Pharmacology

Question 1

What are indications for antidepressants?

Answer 1

• Unipolar depression
• Organic mood disorders
• Schizoaffective disorders
• Anxiety disorders including GAD, panic disorder, OCD, social phobia, PTSD
• Premenstrual dysphoric disorder

Question 2

What is the length of treatment for antidepressants?

Answer 2

• There is a delay, typically of 3-6 weeks after a therapeutic dose is achieved before symptoms improve
• If no improvement is seen after a trial of adequate length (at least 2 months) and adequate dose either switch to another antidepressant or augment with another agent
• When symptoms start to improve/treated, the therapeutic dose needs to be continued up to 6 months after recovery

Question 3

What are the side effects of TCAs?

Answer 3

• Lower seizure threshold
• Cardiotoxic - prolong QTc interval, even at therapeutic serum level
• Lethal in overdose
• Anticholinergic effects - dry mouth, blurred vision, constipation, urinary retention, confusion, cognitive/memory problems
• Antiadrenergic effects (alpha 1 + 2 receptors) - postural hypotension, sexual dysfunction, tachycardia
• Antihistaminic effects - sedation, weight gain

Question 4

Describe tertiary TCAs

Answer 4

• Act primarily on serotonin receptors
• SEs: antihistaminic (sedation + weight gain), anticholinergic (dry mouth + eyes, constipation, memory deficits + potentially delirium), antiadrenergic (orthostatic hypotension, sedation, sexual dysfunction
• Examples: imipramine, clomipramine, amitriptyline, doxepin

Question 5

Describe secondary TCAs

Answer 5

• Act primarily on norepinephrine receipts
• SEs: same as tertiary but generally less severe
• Examples: desipramine, nortriptyline

Question 6

Describe SSRIs

Answer 6

• 1st line in anxiety and depression
• Block presynaptic serotonin reuptake
• Very little risk of cardio toxicity in overdose
• SEs: GI upset, sexual dysfunction, anxiety, restlessness, nervousness, insomnia, fatigue, dizziness
• Can develop discontinuation syndrome - agitation, nausea, disequilibrium + dysphoria
• Examples: fluoxetine, sertraline, citalopram, escitalopram, paroxetine

Question 7

Describe SNRIs

Answer 7

• If no response to SSRI can switch to an SNRI
• Inhibit both serotonin and norepinephrine reuptake
• Like TCAs but without antihistaminic, antiadrenergic or anticholinergic side effects
• Licensed for both depression and anxiety
• Examples: venlafaxine (also for menopausal symptoms) + duloxetine (also for diabetic neuropathy)

Question 8

Describe MAOIs

Answer 8

• Bind to monoamine oxidase thereby preventing inactivation of biogenic amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels
• Very effective for depression
• SEs: orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction + sleep disturbance
• Hypertensive crisis can develop when MAOIs are taken with tyramine-rich food or sympathomimetics

Question 9

What is serotonin syndrome?

Answer 9

Medical emergency due to excessive serotonin

• Autonomic dysfunction: hyperthermia, HTN, hyperreflexia, tachycardia, tremor, agitation, irritability, sweating, diarrhoea, dilated pupils
• Abdo pain, myoclonus, delirium, CV shock + death

Question 10

What is the treatment for serotonin syndrome?

Answer 10

• Discontinue medication
• Benzodiazepines for agitation
• Severe - cyproheptadine-serotonin antagonist
• Active cooling

Question 11

What are the indications for mood stabilisers?

Answer 11

• Bipolar disorder
• Schizoaffective disorder
• Lithium is also licensed for: prophylaxis + treatment of recurrent unipolar depression and impulse control + treatment of aggressive or self-harming behaviour

Question 12

What are the classes of mood stabilisers?

Answer 12

• Lithium
• Anticonvulsants - depakote, lamotrigine, carbamazepine
• Atypical antipsychotics - olanzapine, risperidone, quetiapine, aripiprazole

Question 13

Describe the use of lithium

Answer 13

• GOLD STANDARD of mood stabilisers
• Effective in long term prophylaxis of both mania and depressive episodes in >70% of BPAD Type 1 patients
• Factors predicting positive response to lithium: prior long term response or family member with good response, classic pure mania and mania is followed by depression

Question 14

What do you need to check before starting lithium?

Answer 14

• Baseline U+Es, TFTs, FBC, weight, BMI + ECG

- Check for pregnancy - teratogenic during 1st trimester, associated with Ebstein’s anomaly

Question 15

What is the monitoring for lithium?

