Meds

Question 1

Hypnotics and anxiolytics

Answer 1

Act on GABA receptors
Impair ability to drive/operate machinery
Tolerance and dependence
Short term, for anxiety (use anti-depressants long term)

Question 2

Benzodiazepines

Answer 2

Eg. Diazepam (anxiolytic), temazepam (hypnotic), lorazepam (anxiolytic) and triazolam
Mechanism: Enhance GABA at GABA-A receptors
Cautions: Respiratory failure, breast feeding, previous addiction
Adverse effects: Drowsiness, confusion, disinhibition, aggression, dependency and addiction, memory and balance problems
Quite safe in OD alone but dangerous when combined with alcohol or opiates
GABA antagonist Flumazenil used for overdose
Interactions: Potentiate other sedatives (eg alcohol, anti-histamines, anti-depressants, anaesthesia)
Tolerance: 3-14 days
Withdrawal: insomnia, anxiety, sweating, tremor, perceptual disturbance, delirium and seizures. Can manifest from hours to 3 weeks after dose and may persist for months. Use for a maximum of 2-4 weeks for severe, disabling anxiety or insomnia

Question 3

Barbituates

Answer 3

Avoid as dangerous in overdose

Hypnotic/anxiolytic

Question 4

Chlormethiazole

Answer 4

Hypnotic/anxiolytic
Conjunctival, nasal and gastric irritation
Stimulant properties addictive

Question 5

Z drugs

Answer 5

Zopiclone, Zolipidem, Promethazine, Melatonin
Hypnotic (short acting)
GABA-A agonist
Addictive properties similar to benzos

Question 6

Buspirone

Answer 6

Anxiolytic BUT is a 5-HT-1A receptor agonist
No evidence of addiction or abuse potential
May be less potent than benzos and take 2-3 weeks to develop
Mildly anti-depressant

Question 7

Antidepressants

Answer 7

Do not alter normal mood
Takes 2-4 weeks to develop
May also be used in anxiety
Not addictive, but some are very toxic in overdose and a discontinuation sundrome may occur

Question 8

Tricyclics (eg, mechanism, indications, cautions)

Answer 8

Eg. Amitryptaline/dothiepin (sedative), imipramine, lofepramine, clomipramine
Mechanism: 5-HT/noradrenaline re-uptake inhibitors. Takes some weeks to have benefit
Indications: depression, anxiety
Cautions: cardiac disease, glaucoma, prostatism, epilepsy, hepatic impairment, elderly (hyponatraemia/post hypotension risk)

Question 9

Tricyclics (adverse effects and interactions)

Answer 9

Muscarinic antagonism: dry mouth, blurred vision, constipation, urinary retention, impotence, delirium
Histamine antagonism - sedation and weight gain
Andrenergic antagonism - postural hypotension, sweating
Direct membrane effects - reduced seizure threshold, arrhythmia, heart block
5-HT antagonism - weight gain, weight gain
5-HT/NA re-uptake inhibition - mania
Interactions: Hypertensive crisis with adrenaline or MAOIs

Question 10

MOAIs

Answer 10

Eg. Phenelzine, moclobemide
Mechanism: Inhibit monoamine oxidase → block 5-HT and NA metabolism → ↑ levels of 5-HT and NA
Cautions: Cardiac disease, epilepsy, hepatic impairment, ECT
Adverse effects: Anticholinergic, hypotension, oedema, fits, neuropathy, drowsiness, delirium, mania, hepatitis, leucopenia
Interactions: hypertensive crisis with sympathomimetics and tricyclics, potentiates CNS depression with opiates. Tyramine reaction (a sympathomimetic) → can’t eat cheese, red meat, alcohol. Restrictions apply for two weeks after drug is stopped
Last resort drug.
Need a drug holiday after stopping before give another drug

Question 11

SSRIs

Answer 11

eg. Fluoxetine, sertraline, citalopram
Mechanism: 5-HT reuptake inhibitors
Indications: depression, anxiety, panic, OCD, impulse control disorders
Cautions: Renal/hepatic impairment, pregnancy, epilepsy
Adverse effects: short lived - 3 or 4 days following commencement or dose increase, nausea, anorexia, ↑ anxiety. Long term - throughout tx, headache, insomnia, sexual dysfunction, ↑ risk GI bleeds
Interactions: toxicity with MAOIs and anti-migraine drugs such as sumitriptan

Question 12

Reboxetine

Answer 12

NARI
Depression with anergia, poor motivation and concentration
Caution in renal and hepatic impairment, urinary retention and glaucoma
Adverse effects anticholinergic
Interacts with MOAIs

Question 13

SNRI

Answer 13

Venlafaxine, duloxetine
Inhibit 5HT, NA, DA uptake
Severe and treatment resistant depression
Anxiety disorders incl panic disorder and OCD
Caution if hx of MI
Adverse similar to SSRIs, also hypertension at higher doses
Avoid use with MAOIs

