25.2 Drugs in the management of mental health disorders Flashcards
What is psychosis?
A mental state characterised by a loss of touch with reality.
A psychotic illness is characterised by multiple symptoms affecting thought, perceptions, emotions and volition.
What are neuroleptics?
Aka. antipsychotics.
Used to treat psychoses.
What is the difference between acute and chronic schizophrenia?
Schizophrenia is one of the main conditions associated with psychosis.
- Acute: positive symptoms aka. delusions, hallucinations, abnormal thought processes.
- Chronic: negative symptoms aka. poverty of speech, anhedonia, apathy, attention impairment.
Which neurotransmitters are involved in schizophrenia?
- Dopamine
- 5-HT (serotonin)
- GABA
- Glutamate
What are the 2 antipsychotic drug groups?
EPEs also called Parkinsonisms
Describe the 1st generation (typical) antipsychotics.
Great affinity for D2 receptors.
Dopamine receptor antagonists.
- Phenothiazines e.g. trifluoperazine
- Butyrophenones
Poor for -ve symptoms.
Also have effects on adrenoreceptors, muscarinic receptors and histamine receptors. Leading to adverse effects.
Describe the 2nd generation (atypical) antipsychotics.
Serotonin-dopamine antagonists.
- Benzodiazepine derivatives e.g. clozapine, quetiapine
- Substituted benzamides e.g. sulpiride
Fewer adverse effects.
What risks are associated with clozapine?
- Significant toxicity
- Can have haematological consequences
- Can cause myocarditis and cardiomyopathy (usually develops within first 2 months of treatment)
- Presents as sinus tachycardia
- Treatment must be stopped
Name 8 adverse effects of neuroleptics.
- Acute neurological effects: acute dystonia (e.g. lip smakcing, muscle spasm), Parkinsonism
- Chronic neurological effects: tardive dyskinesia, dystonia
- Neuroendocrine effects: amenorrhoae, galactorrhoea
- Anticholinergic effects: xerostomia, constipation, blurred vision, urinary retention
- Antihistaminergic: drowsiness, sedative effects
- Antiadrenergic: hypotension, arrythmias
- Cardiac toxicity
- NMS (neuroleptic malignant syndrome)
Explain the cardiac toxicity of antipsychotics.
- Antipsychotic drugs delay cardiac repolarisation leading to ventricular arrythmias
- Prolonged QT interval, risk of condition developing called Torsade de Pointes
- Can result in syncope
- Can degenerate into ventricular fibrillation resulting in sudden cardiac death
Olanzapine and risperidone are associated with an increased risk of stroke in the elderly.
Explain NMS.
Neuroleptic malignant syndrome
- Rare idiosyncratic reaction to neuroleptics
- Most serious neuroleptic adverse effect
- If untreated, 20% mortality risk
- Symptoms: hyperthermia, fluctuating consciousness, muscles rigidity, tachycardia, sweating
- Treatment: diazepam, bromocriptine, supportive care
When do NICE recommend the use of atypical antipsychotics?
What are antidepressants used to treat?
- Major depressive disorder
- Bipolar depressive disorder
What are the biologic signs of depression?
- Fatigue
- Apathy
- Poor concentration
- Changes in appetite
- Changes in sleep pattern
- Low libido
What is the monoamine hypothesis of depression?
Depression is caused by a funcitonal defecit in monoamine neurotransmitters: noradrenaline and 5HT (serotonin).
Describe the action of tricylclic antidepressants and SSRIs.
- Tricyclics: prevent reuptake of noradrenaline and serotonin in the neuron
- SSRIs: prevent reuptake of serotonin making more available for transmission
Ultimately making more dopamine and serotonin available in the postsynaptic space.
What does SSRI stand for?
Selective serotonin reuptake inhibitors.
Do patients respond immediately to increases in monoamine neurotransmitters?
No, drug efficacy may require down regulation of receptors which does not occur immediately.
Antidepressants can make pts feel worse before they feel better.
What are the 4 categories of antidepressants?
- Tricyclic antidepressants
- SSRIs
- Monoamine oxidase inhibitors
- Others
Describe tricyclic antidepressants.
- Block noradrenaline and serotonin reuptake
- Extremely toxic in overdose, high risk of mortality, not recommended for first choice medication
- Causes cardiac toxicity in overdose
- Can prolong QT interval
- E.g. amitryptiline, imipramine, clomipramine
What receptors do tricyclic antidepressants have some affinitiy for?
