Bipolar Disorder Flashcards
1
Q
Antipsychotics, first-generation (typical)
Haloperidol, chlorpromazine, prochlorperazine
Common indications
A
- Urgent treatment of severe psychomotor agitation that is causing dangerous or violent behaviour, or to calm patients to permit assessment
- Schizophrenia, particularly when the metabolic side effects of 2nd generation (atypical) antipsychotics are likely to be problematic
- Bipolar disorder, particularly acute episodes of mania or hypomania
- N&V- particularly in the palliative care setting
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
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).
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
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)
6
Q
Antipsychotics, second-generation (atypical)
Risperidone, quetiapine, olanzapine, clozapine
Common indications
A
- Urgent treatment of severe psychomotor agitation leading to dangerous or violent behaviour, or to calm such patients to permit assessment
- Schizophrenia, particularly when extrapyramidal side effects have complicated the use of 1st generation antipsychotics or when negative symptoms are prominent
- Bipolar disorder, particularly in acute episodes of mania or hypomania
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).
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
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
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)
11
Q
CBZ
Common indications
A
- Epilepsy, as a first-choice treatment for focal seizures with and without secondary generalisation and for primary generalised seizures
- Trigeminal neuralgia, as first-choice treatment to control pain and reduce frequency and severity of attacks
- Bipolar disorder, as an option for prophylaxis in patients resistant to or intolerant of other medication
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
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
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
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)
