Psychopharmacology Flashcards

1
Q

List the common drug-classes used to manage depression.

A
  • Selective Serotonin Reuptake Inhibitors (SSRIs) - first-line
  • Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs) (v
  • Mirtazapine - a noradrenergic and specific serotonin antidepressant (NASSA)
  • Tricyclic Antidepressants (TCAs)
  • Monoamine Oxidase Inhibitors (MOIs)
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2
Q

Describe the MoA of SSRIs

A

SSRIs inhibit the re-uptake of serotonin from the synaptic cleft, resulting in more serotonin in the synaptic cleft and this more serotonergic synaptic transmission. SSRIs have also been shown to decrease neuroinflammation through decreased levels of IL-6; neuroinflammation has been implicated in depression.

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3
Q

Why are SSRIs the first-line treatment for depression?

A

Selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatment for the majority of patients with depression. This is because they are as effective as other antidepressants but because they are more ‘selective’ to only serotonin reuptake proteins, they have fewer side-effects. They also have a high toxic dose making it harder to overdose.

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4
Q

When are the different SSRIs used?

A

Pls suggest edits to this card

  • Citalopram (although see below re: QT interval) and fluoxetine are currently the preferred SSRIs (unsure this is really true tbh!!!)
  • Sertraline is useful post myocardial infarction as there is more evidence for its safe use in this situation than other antidepressants
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5
Q

What are the main side-effects and interactions of SSRIs?

A
  • The main side-effects of SSRIs are gastrointestinal including nausea, vomiting, appetite and weight change. There is increased risk of GI bleeding with SSRIs, so if they are prescribed with NSAIDs they should be taken with a PPI.
  • Hyponatraemia
  • Patients should also be counselled to be vigilant for increased anxiety and agitation after starting an SSRI.
  • Citalopram can cause QT prolongation in a dose-dependent manner, and so should be avoided with those with pre-exiting conditions.
  • Avoid SSRIs if the patient is being prescribed triptans or warfarin or heparin.
  • Do not prescribe with monoamine oxidase inhibitors due to risk of serotonin syndrome.
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6
Q

Give an example of a SNRI

A

Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)

These include venlafaxine and duloxetine

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7
Q

What are the side-effects of SNRIs?

A

Because these drugs also increase the amount of noradrenaline in the synapse, side effects include constipation and hypertension as well as all the SSRI symptoms (gastrointestinal symptoms, anxiety, agigation).

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8
Q

What antidepressant is prefered for use in the elderly, and why?

A

Mirtazapine has fewer side effects and interactions than many other antidepressants and so is useful in older people who may be affected more or be taking other medications. Two side effects of mirtazapine, sedation and an increased appetite, can be beneficial in older people that are suffering from insomnia and poor appetite.

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9
Q

What is the MoA of tricyclic antidepressants (TCAs) and list a few

A

TCAs work by inhibiting the reuptake of serotonin and noradrenaline (like SNRIs). I think they are technically SNRIs but are their own drug class because of their tricyclic structure?. TCAs include:

  • Amitriptyline
  • Clomipramine
  • Imipramine
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10
Q

Why are TCAs not used as much for the management of depression?

A

Tricyclic antidepressants (TCAs) are used less commonly now for depression due to their side-effects and toxicity in overdose - lethal cardiotoxicity. They are however used widely in the treatment of neuropathic pain, where smaller doses are typically required.

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11
Q

List the common side-effects of TCAs

A

Common side-effects are due to anticholinergic effect

  • Drowsiness
  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention which can lead to overflow incontinence
  • Lengthening of QT interval
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12
Q

Why are monoamine oxidase inhibitors rarely used?

A

MOIs inhibit the metabolism of monoamines, thus increasing their synaptic levels. They are rarely used due to the danger of hypertensive crises (‘cheese reaction’) which occurs due to build-up of NA after eating tyramine-rich foods such as mature cheese, yeast extracts and fermented soya beans. They should also not be combined with other antidepressants.

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13
Q

How long after initiation of an antidepressant should a patient be reviewed?

A
  • Following initiation of antidepressant therapy, patients should normally be reviewed by a doctor after 2 weeks.
  • For patients under the age of 30 years or at increased risk of suicide, they should be reviewed after 1 week.
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14
Q

What are the indications and therapeutic range for lithium?

A

Lithium is mood stabilising drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.6-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys.

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15
Q

What are the side-effects of lithium?

A

Adverse effects

  • Nausea/vomiting, diarrhoea
  • Fine tremor
  • Nephrotoxicity: polyuria and polydipsia secondary to nephrogenic diabetes insipidus
  • Thyroid enlargement, may lead to hypothyroidism
  • ECG: T wave flattening/inversion
  • Weight gain
  • Idiopathic intracranial hypertension
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16
Q

At what levels is lithium toxic?

