Psychopharmacology Flashcards
What are some examples of selective serotonin reuptake inhibitors?
Citalopram, fluoxetine, sertraline, escitalopram
What are the indications for SSRIs?
- First line to moderate-severe depression, and in mild depression that’s resistant to psychological treatment.
- Panic disorder.
- Obsessive compulsive disorder
What is the mechanism of action of SSRIs?
Inhibit neuronal reuptake of serotonin at 5-HT receptors in the synaptic cleft, thereby increasing is availability for neurotransmission.
What are the important adverse effects of SSRIs?
GI upset, appetite and weight disturbances
Suicidal thoughts and behaviours
Hyponatraemia
Lowers the seizure threshold
Bleeding (serotonin makes platelets aggregate)
Prolong the QT interval
In what patients should you be cautious about prescribing SSRIs?
Epileptics
Peptic ulcer disease
Young people
Hepatic impairment
What are some important interactions of SSRIs?
Monoamine oxidase inhibitors (serotonin syndrome)
Aspirin and NSAIDs (GI bleeding)
Drugs that increase QT interval (antipsychotics)
What are some examples of tricyclic antidepressants?
Amitryptyline, nortriptyline, lofepramine
What are the indications of tricyclic antidepressants?
- 2nd line treatment for moderate-severe depression (after SSRIs do not work)
- Neuropathic pain (not licensed)
What is the mechanism of action for tricyclic antidepressants?
Inhibition of neuronal reuptake of serotonin and noradrenaline.
Also block a wide array of receptors, muscarinic, histamine (H1), alpha-adrenergic (a1 and a2) and dopamine (d2) - this is why lots of side effects
What are the important adverse of effects of tricyclic antidepressants?
Antimuscarinic blockade - dry mouth, constipation, urinary retention and blurred vision.
H1 and a1 blockade - Sedation, hypertension
Cardiac: Arrhythmias and ecg changes
Brain: Convulsions, hallucinations and mania
Dopamine blockade - breast changes, sexual dysfunction, EPSE (tremor and dyskinesia)
Very dangerous in OD
In what patients should you be cautious about prescribing tricyclic antidepressants?
Elderly
H1 and a1 related:
CV disease
Epilepsy
Antimuscarinic:
Constipation
Prostatic hypertrophy
Raised intraocular pressure
What are some important interactions of tricyclic antidepressants?
Monoamine oxidase inhibitors (serotonin syndrome)
Drugs that augment antimuscarinic, sedative or hypotensive adverse effects.
What are some examples of serotonin-noradrenaline reuptake inhibitors?
Venlafaxine, duloxetine,
What are the indications of SNRIs?
- Option for major depression when SSRIs are not tolerated or are ineffective.
- Generalised anxiety disorder
- Social anxiety disorder and panic disorder
What is the mechanism of action of SNRIs?
Interfering of uptake of serotonin and noradrenaline at the dynaptic cleft, increases availability of monoamines for neurotransmission.
Weaker antagonist of muscarinic and histamine (H1) receptors than tricyclic antidepressants.
What are the adverse effects of SNRIs?
GI upset, appetite and weight disturbances
Suicidal thoughts and behaviours
Hyponatraemia
Lowers the seizure threshold
Bleeding (serotonin makes platelets aggregate)
Prolong the QT interval
(Same as SSRIs)
In what patients should you be cautious about prescribing SNRIs?
Elderly
Hepatic or renal impairment.
Cardiovascular disease (arrhythmias)
What is an example of a noradrenaline reuptake inhibitor?
Reboxetine
What is an example of an atypical antidepressant?
Mirtazapine
What are the indications of mirtazapine?
Major depression
PTSD (not licensed)
What are the adverse effects of mirtazapine?
Sedation (helps people sleep)
Weight gain and increased appetite
What is the mechanism of action of mirtazapine?
Increases availability of monoamines for neurotransmission.
Antagonist of inhibitory pre-synaptic a2-adrenoreceptors and a potent antagonist of histamine (H1).
What are the two types of antipsychotics?
1st generation (typical) and 2nd generation (atypical)
What are some examples of 1st generation antipsychotics?
Haloperidol, chlorpromazine, prochlorperazine
What are the indications of 1st generation antipsychotics?
- Urgent treatment of severe psychomotor agitation, to calm the patients to permit assessment.
- Schizophrenia, (when metabolic side effects of 2nd gen. are a problem)
- Bipolar disorder (acute episodes of mania or hypomania)
- Nausea and vomiting (palliative care setting)
What is the mechanism of action of 1st generation antipsychotics?
Block post-synaptic dopamine D2 receptors.