- Muscarinic cholinergic receptors, causes dry mouth as a side effect
- Adrenoreceptors causing postural hypotension in some patients
- Histamine 1 receptors which can cause sexual dysfunction and loss of libido
Describe SSRIs.
- Block serotonin reuptake
- E.g. setraline, fluoxetine, citalopram, paroxetine
- Adverse effects: nausea, diarrhoea, sexual dysfunction, insomnia and agitation
- Interactions: cytochrome P450 inhibitors (e.g. antifungals and erythromycin)
Describe monoamine oxidase inhibitors.
- E.g. phenelzine and moclobemide
- Inhibit monoamine oxidase enzymes (the enzymes responsible for breakdown of monoamine neurotransmitters)
- Historical MAOIs: “The Cheese Reaction” old MAOIs were non-selective, blocked gut enzymes causing tyramine to be absorbed into the body leading to hypertensive crisis, headache, tachycardia arrythmias and stroke
- Newer MAOIs are selective and are selective for MOA-A which is found in the CNS only
Name the “other antidepressants”.
Don’t fit into a specific group:
- Mirtazapine
- Venlafaxine
- Bupropion
- Nefazodone and trazodone
What is St John’s wort?
- Unlicensed herbal remedy for the treatment of mild depression
- Can induce hepatic enzyme
- Well recognised important drug interactions e.g. warfarin, simvastatin, oral contraceptive pill
- Take thorough drug history including herbal medication
What are the 3 main drugs used in the treatment of bipolar disorders?
- Lithium prophylaxis
- Sodium valproate (mood stabilising effects)
- Carbamazepine for prophylaxis of manic episodes in pts unresponsive to lithium
When must sodium valproate be avoided?
In women or girls of childbearing potential unless they’re on the pregnancy prevention programme
Describe lithium prophylaxis in the treatment of bipolar disorders.
- Requires regular therapeutic monitoring
- Therapeutic range is 0.4-1.2mmol/l
- Renal excretion
What are the possible adverse effects of lithium?
- Fatigue, nervousness, GI disturbances, weight gain, oedema
- May damage the distal renal tubule resulting in nephrogenic diabetes
- Maybe hypokalaemia and occasionally hypercalcaemia
- Can disturb thyroid hormone synthesis resulting in hypo or hyper thyroidism
- Can prolong QT interval
- Long term use can result in memory impairment or osteoporosis
What is lithium toxicity?
- Occurs in overdose or when co-prescribed with interacting drugs
- Leads to reduced renal excretion of lithium = cardiac and neurological toxicity, eventually leads to coma and death if untreated
What drugs are contraindicated in patients taking lithium?
- NSAIDs
- Diuretics
- ACE inhibitors
What drugs are used to treat attention deficit hyperactivity disorder?
Central nervous stimulants amphetamine type and related drugs.
- ‘Paradoxical effects’ in children
- Requires specialist initiation
- E.g. Methylphenidate and Atomoxetine
When are beta-blockers used in mental health conditions?
Used to reduce the autonomic symptoms of anxiety (tremor, sweating, reduces heart rate).
For the physical symptoms of anxiety, not the psychological.
Name some benzodiazepines.
- Diazepam (Valium)
- Midazolam (used in dentistry for conscious sedation)
- Lorazepam
Benzos are also used recreationally, addictive.
What are the major uses of benzodiazepines?
A: anixolytics
M: muscle relaxants
A: anti convulsants
I: IV anaesthetics
S: sedatives
Describe the pharmacology of benzodiazepines.
- Benzos are CNS depressants
- Act by potnetiating the actions of GABA, the primary inhibitory neurotransmitter of the CNS
How are benzos metabolised?
Predominantly by the liver.
How do the half-lives of benzos vary?
Midazolam half life = 2-4 hours (sedation)
Diazepam half life = 20-40 hours
What is the antagonist for benzodiazepine overdose?
Flumazenil
- Reverses the sedative effects of benzos when used in anaesthesia
- Not used to reverse overdose, only reverses sedative effects
What are the possible adverse effects of benzodiazepines?
- Normal doses: drowsiness, sedation, dizziness, slurred speech, impaired cognitive function and memory impairment
- Can cause paradoxical hyperactivity in children
- Can cause disinhibition and aggression is some adults
- Dependency and withdrawal symptoms may occur when benzodiazepines are discontinued abruptly after more than 4 weeks of use
- Withdrawal can cause: anxiety, seizures, insomnia, nightmares, headaches
