Adverse Drug Reactions Flashcards
Define tolerance
The need to use increased doses of a drug to maintain a clinical effect.
What can lead to tolerance of a drug?
Down-regulation
Up-regulation
Reduced responsitivity without alterations in receptor numbers
What is down-regulation?
Decreased sensitivity of target receptors due to decreased numbers due to agonists
What is up-regulation?
Increase in numbers of receptors due to antagonists
What is cross-tolerance?
When drugs with similar pharmacological actions can lead to tolerance of the other drug
What is reverse tolerance?
When sensitivity to a drug effect increases over time.
Give an e.g. of downregulation which leads to a therapeutic effect.
When SSRIs are used, the 5HT1A autoreceptors in somatodendritic zones undergo down-regulation secondary to increased serotonin availability when reuptake is blocked; this leads to increase in serotonergic tone of neurons.
Define withdrawl
When drugs are administered for reasonable period of time, physiological adaptation develops which on withdrawl of drug can get disturbed and leads to withdrawl symptoms.
What type of drug leads to withdrawl symptoms?
Abrupt withdrawl of treatment for an agent with short eliminatino half-life
Which has longer half-life; methadone or heroin?
Methadone
Why does methadone lead to less withdrawl than heroin?
Methadone has a longer half-life
Why does Paroxetine lead to withdrawl?
It has anticholinergic properties; withdrawl causes rebound symptoms
Paroxetine inhibitis its own metabolism via CYP2D6, so withdrawl leads to loss of inhibition, excessive paroxetine breakdown, sudden steep drop in levels and then withdrawl symptoms.
Why does Fluoxetine produce fewer withdrawl symptoms?
Its active metabolite, norfluoxetine, has a long half-life
What is the advice of benzodiazepine reducing regime?
10% dose reduction every 2 weeks.
Why must you wait 72 hours before prescribing naltrexone for an opioid detoxified patient?
Prescribing an antagonist can precipitate withdrawl symptoms.
Which cause more withdrawl; full or partial agonists?
Full
What kinetics do sustained release formulations affect?
Absorption kinetics
Do depot or oral preparations have more withdrawl potential?
Oral
Does XL or plan preparation of a drug lead to more withdrawl symptoms?
Neither; both same
Which receptors cause side effect of agitation?
Alpha 2 blockade
5HT2A/2C stimulation
DRI
Which receptors cause side effect of akathisia?
D2 blockade
5HT2A stimulation
Which receptors cause side effect of delirium?
Antimuscarinic
Which receptors cause side effect of EPSE?
D2 blockade reduces with 5HT2A antagonism
Which receptors cause side effect of hyperthermia?
Antimuscarinic action
In serotonin syndrome may be due to 5HT2A/2C.
Which receptors cause side effect of insomnia?
Alpha 1 stimulation
5HT2A stimulation
Which receptors cause side effect of amnesia?
Anticholinergic effect
GABAa stimulation
Which receptors cause side effect of hyperprolactinaemia?
D2 blockade
5HT1A stimulation
Which receptors cause side effect of disrupted slow wave sleep?
Slow wave sleep is maintained by 5HT2A inhibition; hence 5HT2A stimulation disrupts this.
Which receptors cause side effect of sweating?
Cholinergic effect
Increases with noradrenaline reuptake inhibition
Which receptors cause side effect of postural hypotension?
Alpha 1 antagonism
Which receptors cause side effect of appetite loss?
5HT2A stimulation
Which receptors cause side effect of increased appetite?
Antihistamine
Which receptors cause side effect of GI discomfort/nausea?
5HT3 stimulation
Which receptors cause side effect of weight gain?
Antihistamine
5HT2C antagonism
Symptoms of anticholinergic effects?
Blurred vision Delirium Constipation Tachycardia Dry secretions Decreased sweating Urinary retention Hyperthermia
What conditions do anticholinergics increase risk of?
Narrow-angle glaucoma
Photophobia due to mydriasis
Which receptors cause side effect of anorgasmia?
Alpha 1 antagonism
5HT2A/C stimulation
Which receptors cause side effect of retrograde ejaculation?
Alpha 1 block
Anticholinergic
Antihistamine
Which receptors cause side effect of tardive dyskinesia?
