Psychiatric Medications Flashcards
MOA, Examples, positives and negatives of 1st generation/ TYPICAL antipsychotic medications
MOA
- Block post synaptic D2 receptors in mesolimbic, mess cortical, nigrostriatal and tuberoinfundibulnar pathways
EXAMPLES
- Haloperidol (high potency)
- Chlorpromazine (low potency)
POSITIVES
- inexpensive
- injectable/ depot form
- minimal metabolic side effects
NEGATIVES
- Extrapyramidal SE
- Not mood stabilising
- Reduced DA in mesocortiyal pathway can induce negative side effects
- Tardive symptoms in long term use
MOA, Examples, positives and negatives of 2nd generation/ ATYPICAL antipsychotic medications
MOA
- Block post synaptic D2 receptors (less affinity than 1st gen)
- Block 5HT2A on presynaptic dopamine terminals to reverse dopamine blockafe in some pathways
EXAMPLES
- Risperidone
- Olanzapine
- Quetiapine
- Aripiprazole
- Clozapine
POSITIVES
- Fewer EPS
- Low tar dive symptom risk
- mood stabilising
NEGATIVES
- Expensive
- Metabolic SE !!! (increase wt, BGL, lipids, MetSy)
- Exacerbation/ new onset obsession behaviour
Second generation antipsychotics adverse effects
NOTE: see notes for specific SE of specific SGAs (table)
Common ▪ Insomnia ▪ Akathesia (very common!) ▪ Headache ▪ Sedation (esp Quetiapine and olanzapine) ▪ Metabolic syndrome + weight gain ▪ Cardiovascular - May increase the QT interval, increasing the risk of arrhythmia - orthostatic hypotension - some ↑ in VTE risk
Uncommon but Serious
▪ Extrapyramidal Side effects
- Dystonia
- Akathesia
- Pseudo-parkinsonism
-Tardive Dyskinesia
▪ Neuroleptic malignant syndrome (FARM symptoms)
▪ Blood dyscrasias
- anaemia, thrombocytopenia, neutropenia, agranulocytosis
▪ New-onset or worsening obsessive-compulsive symptoms (clozapine)
EXTRAPYRAMIDAL SIDE EFFECTS
▪ highest with haloperidol, fluphenazine and trifluoperazine
▪ lower with chlorpromazine, periciazine
▪ Is dose dependant – so Reduce antipsychotic dose to avoid recurrent EPSE
NOTE: AKATHESIA= inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting
Clozapine - Indications, contraindications, receptor profile/MOA, adverse effects, interactions, patient counselling, monitoring
(Antipsychotic)
INDICATIONS
▪ Schizophrenia in people unresponsive to, or intolerant of, other antipsychotics (ie lack of satisfactory clinical response, despite the use of adequate doses of drugs from at least 2 groups of antipsychotics for a reasonable duration; or development of EPSE, including tardive dyskinesia)
CONTRAINDICATIONS
▪ Contraindicated in bone marrow disorders, drug-induced (including clozapine-induced) neutropenia or agranulocytosis (Neutropenia seems to be more common in children and adolescents than adults)
▪ Severe Renal or Liver impairment
RECEPTOR PROFILE/ MOA ▪ BLOCK 5HT2 to 90% ▪ BLOCK D2 ▪ BLOCK M1 ▪ BLOCK D4 (with high affinity related to plasma concentration) ▪ BLOCK H1, alpha 1
ADVERSE Common - Sedation ++ - Hypersalivation ++ - Increase HR ++ - Constipation - Seizures - Pyrexia - Urinary incontinence
Infrequent
- Hepatitis ++
- Myocarditis ++
- Neutropenia ++
- Angranulocytosis ++
- EPS ++
- Eosinophilia
- Priapism
Rare
- Cardiomyopathy ++
- HTN
- Myoclonic jerks
- Interstitial nephritis
- Fulminant hepatic necrosis
Metabolic
▪ ↑↑ BGL. ↑↑ Lipids, ↑↑ weight
▪ ↑↑ Risk of developing T2DM (must assess before + during treatment)
▪ Blood Dyscaria
▪ ↑↑ Risk of agranulocytosismust monitor for this!
INTERACTIONS
▪ Tobacco smoking—increases clearance of clozapine; dose may need to be adjusted if patient starts or stops smoking (the dose may need to be adjusted by 50%).
▪ Avoid combinations with drugs that may cause agranulocytosis
▪ GI obstruction may be exacerbated by the anticholiergic properties
PATIENT COUNSELLING
▪ Need regular blood tests and other checks to monitor for serious side effects.
