Psychiatric Drugs & Management Flashcards
Give examples of predisposing factors for mental illness.
“inclined”
BIOLOGICAL = genetics, gender, head injury
PSYCHOLOGICAL = personality type, conflict
SOCIAL = role, isolation, gender
Give examples of precipitating factors for mental illness.
“catalyst”
BIOLOGICAL = drug use, head injury
PSYCHOLOGICAL = traumatic life experience, coping style
SOCIAL = poverty, isolation
Give examples of perpetuating factors for mental illness.
“make something continue”
BIOLOGICAL = non-compliance with medication, drug abuse
PSYCHOLOGICAL = hopelessness
SOCIAL = social network, work, family
What are the diagnostic requirements of depression?
2 week history of at least 2 of the core symptoms:
- low mood
- anhedonia
- decreased energy
2/3 of the core symptoms indicates mild/moderate depression
3/3 of the core symptoms indicates major depression
The no. of secondary symptoms also indicates the severity:
- decreased appetite
- sleep disturbance
- hopelessness
- reduced libido
- reduced concentration
- irritability
- self harm/suicidal ideas/acts
- can have psychotic symptoms
Outline the pathophysiology of depression.
Hypothesis 1: deficiency of monoamine neurotransmitters (noradrenaline and serotonin)
Hypothesis 2: abnormality in receptors for monoamine transmission (depletion of neurotransmitter —> up-regulation of post-synaptic receptors)
Hypothesis 3: deficiency in molecular functioning distal to the post-synaptic receptor
Outline the pharmacological options for depression. How long are these usually indicated for?
MAO inhibitors
MAO uptake inhibitors: non-selective noradrenaline AND serotonin or selective noradrenaline OR serotonin
- non-selective = pure (SNRIs) or with additional actions (TCAs)
- selective = noradreline (NARIs) or serotonin (SSRIs)
Other e.g. mirtazepine
First-line pharmacological treatment for depression is indicated for at least 1yr before cessation
Give some examples of SSRIs. Describe the pharmacodynamics and ADRs associated with their use. When are they indicated?
e.g. fluoxetine (Prozac), citalopram (most selective), paroxetine (most potent), sertraline
First-line treatment for moderate to severe depression (along with CBT)
Pharmacodynamics:
- almost completely absorbed from the gut
- long elimination half lives (OD)
- metabolised in liver
- max benefit in 4-6wks (WARN ABOUT!)
- reasonably safe in overdose (if taken on their own)
ADRs: COMMON = - anorexia - nausea - diarrhoea RARE = - precipitation of mania due to increasing mood (lowest risk of all anti-depressants) - increased suicidal ideation within 3 days (?increased motivation/concentration/energy) - tremor - extrapyramidal symptoms
Give some examples of TCAs. Describe their pharmacokinetics and pharmacodynamics. Give some examples of ADRs associated with their use.
e.g. amitryptiline (neuropathic nerve pain), imipramine, clomipramine (OCD), lofepramine
Pharmacokinetics (highly toxic, multiple ADRs):
- inhibition of noradrenaline uptake —> sympathomimetics ADRs
- muscarinic cholinoceptor blockade —> anticholinergic ADRs
- alpha-1-adrenoceptor blockade —> sympatholytic ADRs
Pharmacodynamics:
- lipid soluble
- absorbed from gut
- long half life
- metabolised in liver
ADRs:
- CNS = sedation, impairment of psychomotor performance, lowering of seizure threshold, hyporeflexia
- ANS = reduction in glandular secretions, eye accommodation block, constipation, pupil constriction, hypothermia
- CVS = tachycardia, postural hypotension, impair myocardial contractility (put on cardiac monitor)
- GI = constipation
- metabolic acidosis
Give some examples of SNRIs. When are they indicated? Describe their pharmacokinetics and pharmacodynamics. Give some examples of ADRs associated with their use.
e.g. duloxetine, venlafaxine
Second or third-line treatment for depression
Pharmacokinetics:
- low dose = serotonergic actions
- high dose = noradrenergic actions
Pharmacodynamics:
- short half life (may be withdrawal syndrome on discontinuation)
ADRs: same as with SSRIs: COMMON = - anorexia - nausea - diarrhoea RARE = - precipitation of mania due to increasing mood (increased risk compared with SSRIs) - increased suicidal ideation within 3 days (?increased motivation/concentration/energy) - tremor - extrapyramidal symptoms ADDITIONAL (SNRI-specific) = - sleep disturbance - hypertension - dry mouth - hyponatraemia
Give examples of ADRs associated with MAO inhibitors. What dietary considerations are there when using them?
