Pharmacology

Question 1

Diazepam, lorazepam, temazepam, chlordiazepoxide, midazolam

Answer 1

Class: benzodiazepines.
MOA: enhance binding of GABA to GABA-A receptors —> chloride influx —> inhibition of synaptic transmission.
Indication: anxiety disorders (short-term), acute behavioural control, rapid tranquillisation, insomnia (short-term), alcohol withdrawal.
Side effects/contraindications: drowsiness, sedation, coma, dependence. Lower dose in elderly. Avoid in patients with significant respiratory impairment, neuromuscular disease and liver failure.

Question 2

Citalopram, fluoxetine, paroxetine, sertraline, escitalopram

Answer 2

Class: selective serotonin reuptake inhibitors (SSRIs).
MOA: inhibit neuronal uptake of serotonin, increasing its availability for neurotransmission.
Indication: anxiety and depression.
Side effects/contraindications: GI upset, changes in appetite and weight, hypersensitivity reactions, hyponatraemia. Increased suicidal thoughts. Citalopram prolongs QT interval. Increased risk of bleeding. Serotonin syndrome at high doses or in combination with other serotonergic drugs.

Question 3

Duloxetine, venlafaxine

Answer 3

Class: serotonin and noradrenaline reuptake inhibitors (SNRIs).
MOA: inhibits reuptake of serotonin and noradrenaline from synaptic cleft, increasing their availability for neurotransmission.
Indication: anxiety and depression.
Side effects/contraindications: GI upset, neurological effects, hyponatraemia, serotonin syndrome, increased risk of suicidal thoughts, QT interval prolongation (venlafaxine).

Question 4

Reboxetine

Answer 4

Class: selective noradrenaline reuptake inhibitor.
MOA: inhibits reuptake of NA, increasing its availability.
Indication: depression.

Question 5

Mirtazapine

Answer 5

Class: presynaptic alpha2-adrenoceptor blocker
MOA: antagonist of pre-synaptic alpha2-adrenoceptors, increasing NA and serotonin availability for neurotransmission.
Indication: depression.
Side effects/contraindications: sedation, increased appetite, GI upset, neurological effects.

Question 6

Amitriptyline, imipramine, lofepramine

Answer 6

Class: tricyclic antidepressants (TCAs).
MOA: inhibit neuronal reuptake of serotonin and NA from synaptic cleft, increasing their availability for neurotransmission. Inhibits muscarinic, H1, alpha1, alpha 2 and D2 receptors (side effects).
Indication: depression, chronic/neuropathic pain.
Side effects/contraindications: dry mouth, constipation, urinary retention, blurred vision, sedation, hypotension, arrhythmias, ECG changes, convulsions, hallucinations, mania, breast changes and sexual dysfunction. Dangerous in overdose. Should not be given with MAOIs.

Question 7

Phenelzine, moclobemide

Answer 7

Class: non-selective MAOIs (phenelzine), reversible inhibitor of MAO-A (moclobemide).
MOA: inhibits monoamine oxidase, causing accumulation of amine neurotransmitters (dopamine, NA, A, histamine and serotonin).
Indication: depression, phobia (hypochondria), social anxiety disorder.
Side effects/contraindications: hypertensive crisis if patient eats tyramine rich foods (mature cheese, salami, pickled herring, marmite).

Question 8

Methadone, buprenorphine

Answer 8

Class: opioid agonists.
MOA: binds mu opioid receptors.
Indication: opioid withdrawal, substitution for opioid dependence.

Question 9

Nicotine replacement therapy, bupropion, varenicline

Answer 9

Class: NA and dopamine reuptake inhibitor (bupropion), selective nicotine-receptor partial agonist (varenicline).
Indication: smoking cessation.

Question 10

Chlordiazepoxide

Answer 10

Class: benzodiazepine.
MOA: enhance the binding of GABA to GABA-A receptor, allowing Cl- influx, depressing synaptic transmission.
Indication: alcohol withdrawal, delirium tremens.
Side effects/contraindications: drowsiness, sedation, coma. Dependence.

Question 11

Pabrinex, thiamine

Answer 11

Class: vitamin B1.
Indication: treatment and prevention of Wernicke’s encephalopathy and Korsakoff’s psychosis.
Side effects/contraindications: high dose thiamine IV may rarely cause anaphylaxis.

Question 12

Acamprosate

Answer 12

Class: weak glutamate antagonist and GABA analogue.
MOA: interacts with glutamate and GABA in CNS restoring balance between neuronal excitation and inhibition.
Indication: maintenance of abstinence in alcohol-dependent patients (anti-craving).