▪ Do not stop taking this medicine suddenly unless your doctor tells you to.
▪ Dose may need changing if you vary your caffeine intake (eg tea, coffee, cola
drinks) or if you start or stop smoking tobacco; tell your doctor if any of these habits change.
MONITORING
▪ Start treatment only if white cell count and absolute neutrophil count are normal; blood monitoring is required each week for the first 18 weeks and then each month
▪ Medical supervision and resuscitation facilities must be available when treatment starts because of possible profound orthostatic hypotension with respiratory or cardiac failure
▪ Monitoring for the development of myocarditis:
- Baseline troponin + CRP + ECG + ECHO
- Monitor CRP + TnI weekly for first 4 weeks
- Enquire of symptoms every alternate day (when in patient)
and weekly when out patient
- Discontinuation of clozapine and investigation by
echocardiography is advised if either troponin is in excess of twice the normal maximum or CRP is more than 100 mg/L.
- Clinical – flu like illness, sudden BP drop, chest pain, non-specific ECG changes, basal crepitation’s, S3 heart sound, peripheral oedema, ↑ JVP
Factors contributing to antipsychotic medication adherence
PATIENT FACTORS
▪ Insight into their own condition
▪ Attitude towards taking the
medications
▪ Medication beliefs (e.g. delusional beliefs the drug is poison)
▪ Ongoing substance abuse
▪ Psychotic symptoms (a psychotic person won’t remember to take their meds!)
MEDICATION FACTORS
▪ Side effects –> weight gain, motor symptoms, sedation, hyper- prolactinemia
▪ Daily tablet dosing –> easy to miss or forget
▪ Depo –> factors affecting access and adherence for repetitive doses
▪ Efficacy
▪ Time taken to show effect
Explain Antipsychotic medications to parent/ carer
▪ INDICATION + MECHANISM
- to alleviate the positive symptoms of schizophrenia / psychosis. These include the hallucinations and delusions.
- Work to reduce the effects of the chemicals in the brain that are causing the psychotic symptoms
▪ OPTIONS
- Consider whether a regular injection may suit you better than taking
tablets.
- This maybe an option that can’t be started off with but can be used
once doses etc are titrated.
▪ TAKING THE MEDS
- It is best to avoid using illicit substances as use of cannabis or amphetamine markedly decreases control of psychotic symptoms and increases risk of relapse.
- Taking your antipsychotic medicine regularly is important
- Stopping or taking it irregularly is associated with high risk of relapse and suicide
▪ SIDE EFFECTS
- Extrapyramidal side effects are and what you can do about them
- Risk of tardive dyskinesia with long-term antipsychotic treatment.
- Sedation / drowsiness (↑ effects of alcohol, cannabis or sleeping
tablets) = Do not drive or operate machinery
- Metabolic effects + weight gain
- You may feel dizzy on standing when taking this medicine. Get up
gradually from sitting or lying to minimise this; sit or lie down if you become dizzy.
▪ MONITORING + FOLLOW UP
- Initially will need to check blood (UEC, LFT, prolactin) and ECG
- Need annual / 6 monthly monitoring of metabolic variables and ECG
- Prophylaxis is usually continued for 1–2 years after remission of a first psychotic episode (to prevent relapse) and for longer after >2 episodes
- After stabilisation, the long half-life usually allows the total daily oral dose to be given at night
Lithium Initiation, dose, Patient education, monitoring, interactions, precautions, Adverse effects, what to do in pregnancy
(MOOD STABILISER)
BEFORE COMMENCING/ INITIATION CHECK: ▪ UEC + eGFR (+/- urinalysis) ▪ Calcium + PTH levels ▪ Thyroid function (can cause hypothyroidism) ▪ ECG (can cause QTc prolongation) ▪ FBC (can cause leucocytosis) ▪ Weight + BMI (can cause gain)
DOSE
- 125 to 500 mg orally, BD daily for 2 weeks. Dose should then be adjusted according to the serum concentration determined after 5 to 7 days of steady-dose treatment.
- Therapeutic range = 0.6 – 0.8mmol/L
PATIENT EDUCATION
- Adherence is very very important!
- Regular blood tests are important during treatment.
- Take with food.
- Do not break, crush or chew, and avoid taking with hot drinks.
- Maintain a normal diet with regular salt and fluid intake.
- Drink more non-alcoholic fluid during hot weather to avoid toxicity.
- Avoid sodium bicarbonate (found in products such as indigestion medicines) as it makes lithium less effective.
