Session 11 - Pharmacology in Psychiatry Flashcards
Common receptor effects of muscarinic (acetylcholine) receptors.
- dry mouth
- difficulty swallowing
- thirst
- difficulty urinating
- urinary retention
- hot and flushed skin
- dry skin
Common receptor effects of histamine receptors.
- dry mouth
- drowsiness
- dizziness
- nausea and vomiting
Common receptor effects of adrenergic / noradrenergic receptors.
- sweating
- tremor
- headaches
- nausea
- dizziness
Generally, how long does it take for antidepressants to begin to work?
Two to three weeks.
Types of antidepressants.
- SSRIs (most common)
- SNRIs
- Mirtazapine
- Tricyclic antidepressants
- MAOIs
MOA of SSRIs.
Increase serotonin activity by reducing the presynaptic uptake of serotonin after release, therefore more serotonin sits in the synapse.
This leads to a down-regulation of post-synaptic receptors within 2-3 weeks.
Common side-effects of SSRIs.
- restlessness and agitation on initiation
- nausea
- GI disturbance
- headache
- weight loss / gain
- sexual dysfunction
- bleeding
- suicidal ideation
How can the specific side effects of SSRIs be managed?
a) restlessness and agitation on initiation
b) sexual dysfunction
c) bleeding
d) suicidal ideation
a) judicious use of benzodiazepines on initiation
b) prescribe viagra to help achieve erection
c) co-prescribe PPI if risk factors for bleeding
d) repeat consultation after 2-3 weeks to quantify suicide risk
Dosage of Sertraline (SSRI).
50-200mgs
Safest in cardiac disease.
Dosage of Citalopram (SSRI).
20-40mgs
Dosage of Escitalopram (SSRI).
10-20mgs
Dosage of Fluoxetine (SSRI).
20-60mgs
Dosage of Paroxetine (SSRI).
20-60mgs
Why should an ECG be conducted when prescribing Citalopram or Escitalopram for a patient?
Risk of QTc prolongation and subsequent arrhythmias.
MOA of SNRIs.
Increase serotonin and noradrenaline activity by reducing the presynaptic uptake of serotonin and noradrenaline after release, therefore more serotonin and noradrenaline sits in the synapse.
This leads to a down-regulation of post-synaptic receptors within 2-3 weeks.
Side effects of SNRIs.
Similar side effects to SSRIs, but greater potential for:
- sedation
- nausea
- sexual dysfunction
- weight gain
Other side effects are similar to SSRIs:
- restlessness and agitation on initiation
- GI disturbance
- headache
- bleeding
- suicidal ideation
Dosage of Duloxetine.
60-120mgs
Low dose range.
Dosage of Venlafaxine.
75-375mgs
Greater efficacy than Duloxetine and can go to a higher dose.
Monitoring required at higher Venlafaxine dosing.
Venlafaxine >225mgs cautioned in heart disease - monitor blood pressure.
MOA of Mirtazapine.
Antagonises 5HT-2 and 5HT-3 receptors.
Agonises H1 receptors, causing sedation as side effect.
Side effects are used to a therapeutic advantage.
Side effects of Mirtazapine.
- sedation
- weight gain
Side effects are pronounced even at low doses, therefore a reduction in dose would not help relieve symptoms.
MOA of tricyclics.
Agonise muscarinic and histaminergic receptors, causing sedation.
Can also be used to treat neuropathic pain.
Examples of tricyclics.
Newer tricyclics:
- lofepramine
- nortriptyline
tolerated better than older tricyclics:
- amitriptyline
Risk of tricyclics.
Can be fatal in overdose - cause QTc prolongation and arrhythmias.
MOA of MAOIs.
Inhibit monoamine oxidase, having effects on serotonin, dopamine and adrenaline levels.
Some are irreversible (more dangerous), while some are reversible (less dangerous).
Interactions of MAOIs.
Potential for significant and dangerous interaction with other drugs.
Rarely prescribed.
What foods need to be avoided if prescribing MAOIs?
Avoid tyramine products:
- cheese
- pickled meats
- wine
Potential for tyramine reaction leading to hypertensive crisis.
MOA of Vortioxetine.
Differing effects on serotonergic activity according to receptor.
Side effects of Vortioxetine.
Generally well tolerated.
Most common side effect is nausea.
What factors influence antidepressant choice?
- what has been used before?
- what has been effective before?
- what has been well tolerated before?
- what does the patient want?
- are there any particular symptoms or comorbidities you want to address?
General antidepressant step-up.
- Sertraline
- Different SSRI
- SNRI / Mirtazapine
If SSRI causes major weight changes or sleep difficulty consider Mirtazipine; if comorbid neuropathic pain consider SNRI first line.
When should you switch antidepressant medication?
Switch if no treatment effect within the first 4 weeks.
When should you increase the dose of antidepressant medication?
If there has been partial benefit within the first 4 weeks.
What is discontinuation syndrome?
For some people, the rapid exit of serotonin from the system can cause an unpleasant syndrome.
