Opioids and Analgesics Flashcards
what is the normal mechanism of action of GABA receptors?
GABA (neurotransmitter) binds to GABA receptors which stimulates the opening of chloride channels. Influx of chloride into the cell makes it hyper-polarised and prevents it from being depolarised and excited.
process of action potential from normal resting situation to the generation of the action potential (depolarisation) and finally to repolarisation
NORMAL resting situation:
- the cell has more positive Na+ ions on the outside and more negative ions on the inside (with some K+ on the inside), which means the cell has a negative membrane potential = polarised
- at this point, the sodium-potassium pump is maintaining this negative potential while the other ion channels are closed [sodium channel, potassium channel]
GENERATION OF ACTION POTENTIAL:
- a stimulus must occur to stimulate the ion channels to open and for positive Na+ ions to enter the cell
- note that the stimulus must be large enough to increase the cell’s negative membrane potential from -70 to -55 = all or nothing phenomenon as past this threshold, there is no going back
- the ligand-gated and voltage-gated sodium channels open and causes the membrane potential to become positive = depolarised
- action potential is essentially a brief depolarisation due to change in currents
REPOLARISATION:
- potassium channels open to let K+ from within the cell to flow out and depolarise the charges
- it usually becomes a little too polar and is hyper-polarised, which then requires the sodium potassium pump to take over and bring the negative membrane potential back to -70 and maintain it
when the neuron is undergoing depolarisation or repolarisation, can it be stimulated by other incoming signals?
no it cannot! this is called a refractory period and occurs so that the neuron is not simultaneously repolarising and depolarising.
aim of anaesthetics (2 aims)
analgesia (loss of pain) and paralysis (loss of muscle power)
mechanism of action of local anesthetics
binds to a receptor near the intracellular end of the Na+ channel protein and inhibits it (Na+ cannot enter the cell)
effects:
- reduction of depolarisation (cell cannot be excited)
- prolonging of repolarisation (cell is not excited quickly)
- anti-inflammatory effects
- infections of other channels
examples of local anaesthetics
amide:
- lidocaine
- bopivacaine
ester:
- procaine
- cocaine
usual therapy for local anaesthetics
rapid acting: procaine
intermediate acting: lidocaine
long acting: bopivacaine + vasoconstrictor
what happens when patient is allergic to procaine?
procaine is an ester drug and hence you can give an amide drug such as lidocaine
how does GA differ from LA?
LA is just analgesia and paralysis whereas GA is amnesia, analgesia, paralysis, loss of reflexes and medullary depression.
aims of GA
- smooth inducing with prompt recovery
- wide margin of safety
- no ADR
types of GA
air: nitrous oxide/cyclopropane
liquid: ether
IV: barbiturate, benzodiazepine, propofol, ketamine
inhalation GA (air and liquid) - examples, function and side effect
examples: nitrous oxide/cyclopropane and ether
function: depress everything (HR, RR, BP, renal blood flow, hepatic blood flow) except cerebral blood flow is increased
side effect: hepatotoxicity and nephrotoxicity
IV GA: benzodiazepine (MOA and use)
used for pre-anesthetic + adjuvant for LA
MOA: potentiate GABA receptors indirectly by increasing frequency of Cl channel opening
IV GA: barbiturate (MOA and use)
used for induction of GA
MOA: binds to GABA receptors and activates them
IV GA: propofol (MOA and use)
used for induction and maintenance of GA
MOA: potentiates GABA receptors and Na channel blocker