- Educate about lithium toxicity
= Be alert for signs (eg extreme thirst and frequent urination, nausea and vomiting), esp during illness, excessive sweating or low fluid intake
= If these occur, stop taking the tablets and seek medical attention immediately. - Abrupt cessation leads to relapse of mania within a few months, thus it should be withdrawn slowly over at least 2 months
MONITORING
▪ Measure serum levels 8 – 12 hours after last dose
▪ Serum [lithium] to be reassessed every 3 – 6 months once stable therapeutic
concentration is achieved
▪ UEC+eGFRevery3–6months
▪ Thyroid function every 6 – 12 months
▪ Serum [calcium] annually (if ↑, measure PTH)
Note: Monitor lithium concentration more frequently during illness (eg gastroenteritis), manic or depressive phases, changes in diet or temperature, pregnancy and concomitant medication (eg diuretics)
INTERACTIONS ↓ lithium renal clearance = [serum] ▪ Diuretics ▪ NSAIDs ▪ ACEi or ERBs ▪ Dehydration or intercurrent illness
PRECAUTIONS
▪ Lithium is renally excreted –> ↓ dose in times of renal impairment
▪ Lower dose used in elderly (as they have worse kidney fn)
▪ Hyponatraemia increases the risk of lithium toxicity. Avoid lithium or use it cautiously where sodium levels may decrease (e.g. vomiting, diarrhoea, use of diuretics, dehydration, Addison’s disease).
▪ Psoriasis may be exacerbated or precipitated by lithium.
ADVERSE EFFECTS
L - Leukocytosis
I - Insipidus –> polyuria, polydipsia, decreased GFR, ESKD
T - Tremors + ataxia
H - Hypothyroidism
I - Increased weight
U - Underactive mind (dullness, fatigue, lethargy)
M - Mothers –> teratogenic (esp T1 = Ebstein’s anomaly)
GIT = nausea, vomiting, diarrhoea
ECG = Long QTc, flat T waves, premature beats, conduction delays
PREGNANCY
▪ If possible, avoid use particularly during the first trimester (TERATOGEN)
▪ However, at times keeping Lithium is the best option (as carbamazepine,
valproate and lamotrigine are not suitable alternatives in pregnancy)
▪ More regular monitoring (every month)
▪ Monitor hydration
▪ Essentially a specialist’s job to deal with it + sort shiz out
Lithium toxicity - features, Acute vs. chronic, risk factors, key investigations, management
FEATURES Early ▪ Nausea, vomiting ▪ Tremor ▪ Agitation ▪ Proximal weakness ▪ Poor memory ▪ Flu-like illness
MODERATE ▪ Blurred vision ▪ ↑ diarrhoea, N + V ▪ Muscle weakness ▪ Drowsiness + apathy ▪ Ataxia ▪ Hypotension ▪ ECG changes
SEVERE ▪ Hypertonia ▪ Hyperreflexia ▪ Myoclonic jerks ▪ Coarse tremor ▪ Dysarthria ▪ Disorientation ▪ Psychosis, stupor ▪ Seizures ▪ Severe Hypotension ▪ Coma
ACUTE TOXICITY
- Rapid elimination by the kidneys and slow uptake into the CNS after overdose. Here, serum [ ] DOES NOT correlate to toxicity
CHRONIC TOXICITY
- In patients taking therapeutic doses where there has been a change in dose, addition of other medications or decreased elimination (↓GFR). Here serum [ ] reflect CNS [ ] and they can be used to guide need for dialysis
RISK FACTORS ▪ Impaired kidney function ▪ Dehydration ▪ > 50 years ▪ Drug interactions or med changes ▪ Nephrogenic diabetes insipidus ▪ Thyroid dysfunction
KEY INVESTIGATIONS ▪ ECG ▪ FBC ▪ Serum lithium [ ] ▪ UEC ▪ eGFR
MANAGEMENT
- Acute poisoning require no specific treatment except serial measurement of lithium concentrations to confirm elimination.
- Chronic poisoning has an insidious onset and more often requires treatment with intravenous fluids and occasionally dialysis. Clinical recovery can take days to weeks and is significantly delayed compared with the decrease in serum lithium concentrations. Some neurological effects may be permanent.
(1) Circulation
▪ Sufficient fluid replacement is essential
▪ IV Normal Saline is first line in those with normal renal function
▪ Patient may have DI, this must be taken into consideration when giving IV
fluids (ie larger fluid requirements to replace increased urine output)
(2) Decontamination
▪ Decontamination is not indicated for acute ingestions < 50 g
▪ Activated charcoal does not bind lithium
▪ If ingested >50g, whole bowel irrigation can be considered if given within the first 6 hours and the patient is awake and cooperative
(3) Enhance elimination
▪ Should be discussed with a clinical toxicologist
▪ Haemodialysis increases the clearance of lithium, but is rarely required in
patients with normal kidney function.
