Central Nervous System

Question 1

Diazepam, lorazepam (Anxiolytics)

Answer 1

Benzodiazepine Anxiolytics - bind GABA-BDZ receptor complex and potentiate effect of GABA - inhibitory effect (full agonists)
Indications: severe anxiety (first line treatment is psychological)
ADRs: tolerance and depedance, withdrawal syndrome.
Common - drowsiness, dizziness, psychomotor impairment
Occasional - dry mouth, blurred vision, GI upset, ataxia, headache, low BP
Rare - amnesia, restlessness, rash
Teratogenic - cleft lip and palate, if taken late in pregnancy may cause respiratory depression and feeding.
Overdose - treatment includes flumenazil (antagonist at benzodiazepine receptors)

Question 2

Haloperidol, Chlorpromazine

Answer 2

Typical antipsychotics - multiple sites of action including D2 receptor antagonism, anticholinergic effects, alpha-adrenergic blockade, antihistamine.
Actions: sedation, tranquilisation, antipsychotic effect within days or weeks, activation of negative symptoms (less so with typicals), extrapyramidal side effects.
Indication - psychosis, haloperidol can be used in emergencies.
ADRs: extrapyramidal side effects - parkinsonism, dystonia, akathisia, tardive dyskinesia (irreversible), sedation, tranquilisation, neuroleptic malignant syndrome, postural hypotension, pigmentation
Toxicity - CNS depression, cardiac toxicity (prolonged QTc), sudden death

Question 3

Olanzapine, Risperidone, Quetiapine

Answer 3

Atypical antipsychotics - multiple sites of action, include D2 antagonism. Available in different preparations - dissolvable, some OD.
Indication: 1st line in schizophrenia
ADRs: weight gain, less extrapyramidal side effects than typicals but still present in high doses, hyperprolactinaemia, sedation.
Toxicity - CNS depression, cardiac toxicity (prolonged QTc), sudden death

Question 4

Valproic acid

Answer 4

(valproate) - mood stabiliser (enhances GABA synthesis, reduces inactivation, VGSC blocker and CCB) - sodium valproate is used in epilepsy
Indications: Maintenance therapy in bipolar, treatment of mania.
ADRs: sedation, tremor, ataxia, weight gain, deranged hepatic function and rarely hepatic failure

Question 5

Lithium carbonate

Answer 5

Mood stabilising drug - potential mechanisms include competition with magnesium and calcium ions at channels, altered 5-HT function (increased levels, reduced receptors chronically), attenuating of second messenger response to neurotransmitters without altering receptor density.
Indications: Bipolar disorder, reduced suicidality, 4th line in unipolar depression
ADRs: memory problems, thirst, polyuria, tremor, drowsiness, weight gain, affects renal function, hypothyroidism, hair loss, rashes
Narrow therapeutic window - need to monitor lithium levels and beware toxicity - coarse tremor, dysarthria, cognitive impairment, restlessness, agitation, eventually coma, seizure, death.

Question 6

Citalopram, Fluoxetine, Sertraline,

Answer 6

Selective serotonin reuptake inhibitors (SSRIs) - blocks reuptake of serotonin at synapses and hence increases concentration in synaptic cleft
Indication: 1st and 2nd line therapy for moderate to severe depression (along with CBT)
Fluoxetine = prozac
Sertraline can be used in renal and cardiac disease
Citalopram is less commonly used as it prolongs the QT interval.
Fairly safe in overdose.
ADRs: Common - anorexia, nausea, diarrhoea, headaches, lightheadedness, sexual side effects
Rare: precipitation of mania, increased suicidal ideation, neurological side effects - tremor, extrapyramidal syndromes.