What are the adverse effects of 1st generation antipsychotics?
Extrapyramidal effects (blockade in the nigrostriatal pathway): acute dystonic reaction (parkinsonian movements), akathisia (inner restlessness), neuroleptic malignant syndrome, tardive dyskinesia.
Drowsiness, hypotension, QT-interval prolongation (arrhythmias), erectile dysfunction and hyperprolactinaemia (menstrual disturbance, galactorrhoea and breast pain).
In what patients should you be cautious about prescribing 1st gen. antipsychotics.
Elderly
Dementia
Parkinson’s disease
What are some examples of 2nd generation antipsychotics?
Quetiapine, olanzapine, risperidone, clozapine
What are the indications for 2nd generation antipsychotics?
- Urgent treatment of severe psychomotor agitation (dangerous or violent behaviour)
- Schizophrenia (when EPSE from 1gAP or negative symptoms)
- Bipolar disorder
What is the mechanism of action of 2nd generation antipsychotics?
Block post-synaptic dopamine D2 receptors.
less side effects than 1gAP due to higher affinity to other receptors (5-HT) and “looser binding” to the D2 receptors
What are the adverse effects of 2nd generation antipsychotics?
Sedation, EPSE, metabolic disturbance (weight gain, diabetes mellitus, lipid changes), prolong QT interval (arrhythmias)
What are the adverse effects specific to clozapine?
Agranulocytosis (severe deficiency of neutrophils)
Myocarditis
In what patients should you be cautious about prescribing 2nd gen. antipsychotics?
Cardiovascular disease
Clozapine: severe heart disease, neutropenia
What interactions should you be aware of with 2nd gen. antipsychotics?
Drugs that prolong QT interval (amiodarone, quinine, macrolides, SSRIs)
Dopamine blocking antiemetics (metoclopramide)
What is the treatment algorithm for depression?
- SSRI
- Dose escalation
- Switch to different SSRI or a/d
- Augmentation e.g add lithium, quetiapine etc.
- Combinations - venlafaxine and mirtazapine or olanzapine and fluoexetine
What are the four pathways affected by D2 antagonism and what are the side effects?
Mesolimbic - reduces positive symptoms
Mesocortical - possible increase in negative symptoms
Nigrostriatal (contains 80% of brains dopamine) - EPSEs
Tuberofundibular - hyperprolactinaemia (the role of dopamine release in the tuberoinfundibular pathway is to tonically inhibit prolactin release.)
What is the treatment algorithm for antipsychotics?
- Antipsychotic
- Assess over 2-3 weeks (no affect change dose or medication, some effect continue for 4 weeks)
- Consider clozapine after trying 2 other a/p
- Continue antipsychotic medication for 1/2 years
Name some examples of different mood stabilisers
Lithium
Valproate
Carbamezepine
What are the indications for lithium?
Mania, recurrent depression, bipolar disorder, aggressive behaviour
What is the mechanism of action of lithium?
Currently unknown
What are the short-term adverse effects of lithium?
Stuffy nose, metallic taste Confusion Fine tremor GI disturbances Muscle weakness Polyuria Polydipsia
What are the therapeutic levels of lithium and what constitutes toxicity?
0.4-1.0 mmol/l
> 1.5 is toxicity
What are the signs of lithium toxicity?
Anorexia Nausea Vomiting Diarrhoea Nystagmus Coarse tremor Dysarthria Ataxia
Severe:
Loss of consciousness
Seizures
Death
What can make the levels of lithium in your body too high?
- Dehydration
- Low salt diet
- Other medicines (diuretics etc.)
What time should you check lithium levels and how should they be monitored following initiation of treatment?
Check lithium levels (12 hours following dose):
Five days following starting therapy or changing a dose.
Then check levels weekly until levels have been stable for four weeks.
Once levels have stabilised, check lithium levels every three months.
Consider more frequent monitoring (eg, every two months) in the elderly, in those on interacting medication or in those with renal, thyroid or cardiac disease.
What other systems should be monitored during lithium therapy?
Check thyroid function, U&Es, calcium and creatinine (and possibly urine dipstick for protein) every 6-12 months.
What should you inform the patient of before initiating lithium?
Of potential toxicity and symptoms of this (see ‘Side-effects and toxicity’, below).
That they should ensure they have a regular fluid intake.
Of the need for compliance in taking medication - reinforce this and that they should not stop or omit doses.
Of the dangers of crash diets.
To avoid NSAIDs.
Not to exceed more than 1-2 units of alcohol per day.
That it takes 3-6 months to be established on lithium.
That lithium cards are available from pharmacists.
What interactions should you be aware of with lithium?