Supersensitivity of dopamine receptors which develops due to prolonged therapy with dopamine blocking drugs
Which receptors cause side effect of impotence?
Alpha 2 blockade
5HT2A/C stimulation
Which receptors cause side effect of priapism?
Alpha 1 blockade
Which receptors cause side effect of obsessions?
5HT1D stimuation
Which receptors cause reduced OCD?
5HT1A/2A
Which receptors cause side effect of pathological gambling?
Habituation of dopamine receptors on repeated use of dopamine agonists, leading to dopamine dysregulation syndrome
Which drugs cause insulin resistance?
Valproate
Olanzapine
Which polymorphism leads to weight gain?
Drugs with strong 5HT2C affinity used on patients with specific variant of polymorphism of 5HT2C receptor promotor regions
What types of antipsychotics cause weight gain more than others?
Low-potency produce more weight gain than high potency.
Give examples of EPSE
Acute dystonia Akathisia Parkinsonism Tarde dyskinesia Dystonia Perioral tremor
Which type of antipsychotics lead to EPSEs?
High potency
Which EPSEs are due to late SEs and chronic use of antipsychotics?
Tardive dyskinesia
Dystonia
Perioral tremor
What causes hyperprolactinaemia?
Blocking of D2 receptors on anterior pituitary mammotrophic cells that normally are tonically inhibited by dopamine produced in hypothalamic arcuate nucleus.
Which antipsychotics induce Parkinsonism?
Trifluoperazine Chlorpromazine Raclopride Haloperidol Fluphenazine Risperidone
Why do some antipsychotics cause Parkinsonism?
They bind more tightly than the endogenous ligand dopamine to D2
Which drugs are less likely to cause Parkinsonism and why?
Anticholinergics
Quetiapine
Clozapine
Bind more loosely to D2 than dopamine
Difference between tightly bound and loosely bound antipsychotic drugs
Loosely bound:
Weaker potency, so need higher doses to be clinically effective but can be titrated faster.
Less chance of EPSEs
Which type of antipsychotics are more likely to lead to relapse?
Loosely bound antipsychotics as may dissociate from D2 receptor rapidly
When is drug-induced Parkinsonism seen?
Within 90 days of treatment
Which characteristic of Parkinsons is not seen in its drug-induced form?
Pill-rolling tremor
Coarse tremor seen instead
Who are at high risk of Parkinsonism from antipsychotics?
Elderly
Female
At what D2 receptor occupancy by antipsychotics leads to EPSE?
Higher than 80%
Why are atypical antipsychotics thought to have a lower chance of causing EPSEs?
Anticholinergic
HT2A antagonism
Less avidity of bindng i.e. hit and run profile (clozapine, quetiapine)
What can you use to treat drug-induced Parkinsonism?
Anticholinergics for up to 6 weeks
Why must anticholinergics used to treat drug-induced Parkinsonism be withdrawn after 4-6 weeks?
Tolerance can develop for EPSEs
Longer use of anticholinergics increases risk of Tardive Dyskinesia
What are dystonias?
Brief or prolonged contractions of specific groups of muscles
Give e.g. of dystonias
Oculogyric crises Tongue protrusion Trismus Torticolis Blepharospasm
When in the course of treatment do dystonias occur?
Early
Who is more likely to get dystonias?
Young men starting high-dose of high potency medications, especially IM.
What can be used to treat dystonias?
Reassurance
Anticholinergics
What causes akathisia?
Higher D2 occupancy in striatum
Symptoms of Akathisia?
Inability to relax
Pacing
Rocking with alternation of sitting and standing
What drugs can cause akathisia?
Neuroleptics
Antidepressants
Sympathomimetics
Treatment for Akathisia?
Dose reduction
Changing drug
Adding beta blocker/anticholinergic drug/benzo/cryoheptadine
Risk factors for Tardive Dyskinesia
Female
Elderly
Diabetes
Previous brain damage
Affective illness rather than pure psychosis
Children
Learning difficulties
Afro-carribean
Long-term co-precription of anticholinergics
Frequent drug holidays - will lead to high dose prescription with each relapse
When does tardive dyskinesia occur?
At least 6 months, often 1-2 years of treatment.
What is tardive dyskinesia?