Question 7

Orlistat

Answer 7

Anti-obesity drug - inhibits pancreatic and gastric lipases, fats are excreted unchanged
Indication: Obesity
ADRs: Oily leakage from rectum, flatulence, faecal urgency, liquid or oily stools, faecal incontinence, abdominal distension and pain, malaise, hypoglycaemia, menstrual disturbance

Question 8

Cyclizine

Answer 8

Anti-emetic (H1 antagonist)

Question 9

Metoclopramide

Answer 9

Anti-emetic

Question 10

Domperidone

Answer 10

Anti-emetic (D2 antagonist)

Question 11

Ondansetron

Answer 11

Anti-emetic (5HT3 antagonist)

Question 12

Hyoscine

Answer 12

Anti-emetic

Question 13

Aspirin

Answer 13

NSAID - COX-1 and COX-2 inhibitor (inhibits irreversibly by acetylation), reduces synthesis of prostaglandins from arachidonic acid. Zero-order kinetics at high doses.
Uses: Analgesia, anti-inflammatory and anti-pyretic, prevention of certain malignancies, also cardioprotection (see CVS)
ADRs: peptic ulceration & blood loss, increased bleeding time, confusion, tinnitus, bronchospasm and skin reactions (hypersensitivity - Stevens Johnson), renal compromise, Reyes Syndrome (brain and liver injury in paeds)
DDI: Highly protein bound, interact with sulphonylureas, warfarin and methotrexate

Question 14

Paracetamol

Answer 14

Mechanism: Unknown, weak COX-1 and COX-2 inhibitor, thought to act in CNS on COX-3 isoform.
Indications: mild-moderate analgesia and fever (not anti-inflammatory)
ADRs: Hepatic impairment, especially in overdose (take care in compromised hepatic function and alcoholics) - forms toxic metabolite NAPQI. Fatal in doses >10g - saturate phase II metabolism and then saturate glutathione leads to increasing concentrations of NAPQI and hepatic damage. Can also cause renal failure. Treat overdose with IV N-acetylcysteine, or methionine by mouth if cannot give NAC.

Question 15

Morphine

Answer 15

Opioid analgesic - binds mu-opioid receptors (which are Gi coupled GPCRs). This increases the outward flux of K+. making the cell less excitable, decreases the influx of calcium and decreases cAMP synthesis, inhibiting excitation of the neurones expressing these receptors, and decreasing neurotransmitter release.
Uses: Analgesia, diarrhoea
ADRs: Via mu receptors - nausea, vomiting, constipation, drowsiness, miosis, dependence, tolerance, respiratory depression, hypotension.

Question 16

Diamorphine

Answer 16

(Heroin) Opioid analgesic - quickly hydrolysed to morphine, more rapidly centrally available - binds mu-opioid receptors (which are Gi coupled GPCRs). This increases the outward flux of K+. making the cell less excitable, decreases the influx of calcium and decreases cAMP synthesis, inhibiting excitation of the neurones expressing these receptors, and decreasing neurotransmitter release.
Uses: Analgesia (especially in terminal illness), epidural anaesthesia
ADRs: Via mu receptors - nausea, vomiting, constipation, drowsiness, miosis, dependence, tolerance, respiratory depression, hypotension.

Question 17

Codeine

Answer 17

Opioid analgesic - metabolised to morphine (depends on polymorphisms in CYP2D6) binds mu-opioid receptors (which are Gi coupled GPCRs). This increases the outward flux of K+. making the cell less excitable, decreases the influx of calcium and decreases cAMP synthesis, inhibiting excitation of the neurones expressing these receptors, and decreasing neurotransmitter release.
Uses: Analgesia
ADRs: Via mu receptors - nausea, vomiting, constipation, drowsiness, miosis, dependence, tolerance, respiratory depression, hypotension.

Question 18

Tramadol

Answer 18

Opioid analgesic - binds mu-opioid receptors (which are Gi coupled GPCRs). This increases the outward flux of K+. making the cell less excitable, decreases the influx of calcium and decreases cAMP synthesis, inhibiting excitation of the neurones expressing these receptors, and decreasing neurotransmitter release. Also acts on 5-HT and NA - antidepressant effects.
Uses: Analgesia
ADRs: Via mu receptors - nausea, vomiting, constipation, drowsiness, miosis, dependence, tolerance, respiratory depression, hypotension.