A

Lithium is toxic above 1.2 mmol/L

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17
Q

How is the patient on lithium monitored?

A

Lithium is toxic above 1.2 mmol/L, therefore patient should be monitored weekly after just started and after each dose changeuntil concentrations are stable.

  • Once established, lithium blood level should ‘normally’ be checked every 3 months. Levels should be taken 12 hours post-dose.
  • Thyroid and renal function should be checked every 6 months.
  • Patients should be issued with an information booklet, alert cardand record book
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18
Q

Describe the MoA of valproate and its indications

A

Sodium valproate, valproic acid are the same anticonvulsantwhich works by blocking voltage-gated sodium channels, and increasing levels of GABA in the brain.

Psychiatric indications include:

  • Long-term management of bipolar disorder - second-line as less effective than lithium.
  • Acute mania - third line after antipsychotics and lithium.
19
Q

What are the side-effects of valproate?

A

Side-effects include:

  • GI effects, nausea, vomiting, diarrhoea
  • Liver failure
  • Thrombocytopaenia
  • Alopecia
  • Weight gain through increased appetite
20
Q

What is the MoA and indication of carbamazepine?

A

Carbamazepine is another anticonvulsant used as a mood stabiliser. It works by binding to sodium channels and increasing their refractory period.

21
Q

How is the patient on carbamazepine monitired?

A

Carbamazepine is a potent P450 enzyme inducer and is known to exhibit autoinduction, hence when patients start carbamazepine they may see a return of seizures after 3-4 weeks of treatment. It is therefore important to monitor carbamazepine levels closely as well as checking efficacy and interactions of other drugs such as COCP.

22
Q

What are the side-effects of carbamazepine?

A

Apart from enzyme induction other side effects include:

  • Dizziness and ataxia
  • Drowsiness
  • Headache
  • Visual disturbances (especially diplopia)
  • Steven-Johnson syndrome
  • Leucopenia and agranulocytosis
  • Hyponatraemia secondary to syndrome of inappropriate ADH secretion
23
Q

What is the MoA of antipsychotic drugs?

A

Antipsychotics are dopamine antagonists and their clinical efficacy correlates with their receptor affinity at the D2 receptor. There is no such correlation for histamine or serotonin receptor blockade.

24
Q

List the first-generation antipsychotics

A

Conventional (first generation) antipsychotics are associated with problematic extrapyramidal side-effects which has led to the development of atypical antipsychotics such as clozapine. First generation antipsychotics include chlorpromazine, haloperidol and others.

25
Q

What are the extra-pyramidal side effects associated with antipsychotic medication?

A

Extra-pyramidal side-effects include:

  • Parkinsonism (rigidity, bradykinesia, pill-rolling tremor)
  • Akathisia (severe restlessness)
  • Tardive Dyskinesia (late onset abnormal movements) - choreoathetoid movements of which most common is chewing and pouting of jaw but also includes lip smacking and excessive eye blinking. Onset is usually after months or years of antipsychotic medication, and is usually irreversible.
  • Acute dystonic symptoms such as torticollis which is asymmetrical head or neck positions, oculogyric crisis (upward eye deviations and blinking of the eye, without epileptic features).
26
Q

List few ‘atypical’ antipsychotic medication

A

So-called ‘atypicals’/ second-generation include olanzapine, risperidone and clozapine amongst others. They are less likely than haloperidol (the most widely and typically used antipsychotic) to cause extra-pyramidal symptoms.

27
Q

When would you use clozapine?

A

Most antipsychotic medications have the same efficacy, however, clozapine turns out to be more effective than the rest. In patients with treatment refractory illness, clozapine can be useful. It is the only antipsychotic shown to be better than other antipsychotics. However, can cause agranulocytosis and so FBC should be monitored weekly.

28
Q

Describe the monitoring of patients on antipsychotics other than clozapine

A

Clozapine and other drugs:

Metabolic syndrome is a big issue in schizophrenia, and therefore lipids, weight and blood pressure should be monitored as well as fasting blood glucose and prolactin.

29
Q

What are the non extra-pyramidal side-effects of antipsychotics?

A

Other side-effects of antipsychotics:

  • Antimuscarinic: dry mouth, blurred vision, urinary retention, constipation
  • Sedation, weight gain
  • Raised prolactin: galactorrhoea, impaired glucose tolerance
  • Neuroleptic malignant syndrome: pyrexia, muscle stiffness
  • Reduced seizure threshold (greater with atypicals)
  • Prolonged QT interval (particularly haloperidol)

The Medicines and Healthcare products Regulatory Agency has issued specific warnings when antipsychotics are used in elderly patients:

  • increased risk of stroke
  • increased risk of venous thromboembolism
30
Q

What is the MoA and indications for benzodiazepines?

