Clin Pharm Flashcards
What causes serotonin syndrome
- Life-threatening condition caused by serotonergic overactivity
Cause Psychiatric drugs -MAOI: moclobemide, procarbazine - TCAs: amitriptyline, nortriptyline - SSRI: fluoxetine, sertraline, paroxetine, citaopram, escitalopram - SNRI: venlafaxine, duloxetine - Stimulants: amphetamines, MDMA - Serotonin antagonist: ondansetron - Herbal products: St john's warts - Triptans - Opioids: buprenoprhine, methadone, tramadol - Anticonvulsants: carbamazepine, valproic acid
Clinical features of serotonin syndrome
Classic triad: neuromuscular excitability, autonomic dysfunction, altered mental state
- General: diaphoresis, hyperthermia
- Cardiovascular: HTN, tachycardia
- GIT: nausea, vomiting, diarrhoea
- Psych: delirium, psychomotor agitation, anxiety
- Neurological: hypertonia especially LL extremities, hyperreflexia, myoclonus, tremor, ataxia, mydriasis, seizure, coma
HARM: hyperthermia, autonomic dysfunction, raised blood pressure, myoclonus
Treatment of serotonin syndrome
-Discontinuation of serotonergic drugs
-Supportive Care:
Cooling measures: ice packs, cold compress
Antihypertensives, fluid replacement
Benzodiazepines for sedation
Cyprohepatidine
- Serotonin antagonist
-Used for serotonin syndrome that do not respond to supportive care
-For patients with severe hypertension and tachycardia, treatment with short-acting agents, such as esmolol and nitroprusside
-For hypotension from monoamine oxidase inhibitors (MAOIs), low doses of direct-acting sympathomimetic amines such as phenylephrine, epinephrine, or norepinephrine
A 27 year old man was previously treated with clozepine, however has not taken his medication for two weeks. The primary reason to restart his clozepine at a low dose a titrate up to his original dose is to prevent: A. Myocarditis B. Myelosuppresion C. Postural hypotension D. Acute Psychosis E. Neuroleptic Malignant Syndrome F. Serotonin Syndrome.
he correct answer is C. Postural hypotension:
When treatment with clozapine is interrupted for >48 hours, it must be recommenced from a starting dose and then up-titrated as per protocol. This is because tolerance to its side effects is rapidly lost once the drug is stopped. Orthostatic hypotension is a common adverse effect which occurs early due to interference with the autonomic nervous system, is dose-dependent but tends to improve with time. It is generally the rate-limiting symptom when up-titrating clozapine.
•Clozapine-induced agranulocytosis is a potentially life-threatening side effect of clozapine. It is, however, not an immediate risk when starting or recommencing treatment – peak risk is at 6-18 weeks from time of initiation. Even patients established on a maintenance dose need to be monitored for agranulocytosis – it is not a side effect specifically associated with initiation
•Myocarditis develops at a median of 16 days from time of initiation. It is thought to be the result of a type I IgE-mediated acute hypersensitivity reaction. It is therefore less likely to occur in someone who was already previously safely being treated with clozapine (although still requires monitoring)
•Clozapine increases risk of seizure in those with seizure disorders. There is nothing to suggest this man has any such history.
o Well control seizures before starting clozapine
•Clozapine is less likely than most other antipsychotics to precipitate NMS due to its weak affinity for the dopamine receptor – it is therefore not a common complication
oUse bromacriptine: no evidence for it
Indications for clozapine
Indications include:
- Lack of satisfactory clinical response despite use of adequate doses of drugs from at least two groups of anti-psychotics for a reasonable duration (4-6 weeks)
- Persistent or frequently recurrent suicidal ideation.
- Marked aggression.
- Severe comorbid substance abuse.
SE of clozapine
Unique side effects include agranulocytosis (1%), neutropenia (2-3%), myocarditis and cardiomyopathy.
Monoamine oxidase inhibitors
- MOA
- Medications
- SE
MOA
- Nonselective inhibition of monoamine oxidase –> decrease breakdown of adrenaline, noradrenaline, serotonin, dopamine
Medications: selegiline, phenelzine
SE
- CNS stimulation
- Orthostatic hypotension
- Sexual dysfunction
- Weight gain
HYPERTENSIVE CRISIS: with ingestion of food containing tyramine (eg: aged cheese, beer, cured meats, fava beans
- Tyramine stimulates the sympathetic system to release other neurotransmitters such as noradrenaline
SSRI
- Drugs
- MOA
- SE
Drugs: fluoxetine, sertraline, citalopram, escitalopram
MOA: inhibition of serotonin reuptake in synaptic cleft –> increased serotonin levels
SE - SSRI
- Serotonin syndrome
- SIADH
- Stimulation of CNS - agitation
- Reproduction dysfunction - decreased libido, erectile dysfunction
- Insomnia
SNRI
- Drugs
- MOA
- SE
Drugs: venlafaxine, duloxetine
MOA: inhibition of serotonin and noradrenaline reuptake in synaptic cleft
SE
- Anxiolytic (stimulant) effect
- HTN
- Insomnia
- Can increase cholesterol and triglycerides
Mirtazapine
- MOA
- SE
MOA
- Selective a2-adrenergic antagonist - increase serotonin and noradrenaline release
SE
- Increase appetite and weight gain
- Sedation due to H1 antagonism
- Increase cholesterol + triglyceride
- Dry mouth
Varenicline
MOA
SE
MOA: nicotinic Ach receptor partial agonist
Stimulates dopamine activity - decreases nicotine cravings and withdrawal
SE
- Seizures
- Sleep disturbances
- Mood disturbances
Varenicline makes you very clean from nicotine
Compare serotonin syndrome to neuroleptic malignant syndrome
Serotonin Syndrome
- Anti depressants - SSRIs, MAOi
- Abrupt, faster onset (hours)
- Hyperthermia, autonomic dysfunction, hypertension, myoclonus
- Hyperreflexia
- Mydriasis
- Tx: benzodiazepines, cyproheptadine
Neuroleptic Malignant Syndrome
- Antipsychotics
- Gradual onset
- Diffuse rigidity
- Hyporeflexia
- Normal pupils
- Tx: bromocriptine (dopamine agonist), dantrolene
What contributes to the plasma clearance of a drug?
Hepatic and renal elimination both contribute to clearance
Omeprazole can reduce the absorption of which of the following drugs? A. Digoxin B. Nifedipine C. Warfarin D. Capecitabine
Capecitabine
Digoxin and nifedipine absorption is increased by omeprazole.
Warfarin absorption isn’t altered but the clearance is reduced.
Capecitabine efficacy is reduced by PPIs in a number of gastrointestinal malignancies. Note that the formal studies of the PPIs shows variation between PPIs in these effects but as a general rule it is considered that the reduced stomach acid is the culprit.