Question 19

Carbamezepine

Answer 19

Anti-epileptic - prolongs inactivation state of voltage gated sodium channels.
Indications: Generalised tonic-clonic seizures, partial seizures, not absence seizures.
ADRs: CNS - dizziness, drowsiness, ataxia, motor disturbance, numbness, tingling
GI - upset, vomiting
CV - BP changes
Rashes
Hyponatraemia
Neutropenia
Contraindicated in AV conduction problems
DDIs: Induces its own metabolism so half life falls, interacts with oral contraceptives, phenytoin, warfarin, systemic corticosteroids (via CYP450 induction), antidepressants

Question 20

Lamotrigine

Answer 20

Anti-epileptic - prolongs inactivation state of voltage gated sodium channels. May also block calcium channels or impair glutamate release.
Indications: Partial seizures, generalised tonic-clonic and absence seizures. First line drug, seems safe in pregnancy. Not first line in paeds due to ADRs.
ADRs: Less marked than other anti-epileptics. CNS; dizziness, ataxia, somnolence. Nausea. Skin rashes (mild and serious)
DDIs: Concentration increased by valproate, decreased by oral contraceptives. Often used as adjunct with other AEDs.

Question 21

Phenytoin

Answer 21

Anti-epileptic - Prolongs inactivation state of voltage-gated sodium channels.
Non-linear pharmacokinetics
Indications: Generalised tonic-clonic, partial seizures (Not absence seizures)
ADRs: CNS - dizziness, ataxia, headache, nystagmus, nervousness
Gingival hyperplasia, hypersensitivity and Stevens Johnson
DDIs: Competitive binding with valproate, NSAIDs and salicylate
Oral contraceptives
Cimetidine

Question 22

Sodium valproate

Answer 22

Anti-epileptic - inhibits GABA inactivating enzymes and stimulates GABA synthesising enzymes (increasing inhibitory effect of GABA), blocks voltage gated sodium channels and blocks calcium channels (decreasing rate of discharge)
Indications - partial seizures, generalised tonic-clonic and absence seizures.
ADRs: Generally less sever than other AEDs - sedation, ataxia, tremor, weight gain, increased transaminases and hepatic failure
DDIs - take care with adjunct therapy, interact with antidepressants - inhibit valproate, antipsychotics - antagonise by lowering threshold for seizures, aspirin - competes for binding sites.

Question 23

Apomorphine

Answer 23

Dopamine receptor agonist - given subcutaneously
Indication: patients with severe motor fluctations in parkinsons disease. Given under specialist supervision.
ADRs: Impulse control disorders (pathological gambling, hypersexuality, compulsive shopping, punding, desire to increase dose), psychiatric side effects (dose limiting), sedation, confusion, nausea, hypotension

Question 24

Bromocriptine

Answer 24

Dopamine receptor agonist - ergot derived. Direct acting, has fewer dyskinesias than DOPA, may be neuroprotective, but is less effective.
Indication - Parkinson’s Disease (either de novo or as an add on)
ADRs: Impulse control disorders (pathological gambling, hypersexuality, compulsive shopping, punding, desire to increase dose), psychiatric side effects (dose limiting), sedation, confusion, nausea, hypotension

Question 25

Ropinirole

Answer 25

Dopamine receptor agonist - non-ergot derived. Direct acting, has fewer dyskinesias than DOPA, may be neuroprotective, but is less effective.
Indication - Parkinson’s Disease (either de novo or as an add on)
ADRs: Impulse control disorders (pathological gambling, hypersexuality, compulsive shopping, punding, desire to increase dose), psychiatric side effects (dose limiting), sedation, confusion, nausea, hypotension

Question 26

Levodopa

Answer 26

Dopamine precursor - taken up by dopaminergic cells in substantia nigra and converted to dopamine (effect wears off as cells die). Given with inhibitor of DOPA decarboxylase to reduce systemic side effects and increase delivery to brain (eg carbidopa).
Indications: Idiopathic parkinsons disease
ADRs: Nausea and anorexia (give domperidone), hypotension, psychosis, tachycardia, involuntary movements, motor complications (on/off, waering off, dyskinesias, dystonia, freezing)
DDIs: Pyridoxine (B6) increases peripheral breakdown, MAOIs risk hypertensive crisis, interact with antipsychotics.

