Neuropharmacy II Flashcards
What is an allosteric modulator?
Binds to receptor but to different site to agonist
Causes an allosteric change in the receptor which alters the affinity for the agonist
This accordingly alters the receptor occupancy for the agonist, altering the extent of agonist action
How does benzodiazepines alter GABAergic transmission?
Benzodiazepines are positive allosteric modulators, so increase GABAergic transmission
How does dosage of benzodiazepine affect pharmacological outcome?
Large dose
Anaesthesia Muscle relaxation Hypnosis Sedation Ataxia Anticonvulsant Anxiolytics
Small dose
What is the name and time span of a short term benzodiazepine?
Triazolam
8-16h
What is the name and time span of a medium acting benzodiazepine?
Diazepam
32h
What is the name and time span of a long acting benzodiazepine?
Clonazepam
55 h
What is the cellular effect of GABA(A)-R activation?
Cl pore opens
Cl ions flow into cell
Cell is hyperpolarised
Which benzodiazepine would you use for hypnosis?
Triazolam
Which benzodiazepine would you use as an anxiolytic?
Diazepam
Which benzodiazepine would you use as an anticonvulsant?
Clonazepam
What effects are seen from barbiturates at low doses?
Anxiolytic and sedative
What effects are seen from barbiturates at high doses?
Fatality due to respiratory depression and cardiovascular collapse
Why are barbiturates no longer used as anxiolytics?
Anxiolytic effects are only seen at sedative doses
Induction of P(450) in the liver causes drug tolerance
Dangerous in overdose (problem in suicide prone patients)
They have additive effects with other CNS depressants (e.g. Alcohol)
How is serotinergic transmission targeted in anxiolysis
Busiprone:
Agonist to 5HT(1A) presynaptic autoreceptors to reduce 5HT exocytosis
How is noradrenergic transmission targeted in anxiolysis?
Clonidine:
Agonist to alpha 2 autoreceptors to reduce NA exocytosis
what are the two major categories of epilepsy?
Partial
Generalised
How do the two different types of epilepsy differ?
For partial:
Seizures begin in a particular area of the brain involving only one side
For general:
Seizures begin with an electrical discharge involving both sides of the brain
What ion channels can be targeted to reduce neuronal excitability?
Na-VGIC
T-type Ca-VGIC
Give examples of sodium channel blockers
Phenytoin
Carbamazepine
Valproate
Give an example of a T-type Ca- channel blocker
Ethosuximide
What does valproate do?
Blocks Na channel
Inhibits GABA transaminase (increases brain GABA)
What role does diazepam have as an anticonvulsant
Increases efficacy of Postsynaptic GABA transmission by allosteric modulation
What role does Phenobarbitone have in anti-epileptics?
Increases efficacy for GABA transmission
Directly increases Cl influx
How can the NMDA receptor be targeted for epilepsy?
Felbamate:
Blocks NMDA
Binds to glycine site
How can the AMPA receptor be targeted for epilepsy?
Parampanel:
Non-competitive antagonist of AMPA
Name 3 currently used volatile anaesthetics
Halothane
Isoflurane
Nitrous oxide
How do you increase anaesthetic potency?
Unsaturation
Halogenation
Ether groups
What is a MAC?
Minimum alveolar concentration
The concentration of anaesthesia in the air air inspired giving a safe level of anaesthesia in 50% of patients
Does a potent anaesthetic have a low MAC?
Yes,
Potency is inversely proportional to the MAC
Name 4 intravenous anaesthetics
Thiopentone
Propofol
Etomidate
Ketamine
Which general anaesthetics work through potentiation of GABA(A) receptor transmission
Halothan Isoflurane Thiopentone Propofol Eromidate Nitrous oxide
Which general anaesthetics work through inhibition of excitatory transmission
Halothane Isoflurane Nitrous oxide Thiopentone Propofol Ketamine
Which nerve fibres transmit the perception of pain?
C fibres
Which types of tissue damage produces pain?
Inflammation
Neuropathy
How might hypersensitivity be produced at spinal level?
Repetitive painful stimulation on the c-fibres can cause them to enter a high state of excitability
Different pain states then converge on common pathways to the spine
What voltage channels can be blocked to alleviate pain?
NMDA
AMPA
What drugs block the NMDA channel?
Ketamine
Gabapentin
What drugs block the AMPA channel
Carbamazepine
Lignocaine
How might pain be reduced by suppression of excitatory NT release?
Inhibition of presynaptic Ca channels would prevent NT vesicle exocytosis
K channels may be open hyperpolarising the cell so Ca channels won’t open
What are the endogenous opioids and receptors?
Mu- endorphin
Delta- enkaphalin
Kappa- dynorphin
Orl-1- nociceptin
Name some exogenous opiates used for analgesia
Morphine
Codeine
Which transmitters are involved in the descending pathways that regulate nociception?
Substance P
CGRP
glutamate
Aspartate
