Transmitters and Receptors Flashcards
What do drugs in the CNS affect?
synthesis, storage, inactivation of NTs (reuptake or metabolism or bind to receptor)
What is the action of Phenytoin?
blocks the AP activation of glutamate-releasing nerves to limit excitatory activation of motor nerves in epilepsy; it binds to and inhibits OPEN Na+ channels and is therefore enhanced in high frequency firing
What is the action of benzodiazepines on GABA?
enhance GABA receptor activity by binding at an allosteric site
For sedation and anxiety tx we want to target
GABA - main inhibitory transmitter of the CNS
To treat anxiety alone we want to target
Serotonin (prejunctional CNS receptors); NA (peripheral tachycardia); NPY (1 receptor activation reduces anxiety)
To sedate alone we want to target
Histamine - H1 receptor antagonists are sedative
Benzodiazepines are used in
epilepsy, anxiety, sleep disorders, sedation for medical procedures, and acute alcohol withdrawal
Sedative-hypnotic and anxiolytic agents are used in
sleep disorders (insomnia), anxiety
Barbiturates are used for
anaesthesia and anticonvulsants
Why are barbiturates no longer routinely prescribed?
toxic - low therapeutic index, induce liver enzymes, withdrawal can cause death; highly addictive
Barbiturates cause
general depressants, cause CNS depression - mild sedation, surgical anaesthesia, coma, death
Why are benzodiazepines considered safer than barbiturates?
Wider therapeutic index, less depression, safe in overdose
Benzodiazepines elicit
sedation and induction of sleep (reduced time to fall asleep/increased duration of sleep), reduced anxiety and agression, reduction of muscle tone (anticonvulsant but decreased coordination), obliterate memory
GABA A receptors are
ligand-gated ion channels
GABA B receptors are
GPCRs
Benzodiazepines interact with which receptor?
GABA A only
What is the function of GABA A receptors?
lets Cl- into cell; hyperpolarizes cell decreasing activation
What is the main action of benzodiazepines?
Interfere with GABAergic transmission: binding to the GABA A receptor allosteric site increases affinity for GABA which increases frequency of channel opening (lets in more Cl_)
Benzodiazepines bind to which site on the GABA A receptor?
allosteric site, not orthosteric site
Binding at the allosteric site can modulate
orthostatic ligand affinity and efficacy, and receptor activation level
How do barbiturates act differently on the GABA A receptor to benzodiazepines?
Barbiturates prolong opening of channel (letting more Cl- in) where benzodiazepines increase frequency of opening - this is why you can OD on barbiturates and die, but be ok ODing on benzodiazepines
What are the unwanted effects of benzodiazepines?
drowsiness, confusion, impaired coordination
What are the disadvantages in using benzodiazepines?
interactions with alcohol, antihistamines, and barbiturates; long lasting hang over effects; withdrawal symptoms; dependence/abuse potential
What is potency?
relative position of the dose-effect curve along the dose axis - more potency does not mean a drug is superior
What is efficacy?
The ability of a drug to do the right thing
What is pharmacological efficacy?
Strength of receptor activation ie full agonists have high efficacy, partial agonists have low efficacy
What is clinical efficacy?
The strength of the beneficial effect
Benzodiazepines increase the ________ of GABA
potency; increase the frequency of the Cl- channel opening at the GABA A receptor
Barbiturates increase the _______ of GABA
efficacy; increase the duration of Cl- channel opening at the GABA A receptor
Non-benzodiazepine hypnotics
zolipidem, zopiclone
Non-nenzodiazpine anxiolytics
buspirone
Zolpidem
non-BDZ hypnotic for short term tx of insomnia; binds GABA A at BDZ site, short duration
Zopiclone
non-BDZ hypnotic for short term tx of insomnia; binds GABA A at different site to BDZ site
Buspirone
non-BDZ anxiolytic; partial agonist at 5HT 1A receptors (inhibitory autoreceptors regulating transmitter release)
