Neuropharmacology Flashcards
What is the main side effect of clozapine?
Agranulocytosis
Tricyclic antidepressants have many side effects. Give some side effects and the receptors responsible for these side effects.
TCAs antagonise…
M1 - dry mouth, blurred vision, constipation, urinary retention
H1 - sedation, weight gain
a1 - postural hypotension
For which group of people are TCAs contraindicated?
Which patients do get TCAs?
Contraindications:
Young and old people
Cardiac patients - due to increasde risk of conduction abnormalities
Suicidal patients - due to risk of overdose
Drivers and workers - due to sedation
Uses:
Severe and treatment-resistant depression
Which SSRIs have the highest affinity?
Sertraline and paroxetine
Which type(s) of MAO do the newer forms of MAOIs inhibit? Give an example.
MAOa only - this is responsible for the breakdown of 5-HT and noradrenaline
Old-generation MAOIs break down dopamine too, causing EPSE.
Newer forms block MAOa only - an example is moclopemide.
Name a drug which inhibits 5-HT release? Why is it not used clinically?
Ecstasy. It is addictive and neurotoxic.
Why do antidepressants take a while to work?
Initially levels increase, causing more activation of 5-HT1a receptors found on the neuronal cell body. This receptor inhibits 5-HT secretion.
Eventually, the 5-HT1a receptor become desensitised and this is when the inhibition of 5-HT is stopped.
What are some side effects of antipsychotics due to their interaction with the nigrostriatal pathway?
loss of control of fine movement, EPSE, tardive dyskinesia
How are first generation antipsychotics categorised? Give examples.
Group 1 - sedation = chlorpromazine
Group 2 - anticholinergic = thioridazine
Group 3 - EPSE = fluphenazine
Another first generation antipsychotic is haloperidol.
Give examples of second generation (atypical) antipsychotics.
Clozapine Olanzapine Risperidone Amisulpiride Quetiapine
Give some negative and positive symptoms of schizophrenia…
Positive - disorders of thought, hallucinations, paranoia
Negative - blunted emotions/withdrawal, social withdrawal, apathy
Categorise these neurotransmitters into high and low in anxiety…
- Serotonin
- Noradrenaline
- GABA
- Serotonin is increased
- Noradrenaline is increased
- GABA is decreased
Give a very short half life benzodiazepine and suggest uses for it.
Midazolam
Conscious sedative + status epilepticus
Give a long half-life benzodiazepine and suggest a use for it.
Lorazepam
Chlordiazepoxide - acute alcohol withdrawal
Diazepam (Valium)
They are all anxiolytics used in GAD
Why does diazepam have a long half life?
It undergoes oxidative metabolism into active metabolites.
Why is there a risk of overdose associated with barbiturates?
They work on GABAa receptors.
But they do not require GABA to open the channel, hence risk of overdose as their use is not limited by GABA concentration.
How do Z-hypnotics work?
THey are allosteric modulators of GABAa receptors.
They are more selective to a1 receptors, leading to sedation.
Give examples of Z-hypnotics.
Zopiclone
Zolpidem
Zaleplon
Give a melatonin agonist which is licensed for use.
Which group of people is it licensed for?
Circadin.
Long-lasting melatonin agonist.
Licensed for use in 55+.
Give an example of a SNRI.
Venlafaxine is the most common one.
Give examples of TCAs.
Amytryptiline
Imipramine
Give an example of a 5-HT1A agonist.
Buspirone.
What are some desirable effects of opioids?
Analgesia Euphoria Constipation (if used as antidiarrhoeal) Sedation (used as a hypnotic) Cough suppression (antitussive)
What are some undesirable affects of opioids?
Respiratory depression Euphoria (can be abused) Constipation Histamine release Immunosuppression Sedation Nausea and vomiting Tolerance and dependence
What effects does stimulating the mu opioid receptor have?
Analgesic effects in brain
Respiratory depression
Reward and physical dependence
Miosis
What effects does stimulating the kappa opioid receptor have?
Analgesic effects in the spinal cord
No respiratory effects
No reward or dependence
Miosis
What effects does stimulating the delta opioid receptor have?
Analgesia in CNS and elsewhere
Interacts with enkephalins
Physical dependence and reward
Respiratory stimulation
Which opioid receptors does morphine work on?
Mu and delta
What is the active metabolite of morphine and through which process does it become this metabolite?
GLucuronidation to morphine-6-glucuronide
What is the half life of morphine
3h
What are some indications for morphine
Moderate-severe pain
Acute heart failure (as dilates blood vessels)
What is diamorphine? How does it work? How is it administered?
It is heroine.
Works like morphine after acetylation.
Administration is parenteral.
What is methadone?
It works the same as morphine, but is used as substitution therapy for heroin addicts.
What is the half life of methadone and why is this beneficial?
Half life is 24h which allows once daily dosing at the pharmacy.
What is an opioid used in obstetrics?
Pethidine, it works like morphine but is less potent and less euphoric.
What are some indications for codeine?
Mild pain, diarrhoea, anti-tussive properties
What is dextropropoxyphene?
It is an opioid which works similar to codeine.
Which opioid is mainly a mu agonist?
What other effects does it have other than its analgesic properties?
Tramadol
It also inhibits serotonin and noradrenaline reuptake.
Name an opioid antagonist. Give an indication.
Naloxone. Used for opiate overdose.
Which drug is given for post-withdrawal treatment?
Naltrexone.
Reduces high from heroine in relapses. Also reduces cravings.
Give two drugs that can be used in substitution therapy. How often do they need to be dosed?
Methadone - once daily
Buprenorphine - three times a week.
What is a seizure?
A period of synchronous discharge of neurones.
What is a convulsion?
Muscular contractions which sometimes accompany a seizure.
What is epilepsy?
Epilepsy is a disorder characterised by repeated seizures.
What symptom might somebody with temporal lobe epilepsy get during a seizure?
Hallucinations
What circuit is affected in absence seizures?
Thalamocortical circuits.
What are the three phases of a grand mal seizure?
Tonic - high frequency neuronal activity
Clonic - lower frequency neuronal activity
Post-ictal - electrical depression due to neuronal fatigue.