▪ Dialysis should be continued until lithium concentrations are below 1 mmol/L
and further concentrations should be measured to detect rebound
(4) Monitor lithium levels
- Every 2 - 4 hours
LAMOTRIGINE - MOA, Indication, patient education, monitoring, adverse effects
(MOOD STABILISER)
MOA
Stabilises presynaptic neuronal membranes by blocking voltage-dependent and use- dependent sodium channels and inhibiting glutamate release.
INDICATIONS
- Epilepsy, bipolar mood stabilisation
PATIENT EDUCATION
▪ Tablets may be swallowed whole, chewed or dispersed in water.
▪ This medicine may cause drowsiness, dizziness or blurred vision; if affected, do not drive
or operate machinery.
▪ Lamotrigine may also increase the effects of alcohol.
▪ Tell your doctor immediately if you develop a rash, fever or swollen glands.
▪ Stop treatment immediately if skin reaction or signs of hypersensitivity occur (with or
without rash)
MONITORING Before starting ▪ FBC ▪ UEC + eGFR ▪ LFT Ongoing Monitoring ▪ FBC every 3 – 6 months
ADVERSE EFFECTS Common - diplopia, blurred vision - dizziness - ataxia - headache - somnolence - hyperkinesia - maculopapular rash
Uncommon
- Alopecia
- Severe skin reaction (TEN, SJS)
- Multiorgan hypersensitivity syndrome
- Aseptic meningitis
- Low NE, low platelets
Extra notes
- Hepatically excreted –> avoid use in hepatic impairment
- Teratogenic = patient must be on contraception
SODIUM VALPROATE - MOA, DOSE, INDICATION, PATIENT EDUCATION, MONITORING, ADVERSE EFFECTS
(MOOD STABILISERS)
MOA
- Multiple mechanisms. Prevents repetitive neuronal discharge by blocking voltage‐ and use-dependent sodium channels. Other actions include enhancement of GABA, inhibition of glutamate and blockade of T-type calcium channels.
DOSE
- 200 to 400 mg PO, BD. The dose should be ↑ weekly in increments of 200 to 400 mg/day and the serum concentration determined after 3 days of steady-dose treatment.
- Most patients require a daily dose of 1500 to 3000 mg (1.5g – 3g)
INDICATIONS
- epilepsy, bipolar mood stabilisation, resistant migraines
PATIENT EDUCATION
▪ Take with food to reduce stomach upset. Do not crush or chew tablets.
▪ Valproate may make you feel drowsy; if affected, do not drive or operate
machinery. Valproate may also increase effects of alcohol.
▪ Your appetite may increase when taking this medicine and you may need to pay more attention to your diet to avoid weight gain.
▪ Tell your doctor immediately if symptoms such as fever, rash, abdominal pain,
vomiting, jaundice, bruising or bleeding develop.
▪ Do not stop taking this medicine suddenly unless your doctor tells you to.
MONITORING Before starting ▪ FBC ▪ UEC + eGFR ▪ LFT Ongoing Monitoring ▪ FBC every 3 – 6 months
ADVERSE V - V A - Appetite increase = wt gain L - Liver toxicity P - Pancreatitis R - Reversible hair loss O - Oedema A - Ataxia, tremor T - Teratogen (NTD, congenital anomalies) E - Encephalopathy (from increased ammonia)
NOTE
Valproate reduces BMD and may increase fracture risk; consider BMD monitoring during long-term treatment and ensure vitamin D status and calcium intake are adequate
Valproate OD - Dose required to overdose, Features and management
Dose require to OD
< 400mg/kg=little to no effect >400mg/kg = severe toxicity >1g/kg= life threatening
FEATURES
GIT = nausea, vomit, abdo pain
CNS = drowsy, ataxia, cerebral oedema, seizures, coma
CV = long QTc, ↓ BP, ↑ HR
MET = ↑Na, acidosis, ↑ LDH, ↓ Ca, ↓ BGL, ↑ ammonia
FBC =↓plt, ↓ Ne
MANAGEMENT
Measure = ECG, [valproate], BGL, UEC, FBC
Airway = severe may need support
Circulation = IV saline resus, if severe give IV adrenaline Decontamination = activated charcoal within 2h
Haemodialysis at specialist’s discretion
CARBMAZEPINE - MOA, INDICATIONS, PRECAUTIONS, PATIENT EDUCATION, MONITORING, ADVERSE EFFECTS
(MOOD STABILISER)
MOA
- Prevents repetitive neuronal discharges by blocking voltage-dependent and use- dependent sodium channels.