Extremely toxic
ADRs:
- postural hypotension
- weakness
- dizziness
- headache
- fatigue
- agitation
- anxiety
- weight gain
- impotence
Cannot eat certain foods e.g. cheese
Define psychosis. What conditions can have psychosis as a symptom?
Lack of contact with reality
Encompasses hallucinations and delusions
Seen in:
- paranoid schizophrenia
- mania
- severe depression with psychosis
- organic syndromes
- delusional disorders
- delirium
- dementia
Contrast hallucinations and delusions.
HALLUCINATION = perception in the absence of an external stimulus
DELUSION = fixed false belief that is out of keeping with someone’s culture or religious beliefs
Outline the prevalence of paranoid schizophrenia. What are the signs and symptoms?
PREVALENCE = 1% in general population
- 10%+ risk with one parent with paranoid schizophrenia
- 50%+ risk with both parents with paranoid schizophrenia
- 10% will kill themselves
- die 20yrs younger than the general population (without considering increased suicidal risk)
S&S:
- disturbances of thinking
- auditory hallucinations (hear voices OUTSIDE head)
- persecutory delusions
- unusual speech (thought disorder)
- behavioural changes
- lack of insight
- apathy
- asocial
- self-neglect
What is the pathophysiology of paranoid schizophrenia?
DOPAMINE:
- dopamine antagonists (D2) usually the best treatment for schizophrenia but do not treat the negative symptoms (apathy, asocial, self-neglect)
- some evidence of increased dopamine function in schizophrenics
- amphetamine causes symptoms similar to positive symptoms of schizophrenia (hallucinations, delusions)
- changes in dopamine function may be a response to long-term treatment
SEROTONIN:
- implicated in behaviours disturbed in schizophrenia (perception, attention, mood, aggression, sexual drive, appetite, motor behaviours, sleep)
- most anti-psychotic drugs are 5-HT antagonists (e.g. clozapine)
- precursors of 5-HT exacerbate schizophrenia (e.g. tryptophan)
GLUTAMATE:
- PCP (non-competitive NMDA-type glutamate receptor antagonist) induces symptoms very similar to schizophrenia
- post-mortem studies show increased cortical glutamate receptors of increased binding of glutamate receptor ligands
What are the different dopamine pathways in the brain? How are they involved in schizophrenia?
MESOLIMBIC: emotional response and behaviour
(dramatic therapeutic action of dopamine on positive psychotic symptoms)
MESOCORTICAL: arousal and mood
(enhanced negative and cognitive psychotic symptoms)
TUBEROINFUNDIBULAR (hypothalamus and pituitary gland) —> hyperprolactinaemia (lactation, infertility, sexual dysfunction)
NIGROSTRIATAL:
- Parkinson’s disease
- extrapyramidal side-effects
- tardive dyskinesia
What is tardive dyskinesia?
Mostly irreversible neurological disorder of involuntary movements caused by long-term use of anti-psychotic or neuroleptic drugs
- rapid movement of arms/legs
- tongue protrusion
- grimacing
- rapid eye blinking
- lip smacking/pursing/puckering
Unaware of movements unless looking in the mirror
How effective is the treatment for schizophrenia?
25% dead/unimproved and hospitalised or institutionalised (more community-based care)
25% fully recovered
25% improved and relatively independent
25% improved but need support
Give some examples of typical anti-psychotics indicated for schizophrenia. Describe their pharmacokinetics. Give examples of ADRs associated with their use.
e.g. haloperidol (sedating; safe in emergency), chlorpromazine
Pharmacokinetics:
- dopamine receptor blockade
- anticholinergic blockade
- alpha-adrenergic blockade
- antihistamine
ADRs:
- extrapyramidal = Parkinsonism, acute dystonia, tardive dyskinesia, akathisia
- neuroleptic malignant syndrome
- postural hypotension
- weight gain
- endocrine e.g. prolactinaemia
- pigmentation
Overdose:
- CNS depression
- cardiac toxicity (lengthened QT interval)
- risk of sudden death
Define akathisia.