Question 14

Trazodone

Answer 14

5-HT receptor antagonism
GAD/non-specific sedative/augment SSRIs/SNRIs
Very safe
Adverse effect - sedation, rare serious side effect is priapism

Question 15

Mirtazepine

Answer 15

Complex. Adrenergic alpha-2 receptor antagonism → ↑ 5-HT and NA neurotransmission. Also blocks 5-HT2 receptors which helps treat anxiety and 5-HT3 receptors which helps prevent sexual dysfunction. Blocks histamine receptors → sedation
Caution in epilepsy, hepatic/renal impairment, cardiac disorders, urinary retention, DM
Adverse - weight gain, sedation, rarely a reversible agranulocytosis
2nd line or if problems sleeping

Question 16

Mood stabilisers

Answer 16

Primarily prophylaxis for bipolar
Acute episodes of mania
May also be adjuncts to anti-depressants for depression

Question 17

Lithium

Answer 17

Mechanism unknown. Therapeutic window very close to toxicity, important to check levels at least 3 monthly (weekly initially).
Also: U+E, eGFR, TFT, weight, calcium at baseline and 6 monthly
Cautions: renal/cardiac impairment, pregnancy, breastfeeding
Interactions: diuretics, NSAIDs, ACE-I, MAOIs, carbamazepine, high dose antipsychotics
Adverse effects: polyuria, polydipsia, fine tremor, GI disturbance, oedema, weight gain, hypothyroidism, goitre, ECG changes; teratogenic (ebstein’s anomaly)
Intoxication: Anorexia, vomiting, diarrhoea, weakness, twitching, coarse tremor, ataxia, drowsiness, confusion, coma → renal and circulatory failure, convulsions and death
Treat toxicity: Sodium chloride and water

Question 18

Carbemazepine

Answer 18

Anti-epileptic
Mood stabiliser
Not as effective as lithium but less toxic
Adverse effects: drowsiness, neutropenia
Interactions: MAOIs and lithium → neurotoxicity

Question 19

Sodium Valproate

Answer 19

May be as effective as lithium or better for those with high frequency bipolar, with high proportion of manic episodes.
Adverse effects include hepatic dysfunction, blood disorders, nausea, ataxia and tremor

Question 20

Lamotrigene

Answer 20

Depressed bipolar disorder and for prophylaxis
Associated with serious and sometimes fatal skin disorder (Stevens-Johnson syndrome)
Introduce drug slowly, warn patients to look out for flu-like symptoms and skin rashes
Other adverse effects - headache, nausea, ataxia
Interactions: other anti-convulsants

Question 21

Antipsychotics

Answer 21

Schizophrenia, mania, psychotic depression
Short term sedation
Prophylactic in schizophrenia
May take several weeks for anti-psychotic effect to develop

Question 22

Typical antipsychotics

Answer 22

Mechanism: Block dopamine D2 receptors
Orally or depot
Chlorpromazine, haloperidol
Cautions: cardiovascular and cerebrovascular disease, parkinsonism, epilepsy, pregnancy, breast feeding, renal and hepatic impairment, prostatism, glaucoma
Adverse effects: similar to TCAs plus dystonia of jaw, extraocular muscles and neck, parkinsonism, akathisia, tardive dyskinesia (often irreversible), postural hypotension hyperprolactinaemia → gynaecomastis, galactorrhoea, amenorrhoea, blood dyscrasias, hepatitis, skin rashes and photosensitivity
QT prolongation
Neuroleptic malignant syndrome: rare but potentially fatal: rigidity, hyperpyrexia and clouding of consciousness
Interactions: potentiates hypotensives and sedatives

Question 23

Typical antipsychotic examples
Grouped according to adverse effects
(S=sedation, A=anticholinergic, E=extrapyridamal)

Answer 23

S+++;A++;E++: Chlorpromazine
S++;A+++;E+: Thioridazine
S+;A+;E+++: Trifluoperazine, Haloperidol, Flupenthixol decanoate/Fluphenozine decanoate (depot)

Question 24

Sulprimide

Answer 24

Atypical antipsychotic
‘Clean’ dopamine agonist → fewer side effects than typicals, especially fewer extrapyridamal
Avoid in renal impairment
Less sedating but can still be used in acute psychosis

Question 25

Clozapine

Answer 25

5-HT2/D2 agonist
Higher efficacy than typical antipsychotics in treatment resistant schizophrenics
Associated with fatal agranulocytosis, must have regular blood counts
Other adverse effects: sedation, hypersalivation, anticholinergic effects BUT LESS EPS than typicals

Question 26

Risperidone, Olanzapine, Quetiapine

Answer 26

Varying degrees of 5-HT2/D2 agonism
Marked weight gain but fewer EPS than typicals
Risperidone: anticholinergic, hyperprolactinaemic, EPS at high doses
Olanzapine: sedative, contraindicated in glaucoma, caution in myeloproliferative disease