A

Benzodiazepines enhance the effect of the GABA by increasing the frequency of chloride channels. They therefore enhance inhibitory neurotransmitter transmission, and are used for a variety of purposes:

  • Sedation
  • Hypnotic (cause sleep)
  • Anxiolytic
  • Anticonvulsant
  • Muscle relaxant
31
Q

List some benzodiazepines

A

Examples of benzodiazepines are diazepam, chlordiazepoxide, lorazepam etc.

32
Q

What are the cautions that have to be taken with benzodiazepines?

A

Patients commonly develop a toleranceand dependenceto benzodiazepines and care should therefore be exercised on prescribing these drugs. The Committee on Safety of Medicines advises that benzodiazepines are only prescribed for a short period of time (2-4 weeks).

33
Q

What are the symptoms of benzodiazepine withdrawal?

A

If patients withdraw too quickly from benzodiazepines they may experience benzodiazepine withdrawal syndrome, a condition very similar to alcohol withdrawal syndrome. This may occur up to 3 weeks after stopping a long-acting drug.

Features include:

  • insomnia
  • irritability
  • anxiety
  • tremor
  • loss of appetite
  • tinnitus
  • perspiration
  • perceptual disturbances
  • seizures
34
Q

How should antidepressants be tapered/ how long should you wait to stop them?

A
  • If a patient makes a good response to antidepressant therapy and they want to come off, treatment should be continued for at least 6 months after remission as this reduces the risk of relapse.
  • When stopping a SSRI the dose should be gradually reduced over a 4 week period (though not necessary with fluoxetine)
35
Q

What are the causes of serotonin syndrome?

A

Causes:

  • Monoamine oxidase inhibitors (MOIs)
  • SSRIs
  • Ecstasy
  • Amphetamines
36
Q

What are the features of serotonin syndrome?

A

Features:

  • Neuromuscular excitation (e.g. hyperreflexia, myoclonus, rigidity)
  • Autonomic nervous system excitation (e.g. hyperthermia)
  • Altered mental state
37
Q

What is the management of Serotonin syndrome?

A

Management:

  • Supportive including IV fluids
  • Benzodiazepines
  • More severe cases are managed using serotonin antagonists such as cyproheptadine and chlorpromazine
38
Q

What are the causes of neuroleptic malignant syndrome?

A

Neuroleptic malignant syndrome is a rare but dangerous condition seen in patients taking antipsychotic medication, usually presenting during the first 10 days. It carries a mortality of up to 10% and can also occur with atypical antipsychotics. It may also occur with dopaminergic drugs (such as levodopa) for Parkinson’s disease, usually when the drug is suddenly stopped or the dose reduced.

39
Q

What are the features of Neuroleptic Malignant Syndrome?

A

Features

  • More common in young male patients
  • Onset usually in first 10 days of treatment or after increasing dose
  • Pyrexia
  • Rigidity
  • Tachycardia

A raised creatine kinase is present in most cases. A leukocytosis may also be seen.

40
Q

What is the management of Neuroleptic Malignant Syndrome?

A

Management:

  • Stop antipsychotics
  • IV fluids to prevent renal failure
  • dantrolene* may be useful in selected cases
  • bromocriptine, dopamine agonist, may also be used
41
Q

What are common drugs used to treat dementia?

A

Anticholinesterases: e.g. donepezil, rivastigmine.

They increase levels of ACh in the brain, which is thought to counteract the loss of cholinergic neurones seen.

NMDA receptor antagonists: memantine. This is second line to anticholinesterases, either as an add-on drug or montherapy.

42
Q

How do you manage a benzodiazepine overdose?

A

Supportive treatment:

  • Airway maintenance
  • Cardiorespiratory monitoring + support
  • IV fluids

Flumazenil IV (competitive antagonist of benzos) can revers the CNS depressant effect of overdose.

43
Q

Give examples for MOIs.

A

Phenelzine

rasagiline

44
Q

How is clozapine monitored, and describe the traffic light system

A

The patient, prescriber, and pharmacist (usually hospital pharmacy) are registered with a clozapine patient monitoring service who monitor the patients FBC weekly for 18 weeks, then every two weeks. This may then be reduced, but to no less than once every four weeks.

The clozapine manufacturers use a traffic light system (green, amber, red) for guiding dispensing on the basis of FBC results:

  • Green - clozapine can be dispensed
  • Amber - clozapine can be dispensed, but monitor FBC twice a week
  • Red - stop clozapine