Abnormal, involuntary, irregular choreaoathetotic movements of muscles of head, limbs and trunk.
Most common type of tardive dyskinesia?
Perioral movements
What exacerbates Tardive dyskinesia?
Stress
Absent on sleep
What is particularly striking in Tardive Dyskinesia patients?
Absence of insight
Treatment of Tardive Dyskinesia?
Spontaneously resolve - unlikely in elderly. Clozapine Dose reduction Withdrawl of drug Switch to atypicals Add clonazepam
When can neuroleptic malignant syndrome occur?
Anytime during treatment
Symptoms of NMS?
Extreme hyperthermia Severe muscular rigidity Confusion Autonomic fluctuations (BP, HR) Akinetic/mute
Blood test values of NMS
High WCC, CK, LFTs, plasma myoglobin
Myoglobinuria
Onset of NMS?
24-72 hours
How long does NMS last if untreated?
10-14 days
When is NMS more common?
Young men
After agitation
Using high potency drugs, especially rapid tranq
Dopaminergic drugs on withdrawl
Mechanism underlying NMS?
Dopamine blockade or hypothalamic sympathetic dysregulation
Mortality rate of NMS?
20-30% if untreated
Higher if depot used
Management of NMS?
Fluid replacement & prevent renal failure secondary to myoglobinuria
Prevent aspiration pneumonia
Stop antipsychotic
Which drugs can be used to treat NMS?
Dantrolene
Bromocriptine
Amantadine
What antipsychotics need to be considered after NMS occurs?
Low potency or atypical
How many patients on clozapine develop agrunulocytosis?
1 in 100
When is risk of agrunulocytosis at maximum on clozapine?
Between 4-18 weeks
Main SE of clozapine related to dose?
Salivation Sedation Weight gain Fatigue Lowering of seizure threshold
Which SE of clozapine are not dose realted?
Arganulocytosis
Myocarditis
What happens if yellow result occurs on someone on clozapine?
Monitoring frequency must increase until green signal obtained
Which drug may precipitate clozapine-associated neutropenia?
Paroxetine
Effect of increased dopaminergic transmission on sexual function?
Enhances sexual arousal
Penile erection
Effect of hyperprolactinaemia on women?
Amenorrhoea
Reduced sexual desire
Hirsutism
How do antipsychotics lead to reduced sexual function?
Reduce dopamine transmission
Inducing hyperprolactinaemia
Which drugs cause ejaculatory problems?
Neuroleptics
Which drugs are linked to priapism?
Risperidone Chlorpromazine Clozapine Olanzapine Thioridazine Trazodone
Is priapism drug-dependent or duration-dependent?
Neither
What can priapism lead to if untreated?
Permanent impotance
What is used to treat sexual dysfunction in men due to hyperprolactinaemia?
Bromocriptine
How does Bromocriptine work?
Dopamine agonist
What drugs lower seizure threshold?
Low potency antipsychotics
Dose-dependent
Which antipsyshotic is the most sedating?
Chlorpromazine - due to H1 antihistamine
Which drugs are more likely to cause anticholinergic syndrome; high or low potency drugs?
Low
Impact of neuroleptics on cardiac function?
Reduce cardiac contractility
Increase circulating catecholamines
Prolong atrial and ventricular conduction time
Which drugs are more cardio-toxiac; low or high potency?
Low potency
ECG changes with neuroleptics?
QT and PR prolongation
Blunting of T waves
ST depression
Which psychiatric medications can cause Torsades de Pointes?
Thioridazine
Droperidol
What leads to antipsychotic related sudden death?
Cardiac arrhythmias
Seizures
Asphyixation
Malignant hyperthermia
Which types of drugs cause postual drop?
Low potency drugs
Skin side effects on antipsychotics?
Allergic dermatitis and photosensitivity on low-potency drugs.
What is the skin SE of Chlorpromazine?
Blue-gray discoloration in areas exposed to light - reversible.
Which eye condition is a known SE of Thioridazone?
Irreversible retinal pigmentation if used >1000mg a day
Early symptom: nocturnal confusion due to difficulty with night vision.
Effect of Chlorpromazine on eyesight?
Pigmentation of anterior lens and posterior cornea; white-brown stellate granular deposits.
