Therapeutics Flashcards
NMS clinical features
First 10 days of treatment or after increasing dose
- pyrexia
- muscular rigidity
- confusion
- fluctuating consciousness
- autonomic instability (fluctuating pulse & BP)
- delirium
NMS investigations
- CK - increased (1000s)
- FBC - leucocytosis may be seen
- LFTs - deranged
NMS management
- emergency referral to A&E
- stop antipsychotic
- monitor vitals
- IV fluids
- cooling
- dantrolene (muscle relaxant), 2nd line - bromocriptine (dopamine agonist)
- consider benzodiazepines for acute behaviour disturbance
Delirium tremens
Severe end of the spectrum of alcohol withdrawal & peak incidence is at 72 hours
Delirium tremens symptoms
- confusion
- paranoid delusions
- coarse tremor
- formication - sensation of crawling insects on or under the skin
- autonomic arousal (tachycardia, fever, pupillary dilatation, increased sweating)
Delirium tremens treatment
- large doses of benzodiazepines (eg. chlordiazepoxide)
- haloperidol for any psychotic features
- IV pabrinex
Wernicke’s encephalopathy
An acute encephalopathy due to thiamine deficiency
Wernicke’s encephalopathy symptoms
- delirium
- nystagmus
- ophthalmoplegia: lateral rectus palsy, conjugate gaze palsy
- hypothermia
- ataxia
Wernicke’s encephalopathy treatment
-parenteral thiamine
Korsakoff’s psychosis
Profound, irreversible short-term memory loss with confabulation (the unconscious filling of gaps in memory with imaginary events) and disorientation to time
Acute dystonias
Sustained, often painful, muscular spasms, producing twisted abnormal postures in reaction to an antipsychotic
Oculogyric crisis
Neck arched and eyes rolled back
Acute dystonias treatment
- stop antipsychotic
- administer IM/IV anticholinergics (first-line is procyclidine)
- continue for 1-2 days after dystonia & consider long-term prophylactic
What makes lithium toxicity worse?
- dehydration
- drugs (ACE inhibitors, NSAIDs)
- diuretics (thiazide)
- depletion of sodium
Lithium toxicity symptoms
- confusion
- coarse tremor
- nausea & vomiting
- ataxia
- seizures
Lithium toxicity treatment
- stop lithium
- supportive measures - IV fluids, dialysis if necessary, benzodiazepines for seizures
Clozapine-induced agranulocytosis treatment
- stop clozapine
- stop any other potentially marrow supressing drugs - e.g. sodium valproate
- avoid antipsychotics for a couple of weeks where possible; if needed - aripiprazole
- contact consultant haematologist
- avoid sources of infection, consider broad-spectrum abx
- lithium & G-CSF can be used
ECT
- passage of a small electrical current through the brain with a view to inducing a modified epileptic seizure which is therapeutic
- usually requires around 6-12 treatment sessions, delivered twice a week
ECT procedure
- electric current is applied to the patient’s skull, aiming to induce a seizure for at least 30 seconds
- occurs under GA
- muscle relaxant (suxamethonium) is given by the anaesthetist which limits the motor effects of the seizure
- can be bilateral/unilateral
ECT indications
- prolonged or severe mania
- catatonia
- severe depression (most common)
- treatment-resistant depression
- suicidal ideation or serious risk to others
- life-threatening depression
ECT side effects
- short-term
- peripheral nerve palsies
- cardiac arrhythmias, confusion
- dental and oral trauma
- anaesthetic risks
- muscular aches & headaches
- short-term memory impairment
- status epilepticus
- long-term
- anterograde & retrograde amnesia
ECT contraindications
- MI
- major unstable fracture
- cerebral aneurysm
- raised ICP (only absolute contraindication)
- stroke < 1 month ago
- history of status epilepticus
- severe anaesthetic risk
SSRIs examples
- citalopram
- escitalopram
- fluoxetine
- paroxetine
- sertraline
- fluvoxamine
SSRI indications
- depression
- panic disorder (citalopram, escitalopram, paroxetine)
- social phobia (escitalopram, paroxetine)
- bulimia nervosa (fluoxetine)
- OCD
- PTSD (paroxetine, sertraline)
- GAD (paroxetine)
SSRIs mechanism of action
