Psycho-pharmacology I Flashcards
What are the indications for antidepressants?
Unipolar/bipolar depression Organic mood disorders Schizoeffective disorder Anxiety disorders Impulsivity associated with personality disorders
What delay is associated with antidepressants?
3-6 weeks after therapeutic dose achieved
When are antidepressants changed post-usage?
At least 2 months trial period
What are the main classes of antidepressants?
Tricyclics Monoamine Oxidase inhibitors SSRIs SNRIs Novel antidepressants
What are the side effects associated with Tricyclic antidepressants?
Antihistaminic Anticholinergic Antiadrenergic QT lengthening Lethal in overdose
What are tertiary TCAs?
Tertiary amine side chains
Worsen side effects (antihistaminic, anticholinergic, antiadrenergic)
What are antihistaminic side effects?
Sedation
Weight gain
What are anticholinergic side effects?
Dry eyes, mouth
Constipation
Memory deficits
Delirium
What are antiadrenergic side effects?
Orthostatic hypotension
Sedation
Sexual dysfunction
Tertiary TCAs act on what?
Serotonin receptors
Give an 2 examples of tertiary TCAs?
Imipramine
Amitriptyline
Doxepin
Clomipramine
What are the active metabolites of tertiary TCAs?
Desipramine
Nortriptyline
What are secondary TCAs?
Metabolites of tertiary TCAs
How do secondary TCAs work?
Block noradrenaline
Give 2 examples of secondary TCAs?
Desipramine
Nortriptyline
What side effects are associated with secondary TCAs?
Same as tertiary TCAs (but less severe)
How do Monoamine Oxidase inhibitors work?
Bind irreversibly to monoamine oxidase, prevent inactivation of amines:
Norepinephrine, dopamine, serotonin (increasing levels)
What side effects are associated with Monoamine Oxidase inhibitors?
Orthostatic hypotension Weight gain Dry mouth Sedation Sexual dysfunction Sleep disturbance
What risks are associated with Monoamine Oxidase inhibitors?
Hypertensive crisis when taken with tyramine rich foods or sympathomimetics
Serotonin syndrome
Serotonin syndrome is associated with which antidepressants?
Monoamine Oxidase inhibitors taken with Serotonin increasing drugs/sympathomimetics
What are the symptoms of serotonin syndrome?
Abdominal pain Diarrhoea Sweats Tachycardia HTN Myoclonus Irritability Delirium Hyperpyrexia Cardiovascular shock
How do SSRIs work?
Prevent presynaptic serotonin reuptake
SSRIs are used in the treatment of what?
Anxiety
Depression
What side effects are associated with SSRIs?
Sexual dysfunction GI upset Anxiety Restless/Nervous Insomnia Sedation Discontinuation syndrome
What is discontinuation syndrome?
Effects of stopping SSRIs Agitation Nausea Disequilibrium Dysphoria
What are the advantages of Sertraline?
Weak P450 interactions
Short half life
Slow metabolite build up
Less sedating than paroxetine
What are the disadvantages of Sertraline?
Requires full stomach for absorption
Increased GI ADRs
What are the advantages of Fluoxetine?
Long half life (reduced risk discontinuation syndrome)
Increased energy
Can be given to taper off SSRI use
What are the disadvantages of Fluoxetine?
Active metabolite may build up (risk in hepatic illness)
P450 interactions
Initial anxiety and insomnia
Risk of mania over other SSRIs
Name 3 commonly used SSRIs?
Paroxetine Sertaline Fluoxetine Citalopram Escitalopram Fluvoxamine
How do SNRIs work?
Inhibit Serotonin AND Noradrenergic reuptake
Without antihist/adrenergic/cholinergic sides
SNRIs are used for what?
Depression
Anxiety
Neuropathic pain
Name 2 commonly used SNRIs?
Venlafaxine
Duloxetine
What are the advantages of Venlafaxine?
Minimal drug interactions
Short half life
Fast renal clearance
What are the disadvantages of Venlafaxine?
Can cause 10-15mmHg dose dependent BP increase Nausea (IR tabs) Bad discontinuation syndrome QT prolongation Sexual side effects
What are the advantages of Duloxetine?