Question 27

Acetylcholinesterase inhibitors

Answer 27

Mild -> mod dementia
Eg. Donepezil (1st line), rivastigmine (2nd line)
Mechanism: anticholinesterase → ↑ acetycholine
Cautions: cardiac conductive problems, asthma, COPD, peptic ulceration
Adverse effects: nausea, vomiting, diarrhoea, bradycardia, AV block, peptic ulceration, incontinence
Interactions: antiarrhythmics, beta blockers

Question 28

Disulfiram

Answer 28

Alcohol dependency
Patient must be motivated to take the medication regularly
Unpleasant systemic reaction (tachycardia, palpitations, flushing, headache) if drink alcohol
Large doses of alcohol can produce a severe reaction that can be fatal
Drowsiness, nausea and vomiting
Adverse effects: drowsiness, nausea, vomiting

Question 29

Acamprosate

Answer 29

Aids abstinence in alcohol dependence
GABA agonist/glutamate antagonist
Can cause gastro-intestinal disturbance
Continued alcohol consumption negates therapeutic effect

Question 30

Smoking cessations

Answer 30

Bupropion:
NA/dopamine reuptake inhibitor
Used in US as antidepressant
In UK to help stop smoking

Varencline:
Nicotine receptor partial agonist
Risk of suicidal thoughts

Question 31

Serotonin Syndrome

Answer 31

Neuromuscular hyperacivity: tremor, hyperreflexia, clonus, myoclonus, rigidity
Autonomic dysfunction: Shivering, tachycardia, blood pressure changes, hyperpyrexia, diaphoresis (sweating), diarrhoea
Altered mental state: Agitation, confusion, mania
Risk is increased by drugs that enhance serotonin transmission - MAOIs, triptans, St John’s wort
Treatment: withdraw serotonergic medication, supportive care, specialist advice

Question 32

Depression treatment

Answer 32

Anti-depressants usually require 3-4 weeks for therapeutic effect
1st episode mild depression: at least 6 months
2nd episode or mod/severe depression: at least 2 years. premature dose reduction or withdrawal → increased risk of relapse

Question 33

If antidepressant fails

Answer 33

Try different class or different drug in same class
Reduce first then start second
Before/after MAOIs: Need holiday (usually 2 weeks, 2 weeks for TCAs, 5 weeks for fluoxetine)
Refractory depression: failure to respond to 2 or more antidepressants

Question 34

Refractory depression options

Answer 34

CBT
Lithium augmentation
Venlafaxine up to BNF limits
Atypical antipsychotics
Phenelzine (MAOI)

Question 35

SIADH

Answer 35

Hyponatraemia, no oedema
Lethargy, headache, insomnia, apathy, agitation, confusions, convulsions, coma
Concentrated urine (>300mOsm/kg); low blood urea nitrogen, serum uric acid, creatinine and albumin
SSRIs>TCAs, esp fluoxetine. Use with caution in the elderly
Other causes: diuretics, tumours, hypothyroidism, resp and CNS diseases

Question 36

ECT

Answer 36

Small electrical charge across the brain to induced tonic clonic seizure
Under GA
Severe depression where pharmalogical treatment has been unsuccessful or when rapid improvement is important

Question 37

EPSE

Answer 37

Blocking of dopamine pathways
Dystonias (abnormal movement of tongue and facial muscles)
Bradykinesia
Rigidity
Tremor
Treatment: Procyclidine

Question 38

Akathisia

Answer 38

Motor and psychological restlessness
Foot tapping, moving legs repetitively
Unable to settle or relax
Treatment: beta blockers

Question 39

Tardive dyskinesias

Answer 39

Abnormal movements
Tongue protrusion, lip smacking, rotational tongue movements, facial grimacing
Twisting/gyrating of whole body
Dose reduction or change to atypical

Question 40

Cardiovascular SE of antipsychotics

Answer 40

Postural hypotension (alpha blockade)
Dose related
Prolonged QT -> ventricular arrythmias and sudden death
Haloperidol and pimozide: mandatory ECG

Question 41

Prolactin increase

Answer 41

Blockage of D receptors in tuberoinfundibular pathway -> gynaecomastia, galactorrhoea and menstrual disturbance
Change to atypical or adding a DA may help

Question 42

Other SEs of antipsychotics

Answer 42

Sedation
Weight gain
Seizures
Hypo/hyperthermia
Skin problems (photosensitivity)
Sexual dysfunction
Retinal pigmentation (chlorpromazine)
Corneal and lens opacities
Blood dyscrasias
Osteoporosis
Jaundice

Question 43

Acute mania

Answer 43

Stop antidepressants
Benzos
Anti-psychotics

Question 44

Long term management of mania

Answer 44

Mood stabilisers

eg Carbamazepine, valproate, lamotrigine, lithium (most effective for long term use)

Question 45

Memantine

Answer 45

Mod dementia, AchEi not tolerated or severe dementia
Glutamate receptor antagonist
SE: hypertension, headaches, dizziness, drowsiness