Benign.
Which antipsychotic can lead to cholestatic jaundice?
Chlorpromazine
When does drug-induced obstructive jaundice occur?
First month of treatment
What is associated with drug-induced jaundice?
Rash
Eosinophilia
Treatment for drug-induced jaundice?
Immediately stop antipsychotic
Avoid rechallenge
Signs of Haloperidol OD on EEG?
Diffuse slowing and low voltage
Which typical antipsychotic is safest in an OD?q
Haloperidol isone
What mediates QTc?
Blockade of rapid component of delayed rectifier potassium current responsible for repolarisation of cardiac Purkinje cells and myocardial cells.
How do drugs cause prolonged QTc?
Bind to delayed rectifier K+ channgel and thereby decrease outward movement of K+
Which antipsychotics have greater risk of causing prolonged QTc?
Droperidol
Pimozide
Sertindole
Thioridazine
What are the symptoms of inadvertent intravascular injection event/postinjection delirium sedation syndrome?
Sedation Confusion Dizziness Dysarthria Somnolence
When does inadvertent intravascular injection event/postinjection delirium sedation syndrome occur?
20min - 3 hours after injection of olanzapine pamoate (long-acting depot)
Treatment for inadvertent intravascular injection event/postinjection delirium sedation syndrome?
Supportive medical care; symptoms alleviate within 3-72 hours
What is inadvertent intravascular injection event/postinjection delirium sedation syndrome linked to?
Accidental punctures of vessel or injects into capillary bed leaking
What is Metabolic syndrome composed of?
Obesity Dyslipidaemia Glucose intolerance Insulin resistance HTN
WHO criteria for metabolic syndrome
Insulin resistance and /or impaired fasting glucose and/or impaired glucose tolerance and two or more of the following:
Waist-hip ratio >0.9 (mean), >0.85 (women) or BMI 30
Triglyceride level 1.7 or high-density lipoprotein M0.9 (men) or <1 (women)
BP 140/90 or treated HTN
Microalbuminuria
Prevalence of Diabetes on schizophrenics?
Twice as prevalent than in general population
Drugs that are most linked with metabolic syndrome/
Olanzapine Clozapine Quetiapine Risperidone Aripiprazole (worst at top)
Which gender have higher risk of metabolic syndrome if schizophrenic?
Females
What type of study was the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)?
Double-blind pragmatic RCT
What drugs were looked at in CATIE?
Olanzapine Quetiapine Risperidone Ziprasidone Perphenazine
Which antipsychotic has lowest discontinuation rate?
Olanzapine
What type of study was CUtLASS (Cost utility of latest antipsychotic drugs in schizophrenia study)?
Unblinded RCT comparing first-generation and second-generation antipsychotics
Which 2nd-generation antipsychotics were used in CUtLASS?
Amsulpride Olanzapine Quetiapine Risperidone Clozapine (in second phase)
Outcome of CUtLASS?
Those on 1st generation antipsychotics did relatively better.
Advantage of clozapine in symptom improvement over 1 year and patients preferred it.
Long-term SE of Lithium
Hypothyroidism
Irreversible nephrogenic diabetes insipidus
Reduced GFR (chronic kidney disease)
Hyperparathyroidism
Which diuretic has no effect on Lithium levels?
Loop diuretics
What score is used to assess severity of Lithium toxicity
AMDISEN 0 - no signs 1 - mild 2 - moderate 3 - severe
Which antipsychotic is best to treat negative symptoms?
Amisulpride
Which SSRIs cause prolonged QTc?
Citalopram
Which TCA is the most selective inhibitor of serotonin?
Clomipramine
Which TCA is the most selective inhibitor of noradrenaline?
Desipramine
Which TCAs have the least anticholinergic activity?
Amoxapine
Nortriptyline
Desipramine
Maprotiline
Which TCAs have the most antihistaminic activity?
Doxepin
Which TCA is associated with weight gain
Amitriptyline
Cardiac SE of TCAs?
QT prolongation
Tachycardia
Flattened T waves
Depressed ST segment
Effect of TCAs on overdose?
Cardiac arrhythmias
Anticholinergic delirium
May occur 3-4 days after due to long half-life
Treatment for TCA overdose?
