Psychiatry Flashcards
Name 4 SSRIs
Fluoxetine
Sertraline
Paroxetine
Citalopram
What is the mechanism by which SSRIs work?
Presynaptic blockage of serotonin reuptake pumps.
Increases postsynaptic binding
Do NOT inhibit NA reuptake
What are the indications for SSRIs?
Depression - 1st line moderate to severe
Anxiety disorders
OCD
Bulimia nervosa (fluoxetine)
What are the SEs of SSRIs?
8 S’s
- Stress (anxiety/worry) - early
- stomach upset/bleeding - early
- Size (weight gain)
- Sexual dysfunction
- Skin rash (hypersensitivity)
- Suicidal thoughts
- Seizure threshold reduced
- Serotonin syndrome - triad of altered mental state, neuromuscular excitability, autonomic hyperactivity (hyperthermia)
What are the CIs for SSRIs?
- Mania
- Under 18s (except Fluoxetine) - reduced efficacy, increased risk of suicidal thoughts and self harm
- Epileptics - lowers seizure threshold
- Peptic ulcer disease - increased risk of bleeding
- Hepatic impairment - metabolised by liver
Why are there fewer SEs for SSRIs vs TCAs?
Because SSRIs do not block other receptors (dopamine, histamine, cholinergic, alpha-adrenergic), resulting in associated SEs
What are the drug interactions of SSRIs? (Citralopram, sertraline, fluoxetine)
- Do not combine with other serotonin increasing drugs,
- > e.g. MAOIs, TCAs - serotonin syndrome and potential overdose (convulsions, coma and cardiotoxicity- arrythmias)
- Avoid combo with drugs that prolong QT duration
- Increase plasma conc of TCA’s
How long should antidepressant drugs be taken for?
6 Months
What should be avoided wren taking anti-depressants?
- St John’s wort
- alcohol
- reduce caffeine
How are SSRIs metabolised?
Liver
What are the discontinuation Sx’s of SSRIs?
FINISH Sx
- flu like symptoms
- insomnia
- nausea
- imbalance
- sensory disturbance
- hyper-arousal
What are the symptoms of serotonin syndrome?
HARMED
- hyperthermia
- autonomic instability
- rigidity
- myoclonus
- encephalopathy
- diaphoresis
Name 4 tricyclic antidepressants
Amitriptyline
Clomipramine
Imipramine
Lofepramine
What is the mechanism by which TCAs work?
- blocks pre-synaptic 5-HT and noradrenaline re-uptake . Also blocks dopamine, histamine, alpha-adrenergic and muscarinic/cholinergic receptors.
Increases availability for post-synpatic transmission.
What are the indications for TCAs?
- 2nd Line for moderate-severe depression where SSRIs not effective
- Anxiety disorders and OCD
Tx option for neuropathic pain (not licensed for use), narcolepsy
What are the SEs for TCAs?
Brain - hallucinations, convulsions, mania
CV - arrthymias, prolongs QT and QRS (TOXIC in overdose)
Anticholinergic - dry mouth, constipation, urinary retention, blurred vision (can’t see, can’t pee, can’t shit, can’t spit)
Alpha-adrenergics - postural hypotension
Histamine - sedating, weight gain
Dopamine blockage - breast changes/gynaecomastia, sexual dysfunction, extrapyramidal Sx (PAAT: parkinson sx, akathisia, Acute dystonias, tardive dyskinesia)I
What are the CIs for TCAs?
- CV disease
- Elderly
- Mania
- Epileptics (reduces seizure threshold)
- Prostatic hypertrophy - urinary retention
- Glaucoma
- Hepatic impairment
What are the potential interactions of TCAs?
Should not be combined with MAO inhibitors/SSRIs or any other drugs that increase 5-HT/NA - serotonin syndrome
Should also not be combined with drugs that block dopamine, muscarinic, histamine or hypotensive drug
How are TCAs metabolised?
Liver
Name 3 Monoamine oxidase inhibitors
Phenelzine
Tranylcypromine
Moclobemide
What is the mechanism by which MAOIs work?
Non selective and irreversible inhibition of monoamine oxidase A and B (degrades monoamines in synaptic cleft)
What are the indications for MAOIs?
Depression (atypical/resistant - hypersomnia, overeating, anxiety)
What are the SEs of MAOIs?