Question 13

Naltrexone

Answer 13

Class: opioid receptor antagonist.
MOA: reduces the reinforcing effects of alcohol.
Indication: prevent relapse in alcohol-dependent patients and opioid-dependent patients.

Question 14

Disulfiram

Answer 14

Class: inhibitor of acetaldehyde dehydrogenase.
MOA: prevents breakdown of acetaldehyde to acetate.
Indication: treatment of alcohol dependence.
Side effects/contraindications: if taken with alcohol causes unpleasant side effects such as facial flushing, N+V.

Question 15

Methadone

Answer 15

Class: opioid agonist.
MOA: binds mu-opioid receptors.
Indication: opioid dependence.
Side effects/contraindications: N+V (on initiation), constipation, arrhythmias, respiratory depression (high doses), dizziness, drowsiness.

Question 16

Naloxone

Answer 16

Class: opioid antagonist.
MOA: binds mu-opioid receptor acting as a competitive antagonist. When an opioid is present, naloxone displaces it from its receptors, reversing the opioid effects.
Indication: opioid overdose/toxicity associated with respiratory and/or neurological depression.
Side effects/contraindications: may be a significant withdrawal reaction in opioid-dependent patients (pain, restlessness, N+V, dilated pupils, and cold, dry skin with piloerection.

Question 17

Lithium

Answer 17

Class: mood stabiliser.
MOA: inositol depletion theory, leading to reduced excitatory and increased inhibitory neurotransmission.
Indication: bipolar disorder.
Side effects/contraindications: hypothyroidism, hyperparathyroidism, idiopathic intracranial hypertension, leucocytosis, QT prolongation, renal impairment and weight gain. Long-term use associated with thyroid problems and mild cognitive and memory impairment.

Question 18

Sodium valproate

Answer 18

Class: mood stabilising anticonvulsant.
MOA: weak inhibitor of sodium channels, reducing neuronal excitability. It also increases GABA content in brain.
Indication: bipolar disorder.
Side effects/contraindications: GI upset, tremor, ataxia, behavioural disturbance, thrombocytopenia, increase in liver enzymes, hypersensitivity (hair loss). Avoid in women of child bearing age (foetal abnormalities) and hepatic impairment.

Question 19

Carbamazepine

Answer 19

Class: mood stabilising anticonvulsant.
MOA: inhibits sodium channels.
Indication: bipolar disorder.
Side effects/contraindications: GI upset, dizziness, ataxia, hypersensitivity.

Question 20

Lamotrigine

Answer 20

Class: mood stabilising anticonvulsant.
MOA: inhibits voltage-gated sodium channels and inhibits post-synaptic glutamate (AMPA) receptors.
Indication: bipolar disorder.
Side effects/contraindications: headache, drowsiness, irritability, blurred vision, dizziness, GI symptom, skin rash.

Question 21

Risperidone, olanzapine, clozapine, aripiprazole, quetiapine

Answer 21

Class: second-generation (atypical) antipsychotics.
MOA: block post-synaptic dopamine D2 receptors. Antipsychotic effects come from blockade of mesolimbic/mesocortical pathway. Aripiprazole is a partial D2 agonist.
Indication: psychosis, schizophrenia (clozapine —> treatment resistant schizophrenia), mania, rapid tranquillisation.
Side effects/contraindications: sedation, extrapyramidal side effects (more common in typical antipsychotics), metabolic disturbance (weight gain, diabetes, lipid changes), prolong QT interval (arrhythmias). Risperidone - hyperprolactinaemia, breast symptoms and sexual dysfunction. Clozapine - agranulocytosis, myocarditis.

Question 22

Haloperidol, chlorpromazine, flupentixol, sulpiride, prochlorperazine

Answer 22

Class: first-generation (conventional/typical) antipsychotics.
MOA: block post-synaptic dopamine D2 receptors.
Indication: psychosis, schizophrenia, mania, rapid tranquillisation.
Side effects/contraindications: sedative (chlorpromazine), extrapyramidal side effects (movement abnormalities arising from blockade of D2 receptors in nigrostriatal pathway), drowsiness, hypotension, QT interval prolongation (arrhythmias), erectile dysfunction, hyperprolactinaemia (menstrual disturbance, galactorrhoea, breast pain). Avoided in dementia, Parkinson’s disease.

Question 23

Describe the extrapyramidal side effects of antipsychotics

Answer 23

Acute dystonia - involuntary parkinsonian movements or muscle spasms.
Akathisia - restlessness.
Neuroleptic malignant syndrome - rigidity, confusion, autonomic dysfunction, pyrexia.
Tardive dyskinesia - involuntary repetitive movements e.g. lip smacking.