PPT - DEPRESSION, BIPOLAR, MANIA, SCHIZO Flashcards
What drug class is citalopram?
SSRI
What drug class is citalopram?
SSRI
What drug class is agomelatine?
Melatonin receptor agonist and serotonin receptor antagonist
What drug class is phenelzine?
Non-selective MAOI
What drug class is duloxetine?
SNRI
What drug class is mirtazapine?
Presynaptic alpha2 adrenoreceptor blocker
What drug class is fluoxetine?
SSRI
What drug class is reboxetine?
Selective noradrenaline reuptake inhibitor
What drug class is trazadone?
Serotonin receptor blocker
What drug class is imipramine?
TCA
What drug class is moclobemide?
Reversible inhibitor of MAO A
What drug class is trancyclopromine?
Non-selective MAOI
What drug class is paroxetine?
SSRI
What drug class is venlafaxine?
SNRI
What drug class is amitryptiline?
TCA
What drug class is lofepramine?
TCA
Why are TCAs not used as widely as they used to?
They are much more dangerous in overdose as they cause prolongation of QT, sinus tachycardia and widened QRS = arrythmia risk
Widening of QRS >100ms is associated with an increased risk of seizure
Widening of QRS >160ms is associated with ventricular arrhythmias
What is the monoamine theory of depression?
Depression is caused by a functional deficit in monoamine transmitters, noradrenaline and 5HT at certain sites in the brain whilst mania results from a functional excess
Evident by TCA, MAOIs increasing mood and methyldopa which inhibits noradrenaline synthesis decreases mood
Whats the moa of TCAs?
They block the reuptake of serotonin and norepinephrine in presynaptic terminals, which leads to increased concentration of these neurotransmitters in the synaptic cleft
What is the hypothalamic-pituitary-cortisol system in depression?
Chronic stress causes upregulation of Hypothalmopituitaryadrenal system = increases CRH so ACTH so cortisol secretion = inhibitory effect on hypothalamus and hippocampus
Injected into the brain of experimental animals, CRH mimics some aspects of depression in humans, such as diminished activity, loss of appetite and increased signs of anxiety. Furthermore, CRH concentrations in the brain and cerebrospinal fluid of depressed patients are increased.
Explains depression in those overweight, Cushings
Outline the role of brain-derived neurotrophic factor?
Lowered levels of BDNF or malfunction of its receptor is typically seen in depression and antidepressants tend to elevate BDNF levels
Outline the chronic adaptive changes seen in SSRI use?
when SSRIs are administered, they inhibit the reuptake of 5-HT into nerve terminals, which should increase the levels of 5-HT in the synapse. However, the increase is less than expected because 5-HT1A receptors on the soma and dendrites of 5-HT-containing raphe neurons are activated, which reduces 5-HT release. This partially cancels out the effect of inhibiting reuptake. But, with prolonged drug treatment, the increased level of 5-HT in the somatodendritic region desensitizes the 5-HT1A receptors, reducing their inhibitory effect on 5-HT release from nerve terminals. This explains the slow onset of antidepressant action of 5-HT uptake inhibitors because it takes time to desensitize the somatodendritic 5-HT1A receptors.
Why are SSRIs first line?
Safer in overdose
Less likely than TCAs to cause anticholinergic side effects
Dont cause ‘cheese reactions’
Better tolerated
Sertraline safe in unstable angina and recent MI
Not sedating like TCAs
What are the unwanted effects of SSRIs?
Nausea
Anorexia
Insomnia
Loss of libido
Failure of organism
SIADH - hyponatraemia
Anxiety and agitation
Increased risk of bleeding particularly if taking NSAIDs
Increased risk of suidicdal thoughts and behaviour particularly in young people
Serotonin syndrome
How soon do SSRIs work?
2 weeks but it often gets worse before it gets better - u
What are the characteristic symptoms of serotonin syndrome?
Neuromuscular hyperactivity - tremor, hyperreflexia, clonus, myoclonus, rigidity
Autonomic dysfunction - tachycardia, blood pressure changes, hyperthermia, diaphoresis, shivering, diarrhoea
Altered mental state - agitated, confused, manic
How often should you be monitoring on SSRIs?
Review every 1-2 weeks at start of treatment
Continue treatment for at least 4 weeks (6 weeks in elderly)
Following remission, continue treatment at same dose for at least 6 months (12 if GAD)
Which SSRIs cause QT interval prolongation?
Citalopram and escitalopram
What are the important interactions for SSRIs?
NSAIDS - if co-prescribing give PPI
Warfarina nd heparin - avoid
Aspirin
Triptans - avoid
What should you give instead of SSRIs in a pt on warfarin or heparin?