Efficacy for physical symptoms of depression
Less BP increase than Venlafaxine
What are the disadvantages of Duloxetine?
CYP2D6 and CYP1A2 inhibitor
Active ingredient not stable in stomach (cannot break capsule)
Name 2 commonly used Novel antidepressants?
Mirtazepine
Buproprion
What are the advantages of Mirtazepine?
Different mechanism to SSRIs
Hypnotic at lower doses (antihistaminic)
What are the disadvantages of Mirtazepine?
Increased Cholesterol and triglycerides
Very sedating at low doses
Weight gain at low doses
What are the advantages of Buproprion?
Augmenting agent Inhibits dopamine + norepinephrine No weight gain, sexual sides Low mania 2nd line for ADHD
What are the disadvantages of Buproprion?
Seizure risk
Avoid in TBI, bulimia, anorexia
Can cause anxiety, agitation and insomnia
Psychotic at high doses
How can resistance to antidepressants be managed?
Combination of antidepressants
Add lithium
Add atypical antipsychotic
What atypical antipsychotics may be used to aid in antidepressant resistance?
Quetiapine
Olanzapine
Aripiprazole
What are the indications for the use of mood stabilisers?
Bipolar
Cyclothymia
Schizoeffective disorder
What are the classes of mood stabilisers?
Lithium
Anticonvulsants
Antipsychotics
What are the indications for lithium?
Patient at risk of suicide
Long-term mania and depressive episodes
What are the factors predicting a positive response to lithium?
FH of good response
Prior long-term response
Classic pure mania
Mania followed by depression
Outline the use of Lithium
Baseline U+E and TSH Pregnancy test Monitor until steady state achieved Check TSH and creatinine 3 and 6mo, Thyroid function Blood level between 0.6 and 1.2
Lithium use during pregnancy is associated with what?
Ebstein’s anomaly
What are the side effects of lithium use?
GI distress, reduced appetite Thyroid abnormalities Nonsignificant leukocytosis Polyuria (can cause interstitial renal fibrosis) Hair loss Acne Reduced seizure threshold
What are the levels of Lithium toxicity?
Mild - 1.5-2
Moderate - 2-2.5
Severe - >2.5
What are the symptoms of mild lithium toxicity?
Vomiting Diarrhoea Dizziness Ataxia Nystagmus
What are the symptoms of moderate lithium toxicity?
N+V Anorexia Blurred vision Clonus Convulsions Delirium Syncope
What are the symptoms of severe lithium toxicity?
Convulsions
Oliguria
Renal failure
What are the main groups of anticonvulsants?
Valproic acid
Carbamazepine
Lamotrigine
What factors predict a positive response to Valproic acid?
Rapid cycling patients Female Comorbid substance abuse Mixed patients Comorbid anxiety disorders
What is the first line agent for acute mania/mania prophylaxis?
Carbamazepine
When is Carbamazepine indicated?
Acute mania
Mania prophylaxis
Rapid cycling/mixed patients
Outline the use of Carbamazepine?
Before: LFTs, FBC, ECG
Monitor: steady state, repeat FBC, LFTs
Target: 4-12mcg/ml
Check after a month
What side effects are associated with use of Carbamazepine?
Rash N+V, Diarrhoea Sedation Dizziness, ataxia AV conduction delay Drug-drug interactions Hyponatremia
What side effects are associated with Lamotrigine?
N+V
Sedation, dizziness
TEN/SJS
What are the indications for discontinuing Lamotrigine use?
ANY Rash
What drugs increase lamotrigine use?
VPA
Sertraline
What antipsychotics are indicated for Bipolar disorder?
Aripiprazole
Risperdone
Quetiapine
Olanzapine
How do anticonvulsants affect liver function?
LFT increase expected
No change unless >3x change
What are the indications for antipsychotics?
Schizophrenia Schizoaffective disorder Bipolar (mood stabilisation or for psychotic features) Psychotic depression Augmenting agent (anxiety)
What pathways in the brain are affected by dopamine?
Mesocortical
Mesolimbic
Nigrostriatal
Tuberoinfundibular
Outline the mesocortical pathway and its role in psychosis?