Lavage
QRS monitoring
No antidose
Symptoms of anticholinergic delirium?
Confusion Visual hallucinations Hyperpyrexia Loss of visual accommodation Peripheral vasodilatation Drying of mucous membranes
Which TCA can cause hyperprolactinaemia?
Amoxapine
SEs of all TCAs?
SIADH Hyponatraemia Fine rapid tremor Dysarthria Precipitate angle closure glaucoma
What happens if TCAs are reduced too quickly?
Cholinergic rebound
What is the best way to reduce TCAs?
Reduce 25-50mg per 2-3 days
When can discontinuation reaction occur with TCAs?
48 hours - 2 weeks after
Mechanism of serotonin syndrome
Excessive serotonergic transmission in brain. Most CNS symptoms due to 5HT 2A stimulation
Features of serotonin syndrome
Diarrhoea Myoclonus Diaphoresis Hyperactive reflexes Ataxia Hypomania/labile mood Disorientation
Which drugs are high risk of serotonin syndrome?
Combination of SSRI with MAOI/RIMA/Serotonergic TCAs/SNRI/Lithium/L-tryptophan
Combination of TCA and MAOI
Combining any of the above with Tramadol, pethidine, meperidine
Oxazolidionine antibacterial linezoloid
Tetrabenazine
Entacapone
Selegiline
What is oxazolidinone antibacterial linezolid?
Reversible non-selective MAOI
What is Tetrabenazine?
Acts via dopamine and serotonin depletion at nerve endings
What is entacapone?
COMT inhibitor
Treatment of serotonin syndrome?
Stop agent
Correct vital signs
Benzos
5HT2A antagonists
Name some 5HT2A antagonists that can be used in the treatment of serotonin syndrome
Cyproheptadine
Atypical antipsychotics
Chlorpromazine
Why do SSRIs cause anorexia when starting, then weight gain late during therapy?
Desensitization and down-regulation of receptors.
What is fluoxetine associated with in particular?
Change in duration of menstrual period
Effect of SSRIs on platelets?
Thrombasthenia - functional impairment of platelet aggregation
Impact of Thrombasthenia?
Easy bruising
Prolonged bleeding
(in those with gastric ulcers or bleeding diathesis)
In which patients is SIADH more likely who are on SSRIs?
Alcoholics
Elderly
SEs of SSRIs
Nausea Diarrhoea Anorexia (initially) Thrombasthenia SIADH Severe sweating Nocturnal myoclonus Restless legs Acute angle-closure glaucoma
Treatment for severe sweating from SSRI?
Terazosin
What is nocturnal myoclonus?
Repetitive leg movement every 2-60 seconds; extension of large toe and flexion of angle, knee and hips.
Treatment of nocturnal myoclonus?
Benzo
Levodopa
Treatment for restless legs
Ropinirole
Benzo
Levodopa
Which SSRIs/SNRIs cause acute angle closure glaucoma?
Duloxetine Venlafaxine Citalopram Fluoxetine Paroxetine
Which SSRIs are associated with SSRI discontinuation syndrome?
Paroxetine - additional cholinergic rebound
Fluvoxamine - short half-life
When does SSRI discontinuation syndrome occur?
If someone is on SSRI for 4-6 weeks at least, and it is stopped abruptly.
Which SSRI is least likely to cause discontinuation syndrome?
Fluoxetine - long half-life
Symptoms of SSRI discontinuation syndrome
2 or more of the following within 1-7 days of SSRI reduced/stopped after being taken for at least 1 mnoth: dizziness lightheadedness Paresthesias Diarrhoea Fatigue Gait instability Headache Insomnia Nausea Tremors Visual Disturbances
What is the link between SSRI and suicide risk?
Only in those up to age 24 if used between 4-16 weeks.
How do SSRIs increase the risk of UGIB?
They inhibit uptake of serotonin into platelets, which is needed for haemostatic response of promoting platelet aggregation.
SSRIs increase gastric acid secretion.
What increases risk of UGIB if on SSRI?
Elderly
NSAIDs
H. Pylori
Which SSRIs are at higher risk of causing UGIB?
Those with high inhibition of serotonin reuptake: Clomipramine Paroxetine Sertraline Fluoxetine
Which SSRIs are at lower risk of causing UGIB?