Answer 15

• Steady state achieved after 5 days
• Blood sample taken 12hrs after first dose, then after 5 days
• TSH + U+Es 6 monthly
• Then check every week until stable for 4 weeks
• Once stable check 3 monthly

Question 16

What are the side effects of lithium?

Answer 16

• GI disturbance - abdo pain, nausea
• Metallic taste
• Fine tremor
• Water symptoms: thirst, polyuria, weight gain, oedema
• Hair loss, acne

Question 17

What are the symptoms of lithium toxicity?

Answer 17

• GI - anorexia, diarrhoea, vomiting
• Neuromuscular - dizziness, tremor, twitching, unable to walk straight, reduced coordination
• Others - drowsiness, restlessness, lack of interest or enthusiasm
• If any of these are experience - patient contacts doctor urgently, especially if d+v as can cause dehydration leading to increased lithium
• Stop lithium, check level and refer for urgent assessment (encourage fluids (lithium excreted via kidneys), stop diuretics, monitor electrolytes and renal function)
• Don’t take NSAIDs with lithium - NSAIDs can reduce renal function

Question 18

What are the complications of lithium?

Answer 18

• Renal impairment
• Nephrogenic diabetes insipidus
• Clinical or sub clinical hypothyroidism
• Cardiac Arrhythmias, leucocytosis, reduced seizure threshold, cognitive slowing

Question 19

What are the contraindications of lithium?

Answer 19

• 1st trimester pregnancy
• Breastfeeding - can pass to baby
• Cardiac disease
• Significant renal impairment
• Addison’s
• Low sodium diets
• Untreated hypothyroidism
• Avoid alcohol if possible - do not drink >1-2 units of alcohol/day

Question 20

What are the lithium toxicity ranges?

Answer 20

• Mild (1.5-2.0mmol/l) - vomiting, diarrhoea, ataxia, dizziness, slurred speech, nystagmus
• Moderate (2.0-2.5mmol/l) - nausea, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
• Severe (>2.5mmol/l) - generalised convulsions, oliguria + renal failure

Question 21

Describe sodium valproate

Answer 21

• Anti-epileptic drug - epilepsy, seizures
• Better tolerated than lithium in mania + less monitoring
• Adults and children

Question 22

What is the treatment programme of sodium valproate?

Answer 22

• Take at same time everyday
• If you forget to take a dose, take it as soon as you remember, unless it is time for next dose then leave out missed dose
• Generally lifelong unless unresponsive, contraindicated or other medications trialled to achieve best outcome
• May take a few weeks to start working, don’t stop even if symptoms such as seizures are experienced as dose monitored and tailored to patient
• Bloods before and during treatment

Question 23

What are the side effects of sodium valproate?

Answer 23

Very common:
- Nausea/abdo pain - avoid spicy foods
- Feeling shaky - can speak to doctor
Common:
- Hair loss - temporary
- Headache
- Drowsiness - avoid alcohol/driving
- Diarrhoea
- Increased weight - good diet
- Liver problems - LFTs monitoring

Question 24

What are complications of sodium valproate?

Answer 24

• Unexplained bruising/bleeding (thrombocytopenia) - more important if undergoing surgery
• Unexplained sore throat/cough
• Extreme tiredness
• Yellowing of eyes and skin
• Sickness
• Dark urine

Question 25

What are contraindications of sodium valproate?

Answer 25

- PREGNANCY - Breastfeeding - Personal or FH of liver issues - Renal impairment - SLE - Porphyria - inherited blood disorder

Question 26

What is the indication for lamotrigine?

Answer 26

Indicated for bipolar type 2, when patients mainly have depression symptoms, with brief period of hypomania (antidepressant mood stabiliser). NOT indicated for mania.

Question 27

What is the treatment plan for lamotrigine?

Answer 27

- Initiation/titration: start with 25mg OD x2wks, then increase to 50mg x2wks then to 100mg - Faster titration has higher incidence of serious rash - Be careful when switching from sodium valproate to lamotrigine as sodium valproate will increase availability of lamotrigine - Before starting check LFTs - dose adjustment in hepatic impairment

Question 28

What are the side effects of lamotrigine?

Answer 28

- N+v - Sedation, dizziness, ataxia, confusion - Most severe is toxic epidermal necrolysis (TENs) and Stevens Johnson's Syndrome (SJS) - if any rash develops stop using immediately - Blood dyscrasias seen in rare cases

Question 29

What are the drug interactions of lamotrigine?

Answer 29

Sertraline and valproic acid increases levels