Bipolar Disorder Flashcards

1
Q

Antipsychotics, first-generation (typical)

Haloperidol, chlorpromazine, prochlorperazine

Common indications

A
  1. Urgent treatment of severe psychomotor agitation that is causing dangerous or violent behaviour, or to calm patients to permit assessment
  2. Schizophrenia, particularly when the metabolic side effects of 2nd generation (atypical) antipsychotics are likely to be problematic
  3. Bipolar disorder, particularly acute episodes of mania or hypomania
  4. N&V- particularly in the palliative care setting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Antipsychotics, first-generation (typical)

Haloperidol, chlorpromazine, prochlorperazine

MOA

A
  • Antipsychotic drugs block post-synaptic dopamine D2-receptors
  • There are three main dopaminergic pathways in the CNS
  • The mesolimbic/mesocortical pathway runs between the midbrain and the limbic system/ frontal cortex
  • D2-blockade in this pathway is probably the main determinant of antipsychotic effect, but this is imcompletely understood
  • The nigrostriatal pathway connects the substantia nigra with the corpus striatum of the basal ganglia
  • The tuberohypophyseal pathway connects the hypothalamus and pituitary gland
  • D2-receptors are also found in the CTZ, where blockade accounts for their use in N&V
  • All antipsychotics, but particularly chlorpromazine, have some sedative effect
  • This may be beneficial in the context of acute psychomotor agitation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Antipsychotics, first-generation (typical)

Haloperidol, chlorpromazine, prochlorperazine

Adverse effects

A
  • Extrapyramidal effects- movement abnormalities that arise from D2 blockade in the nigrostriatal pathway- are the main drawback of first-generation antipsychotic
  • They take several forms: acute dystonic reactions are involuntary parkinsonian movements or muscle spasms; akathisia is a state of inner restlessness and neuroleptic malignant syndrome is rare but life-threatening side effect charactised by rigidity, confusion, autonomic dysregulation and pyrexia
  • These all tend to occur early in treatment. By contrast, tardive dyskinesia is a late adverse effect (tardive, late), occurring after months or years of therapy
  • This comprises movements that are pointless, involuntary and repetitive (e.g. lip smacking)
  • It is disabling and may not resolve on stopping treatment. Other adverse effects include drowsiness, hypotension, QT-interval prolongation (and consequent arrhythmias), erectile dysfunction, and symptoms arising from hyperprolactinaemia due to tuberohypophyseal D2 blockade (e.g. menstrual disturbance, galactorrhoea and breast pain).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Antipsychotics, first-generation (typical)

Haloperidol, chlorpromazine, prochlorperazine

Warnings

A
  • elderly- patients are particularly sensitive to antipsychotics, so start with lower doses
  • Antipsychotics should ideally be avoided in dementia, as they may increase the risk of death and stroke
  • They should be avoided if possible in Parkinson’ss disease due to the extrapyramidal side effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Antipsychotics, first-generation (typical)

Haloperidol, chlorpromazine, prochlorperazine

Important interactions

A
  • Consult BNF when prescribing for a patient taking antipsychotics as there is an extensive list of interactions
  • Prominent among these are drugs that prolong QT interval (amiodarone, macrolides)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Antipsychotics, second-generation (atypical)

Risperidone, quetiapine, olanzapine, clozapine

Common indications

A
  1. Urgent treatment of severe psychomotor agitation leading to dangerous or violent behaviour, or to calm such patients to permit assessment
  2. Schizophrenia, particularly when extrapyramidal side effects have complicated the use of 1st generation antipsychotics or when negative symptoms are prominent
  3. Bipolar disorder, particularly in acute episodes of mania or hypomania
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Antipsychotics, second-generation (atypical)

