calabar Bean aka “The Ordeal Bean”
First anticholinesterases found
1st clinical use:
1877 for glaucoma

Question 24

clinical uses of neostigmine

Answer 24

reversal of neuromuscular paralysis

Question 25

clinical uses of Edrophonium

Answer 25

diagnosis of myasthenia gravis

Question 26

clinical uses of Neostigmine & pyridostigmine

Answer 26

treatment of myasthenia gravis

Question 27

clinical uses of Physostigmine & ecothiopate

Answer 27

treatment of glaucoma (previously)

Question 28

clinical uses of Donepezil (Aricept), Galantamine, Rivastigmine

Answer 28

Alzheimer’s Disease

Question 29

physiological effects of neostigmine, edrophonium, neostigmine, pyridostigmine, phsostigmine, ecotigmine, ecothiopate, donepezil, galantamine and rivastimine

Answer 29

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

Question 30

atropine

Answer 30

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

Question 31

reversal of organophosphate nerve agent effects (name the 3 compounds for this)

Answer 31

ATROPINE counteract effects of excessive mACh stimulation ``` OXIMES eg pralidoxime (2-PAM) antidote to nerve agent reactivate the AChE But…ageing…. ``` VALIUM for seizures

Question 32

organophosphate working as insecticides

Answer 32

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)

Question 33

monoamine oxidase | MAO

Answer 33

inhibitors used for depression

Question 34

catechol-o-methyl transferase (COMT)

Answer 34

inhibitors used for parkinsons disease to increase the dopamine levels in the brain

Question 35

aldehyde dehydrogenase (ADH)

Answer 35

??

Question 36

α-methylparatyrosine

Answer 36

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

Question 37

antabuse effects (2)

Answer 37

- 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.

Question 38

tyramine

Answer 38

(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

Question 39

noradrenaline (NA)

Answer 39

Arousal/wakefulness/alertness - forebrain Mood - amygdala/hippocampus Control of pain – spinal cord Blood pressure/autonomic function - hypothalamus & NTS

Question 40

dopamine (DA)

Answer 40

Nigrostriatal system - motor control Mesolimbic/mesocortical systems - behaviour / mood Tuberohypophyseal system - endocrine control

Question 41

serotonin (5-HT)

Answer 41

- sleep, wakefulness and mood - feeding behaviour - control of sensory transmission (especially pain pathways)

Question 42

MDMA effect on monoamine uptake

Answer 42

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

Question 43

cocaine effect on monoamine uptake

Answer 43

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

Question 44

amphetamine effect on monoamine uptake

Answer 44

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

Question 45

stimulant properties of amphetamines

Answer 45

``` 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

Question 46

clinical uses of amphetamines

Answer 46

- 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

Question 47

stimulant properties of cocaine

Answer 47

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.

Question 48

modafinil effects

Answer 48

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)