Postural hypotension GI Headache/dizzy Hepatocellular necrosis (rare) Monoaminergic crisis - Hypertensive crisis (see interactions)
What are the CIs for MAOIs?
- Mania
- Hepatic dysfunction
- Phaeochromocytoma (risk of hypertensive crisis)
- Cerebrovascular disease
What are the interactions of MAOIs? What is the mechanism?
- MAO A blockage -> amine NT accumulation and impairs food-amine metabolism.
High amines = hypertensive crisis, hyperpyrexia and psychosis.
∴ Avoid in combo with:
- Sympathomimetics e.g. cough/decongestant meds
- SSRIs and TCAs (also increased risk of serotonin syndrome)
- Levodopa
- Opioid analgesics
- Tyramine containing foods (e.g. cheese, beer, marmite)
How long should you leave it before starting another anti-depressant after MAOI? Why?
2 weeks after stopping - Due to irreversible MAO inhibition
Name one serotonin-NA reuptake inhibitor (SNRI)
Venlafaxine
Duloxetine
What is the mechanism by which SNRIs works?
Presynaptic blockage of both 5-HT and NA reuptake pumps
Negligible effects on dopamine, histamine, alpha-adrenergic and cholinergic receptors.
What are the indications for SNRIs?
- Major depression where SSRIs are not effective/tolerated
- GAD
Wha are the SEs of SNRIs?
- GI upset (dry mouth, nausea, constipation)
- PALPITATIONS
- Changes in weight/appetite
- CNS disturbances (e.g. headache, abnormal dreams, insomnia, confusion)
- reduces seizure threshold
- Hyponatraemia
- Serotonin syndrome
- Suicidal thoughts (increases motivation) and behaviour
- Major discontinuation Sx
What are the CIs for SNRIs?
- Elderly
- Hepatic and renal impairment
- CV disease - prolongs QT duration, increase risk of arrhythmias
What are the potential interactions for SNRIs?
Avoid combo with other antidepressants (serotonin syndrome)
What type of antidepressant is mirtazapine?
Noradrenergic and specific serotonergic antidepressant (NaSSA)
What is the mechanism by which mirtazapine works?
Presynaptic alpha 2 receptor blockage (results in increased release of NA and serotonin from presynaptic neurons)
What are the indications for mirtazapine?
- Major depression where SSRIs are not effective/tolerated
- GAD
What are the SEs of mirtazapine?
- Increased appetite, weight gain and sedation (histamine antagonism)
- Headache and dry mouth
Rarely…
- Dizziness
- Postural hypotension
- Tremor
- Peripheral oedema
- Hyponatraemia
- Serotonin syndrome
- (Negligible anticholinergic effects)
What are the CIs for mirtazapine?
Elderly
Mania
Hepatic and renal impairment
CV disease (increased risk of arrythmias)
What are the potential drug interactions for mirtazapine?
Combo with other antidepressant classes - serotonin syndrome
When should mirtazapine be taken?
At night - minimise/take advantage of it’s sedative effects.
What type of drug is lithium?
Mood stabiliser
What is the mechanism by which lithium exerts its action?
Not really known
Might modulate the neurotransmitter-induced activation of second messenger systems
What are the indications for lithium?
- Acute Mania
- Prophylaxis of bipolar affective disorder (relapse prevention)
- Tx of resistant depression (lithium augmentation)
- Other: adjunct to antipsychotics in schizoaffective disorders and schizophrenia
What are the SEs of lithium?
75% patients on lithium will experience some SEs
- Leucocytosis/lethargy
- Insipidus (polyuriabpolydipsia)
- Tremor (fine)/Teratogenicity (Epstein’s abnormality - malformation of tricuspid valve in 1st T. Also causes floppy baby syndrome, hypothyroidism, and polyhydraminos)
- Hypothyroidism
- Increased weight
- Vomiting
- Metallic taste
Long term SEs:
kidney - 10-20 % have morphological kidney changes (>1% develop kidney failure after 10yrs)
Hypothyroidism (5-35%) - more in women (6-18 months after starting)
When should lithium be discontinued in pregnancy?