Movement disorder characterised by feeling of inner restlessness and a compelling need to be in constant motion
e.g. rocking, marching on the spot, crossing and uncrossing legs
What is neuroleptic malignant syndrome?
Neurological disorder most often caused by adverse reaction to neuroleptic or anti-psychotic drugs
S&S:
- severe rigidity = shuffling gait, dysphagia, dyspnoea
- hyperthermia
- autonomic lability
- confusion
- fluctuating consciousness
EMERGENCY!!! (10% mortality)
Treatment = withdraw anti-psychotics and supportive treatment
Give examples of atypical anti-psychotics. When are they indicated? Describe their dosing regimen. Give some examples of ADRs associated with their use.
e.g. olanzapine, risperidone, quetiapine, clozapine (most powerful, used for treatment resistant schizophrenia)
First-line treatment for schizophrenia
Given OD; different preparations available e.g. PO, short-acting (days) or long-acting (weeks) depot injections (if they refuse to take medications - Mental Health Act or poor adherence)
ADRs:
- extrapyramidal symptoms (less so than typical anti-psychotics)
- significant weight gain (esp. olanzapine) by affecting satiety centre —> diabetes, hypercholesterolaemia
- prolactinaemia (esp. risperidone)
- sedation
- agranulocytosis causing neutropenia (clozapine); frequent FBCs req.
- QT lengthening (risperidone)
- lowered seizure threshold (risperidone)
What are the general actions of anti-psychotics and their approximate timelines?
Sedations (hrs) Tranquilisation (hrs) Anti-psychotic (days-wks) Activating effect (removal of negative symptoms) (wks) Extra-pyramidal symptoms (hrs-days)
What are the signs and symptoms of anxiety disorders? How can anxiety disorders present?
Situational (phobias) or continuous (GAD)
- fear out of proportion to situation
- avoidance
- fear of dying/going crazy
- light-headedness
- shortness of breath
- hot and cold flushes
- nausea
- palpitations
- numbness
- pins and needles
Outline the treatment options for anxiety disorders.
First-line: non-pharmacological treatments e.g. CBT, exposure and response therapy (phobias)
Treat co-existent disorders
Pharmacology:
- anti-depressants (serotonin and noradrenaline)
- anxiolytics (GABA)
- anti-psychotics
Give some examples of benzodiazepines. Describe their pharmacokinetics and pharmacodynamics. Give examples of ADRs associated with their use.
e.g. diazepam, lorazepam
Pharmacokinetics:
- high affinity agonists at GABA-BZ receptor complex —> anxiolytic, hypnotic, anticonvulsant effects
- tolerance (give short-term, one-off doses to prevent e.g. less than 2wks)
- dependence —> withdrawal (insomnia, agitation, anxiety)
Pharmacodynamics:
- oral bioavailability (~30-90min)
- highly lipid soluble (rapid CNS diffusion)
- renal excretion
- long half life
ADRs: COMMON = - drowsiness - dizziness - psychomotor impairment OCCASIONAL = - dry mouth - blurred vision - GI disturbances - ataxia - headache - hypotension RARE = - amnesia - restlessness - rash
+ cleft lip/palate in pregnancy
+ resp. depression and feeding difficulties in newborn
Overdose: resp. depression (reversed by flumazenil; shorter half life than benzos so multiple doses may be required)
note: flumazenil lowers seizure threshold
What is bipolar disorder characterised by?
Episodes of depression and (hypo)mania
Define mania. What are the signs and symptoms of mania?
Elevated mood, physical and mental over-activity, self-important ideas
Minimum of 1wk
S&S:
- feeling of unusually excited, happy, optimistic, irritable
- overactive
- poor concentration/short attention span
- poor sleep
- rapid speech (jump from one idea to another)
- poor judgement
- increased interest in sex
- psychosis (hallucinations, grandiose delusions)
What are the pharmacological treatment options for bipolar disorder?