INDICATIONS
Epilepsy, Bipolar mood stabilisation, trigeminal neuralgia
PRECAUTIONS
- Do not use in BM suppression, with clozapine or hypersensitivity history, hepatic ally excreted avoid use in hepatic impairment, teratogenic all female patients must be on contraception
PATIENT EDUCATION
▪ Take with food to help prevent stomach upset. Do not chew or crush tablets
▪ May cause drowsiness, dizziness or blurred vision especially at the start of treatment or when
the dose is increased; if affected, do not drive or operate machinery.
▪ May increase the effects of alcohol.
▪ Interacts with grapefruit juice and many other drugs; avoid grapefruit juice and tell your doctor
and pharmacist that you are taking carbamazepine before starting any new medication
▪ Tell your doctor immediately if rash, sore throat, fever, mouth ulcers, bruising or bleeding occur.
▪ Do not stop taking this medicine suddenly unless your doctor tells you to.
MONITORING Before starting - FBC - UEC + eGFR - LFT Ongoing Monitoring - FBC every 3 - 6 months (BM suppression) - Monitor skin reactions - Consider BMD monitoring and vitamin D and calcium supplements
ADVERSE C - Confusion A -Ataxia R - Rash/ SJS / TEN T - Teratogen (contraception!!)
D - Dizzy D - Diplopia, blurred vision D - Drowsy H - Hypernatremia H - H reduced WCC H - Hepatotoxic
Anticonvulsant Hypersensitivity Syndrome - Onset, symptoms, management
ONSET
- 1 – 4 weeks after starting therapy
SYMPTOMS
- fever, rash and systemic organ involvement (lymphadenopathy, hepatitis,
myositis, myocarditis, pneumonitis)
- skin involvement (rash, SJS, TEN)
- may affect the liver, kidneys and lungs and can lead to hepatic or renal failure
MANAGEMENT
- Stop offending drug, resus, rehydration, analgesia, burns
dressings, corticosteroids, ABx if infection suspected, consider plasma exchange
SSRIs - Examples, MOA, clinical pearls, side effects, risks
Examples - fluoxetine, citalopram, Escitalopram, Fluvoxamine Paroxetine Sertraline
MOA
- selectively inhibit the presynaptic serotonin reuptake transporter –> ↑ 5HT in synapse↑ 5HT transmission in the brain
- ↑ stimulation of 5HT receptors ↑ BDNF (↑gene transcription) BDNF increases neurogenesis in hippocampus and increases development of dendritic processes –> neuroplasticity too!
Clinical Pearls
- First Line + effective
- Well tolerated in most people
- Safe in OD
- Can be used in pregnancy and breastfeeding (? Some PTL)
- taken in the morning to minimise insomnia
- Caution of increased suicidal thoughts and behaviour can occur soon after starting
SE/RISKS
- COMMON = nausea, diarrhoea, insomnia, drowsy, tremor, dry mouth, dizzy, sexual dysfunction, myalgia, rash
- UNCOMMON = EPS, sedation, confusion, palpitations, ↓BP, ↑ bleeding re: ↓ plt function
- SERIOUS = hepatitis, ↑ prolactin, akathisia, acute glaucoma
- GI bleeding (caution if >80y, past UGI bleed or on NSAIDs) – by blocking 5HT uptake into platelets
- Hyponatremia (esp in elderly)
- Monotherapy in BPAD can precipitate mania
- ↓ Dose in hepatic impairment
- Serotonin syndrome (when combined with SNRI or MAOI) + QTc prolongation o Discontinuation syndrome (when stopping SSRI treatment taper over several weeks)
SNRI - Examples, MOA, Clinical pearls, SE/ RISKS
EXAMPLES
- Duloxetine Venlafaxine Desvenlafaxine
MOA
- Inhibit serotonin and noradrenaline reuptake.
- As they lack major receptor blocking actionsfewer side effects than TCAs
Clinical Pearls
- Check BP before starting treatment, and then check regularly
- Do UECs for [Na] at baseline, and then soon after starting treatment
- Caution of increased suicidal thoughts and behaviour can occur soon after starting
- You must taper dose if stopping
SE/ RISKS
- COMMON = nausea, dry mouth, constipation, yawning, sweating, dizziness, increased BP, sexual dysfunction
- UNCOMMON = orthostatic hypotension and fainting, palpitations, ↑HR o SERIOUS = seizures, akathisia, ↑ prolactin
- GI bleeding (caution if >80y, past UGI bleed or on NSAIDs)
- Hyponatremia (esp in elderly)
- Monotherapy in BPAD can precipitate mania