Mild/stable forms of bipolar: taper dose and stopped pre pregnancy
Moderate risk of relapse: lithium should be tapered and discontinued during first trimester
Severe bipolar with high risk of relapse: lithium = maintained during pregnancy (with informed consent, appropriate counselling of risk to foetus, prenatal diagnosis and echo at 16-18 weeks gestation)
What is the therapeutic ranger for lithium? What are the signs of toxicity?
Narrow therapeutic range (0.5-1.0 mmol/
Cause of toxicity Drugs: ACEi, NSAIDs, diuretics - Renal failure - UTI - Dehydration
- 5-2 mmol/L Toxic
- N&V, apathy, coarse tremor, ataxia, muscle weakness
> 2 mmol/L Very Toxic
- nystagmus, dysarthria (diff speaking), impaired consciousness, hyperactive, tendon reflexes, oliguria, hypotension (precede circulatory collapse), myoclonus jerks, convulsions, coma
What is the Tx for lithium toxicity?
Supportive - adequate hydration, renal function and electrolyte balance.
If convulsions - anti-convulsions
If renal failure - dialysis
What investigations should be completed prior to lithium Tx?
- lithium levels
- FBCs and U&Es (renal function and electrolyte balance)
- TFTs
- ECG - cardiac abnormalities
– pregnancy test (if female)
How is lithium metabolised?
Renally
What are the CIs for lithium?
- Pregnant/breastfeeding (8x increased risk of Ebstein’s anomaly in first trimester during the first trimester of pregnancy)
- Renal impairment (older adults, dehydration)
- Hypothyroid
- Cardiac impairment
- Neurological conditions e.g. Parkinson’s/Huntingdon’s
What are the potential drug interactions of lithium?
Clearance of lithium = decreased with renal impairment and sodium depletion
∴ diuretics (esp thiazides), NSAIDs and ACEi increase lithium levels
-Antipsychotics may synergistically increase lithium-induced NEUROTOXICITY
How should lithium Tx be monitored?
Lithium is long term treatment to stabilise patients mood. Regular review by psychiatrist to determine whether the dose and/or formulation is adequate
Initially
- check lithium level after 5days of initial dose (titration up as required until suitable maintenance dose).
- Review frequently (weekly) at beginning of treatment to determine lithium level until therapeutic level = stable for 4 weeks
- lithium levels should be checked every 3 months
- U&Es and TFTs checked every 6 months due to SEs on these organs
Need to inform doctor that taking lithium (due to multiple interactions)!!
What is the mechanism by which sodium valproate works?
Weak inhibitor of Na channels -> stabilises resting membrane potentials and reduce neuronal excitability
Increases brain content of GABA (principle inhibitory NT) - reduces neuronal excitability
What are the indictions for sodium valporate?
- Epilepsy (1st for generalised or absence seizures, 2nd for focal seizures)
- 2nd line - Bipolar disorder (acute Tx/prophylaxis against recurrence)
What are the SEs of sodium valporate?
- Valproate
- Appetite increase/weight gain
- Liver failure (monitor LFTs during 1st 6 months)
- Pancreatitis
- Reversible hair loss (grows back curly)
- Oedema
- Ataxia
- Teratogenicity, Tremor, Thrombocytopaenia
- Encephalopathy (due to hyperammonaemia) / Enzyme inducer
What are the CIs for sodium valporate?
- Pregnant women (1st tremester)
- Hepatic/renal impairment
- Porphyria
What are the potential drug interactions of Sodium valporate?
- CYP450 INHIBITOR - increases concentration/risk of toxicity of drugs metabolised by CYP450 e.g. warfarin - sodium valproate metabolised by CYP450
- drugs that induce CYP450 reduces sodium valproate concentration and increases risk of seizures (e.g. carbamezapine, phenytoin)
- Drugs that lower seizure threshold e.g. SSRIs, anti-psychotics, tricyclic antidepressants, tramadol
What is the mechanism by which carbamazepine exerts its action?
Inhibits neuronal Na channels - stabilising resting membrane potentials and reducing neuronal excitability
Block synaptic tranmission in trigeminal nucleus
Stabilise mood - reducing electrical kindling in temporal lobe and limbic system
What are the indications for carbamezapine?
- Epilepsy - 1st for focal seizures (with/without 2o generalisation) and generalised seizures
- Trigeminal neuralgia - 1st line
- Bipolar disorder - option for prophylaxis in pts resistant/intolerant to other meds
What are the SEs of carbamezapine?
