Please enable JavaScript.
Coggle requires JavaScript to display documents.
Nervous Pharmacology - Coggle Diagram
Nervous Pharmacology
Lithium
-
MOA: very complex and not fully understood. It mimics the role of sodium in excitable tissues, but can accumulate and cause depolarisation
Has a narrow therapeutic window (0.5-1mmol/l) due to producing a variety of toxic effects above 1.5mmol/l
Given by mouth as a salt and is excreted by the kidney (about ½ the oral dose is excreted within 12 hours, the remainder over 1-2 weeks)
Side effects: nausea, vomiting, diarrhoea, tremor, and renal side effects (such as polyuria)
Acute lithium toxicity results in various neurological effects, progressing from confusion and motor impairment to coma, convulsions and death
Lithium plasma levels must be measured 1 week after starting and 1 week after veery dose change until the levels are stable. Aim to maintain plasma lithium level between 0.6 and 0.8 mmol per litre in people being prescribed lithium for the first time (can be higher if patient relapses)
When starting lithium, you must measure BMI, do bloods, do an ECG, and offer education to patient of side effects and risk of relapse etc
Antidepressants
-
They take at least 2 weeks to produce any beneficial effect (pharmacological effects are immediate, but the secondary adaptive changes are more important)
-
-
-
-
Anti-epileptics
-
They have 3 main MOAs
-
Inhibition of sodium channel function – examples: carbamazepine, phenytoin, and lamotrigine
• Na+ channel is prevented from returning to the resting state so there are fewer functional channels to generate APs
-
Carbamazepine
-
-
Pharmacokinetics: mainly eliminated by CYP450 (major metabolite, carbamazepine epoxide, active anticonvulsant thought to have same MOA)
Phenytoin
-
Side effects: vertigo, ataxia, and headaches
May also be involved in increased incidence of foetal malformations in children born to epileptic mothers (such as cleft palate)
Valporate
-
-
MOA: enhances GABA action by inhibiting GABA transaminase and succinic semialdehyde dehydrogenase. It also weakly inhibits sodium channels which supresses repetitive neuronal firing
Side effects: hepatotoxicity, thinning/curling of hair, and risk of teratogenesis (significant risk of birth defects)
-
Lamotrigine
Indications: partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome (childhood epileptic encephalopathy)
MOA: inhibits sodium currents and selectively binds to inactivated state. It also suppresses glutamate release
Side effects: nausea, dizziness, dose-dependent prolongations of PR interval, widening of QRS complex, and, at higher doses, complete AV block
-
-
Antipsychotics
-
Dopamine is a monoamine neurotransmitter (the receptor ‘D2’ is the main target of antipsychotics) that has 4 major pathways
Mesolimbic pathway: hyperactive in schizophrenia (positive symptoms of psychosis (delusion/hallucination))
Mesocortical pathway: underactive in schizophrenia (negative symptoms of psychosis (lack of motivation/social withdrawal))
-
Tuberoinfundibular pathway: controls prolactin secretion. Dopamine inhibits prolactin release (prolactin is responsible for milk release and sexual desire)
-
At least 40% of schizophrenic patients don’t take their drugs as they’re prescribed, making it difficult to get them on the right dosage as this often must be done via a trial-and-error method. Fortunately, they don’t have a big toxicity
The plasma half-life of most antipsychotic drugs is 15-30 hours, clearance depending entirely on hepatic transformation by a combination of oxidative and conjugative reactions
They are usually given orally but can be given IM in an emergency. Slow-release (depot) preparations are given as IM, the drug acts for 2-4 weeks, but initially may produce acute side effects. These preparations are widely used to minimise compliance problems
Anxiolytics
Antidepressants (SSRIs, SNRIs, TCAs, and MAOIs)
Benzodiazepines
-
MOA: act selectively on GABA-A receptors that mediate inhibitory synaptic transmission through the CNS
-
They bind between alpha and gamma subunits on a GABA-A receptor, increasing the affinity of GABA to the GABA binding site
This increases the frequency of the channel opening, increasing the Cl ion influx and making the post-synaptic cell more negative, and therefore less likely to dire an AP from external excitatory stimuli. This causes calm and relaxation
Benzos do not affect receptors for other amino acids, such as glycine or glutamate
Main effects: reduce anxiety and aggression, induction of sleep, reduction of muscle tone, anticonvulsant effect (not all benzos have all these effects)
Side effects: drowsiness, confusion, dizziness, impaired co-ordination, enhance depressant effect of other drugs
An overdose is less dangerous than other anxiolytics as it causes prolonged sleep without serious depression in cardio/respiratory function. However, if mixed with other depressants, they can be severe and potentially life-threatening
Well absorbed orally, usually have a peak plasma concentration after approx. 1 hour (but some are absorbed more slowly)
They are normally given orally, but can be given IV or rectally (IM injection has slow absorption)
Other examples: gabapentin, pregabalin, antipsychotics, and BBs