Mirtazepine
What are the SSRI discontinuation symptoms?
Flu-like symptoms
Insomnia
Nausea and vomiting
Increased mood changes and imbalance (unsteady)
Sensory disturbances (paraesthesia, electric shock)
Hyperarousal
Whats the goal for treatment of mania?
Remission - resolve mood symptoms or improvement to the point that only 1 or 2 of symptoms of mild intensity persist
If there are psychotic symptoms, resolution of psychosis is required for remission
What are mood-stabilising drugs?
Lithium
anti-convulsants:
- sodium valproate
- carbamazepine
- lamotrigine
Antipsychotics for psychotic symptms or mania
Whats the theory of how lithium therapy works?
Either:
Inhibition of inositol monophosphate or inhibitor of glycogen synthase kinase 3
Why is lithium a dangerous drug?
Narrow therapeutic range of 0.4-1 and above 1.5 it produces its toxic effects
What are the adverse effects of lithium?
nausea/vomiting, diarrhoea
fine tremor
nephrotoxicity: polyuria, secondary to nephrogenic diabetes insipidus
thyroid enlargement, may lead to hypothyroidism
ECG: T wave flattening/inversion
weight gain
idiopathic intracranial hypertension
leucocytosis
hyperparathyroidism and resultant hypercalcaemia
How should lithium be monitored?
when checking lithium levels, the sample should be taken 12 hours post-dose
after starting lithium levels should be performed weekly and after each dose change until concentrations are stable
once established, lithium blood level should ‘normally’ be checked every 3 months
after a change in dose, lithium levels should be taken a week later and weekly until the levels are stable.
BMI, thyroid and renal function should be checked every 6 months
patients should be issued with an information booklet, alert card and record book
What are contraindications?
Dehydration - more likely for toxicity
Renal impairment
Hyponatraemia e.g. addisons disease or low dosing diets
CVD
How can lithium affect thyroid?
It can cause hypothyroidism
How does lithium affect the kdineys?
It can cause renal diasbetes insipidus
Renal tubular damage after prolonged treatment
Na+ retention due to increased aldosterone secretion
What is the patient and carer advice for lithium?
Advise them to report signs and symptoms of toxicity, hypothyroidism, renal dysfunction (polyuria and polydypsia), benign intracranial hypertension (persistent headache and visual disturbance)
Maintain adequate fluid intake and dont make dietary changes which change sodium intake
What is in a lithium treatment pack?
Pt information booklet
Lithium alert card
Record book for tracking serum-lithium concentration
Whats the key thing about the bioavailability of lithium?
Different brands or types have different concentrations so be careful with switching between
What are drug interactions with lithium?
Thiazide diuretics (and other diretics to a lesser extent) - as hyponatraemia worsens lithium toxicity
ACEi/ARBs
NSAIDs
(I.e. any drug that can cause AKI because it’s really excreted so higher likelihood of toxicity)
What can severe lithium toxicity cause?
Coma
Convulsions
Profound hypotension with oliguria
What type of drug is chlorpromazine?
Typical antipsychotic
What type of drug is aripiprazole?
Atypical antipsychotic
What type of drug is clozapine?
Atypical antipsychotic
What type of drug is flupentixol?
Typical antipsychotic
What type of drug is Lurasidone?
Atypical antipsychotic
What type of drug is fluphenazine?
Typical antipsychotic
What type of drug is haloperidol?
Typical antipsychotic
What type of drug is olanzapine?
Atypical antipsychotic
What type of drug is pimozide?
Typical antipsychotic
What type of drug is quetiapine?
Atypical antipsychotic
What type of drug is risperidone?
Atypical antipsychotic
What type of drug is sulpiride?
Typical antipsychotic
What are antimuscarinic effects?
Drowsiness
Dry mouth
Constipation
Blurred vision
Urinary retention
What causes the SE in antipsychotic therapy?
The drugs can’t discriminate between D2 receptors so other brain pathways other than mesolimbic pathway are affected:
Nigrostriatal - EPS and TD
Tuberoinfundibular - enhances prolactin secretion
Mesolimbic reward component - reduce pleasure
Prefrontal cortex - worsens negative sympotms
How are the new drugs able to produce less EPS?
They have 5HT2A antagonist properties which enhance dopamine release in the striatum whic can reduce EPS
What are acute dystonia?
Involuntary movements often accompanied by symptoms of parkinsons
Occur commonly in the first few weeks, decline in time and are reversible
What is tardive dyskinesia?
Developers after months or years of typical antipsychotics
Disabling and often irreversible and often worsens when antipsychotics are stopped
Resistanc to treatment
Involuntary movements often face and tongue trunk and limbs