- GI upset
- Neurological effects - dizziness/ataxia
- Carbamezapine hypersensitivity (mac-pap skin rash)
- Antiepileptic hypersensitivity syndrome - severe skin reactions (SJS), fever, lymphodenopathy, haemotological abnormalities/pancytopaenia (↓WCC), ↑LFTs
Why shouldn’t pregnant mothers take carbamezapine?
- Teratogenic (neural tube defects, cardiac, urinary tracts abnormalities, cleft palate)
What are the CIs to carbamezapine?
- pregnancy - high folic acid supplements
- Hepatic, renal or cardiac impairment (increased risk of toxicity)
- Antiepileptic hypersensitivity syndrome
What are the important interactions of carbamezaine?
CYP450 inducer - ↓ efficacy and concentration of P450 drugs e.g. warfarin
↑Concentration and adverse effects with P450 inducers
Efficacy ↓ with drugs that lower seizure threshold (e.g. SSRIs, TCAs, antipsychotics)
How is carbamezapine metabolised?
Hepatic (P450)
What type of drug is lamotrigine?
Anti-convulsants/mood stabiliser
What is the mechanism by which lamotrigine works?
Blocks Na channels - stabilising neurons and reducing neuronal excitability
What are the indications for lamotrigine?
- 2nd line for generalised seizures (inc Lennox-Gestault and tonic-clonic seizures)
- Bipolar disorders - stabilises mood and reduces depression
What are the SEs of lamotrigine?
- GI - N&V
- Neuro - confusion, agitation, drowsiness, ataxia, diplopia, nystagmus
- STEVEN JOHNSON SYNDROME - therefore titrate dose
What are the CIs for lamotrigine?
- Can be SAFELY used in pregnancy!!
- Hypersensitivity reactions - rash
- Steven Johnsons syndrome (serious reaction)
- Renal and hepatic impairment (increased risk of toxicity)
What are the important drug interactions for lamotrigine?
- Efficacy reduced by drugs that lower seizure threshold - e.g. SSRIs, tricyclics, anti-psychotics, tramadol
- Metabolised by CYP450 - concentration increased by (CYP450 inhibitors and reduced by CYP450 inducers
Name 3 first generation (typical) antipsychotics
Haloperidol
Chlopromazine
Prochlorperazine
What is the mechanism by which first generation antipsychotics work?
Block post-synaptic dopamine D2 receptors
What are the three main dopaminergic pathways in the CNS? WHat else has D2 receptors?
- Mesolimbic/mesocortical
- Nigrostriatal pathway
- Tuberohypophyseal pathway
- Chemoreceptor trigger zone
What does the mesolimbic/mesocortical pathway comprise? what is the effect of blocking this pathway?
Runs between the midbrain and the limbic/frontal system
Considered main determinant of antipsychotic effects
Overactivity of mesolimbic system (high dopamine) = positive symptoms seen in schizo
Mesocortical dysfunction (high dopamine levels) = negative and cognitive symptoms seen in schizo
What does the the nigrostriatal pathway comprise/ What is the effect of blocking this pathway?
Connects the substantia nigra with the corpus striatum of the basal ganglia
Extrapyramidal effects
What does the tuberohypophyseal pathway comprise? What is the effect of blocking this pathway?
- Connects hypothalamus with pituitary gland
- Hyperprolactinaemia (menstrual disturbance, galactorrhoea, breast pain, gynaecomastia)
- Temperature dysregulation(?)
What are the main SEs of the first generation anti-psychotics? (haloperidol, chlorpromazine, prochlorperazine)
EXTRAPYRAMIDAL EFFECTS EARLY - Parkinsonism - acute dystonic reactions - Akathisia (inner restlessness) - Neuroleptic malignant syndrome LATE - Tardive dyskinesia - pointless, involuntary, repetitive movements e.g. lip smacking
OTHERS
- drowsiness
- ↓ BP
- ↑QT + arrythmias
- Erectile dys
- Hyperprolactinaemia Sx
What are the CIs for first generation anti psychotics?
Elderly
Dementia
Parkinson’s disease - extrapyramidal effects
What are the important drug interactions of first generation antipsychotics?
Drugs that…
- prolong QT interval e.g. amiodarone, macrolides
- Opioids
- Enhance CNS depression
- Lower seizure threshold
How are anti-psychotics metabolised?