Brain stem to the cerebral cortex
Causes negative symptoms and cognitive disorders
Psychosis is related to too little dopamine here
Outline the mesolimbic pathway and its role in psychosis?
Dopaminergic cell bodies in ventral tegmentum to limbic system
Positive symptoms
Psychosis is related to too much dopamine here
What are positive symptoms?
Hallucinations
Delusions
Thought disorders
Outline the nigrostriatal pathway and its role in psychosis?
Dopaminergic cell bodies in substantia nigra to basal ganglia
Involved in movement
Dopamine hypoactivity can cause parkinsonian movements, akathisia, dystonia
How does dopamine affect acetylcholine?
Dopamine suppresses acetylcholine activity
Outline the tuberoinfundibular pathway and its role in psychosis?
Hypothalamus to anterior pituitary
Blocking dopamine to TI pathway predisposes patient to hyperprolactinaemia
How does dopamine affect prolactin release?
Dopamine release inhibits prolactin release
What are the symptoms of hyperprolactinaemia?
Gynaecomastia
Galactorrhea
Decreased libido
Menstrual dysfunction
How do high potency typical antipsychotics affect dopamine?
D2 dopamine receptor antagonists
Bind to D2 receptors with high affinity.
High potency typical antipsychotics increase the risk of what?
Extrapyramidal side effects
Give 2 examples of typical antipsychotics?
Fluphenazine
Haloperidol
Pimozide
How do low potency typical antipsychotics affect dopamine?
Less affinity for D2 receptors
Interact with non-dopaminergic receptors
Cardiotoxic + anticholinergic ADRs
How do Atypical antipsychotics work?
Serotonin-dopamine 2 antagonists
Affect dopamine AND serotonin in 4 pathyways
What side effects are associated with Risperidone?
Extrapyramidal
Hyperprolactinaemia
Weight gain
Sedation
What side effects are associated with antipsychotics?
Tardive Dyskenesia
Neuroleptic Malignant syndrome
Extrapyramidal side effects
What is tardive dyskinesia?
Involuntary muscle movements
may not resolve with drug discontinuation
What is Neuroleptic Malignant syndrome?
Severe muscle rigity Fever Altered mental state Autonomic instability Elevated WBC, CBK, LFTs
What are Extrapyramidal side effects?
Acute Dystonia
Parkinson syndrome
Akathisia
What agents treat extrapyramidal side effects?
Anticholinergics
Dopamine facilitators
Beta blockers
What are the indications for anxiolytics?
Panic disorder Generalised anxiety disorder Substance related/withdrawal Insomnias Parasomnias
What are the indications for benzodiazepines?
Insomnia Parasomnia Anxiety disorders CNS depressant withdrawals Acute sedation
What side effects are associated with benzodiazepines?
Somnolence Cognitive deficits Amnesia Disinhibitions Tolerance Dependence
What are the pros and cons of buspirone?
Pro: No sedation Con: 2 week to take effect Will not work on patients used to benzodiazepines
What are the main Anxiolytics?
Buspirone
Benzodiazepines
Name 2 atypical antipsychotics?
Risperidone Olanzapine Quetiapine Clozapine Aripiprazole
What antidepressants are associated with hypertensive crisis?
MAOIs and tyramine rich foods/sympathomimetics
What foods are rich in tyramine?
Cheese
Red wine
Processed meat
Beans
How long after 1st, 2nd and 3rd incidences of depression should a patient be on antidepressants?
1st - 6 months
2nd - 2 years
3rd - lifelong
What are the side effects of low-potency antipsychotics?
Cardiotoxic
Anticholinergic effects - sedation, hypotension
How are first line drugs for schizophenia chosen?
Choose based on a drugs side effect profile for first line
What is the rule of efficacy for antipsychotics?
1/3 Very effective
1/3 reasonably effective
1/3 inaffective
How is clozapine use managed?
Check bloods continuously though use to monitor for agranulocytosis
What is seen before a psychosis relapse?
Loss of compliance
Lack of insight
May need to use mental health act
How is akathisia as a side effect managed?
(Reduce dose if possible)
Benzodiazepine
Propanalol