FIRM STOP:
Flu like Sx
Insomnia
Restlessness
Mood swings
Sweating
Tummy problems (pain, cramps, D+V)
Off balance
Parasthaesia
Is discontinuation syndrome life-threatening?
No - it is unpleasant but not life-threatening.
Which antidepressants are particularly associated with discontinuation syndrome?
Those with a short half life:
- Venlafaxine
- Paroxetine
How can the risk of discontinuation syndrome be reduced?
- alternate days of taking
- snap tablets in half
- switch to Fluoxetine* (long half life) then reduce
*Fluoxetine comes in liquid preparation so can make micro-adjustments in dose.
What is serotonin syndrome?
A potentially life-threatening side effect of antidepressants, characterised by excess serotonin.
Presentation of serotonin syndrome:
a) cognitive
b) autonomic
c) somatic
a) headaches; agitation; hypomania; confusions; coma
b) shivering; sweating; hyperthermia; tachycardia; nausea and diarrhoea
c) myoclonus; hyper-reflexia; tremor
Can cause seizures and sudden death.
Treatment of serotonin syndrome.
Supportive - fluids and monitoring.
What are the four dopaminergic pathways in the brain?
- mesocortical pathway
- mesolimbic pathway
- nigrostriatal pathway
- tuberoinfundibular pathway
MOA of antipsychotics.
Reduce level of dopamine activity at D2 receptors:
- target pathways are mesocortical and mesolimbic
- unwanted effects come from nigrostriatal and tuberoinfundibular
Difference between typical and atypical antipsychotics.
Typical are older and more likely to cause extra-pyramidal side effects.
Atypical tend to bind to more muscarinic and histaminic receptors.
Atypical tend to have more serotonergic activity.
Examples of typical antipsychotics.
- haloperidol
- chlorpromazine
- flupenthixol
Examples of atypical antipsychotics.
- clozapine
- olanzapine
- resperiodone
- quetiapine
- aripiprazole
Side effects of all antipsychotics.
- sedation
- weight gain
- QTc prolongation
Side effects more associated with typical antipsychotics.
- extra-pyramidal side effects (as stronger D2 antagonist)
- dizziness
- sexual dysfunction
What are the extra-pyramidal side effects?
Side effects caused by impaired motor control, due to dysfunction of the basal ganglia secondary to dopamine dysregulation.
- bradykinesia
- muscle stiffness
- tremor
- tardive dyskinesia (chewing like a horse)
- akathisia
Side effects more associated with atypical antipsychotics.
- weight gain
- dyslipidaemia
- diabetes
Baseline monitoring of antipsychotics.
- FBC (bone marrow suppression)
- lipid profile (dyslipidaemia)
- LFTs (steatohepatitis)
- HbA1c (DM)
- weight (weight gain)
- ECG (QTc prolongation)
- blood pressure and pulse (early sign of metabolic syndrome)
Weekly monitoring of antipsychotics.
Weekly monitoring of weight to prevent weight gain.
Monitoring of antipsychotics at 3 months.
- FBC (bone marrow suppression)
- lipid profile (dyslipidaemia)
- LFTs (steatohepatitis)
- HbA1c (DM)
- weight (weight gain)
- ECG (QTc prolongation)
- blood pressure and pulse (early sign of metabolic syndrome)
Monitoring of antipsychotics at 1 year.
- FBC (bone marrow suppression)
- lipid profile (dyslipidaemia)
- LFTs (steatohepatitis)
- HbA1c (DM)
- weight (weight gain)
- ECG (QTc prolongation)
- blood pressure and pulse (early sign of metabolic syndrome)
What is neuroleptic malignant syndrome?
A rare, life-threatening reaction to antipsychotics due to:
- rhabdomyolysis
- renal failure
- seizures
Risk factors for neuroleptic malignant syndrome.
- typical antipsychotics
- antipsychotic naive
- high doses
- young men
How can neuroleptic malignant syndrome be differentiated from serotonin syndrome via investigation?
Neuroleptic malignant syndrome causes rhabdomyolysis, therefore CK will be raised.
Presentation of neuroleptic malignant syndrome.
a) cognitive
b) autonomic
c) somatic
a) headaches; agitation; hypomania; confusions; coma
b) shivering; sweating; hyperthermia; tachycardia; nausea and diarrhoea
c) myoclonus; hyper-reflexia; tremor
Can cause seizures and sudden death.
Treatment of neuroleptic malignant syndrome.
- Stop antipsychotic
- Emergency referral to A&E
- Fluid resuscitation
- Reduce temperature (cooling blankets)
- Benzodiazepine for acute behavioural disturbance
Give fluids and sodium bicarbonate to alkalise the urine in rhabdomyolysis.
Give dantrolene or lorazepam to relax muscles.
How can extra-pyramidal side effects (EPSEs) be treated?
Low ratio of dopamine:acetylcholine in nigrostriatal pathway leads to extrapyramidal side effects.
By reducing acetylcholine, the ratio of doapmine:acetylcholine increases and EPSEs are reduced.
Examples of medication used to treat EPSEs.
Acetycholine receptor antagonists.
Procyclidine most commonly used drug; potential for misuse as causes a ‘high’.