Lithium
Anti-epileptics
- sodium valproate for extreme manias
- carbamazepine for rapid cycling
- lamotrigine for bipolar depression
Anti-psychotics for bipolar depression or psychosis in bipolar disorder
Describe the pharmacokinetics and pharmacodynamics of lithium. When is it indicated? What monitoring is required? Give some examples of ADRs associated with lithium.
Pharmacokinetics: acts on-
- electrolytes and channels
- 5-HT
- secondary messenger systems
Reduces suicidality
Pharmacodynamics:
- renal excretion (potentially nephrotoxic)
- OD slow release
- take 12hrs after last dose (narrow therapeutic window)
Indications:
- prophylaxis for mania and depression in bipolar disorder
- augmentation of anti-depressants in unipolar depression
Monitoring:
- levels need to be monitored at least 3/month
- check renal and thyroid function before starting and every 6 months
ADRs:
- memory problems
- thirst
- polyuria
- tremor
- drowsiness
- weight gain
- hypothyroidism
- hair loss
- rashes
- nephrotoxicity
Overdose:
- vomiting and diarrhoea (increases conc. of lithium)
- coarse tremor
- dysarthria
- cognitive impairment
- restlessness
- agitation
- confusion
- ataxia
- coma
- death
Treatment for overdose:
- supportive
- anti-convulsants
- increase fluid intake/IV fluids
- haemodialysis may be necessary
Outline the pharmacological treatment for dementia.
ACH-ase inhibitors
NMDA antagonists
Give some examples of anticholinesterase inhibitors indicated for dementia. When are they indicated? Give some examples of ADRs associated with their use.
e.g. donepezil, galantamine, rivastigmine
Indicated for mild to moderate dementia to reduce progression of symptoms (extra year at home)
ADRs:
- N&V, vomiting, anorexia, diarrhoea
- fatigue, insomnia, headache
- bradycardia (measure pulse before initiating treatment)
- worsening of COPD
- gastric/duodenal ulcers
Give an example of a NMDA antagonist indicated for dementia. Give some examples of ADRs associated with its use.
Memantine
Indicated for moderate to severe dementia
ADRs:
- hypertension
- dyspnoea
- headache
- dizziness
- drowsiness
In general, what are the actions of CNS drugs?
Neurotransmitter receptor agonists and antagonists
Regulatory enzyme inhibitors (involved in the production or destruction of neurotransmitters)
How can a confused or delirious violent psychiatric patient be managed?
Call security to restrain
Small dose PO/IV haloperidol (quick acting typical anti-psychotic which causes sedation)
Manage cause e.g. UTI
\+ give visible clock \+ give light room \+ give music \+ keep sleep pattern constant \+ talk to (de-escalation) \+ include family/friends/carers
SEDATIVES MAKE WORSE!!!
Define delirium. Give some examples of causes.
State of mental confusion which fluctuates/acute disturbance of consciousness (differentiates from dementia)
DELIRIUMS = Drugs Electrolyte disturbance/Environmental change Low O2, Little hearing/seeing Infection Retention (urine/faeces) Ictal state Underhydration/nutrition Metabolic e.g. diabetes, Na+ abnormalities Subdural haematoma
How can the severity of depression be assessed?
1-10 mood rating
Beck’s depression inventory (American pop.)
SAD PERSONS score (determine action needed): Sex (1 point for male) Age (1 point if younger than 20yrs or older than 44yrs) Depression (1 point) Previous attempt (1 point) Ethanol abuse (1 point) Rational thinking loss (1 point) Social support lacking (1 point) Organised Plan (1 point for lethal plan) No spouse (1 point) Sickness (1 point for chronic, debilitating, severe conditions)
PHQ-9
- Little interest or pleasure in doing things (anhedonia)
- Feeling down, depressed, or hopeless
- Trouble falling or staying asleep/sleeping too much
- Feeling tired or having little energy
- Poor appetite/overeating
- Feeling bad about yourself/failure/let yourself or family down
- Trouble concentrating on things e.g. reading newspaper, watching TV
- Moving or speaking so slowly that other people could have noticed/so fidgety or restless that you have been moving a lot more than usual
- Thoughts that you would be better off dead
Suicidal ideation:
- ?access to methods
- ?planned in detail (non-compulsive)
- what did you expect to happen? (hospitalisation v.s. death)
- ?long-term planning