Question 27

Selegiline

Answer 27

MAOI type B inhibitor - inhibits metabolism of dopamine (predominantly in dopamine containing brain regions), may be neuroprotective.
Indications - Idiopathic Parkinsons disease, can use alone or to prolong action of L-DOPA, smooth out motor response.
ADRs: Many - nausea, constipation, diarrhoea, dry mouth, stomatitis, mouth ulcers, bradycardia, mood disorders, enhanced side effects of L-DOPA

Question 28

Entacapone

Answer 28

COMT inhibitors - doesn’t cross BBB, used to potentiate L-DOPA: reduces peripheral breakdown to 3-O-methyldopa (which competes with L-DOPA for transport into CNS) - sparing effect on L-DOPA and prolongs motor response
Indications - Parkinson’s disease treated with L-DOPA
ADRs: Nausea, vomiting, abdominal pain, constipation, diarrhoea, red-brown discolouration of urine, dry mouth, IHD, confusion, dizziness, dyskinesia etc.

Question 29

Amantadine

Answer 29

Antiparkinsonian - mechanism unknown, may act by enhancing dopamine release, anticholinergic NMDA inhibition. Low efficacy, few side effects, little effect on tremor.

Question 30

Procyclidine

Answer 30

Antimuscarinic- reduces activity of acetylcholine which may antagonise dopamine. Treats tremor, doesn’t act by dopaminergic systems. No effect on bradykinesia
Indication: Parkinsons disease
ADRs: confusion, drowsiness, anticholinergic side effects

Question 31

Donepezil, Galantamine

Answer 31

Acetylcholinesterase inhibitor - used in treatment of mild to moderate Alzheimer’s disease. Improve symptoms for 6-12 months.
ADRs: headache, reduced appetite, diarrhoea, nausea, vomiting, sleepiness, urinary retention, seizures, bradycardia (risk falls), Steven’s Johnson Syndrome.

Question 32

Memantine

Answer 32

NMDA receptor antagonist (reduced the activity of overactive NMDA receptors and corresponding excitotoxicity). Used in severe Alzheimers disease.
ADRs: sleepiness, dizziness, constipation, headache, shortness of breath, hallucinations, confusion, vomiting, abnormal gait

Question 33

Imipramine, Lofepramine

Answer 33

Tricyclic antidepressants: inhibit NA uptake, enhances NA neurotransmission, blockade of muscarinic cholinoceptors, blockade of alpha-1-adrenoceptors.
Indication = depression - not first line. “dirty” drugs, not well tolerated.
ADRs: dangerous in overdose - can cause sudden cardiac death.
CNS - sedation, reduced psychomotor performance, lowering of seizure threshold.
ANS - reduced glandular secretions, accommodation block
CVS - tachycardia, postural hypotension, impaired myocardial contractility
GI - constipation

Question 34

Venlafaxine

Answer 34

SNRIs (prevent the reuptake of serotonin and noradrenaline). More potent than SSRIs, but more dangerous in overdose and more ADRs.
Indication: second or third line in depression.
ADRs: Same as SSRIs - Common - anorexia, nausea, diarrhoea, headaches, lightheadedness, sexual side effects
Rare: precipitation of mania, increased suicidal ideation, neurological side effects - tremor, extrapyramidal syndromes.
Also (specific to SNRIs) - sleep disturbance, hypertension, dry mouth, hyponatraemia, withdrawal syndrome on discontinuation (headaches, dizziness, light-headedness)

Question 35

Clozapine

Answer 35

Atypical antipsychotic - more effective than any other antipsychotic.
Indication: 3rd line treatment for schizophrenia
ADRs: agranulocytosis - do regular FBCs, hypersalivation, weight gain, constipation, sedation