Avoid any medicines that can impair renal function or induce hyponatraemia:
Angiotensin-converting enzyme (ACE) inhibitors.
Diuretics (particularly thiazides).
Non-steroidal anti-inflammatory drugs (NSAIDs).
Selective serotonin reuptake inhibitors (SSRIs).
In what patients should you be cautious about prescribing lithium?
Cardiac disease.
Significant renal impairment.
Addison’s disease and patients with low body sodium levels.
Untreated hypothyroidism.
What are the indications for valproate?
- Epilepsy
2. Bipolar disorder
What is the mechanism of action of valproate?
Not fully understood. Weak inhibitor of neuronal sodium channels. Increases the brain content of GABA (principal inhibitory neurotransmitter which regulates neuronal excitability)
What are the side effects of valproate? (VALPROATE)
Vomiting and GI upset Alopecia (regrowth curly) Liver toxicity Pancreatitis/ Pancytopenia Retention of fats (weight gain) Oedema (peripheral) Anorexia Tremor Enzyme inhibitor (liver)
In what patients should you be cautious about prescribing valproate?
Women of child bearing age (especially around the time of conception and in the first trimester)
Hepatic impairment
Severe renal impairment
What are the interactions of valproate?
Valproate is a P450 inhibitor and is metabolised by P450. (increases concentration of warfarin and other antiepileptics)
Effect of drug reduced by other p450 inducers (phenytoin, carbamezepine)
Effect of drug increased by other p450 inhibitors (macrolides, protease inhibitors)
Drugs that lower the seizure threshold (SSRIs, tricyclic antidepressants, antipsychotics, tramadol)
What are the indications for carbamezepine?
- Epilepsy
- Trigeminal neuralgia
- Bipolar disorder (if patients resistant or intolerant to other treatments)
What is the mechanism of action of carbamezepine?
Incompletely understood. Inhibits neuronal sodium channels.
What are the side effects of carbamezepine?
GI upset
Neurological effects (ataxia and dizziness)
Oedema and hyponatraemia (antidiuretic hormone-like effect)
In what patients should you be cautious about prescribing carbamezepine?
Pregnancy (can cause cardiac and urinary tract abnormalities and cleft palate)
Hepatic, renal or cardiac disease
What interactions should you be aware of with carbamezepine?
It is a P450 inducer!
Drugs that lower seizure threshold.
What anxiolytics are offered to patients in the NHS?
SSRIs SNRIs Pregabalin Benzodiazepines Beta blockers
What are some examples of benzodiazepines?
Diazepam, temazepam, lorazepam, chlordiazepoxide, midazolam
What are the indications for benzodiazepines?
- 1st line management of seizures and status epilepticus
- 1st line management of alcohol withdrawal reactions
- Sedation for interventional procedures
- Short term treatment of severe, disabling or distressing anxiety.
- Short term treatment of severe, disabling or distressing insomnia
What is the mechanism of action of benzodiazepines?
Facilitate and enhance binding of GABA to the GABAa receptor.
What are the side effects of benzodiazepines?
Drowsiness, sedation and coma.
Respiratory depression in OD
Dependence (withdrawal reaction similar to alcohol)
In what patients should you be cautious about prescribing benzodiazepines?
Elderly
Respiratory impairment or neuromuscular disease
Liver failure (use lorazepam in alcohol patients as eliminated less by the liver)
What are the important interactions of benzodiazepines?
Metabolised by P450 so be aware!
What are some examples of Z-drugs and what are their indications?
Zopiclone, zolpidem
- Short-term treatment of insomnia which is debilitating or distressing.
What is the mechanism of action for the Z-drugs?
Similar mechanism of action to benzodiazepines, although are chemically distinct and have a generally shorter duration of action.
They facilitate and enhance binding of GABA to the GABAa receptor.
What are the important adverse effects of z-drugs?
Daytime sleepiness
Rebound insomnia when stopped
CNS effects (headache, confusion, nightmares and (rarely) amnesia)
Dependence
Zopiclone - taste disturbance
Zolpidem - GI upset
In what patients should you be cautious about prescribing z-drugs?
Elderly
Obstructive sleep apnoea
Respiratory muscle weakness or respiratory depression
What are the important interactions of z-drugs?
Enhance the sedative effects of alcohol, antihistamines and benzodiazepines.
Enhance hypotensive effect of antihypertensives.
Metabolised by P450 system!!!
What are the long term adverse effects of lithium?
Weight gain Oedema Goitre and hypothyroidism Hyperparathyroidism Nephrogenic diabetes insipidus Irreversible renal damage Cardiotoxicity Exacerbation of acne and psoriasis Raised leucocyte and platelet count