Risperidone, quetiapine, olanzapine, clozapine

MOA

A
  • Antipsychotic drugs block post-synaptic dopamine D2 receptors. There are three main dopaminergic pathways in the central nervous system.
  • The mesolimbic/mesocortical pathway runs between the midbrain and the limbic system/frontal cortex. D2 blockade in this pathway is probably the main determinant of antipsychotic effect, but this is incompletely understood.
  • The nigrostriatal pathway connects the substantia nigra with the corpus striatum of the basal ganglia.
  • The tuberohypophyseal pathway connects the hypothalamus with the pituitary gland. Features that distinguish second-generation antipsychotics from first-generation agents are improved efficacy in ‘treatment-resistant’ schizophrenia (particularly true of clozapine) and against negative symptoms, and a lower risk of extrapyramidal symptoms.
  • Possible mechanisms for these differences include a higher affinity for other receptors (particularly 5-HT2A receptors), and a characteristic of ‘looser’ binding to the D2 receptors (in the case of clozapine and quetiapine).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Antipsychotics, second-generation (atypical)

Risperidone, quetiapine, olanzapine, clozapine

Adverse effects

A
  • Most antipsychotics cause some degree of sedation
  • blocking dopamine in the nigrostriatal pathway may produce movement abnormalities called extrapyramidal effects
  • These are more common with 1st gen, where they are discussed more fully
  • Metabolic disturbance, including weight gain, diabetes and lipid changes, is a common problem with 2nd gen
  • Anti-psychotics can prolong the QT interval and thus cause arrhythmias
  • Risperidone has particular effects on dopaminergic transmission in the tuberohypophyseal pathway, which regulates the secretion of prolactin
    • This causes breast symptoms and sexual dysfunction
  • Clozapine causes a severe deficiency of neutrophils (Agranulocytosis) in about 1% of patients and rarely myocarditis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Antipsychotics, second-generation (atypical)

Risperidone, quetiapine, olanzapine, clozapine

Warnings

A
  • Antipsychotics should be used with caution in patients with CVD
  • Clozapine must not be used in patients with severe heart disease or a history of neutropenia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Antipsychotics, second-generation (atypical)

Risperidone, quetiapine, olanzapine, clozapine

Interactions

A
  • Sedation may be more pronounced when used with other sedating drugs
  • They should not be combined with other dopamine-blocking antiemetics and drugs that prolong QT interval (e.g. amiodarone, macrolides, SSRI, quinine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

CBZ

Common indications

A
  1. Epilepsy, as a first-choice treatment for focal seizures with and without secondary generalisation and for primary generalised seizures
  2. Trigeminal neuralgia, as first-choice treatment to control pain and reduce frequency and severity of attacks
  3. Bipolar disorder, as an option for prophylaxis in patients resistant to or intolerant of other medication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CBZ

MOA

A
  • The mechanism of action of CBZ is incompletely understood
  • It appears to inhibit neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability
  • This may inhibit spread of seizure activity in epilepsy, control neuralgic pain by blocking synaptic transmission in the trigeminal nucleus and stabilise mood in bipolar disorder by reducing electrical kindling in the temporal lobe and limbic system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CBZ

Adverse effects

A
  • The most common dose-related adverse effects are GI upset, neurological effects (dizziness and ataxia)
  • CBZ hypersensitivity affects about 10% of people and most common is just a rash
  • Antiepileptic hypersensitivity syndrome affects about 1 in 5000 people taking CBZ or phenytoin, usually within two months of starting treatment.
  • Clinical features include severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), fever with systemic (haem, hepatic, renal)
  • Other common adverse effects include oedema and hyponatraemia due to an antidiuretic hormone-like effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CBZ