- work by inhibiting the reuptake of serotonin from the synaptic cleft into pre-synaptic neurones
- SSRIs increase the concentration of serotonin in the synaptic cleft
SSRIs SEs
- GI: nausea, dyspepsia, bloating, flatulence, diarrhoea and constipation
- sweating
- tremor
- rashes
- EPSEs (uncommon)
- sexual dysfunction
- somnolence
- discontinuation syndrome - GI symptoms, ‘chills’, insomnia, hypomania, anxiety and restlessness
SSRIs contraindications & cautions
- cautions
- history of mania
- epilepsy
- cardiac disease
- acute angle-closure glaucoma
- diabetes mellitus
- contraindications
- mania
SSRIs route
oral
SNRIs examples
- venlafaxine
- duloxetine
SNRIs indications
- second/third line treatment for depression and anxiety
- have a faster onset & more effective than SSRIs (for major depression)
SNRIs mechanism of action
- work by preventing the reuptake of noradrenaline and serotonin
- do not block the cholinergic receptors and therefore do not have as many anti-cholinergic side effects as TCAs
SNRIs SEs
- nausea
- dry mouth
- headache
- dizziness
- sexual dysfunction
- hypertension
SNRIs contraindications & cautions
- cautions: similar to SSRIs
- contraindications: high risk of cardiac arrhythmia, uncontrolled hypertension
SNRIs route
oral
Mirtazapine indications
- second line for depressed patients who:
- would benefit from weight gain
- suffer from insomnia
Mirtazapine mechanism of action
- weak noradrenaline reuptake inhibiting effect
- has anti-histaminergic properties
- alpha-1 and alpha-2 blocker
- therefore increases appetite and is a sedative
Mirtazapine SEs
- increases appetite
- weight gain
- dry mouth
- postural hypotension
- oedema
- drowsiness
- fatigue
- tremor
- dizziness
- less common: syncope, mania, hallucinations, movement disorders
Mirtazapine contraindications & cautions
- cautions
- elderly
- cardiac disorders
- hypotension
- urinary retention
- diabetes
- psychoses
Mirtazapine route
oral
TCA examples
- amitriptyline
- clomipramine
- imipramine
- nortriptyline
TCA indications
- depressive illness
- nocturnal enuresis in children
- neuropathic pain (unlicensed)
- migraine prophylaxis (unlicensed)
TCA mechanism of action
- work by inhibiting the reuptake of adrenaline and serotonin in the synaptic cleft
- also have affinity for cholinergic receptors & 5HT2 receptors → contribute to side effects
TCA SEs
- anticholingeric: dry mouth, constipation, urinary retention
- cardiovascular: arrhythmias, postural hypotension, tachycardia
- hypersensivity: urticaria, photosensitivity
- psychiatric: confusion, delirium (especially in elderly)
- metabolic: increased appetite and weight gain
- endocrine: testicular enlargement
- neurological: convulsions, movement disorders
TCAs contraindications & cautions
- cautions
- cardiac disease
- history of epilepsy
- pregnancy
- breast feeding
- elderly
- contraindications
- recent MI
- arrhythmias (particularly heart block)
- mania
TCAs route
oral - tablet/solutions
MAOI examples
- irreversible: phenelzine, isocarboxide
- reversible: moclobemide
MAOI indications
- third-line treatment for depression: atypical/treatment-resistant depression
- social phobia
MAOI mechanism of action
inactivate monoamine oxidase enzymes that oxidise the monoamine neurotransmitters dopamine, noradrenaline, serotonin & tyramine
MAOI SEs
- CVS: postural hypotension, arrhythmias
- neuropsychiatric: drowsiness/insomnia, headache
- GI: increased appetite, weight gain
- anorgasmia
- increased LFTs
- hypertensive reactions with tyramine containing foods
MAOI contraindications & cautions
- cautions
- avoid in agitated/excited patients
- thyrotoxicosis
- hepatic impairment
- bipolar disorders
- contraindications
- acute confusional states
- phaeochromocytoma
MAOI route
oral
NARI examples
reboxetine
NARI indications
second or third-line for major depression
NARI mechanism of action
highly specific noradrenaline reuptake inhibitor
NARI SEs
- nausea
- dry mouth
- constipation
- anorexia
- tachycardia
- palpitations
- vasodilatations
NARI contraindications & cautions
- cautions
- history of cardiovascular disease
