Psychiatric Disease Flashcards
What are the general actions of CNS drugs?
Agonists/antagonists of neurotransmitter receptors
Inhibitors of regulatory enzymes
What are the key transmission/modulatory CNS pathways?
Noradrenaline Dopamine Serotonin GABA Acetylcholine Glutamate
What factors can affect psychiatric disorders?
Genetic vulnerability Life events Individual personality Coping skills/social support Environmental influences (viruses, toxins, drugs, health)
What are the secondary symptoms of depression?
Decreased appetite Sleep disturbance Hopelessness Poor concentration Irritability Self harm/suicidal ideas or acts Reduced libido May have psychotic symptoms
Why are monoamine oxidase inhibitors (MAOIs) not often given? (MAOIs inhibit destruction of neurotransmitters)
Dietary restrictions (tyramine, found in a lot of foods), which if broken can manifest as severe hypertension with a risk of death.
What are the three theories of depression cause?
Monoamine hypothesis (deficit of serotonin/noradrenaline) Neurotransmitter receptor hypothesis (malformations of receptor shape for neurotransmission) Monoamine hypothesis of gene expression (deficiency in molecular functioning)
What are SSRIs used to treat?
Moderate to severe depression (first line)
Which SSRIs are given?
Fluoxetine
Citalopram (most selective)
Paroxetine (most potent)
Sertraline
Should SSRIs be given alone?
No - Psychiatric therapy in conjunction for max effectiveness (eg: CBT)
What are the pharmokinetic features of SSRIs?
Almost totally absorbed from the gut
Long elimination half-life lives (dose once daily)
Metabolised in liver
What are the side effects of SSRIs?
(common)
Anorexia, nausea, diarrhoea
(Rare)
Precipitation of mania, increased suicidal ideation, tremor, extrapyramidal syndromes
Reasonably safe in overdose if taken alone
What are TCAs?
Tricyclic antidepressants
(Not first line)
Amitriptyline, imipramine, clomipramine, lofepramine
What are the effects of TCAs?
Inhibition of noradrenaline uptake (↑ transmission)
Muscarinic cholinoceptor blockade (↓ transmission)
Alpha 1 adrenoreceptor blockade (suppresses transmission)
What are the pharmokinetics of TCAs?
As SSRIs
Lipid soluble
What are the side effects of TCAs?
Sedation, impairment of psychomotor performance, low seizure threshold
Reduction in glandular secretions, eye accomodation block
Tachycardia, postural hypertension, ↓myocardial contractility
Constipation
MORE dangerous in overdose
What are SNRIs?
Serotonin and noradrenaline uptake inhibitors
(Second/third line)
Eg: venlafaxine and duloxetine
Can be anxiolytic at high doses
What are the side effects of SNRIs?
As with SSRIs
Sleep disturbance, ↑BP, dry mouth, hyponatremia
Short half life, thus potential for withdrawal on discontinuation
What are the symptoms of schizophrenia?
Disturbance of thinking Hallucinations Delusions Unusual speech-thought disorder Behavioural changes Lack of insight
What is the dopamine theory of schizophrenia?
Excess dopaminergic pathway stimulation in schizophrenia
(Dopamine antagonists are best schizophrenia treatment, BUT other methods (eg amphetamine) only cause positive symptoms, not negative, and dopamine antagonists don’t treat negative symptoms)
What are the main dopaminergic pathways?
Mesolimbic ()
Mesocortical ()
Nigrostriatal
Tuberoinfundibular
What does the mesolimbic pathway handle?
Emotional response and behaviour
What does the mesocortical pathway handle?
Arousal and mood
What are the effects of blocking D2 receptors?
Mesolimbic: ↓ positive psychotic symptoms
Mesocortical: ↑ negative and cognitive psychotic symptoms
Nigrostriatal: tardive dyskinesia, extrapyramidal side effects
Tuberoinfundibular: hyperprolactinaemia (lactation, infertility, sexual dysfunction)
Is schizophrenia associated with increased 5HT function?
Yes - 5HT-2A antagonists are effective antipsychotics
5HT implicated in behaviours disturbed during schizophrenia (appetite, mood, attention, aggression, sexual drive)
Is schizophrenia associated with decreased cortical glutamate function?
Post mortems show ↑ cortical glutamate receptors and binding of receptor ligands in cortex, basal ganglia, and hippocampal formation.
However, no current treatments targeting this system.
What are the actions of antipsychotics?
Sedation, tranquillisation (in hours)
Antipsychotic (days to weeks)
(Side effects - ↑ negative symptoms in weeks (unlikely in typical antipsychotics), extrapyramidal in hours to days (unlikely in atypical antipsychotics))
What are the benefits of atypical antipsychotics?