Liver
How should Neuroleptic malignant syndrome be managed? What is the cause?
- Stop antipsychotics (IV dialysis?)
- ↓ temp, vent support
- Start dopaminergic and anti-cholinergic drugs
- ↓agitation e.g. benzos
- Restart anti-P hesitantly
- ↓dopamine levels due to D2 blockage
Name 4 second generation anti-psychotic drugs?
Quetiapine
Olanzapine
Risperidone
Clozapine
What is the mechanism by which second generation anti-psychotics exert their action?
Block post synaptic dopamine receptors
What are the main difference between 1st generation and second generation antipsychotics? What are the proposed mechanisms for this difference?
Improved efficacy in treatment-resistant schizophrenia (especially clozapine) and against negative symptoms
Lower risk of extra pyramidal Sx
Possible mechs: higher affinity for other receptors (particularly 5-HT2a receptors) looser binding to D2 receptors (in the case of clozapine/quetiapine)
What are the indications for 2nd generation antipsychotics?
- Urgent Tx of severe psychomotor agitation
- 1st line for Schizophrenia - esp pt’s who do not tolerate 1st generation (extrapyramidal Sx), where -ve Sx are prominent , Tx resistant
- Bipolar disorder (acute episodes)
What are the important SEs of 2nd generation anti psychotics?
- Sedation
- Dry mouth, blurred vision, constipation, urinary retention- ACh binding - (‘can’t see, can’t pee, can’t shit, can’t spit’)
- Extrapyramidal effects (H2 blocking of nigrostriatal pathway) - ↑ in 1st generation
- Metabolic disturbance (↑weight, DM, ↑lipid) - ESP the ‘-PINES’
- Prolong QTc/arrhythmias (alpha-1 binding)
- Hyperprolactinaemia (esp respiridol) - H2 blocking of tuberphypophyseal pathway - lactation, gynaecomastia, sexual dysfunction (amenorrhea/infertility)
When is clozapine indicated?
Tx resistant schizophrenia - where 2 other antipsychotics have been tried for sufficient amount of time (ie not because patient stopped/did not tolerate)
What are the specific side effects of clozapine?
- Agranulocytosis ~1%
- QTc prolongation/arrhythmias
- life threatening constipation (prescribe 2 laxatives)
- hypersalivation
- sedation
- postural hypertension
- Weight gain etc
What are the CIs to 2nd generation antipsychotics?
CV disease
Parkinson’s/dementia
Clozapine - severe heart disease or Hx of neutropenia
What are the important drug interactions of 2nd generation anti-psychotics?
- Other sedating drugs
- Do not combine with other dopamine-blocking meds
- Drugs that prolong QT interval (e.g. amiodarone, quinine, macrocodes, SSRIs)
How are 2nd antipsychotic medication monitored?
Blood tests (FBC, U&E, creatine, LFTs) at start of Tx and periodically thereafter (weekly then monthly FBCs for clozapine)
- Metabolic and CV SEs (weight, lipid profile, fasting blood glucose)
What is the speed of action of antipsychotics for: Tranquilizing effects
Side effects
Anti-psychotic effects
Tranquillising - Hours
SEs - Hours to days
Anti-psych - Days to weeks
What type of drugs are benzodiazepines?
anxiolytic (i.e. ↓ anxiety)
hypnotic (i.e. sedative)
Name 5 benzos
Diazepam Temezepam Lorazepam Chlordiazepoxide Midazolam
What is the mechanism by which benzos work?
- Benzos facilitate and ENHANCE binding of GABA to GABAa receptor
- Widespread depressant effect of synaptic transmission → Causes ↓ anxiety, sleepiness, sedation, anti-convulsant effects
- Ethanol also acts on same receptor - benzo = Tx for alcohol withdrawal
What are the indications for benzos?
- 1st line - seizures/status epilepticus
- 1st line - alcohol withdrawal
- Common sedative for intervention procedures
- Short term Tx for severe anxiety
- Short term Tx for severe insomnia
- Akathisia, muscle spasms
What are the important SEs of Benzos?
- Drowsiness → Sedation → Coma (dose dependent) (AVOID DRIVING/MACHINERY)
- Few weeks use (>4 weeks) - DEPENDENCE
- Withdrawal reaction (similar to alcohol) with abrupt cessation
- OVERDOSE: Airway obstruction → death
What are the CIs for benzos?