- bipolar disorder
- urinary retention
- prostatic hypertrophy
- pregnancy
NARI route
oral
typical anti-psychotics examples
- haloperidol
- chlorpromazine
- flupentixol
- fluphenazine
- sulpiride
- zuclopenthixol
typical anti-psychotic indications
- indicated for patients suffering from psychotic symptoms eg. delusions and hallucinations
- can be used for other conditions when they present with positive psychotic symptoms
- depression
- mania
- delusional disorders
- acute & transient psychotic disorders
- delirium
- dementia
- violet/dangerously impulsive behaviour and psychomotor agitation
typical anti-psychotic mechanism of action
reducing abnormal transmission of dopamine through blocking dopamine receptors in the brain
typical anti-psychotic SEs
- sedation
- weight gain
- QTc prolongation
- extra-pyramidal side effects - bradykinesia, muscle stiffness and tremor, tardive dyskinesia, akathisia
- anti-cholinergics used to treat EPSEs
- procyclidine (potential for misuse)
- anti-cholinergics used to treat EPSEs
typical anti-psychotics monitoring
- baseline: FBC, lipids, LFT, HbA1c, weight, ECG, blood pressure & pulse
- weekly: weight in an ideal world
- three months: FBC, lipids, LFT, HbA1C, weight, ECG, blood pressure & pulse
- yearly: FBC, lipids, LFT, HbA1C, weight, ECG, blood pressure & pulse
typical anti-psychotics contraindications & cautions
- cautions
- CVD
- parkinson’s disease
- epilepsy
- depression
- myasthenia gravis
- prostatic hypertrophy
- contraindications
- comatose states
- CNS depression
- phaeochromocytoma
typical anti-psychotics route
- usually oral
- can also be given by short-acting IM injection
- some antipsychotics can be given as depot injections every 1-4 weeks (long acting, slow release)
- numerous eg. flupentixol, fluphenazine, zuclopenthixol
atypical antipsychotics examples
- olanzapine
- risperidone
- quetiapine
- amisulpride
- aripiprazole
- clozapine
atypical antipsychotics indications
- indicated for patients suffering from psychotic symptoms eg. delusions and hallucinations (mainstay of treatment for schizophrenia)
- can be used for other conditions when they present with positive psychotic symptoms
- depression
- mania
- delusional disorders
- acute & transient psychotic disorders
- delirium
- dementia
- violet/dangerously impulsive behaviour and psychomotor agitation
- clozapine - third-line treatment for schizophrenia
- should only be prescribed after failing to respond to two other antipsychotics (treatment-resistant schizophrenia)
atypical antipsychotics mechanism of action
- specific dopaminergic action, blocking the D2 receptor
- also have serotonergic effects
atypical antipsychotics SEs
- sedation
- weight gain
- QTc prolongation
- dyslipidaemia
- diabetes
- metabolic syndrome
- clozapine
- agranulocytosis
- constipation, potentially fatal bowel obstruction
- hypersalivation
- urinary incontinence
atypical antipsychotics monitoring
- baseline: FBC, lipids, LFT, HbA1c, weight, ECG, blood pressure & pulse
- weekly: weight in an ideal world
- three months: FBC, lipids, LFT, HbA1C, weight, ECG, blood pressure & pulse
- yearly: FBC, lipids, LFT, HbA1C, weight, ECG, blood pressure & pulse
- clozapine
- weekly FBC for first 18 weeks, then fortnightly for up to a year, then monthly
atypical antipsychotics contradications & cautions
- cautions
- CVD
- parkinson’s disease
- epilepsy
- depression
- myasthenia gravis
- prostatic hypertrophy
- contraindications
- comatose states
- CNS depression
- phaeochromocytoma
atypical antipsychotics route
- usually oral
- some can also be given by short-acting IM injection
- some can also be given as depot injections
- risperidone
- olanzapine
- aripiprazole
Benzodiazepines examples
- long acting (> 24 hours duration)
- diazepam
- nitrazepame
- chlordiazepoxide
- short-acting (< 12 hours duration)
- lorazepam
- oxazepam
- midazolame
Benzodiazepines indications
- insomnia (short-term)
- anxiety disorders
- delirium tremens and alcohol detoxification
- acute psychosis
- violent behaviour
