PH2113 - Neuropharmacology 3 Flashcards
Give examples of local anaesthetics that target the voltage-gated sodium channel
Lidocaine Bupivacaine Prilocaine Tetracaine Benzocaine Chinocaine Cocaine
Give examples of antiepileptics that target the voltage-gated sodium channel
Phenytoin Carbamazepine Oxcarbazepine Sodium valproate Lamotrigine Zonisamide Topiramate
Give examples of neuropathic pain killers that target the voltage-gated sodium channel
Carbamazepine Oxcarbazepine Topirimate Lamotrigine Lidocaine
Give examples of antiarrhythmics that target the voltage-gated sodium channel
Propafenone
Flecainide
Procainamide
Quinidine
Give examples of channelopathies that affect the voltage-gated sodium channel
Generalised epilepsy with febrile seizures (GEFS) Intractable childhood epilepsy (Dravet's syndrome) - central nervous system Familial primary erythermalgia - peripheral nervous system Periodic paralysis - muscle Long QT - cardiac
What is use-dependent block?
binding site hidden within the pore. Only accessible from the cytoplasmic side and only when the channel is open. Highly lipophilic so enter the axon, protonated inside the axon so when channel is open they enter he channel and bind to it. H gates then inactivated so channel cannot reopen so a Ph dependent physical plug. Degree of block is proportional to rate of neve stimulation but NOT state dependent as channel blocked whether activated or not.
Longer stimulation = stronger block
What causes epilepsy?
Overactivation of neurones in the brain
Why is epilepsy hard to treat?
Don’t want to dampen all neuronal activity
- just abnormal activity
- high frequency
What is the mechanism of action of Lamotrigine, phenytoin and carbamazepine?
Lamotrigine, phenytoin and carbamazepine bind preferentially to open sodium channels during inactivation
- little effect on normal action potential generation in neurones at normal resting potentials
How is regulation of voltage-gated calcium channels regulated?
Antiport and uniport mechanisms
What is the concentration of intracellular calcium due to antiport and uniport mechanisms?
Very low
- 100 nM
What are the three 3 subfamilies of voltage-gated calcium channels?
HVA
- L type
LVA
- T type
What is the difference between the different classes of voltage-gated calcium channels?
Activated over different voltage ranges
What is the structure of the calcium channel?
Large alpha-1 subunit - pore forming subunit Alpha-2 subunit - drug binding Beta subunit Gamma subunit
What are the similarities and differences between sodium and calcium voltage-gated channels?
Sodium
- excitability
- 4 domains transmembrane segments
- P-loop S5-S6
- D-E-K+A filter
- S4 region voltage sensor
- local anaesthetics, antiepileptics, analgesics
- alpha, beta-1, beta-2 subunits
Calcium
- excitability, neurotransmitter release
- 4 domains transmembrane segments
- P-loop S5-S6
- E-E-E-E
- S4 region voltage sensor
- antiepileptics, analgesics, antihypertensives
- alpha-1, alpha-2, gamma, beta subunits
What are the two main types of receptors?
Ionotrophic
Metabotropic
What is a receptor?
The site of competition for agonists and antagonists and the vehicle for the transmission of the stimulus of agonist interaction to the cell for the production of a physiological response
What is an ionotropic receptor?
A receptor protein that includes an ion channel that is opened when the receptor is bound by an agonist
- ligand-gated ion channel
What was the first ligand-gated ion channel that was first identified?
Nicotinic Acetylcholine receptor
- nACh-R
What are the three families of ligand-gated ion channels?
Nicotinic - anion - GABA - cation - nACh - 5-HT3 Glutamate - cation P2X - cation