- Elderly
- Respiratory impairment/neuromuscular disease
- Liver failure (may precipitate hepatic encephalopathy)
What is the best benzo for alcohol withdrawal and why?
Lorazepam - depends less on liver for elimination
What are the important drug interactions with benzos?
Additive sedative effect - avoid with alcohol and opioids
- Metabolised by CYP450 - CYP450 inhibitors may increase effects
What type of drugs are the Z drugs?
Hypnotics
Name 2 Z drugs?
Zopiclone
Zolpidem
What is the mechanism by which Z drugs work?
Similar to benzos - enhance GABA binding to GABAa receptor
- Widespread depressant effect of synaptic transmission - ↓anxiety, sleepiness, sedation
(NOT anticonvulsant as only taken ORALLY)
How long is the length of Z drug action?
Short
What are the indications for Z drugs?
Short term Tx of severe insomnia
What are the SEs of Z drugs?
- Daytime sleepiness (don’t drive/do complex tasks)
- Rebound insomnia when stopped
- CNS effects - headache, confusion, nightmares, amnesia
- Zopiclone - taste disturbance
- Zolpidem - GI upset
- PROLONGED USE (>4 weeks) - dependence and withdrawal effects if stopped
- OVERDOSE - drowsiness, coma, resp depression
What are the CIs for Z drugs?
- Elderly (caution)
X Obstructive sleep apnea
X Resp muscle weakness
X Resp depression
What are the important interactions of Z drugs?
- Enhance sedative effects of antihistamines, alcohol, opioids
- Enhance hypotensive effects of antihypertensive meds
- Metabolised by CYP450 - inhibitors ↑, inducers ↓
What is neuroleptic malignant syndrome?
RARE, LIFE THREATENING
- insidious onset (4-11 days from initiation/change in dopamine antagonist)
- rigidity (lead pipe)
- confusion
- autonomic dysfunction (↑BP)
- pyrexia
↑WCC, ↑CPK (muscle activity), ↑LFTs
Name 3 anti-cholinesterase inhibitor
DONEPEZIL
Rivastigmine
Galantamine
What is the mechanism by which anticholinesterase inhibitors exert their action?
Alzheimer’s - mechanism ↓ACh in the brain
Donepezil - reversible, non-competitive inhibitor of anticholinesterase. ↓ ACh hydrolysis in brain, ↑ availability for neurotrans.
What are the indications for donepezil?
1st line for mild-moderate Alzheimers
What are the CIs for donepezil?
Cholinergic effects!
- Asthma/COPD
- sick sinus syndrome/supravent conduction abnormalities
- Peptic ulcers
- Antipsychotic Tx
What are the SEs of donepezil?
- Insomnia/weird dreams
- Hallucinations
- Agitation/aggression
- Fatigue
- Dizziness/drowsiness
- Urinary incontinence
- N/V/D
- Muscle cramps
- Rash/urticaria
How does electroconvulsive therapy works?
Unknown mechanism - release of NTs and hypothalamic/pituitary hormones?
What are the indications for ECT?
DEPRESSION
- life threatening/suicidal
- psychotic features/stupor
- treatment resistant
MANIA (severe)
SCHIZOPHRENIA - catatonic, +ve Sz, schizoaffective
SEVERE POSTNATAL DEPRESSION
How is ECT administered?
2-3x per week (between 4-12 Txs. Can be more)
Bilateral or unilateral placement
Charge should be sufficient to induce generalised seizure lasting ~15secs
What do anaesthetists administer before ECT? Why?
Administered by an anaesthetist
Short acting induction agent eg methohexital - should last approx 5 mins. Not painful.
Muscle relaxant
What are the SEs of ECT?
Mortality - 1 in 50,000
Loss of memory - short term/autobiographical (reduced with unilateral ECT)
Confusion headache, nausea, muscle pain - 80% pts
What are the important drug interactions to consider with ECT?
SEIZURE LOWERING eg antidepressants, antipsychotics
SEIZURE INCREASING - eg benzos, anticonvulsants
What are the CIs for ECT?
No absolute CIs!!
Caution with…
- heart disease
- raised intracranial pressure
- risk of cerebral bleeding
- poor anaesthetic risk