Benzodiazepines mechanism of action
- enhance the effect of the inhibitory neurotransmitter GABA by increasing the frequency of chloride channels via the benzodiazepine-binding site of the GABA-A receptor
- receptors are located throughout the cortex and limbic system in the brain & function to inhibit neuronal activity
Benzodiazepines side effects
- drowsiness & light-headedness the next day
- confusion and ataxia, especially in the elderly
- amnesia
- dependence
- paradoxical increase in aggression
- muscle weakness
- respiratory depression
Benzodiazepine withdrawal syndrome
May develop at any time up to 3 weeks after stopping a long-acting benzodiazepine, but may occur within a day in the case of a short-acting one
SE: insomnia, anxiety, loss of appetite, tremor, muscle twitching, sweating, tinnitus, perceptual disturbances & seizures (rarely)
Benzodiazepine cautions & contraindications
- respiratory depression
- hepatic impairment
Benzodiazepines route
- PO
- IM, IV & PR benzodiazepine preparations are mainly for non-compliant patients & status epilepticus
Pregabalin use in anxiety
Inhibitor of glutamate, noradrenaline and substance P
Uses: GAD, neuropathic pain, epilepsy
SE: dizziness, drowsiness, blurred vision, diplopia, confusion, vivid dreams, sedation, weight gain
Beta blockers use in anxiety
Notably propranolol, at a starting dose of 40mg, can be used in anxiety disorder for reducing somatic symptoms eg. tachycardia, palpitations & tremor
Contraindicated in asthma, COPD, bronchospasm, heart block, marked hypotension & acute LVF
Buspirone use in anxiety
Non-sedating anxiolytic used for GAD
Works as a 5HT-1A agonist
Does not cause dependence, but its anxiolytic effect develops more slowly
SE: nausea, headache, light-headedness & dizziness
Hypnotics types
Benzodiazepines - temazepam, lormatazepam & nitrazepam
Nonbenzodiazepines - zopiclone, zolpidem
Hypnotics (‘Z drugs’) mechanism of action
Work like BZDs by enhancing GABA transmission but are mainly used as hypnotics as they have:
- shorter half lives
- reduced risk of tolerance & dependence
- reduced psychomotor & hangover effects
Hypnotics use
Only for two weeks and take for only 5 out of 7 days each week to reduce potential for tolerance
Mood stabilisers
Used to treat bipolar mood disorder
Come from one of the following groups:
- lithium
- anticonvulsants
- second generation antipsychotics
Lithium indications
One of the most effective mood stabilisers
Reduction of self-harm
Augment antidepressants
Lithium monitoring
Narrow therapeutic window → regular serum lithium levels → weekly after dose change until level stable then 3 monthly once stable
Sample taken 12 hours post-dose
U&Es and TFTs every 6 months
Lithium SEs
GI disturbance, metallic taste and/or dry mouth, fine tremor, polydipsia & polyuria, weight gain
Long-term effects: hypothyroidism (usually reversible), renal impairment (usually irreversible)
Lithium interactions
Following can increase levels dangerously include:
- NSAIDs
- loop diuretics
- ACE inhibitors
SGAs in bipolar mood disorder
Quetiapine now first line treatment for bipolar
All SGAs have effectiveness & so do FGAs
Doses and monitoring the same as for psychosis
Anticonvulsants as mood stabilisers
Various modes of action - GABA receptors, calcium channels, sodium channels
Most common used:
- sodium valproate - avoid in women of child bearing age due to teratogenicity; check LFTs before and soon after starting
- carbamazepine
- lamotrigine - potential for Stevens Johnson Syndrome
Most anticonvulsants have potential to cause thrombocytopenia so check FBC
SEs: sedation & weight gain
ADD & ADHD medication
Most treatments are CNS stimulants
1) methylphenidate
- most commonly prescribed
- often given with a combination of immediate & sustained release
2) dextroamphetamine
- stimulants have potential for misuse & dependency
- monitor weight, height (in children) & pulse
Atomoxetine - noradrenaline re-uptake inhibitor
- used according to patient preference, unable to tolerate stimulants or in instances of previous drug dependence