Warnings

A
  • CBZ exposure in utero is associated with neural tube defects, cardiac and urinary tract abnormalities and cleft palate
  • Women with epilepsy planning pregnancy should discuss treatment with a specialist and start taking high dose folic acid supplements before conception
  • Prior antiepileptic hypersensitivity syndrome is a contraindication to both CBZ and phenytoin, due to potential cross-sensitivity
  • CBZ should be prescribed with caution in patients with hepatic, renal or cardiac disease, due to increased risk of toxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CBZ

interactions

A
  • CBZ induces cytochrome P450 enzymes, reducing plasma concentration and efficacy of drugs that are metabolised by P450 enzymes (e.g. warfarin, oestrogens, progestogens)
  • CBZ is itself metabolised by these enzymes, so it’s concentration and adverse effects are increased by CYP P450 (e.g. macrolides)
  • Complex interactions occur with other antiepileptic drugs as most alter drug metabolism
  • The efficacy of antiepileptic drugs is reduced by drugs that lower the seizure threshold (e.g. SSRIs, TCA, antipsychotics, tramadol)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

CBZ

Monitoring

A
  • EFFICACY is monitored by comparing seizure frequency before and after starting a treatment or dose adjustment
  • SAFETY is monitored by asking the patient to report any unusual symptoms immediately
  • Routine measurement of FBC and liver enzymes is unlikely to coincide with unpredictable hypersensitivity
  • Plasma CBZ concentrations are not routinely measured, but may be useful in the selected cases
  • Blood should be taken immediately before the next dose, when CBZ concentration should be between 4-12mg/L
17
Q

Valproate

Common indications

A
  1. Epilepsy, as a first choice drug for the control of generalised absence seizures and as a treatment option for focal seizures
  2. Bipolar disorder, for the acute treatment of manic episodes and prophylaxis against recurrence
18
Q

Valproate

MOA

A
  • The mechanism of action of Valproate is incompletely understood
  • It appears to be a weak inhibitor of neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability
  • It also increases the brain content of GABA, the principle inhibitory neurotransmitter, which regulates neuronal excitabiltiy
19
Q

Valproate

Adverse effects

A
  • The most common dose-related adverse events are GI upset, neurological and psychiatric, thrombocytopenia and transient increase in liver enzymes
  • Hypersensitivity reactions include hair loss, with subsequent regrowth being curlier than original hair
  • Rare, life-threatening idiosyncratic adverse effects include severe liver injury, pancreatitis, bone marrow failure and antiepileptic hypersensitivity syndrome
20
Q

Valproate

Warnings

A
  • Valproate should be avoided where possible in women of child-bearing age, particularly around the time of conception and in the first trimester of pregnancy
  • It is the antiepileptic drug associated with the greatest risk of fetal abnormalities, including neural tube defects, crainofacial, cardiac and limb abnormalities and developmental delay
  • It should be avoided in patients with hepatic impairment and dose reduction is required in patients with severe renal impairement
21
Q

Valproate

Interactions

A
  • Valproate inhibits hepatic CYP P450 enzymes increasing plasma concentrations and toxicity of drugs metabolised by P450 enzymes (Warfarin, AEDs)
  • P450 inducers (Phenytoin, CBZ) will reduce valproate concentration
22
Q

Valproate

Communicating

A
  • Explain that the aim of treatment is to reduce the frequency of seizures
  • Warn patients that they may have some indigestion or tummy upset when starting valproate, but that these will settle in a few days and can be reduced by taking tablets with foods
  • As the most serious potential adverse effects are unpredictable, patients should seek urgent medical advice for unexpected symptoms including lethargy, loss of appetite, vomiting or ab pain. or bruising, high temperature or mouth ulcers
  • For women, discuss contraception and pregnancy
  • Advise patients not to drive unless seizure free for 12 months. They should not drive for 6 months after changing or stopping treatment
23
Q

Valproate

Monitoring

A
  • EFFICACY- by comparing seizure frequency before and after starting a treatment or dose adjustment
  • Monitor safety by patient report
  • Measurement of liver function (including prothrombin time) before and during the first 6 months of treatment may be useful
  • Plasma valproate concentrations (Usually 40-100 mg/L)
  • Do not correlate well with therapeutic effect. They should therefore only be measured to check for adherence or toxicity
24
Q
A