What are acute dystonias?
Sustained, painful muscular spasms, producing abnormal postures.
Associated with typical antipsychotic use.
How long after initiating antipsychotics do acute dystonias present?
Around half in the first 48 hours.
90% within the first 5 days.
Management of acute dystonias.
- stop antipsychotic
- IM or IV anticholinergic (procyclidine)
- continue for 1-2 days after dystonia and consider long-term prophylactic
MOA of Clozapine.
Atypical antipsychotic.
D2 antagonist; 5HT-2 antagonist.
Indication of Clozapine prescription.
Should be used in schizophrenia after two other antipsychotics have not been effective.
Side effects of Clozapine.
Agranulocytosis, plus:
Autonomic side effects:
- constipation
- fatal bowel obstruction
- hypersalivation
- urinary incontinence
Dose titrated slowly upward over two weeks, with vital signs and FBCs monitored closely.
Monitoring when on Clozapine.
FBC monitoring to assess for agranulocytosis.
Weekly for first 18 weeks; fortnightly up to 52 weeks; monthly thereafter.
Treatment of agranulocytosis.
- stop Clozapine (and other bone marrow suppressants e.g. sodium valporate)
- avoid other antipsychotics
- consider broad spectrum abx prescription
- contact consultant Haematologist as an emergency
Lithium and G-CSF can be used to increase WCC and neutrophil count, under specialist instruction.
Which antipsychotic has the least potential for bone marrow suppression?
Aripiprazole - used as antipsychotic if agranulocytosis occurs.
Only use if really needed.
Medications used to treat anxiety.
- SSRIs
- beta blockers
- benzodiazepines
- pregabalin
MOA of beta-blockers.
Reducing autonomic nervous system activation, having a bio-psychofeedback mechanism that dampens anxiousness.
Contraindications of beta-blockers.
Asthma
Most commonly used beta-blocker.
Propanolol
Most commonly used benzodiazepines.
- diazepam (long half-life)
- lorazepam (short half-life)
MOA of benzodiazepines.
Bind to GABA receptors to potentiate the effect of GABA, and therefore reduce the excitability of neurones.
(GABA is an inhibitory neurotransmitter).
Cautions of benzodiazepines.
- tolerance
- dependence
- misuse
Due to cautions, use for no more than 6 weeks.
MOA of Pregabalin.
Binds to voltage-gated calcium channels on neurones, reducing neuronal activity.
Indications of Pregabalin.
- anxiety
- neuropathic pain
- epilepsy
Side effects of Pregabalin.
- sedation
- weight gain
Less potential for misuse and dependence than benzodiazepines, but still misused.
What are the classes of sleeping tablets?
Benzodiazepines: Temazepam, Lormatazepam, Nitrazepam.
Nonbenzodiazepines: Zopiclone, Zolpidem (Z-drugs).
Note Z-drugs are usually favoured.
Prescription advise for sleeping tablets.
- two weeks max
- take for 5 out of 7 days each week
What is used to treat bipolar disorder?
Mood stabilisers:
- lithium
- anticonvulsants
- atypical antipsychotics
Monitoring of serum lithium levels.
Narrow therapeutic window:
- weekly serum lithium levels until stable
- 3 monthly lithium levels once stable
What is the effect of Lithium use in depression?
Significant evidence that Lithium reduces suicide risk - and it has a license for reduction of self-harm.
Can also be used to augment antidepressants.
Side effects of Lithium.
- GI disturbance
- metallic taste
- dry mouth
- fine tremor
- polydipsia
- polyuria
- weight gain
Long-term effects of Lithium, and extra monitoring therefore required.
- hypothyroidism
- renal impairment
Therefore annual U&Es and TFTs.
Monitoring of LFTs when on Lithium.
Not required as Lithium completed excreted by the kidneys - has no effect on the liver at all.
Presentation of Lithium toxicity.
- confusion
- coarse tremor
- nausea and vomiting
- ataxia
- seizures
Treatment of lithium toxicity.
- stop lithium
- IV fluids
- dialysis if necessary
- benzodiazepines for seizures
Dangerous interactions with lithium.
- NSAIDs
- loop diuretics
- ACE inhibitors
First line treatment for bipolar disorder.
Atypical antipsychotic
Quetiapine.
Most commonly used anticonvulsants in bipolar disorder.
- Sodium valporate
- Carbamazepine
- Lamotrigine
Cautions of Sodium Valporate.
Avoid in men and women of child bearing age due to teratogenicity - must stop >6 months before pregnancy.
Check LFTs before and soon after starting.
Cautions of Lamotrigine.
Potential for Stevens Johnson syndrome:
Type IV hypersensitivity reaction, causing blistering of mucosal membranes.
Why are FBCs monitored when taking anticonvulsants?
Potential for thrombocytopenia.
Side effects of anticonvulsants.
- sedation
- weight gain
Medication prescribed for ADHD.
- Methylphenidate
- Dextroamphetamine
- Atomoxetine
Monitoring required when prescribing ADHD medications.
Monitor weight and height in children (stunted growth).
Monitor pulse in children.