Less extrapyramidal side effects
Different preparations - dissolvable
Some only need one dose daily
Which atypical antipsychotics are usually given?
Risperidone
Quetiapine
Olanzapine
What are the side effects of atypical antipsychotics?
Sedation Can have extrapyramidal side effects at high doses Very drug to drug: Olanzapine - weight gain Risperidone - increased prolactin
What is clozapine?
The most effective antipsychotic, atypical.
However, severe side effects thus given as third line agent.
What are the side effects of clozapine?
Severe constipation Sedation Hypersalivation Extreme weight gain Neutropenia/agranulocytosis
What is haloperidol?
A typical antipsychotic
Safe to give in emergencies (side effects well known)
Sedating effect
What is the range of action of haloperidol?
Dopamine receptor blockade
Anticholinergic effects
Alpha-adrenergic blockade
Antihistamine effects
What are the side effects of haloperidol?
Extrapyramidal: Parkinsonism, acute dystonia, akathisia, tardive dyskinesia Neuroleptic malignant syndrome: Severe rigidity, hyperthermia, ↑CPK, autonomic lability Postural hypertension Weight gain Pigmentation Hyperprolactinaemia
What are the toxic effects of haloperidol?
CNS depression
Cardiac toxicity
Risk of sudden death with high dose
What is anxiety?
Fear out of proportion to the situation
Manifests in: avoidance, fear, light headedness, shortness of breath, hot and cold flush, nausea, palpitations, numbness, pins and needles
How is anxiety treated?
Non pharmacologically at first (CBT)
Treat coexisting disorders
Drugs - antidepressants, anxiolytics, very occasionally antipsychotics
What are the principle neurotransmitter systems involved with anxiety?
GABA
Serotonin
Noradrenaline
What are benzodiazepines? (Eh: diazepam, lorazepam)
Exerts effects through binding to high affinity BDZ receptor, which normally forms a GABA-BDZ complex.
Full agonist at these receptor sites, enhancing GABA.
What issues are there with benzodiazepines?
Highly addictive (dependence leads to withdrawal)
Negative side effects
Reduced benefit over time (tolerance)
What are the pharmokinetics of benzodiazepines?
Readily bioavailable following oral administration
Rapid acting: 30-90 minutes
Highly lipid soluble, allowing for rapid CNS diffusion
Renally excreted
Long half life
What are the side effects of benzodiazepines?
Common:
Drowsiness, dizziness, psychomotor impairment
Occasional:
Dry mouth, blurred vision, GI upset, ataxia, headache, ↓BP
Rare:
Amnesia, restlessness, rash
What is bipolar disorder?
A psychiatric disorder consisting of episodes of depression and hypomania/mania
Which drugs act as mood stabilisers?
Lithium Sodium valproate Carbamezepine Lamotrigine Antipsychotics
What is the action of lithium?
Unknown
May compete with Mg/Ca ions in ion channels
↑5HT
Attenuates effect of some neurotransmitters on their receptors
What are the pharmokinetics of lithium?
Renally excreted
Slowly release preparations once daily
Levels need to be monitored and taken 12 hours after last oral dose
Check renal and thyroid function every 6 months and before starting
What are the uses of lithium?
Prophylaxis of mania and depression in bipolar disorder
Augmentation of antidepressants in unipolar depression
Reduces suicidality
Best evidence as a mood stabiliser
What are the side effects of lithium?
(Hypothyroidism, hair loss, rashes) Memory problems (52%) Thirst (42%) Polyuria (38%) Tremor (34%) Drowsiness (24%) Weight gain (18%)
What are the toxic effects of lithium?
Monitor blood levels closely
Vomiting, diarrhoea
Coarse tremor, dysarthria
Cognitive impairment, restlessness, agitation
Which antiepilieptics work as mood stabilisers?
Sodium valproate
Lamotrigine
Carbamezepine
What is the chief side effect of antiepilieptic mood stabilisers?
Teratogenic if taken during pregnancy
Which groups of drugs are used to treat dementia?
Acetylcholine cholinesterase inhibitors
(Donepezil, galantamine, rivastigmine)
NDMA antagonists
(Memantine)
What are AChE-I drugs used to treat?
Mild to moderate dementia
What does ACh handle?
Arousal, memory, attention, mood
What are the side effects of AChE-Is?
Nausea, vomiting, diarrhoea, gastric/duodenal ulcers
Fatigue, insomnia, headache
Bradycardia
Worsens COPD
What is memantine used to treat?
Moderate to severe dementia
NDMA receptor antagonist
What are the side effects of memantine?
Usually well tolerated
Hypertension, dyspnoea, headache, dizziness, drowsiness