Those with low inhibition f serotonin reuptake;
Nortriptyline
Doxepin
Trazadone
Which antidepressants are associated with lower risk of sexual dysfunction?
Bupropion Mirtazapine Moclobemide Nefazodone Reboxetine
What drugs reverse sexual dysfunction due t SSRI use?
5HT2 antagonists - cyproheptadine, mirtazapine
5HT1A agonists - buspirone
Bupropion - dopamine reuptake inhibitor
Sildenafil - inhibits phosphodiesterase type 5
Which patients must Sildenafil be avoided in?
Patients with arrhythmias, unstable angina / uncontrolled HTN
In which antidepressant is sweating most common?
Venlafaxine
SEs of Venlafaxine?
Sweating Increase in diastolic BP if >300mg/day Mydriasis Exacerbation of ange closure glaucoma Disctoninuation reaction (short half life)
SEs of Duloxetine?
Similar to Venlafaxine but less likely to affect BP
How to stop Venlafaxine?
Over 2-4 weeks
How to treat priapism?
Intracavernosal injection of an alpha1 agonist
E.g. of alpha1 agonist used in priapism?
Metaraminol
Epinephrine
When is there risk of priapism?
Starting Trazadone (high risk) - early phases of treatment
How does Nefazodone work?
Inhibits CYP3A4
Why is Nefazodone not used as often?
Can cause serious hepatic damage
Who is Trazadone and Nefazodone best for?
Elderly
Those with cardiac illness
SEs of Bupropion
No anticholinergic effects Exacerbates ADHD and Eating Disorders, panic attacks Enhances sexual activity Increases risk of seizures - dose-dependent Dry mouth, tremor, headache Psychotic symptoms Delirium Word-finding difficulties
Why can Bupropion cause psychotic symptoms?
Dopaminergic
Which antidepressants can cause agranulocytosis?
Mirtazapine
Which combinations of Buspirone do you need to be careful with?
Haloperidol - increases conc of haloperidol
MAOI - causes serotonin syndrome
Which drugs increase buspirone plasma conc?
CYP3A4 inhibitors: Erythromycin Itraconazole Nefazodone Grapefruit juice
SEs of Mianserin and Mirtazapine
Drowsiness first few weeks of treatment
Increased weight gain and appetite
Why is Mirtazapine preferred option to treat depression in chemotherapy?
5HT3 blockade - reduced vomiting and nausea
What type of antidepressant is Reboxetine?
NARI
Which patients is Reboxetine good for?
Elderly
Cardiac history
What type of drug is Atomoxetine?
NARI
What illness is Atomoxetine used in?
ADHD
SEs of Reboxetine
Due to noradrenergic effect:
urinary hesitancy in males
What can help with urinary hesitancy SE
Tamsulosin - peripheral alpha1 blocker
Doxazosin
What type of drug is phenelzine?
MAOI
SEs of MAOIs?
Orthostatic hypotension Pedal oedema Insomnia Cheese reaction Serotonergic syndrome - with SSRIs Weight gain Sexual dysfunction
Why is it best to give MAOIs such as Phenelzine and Tranylcypromine at 6pm?
Can have stimulating effects leading to insomnia
Explain the cheese reaction with MAOIs
MAOIs and tyramine rich foods cause cheese reaction.
Tyramine directly and indirectly (via vesicles) causes sympathomimetic actions 20min-1h after food.
Signs of cheese reaction
Nausea Apprehension Chills Sweating Restlessness Hypotension - with occipital headache, palpitations and vomiting Dilated pupils Fever
Severe effect of cheese reaction?
Cerebral haemorrhage
Which MAOIs are safest for severity of hypertensive crisis?
Reversible MAOIs
Which foods must be avoided re tyramine-rich?
Stilton Blue cheese Old cheddar Mozarella Fish Sausage Cured meats Mature poultry Wild game Liqueurs Concentrated yeast extract
How to treat MAOI-induced hypertensive crisis?
Alpha-adrenergic antagonists
Give eg. of alpha-adrenergic antagonists for hypertensive crisis treatment?
Phentolamine
Chlorpromazine
What can help reduce polyuria in Lithium use?
Once daily rather than twice daily dosing
What causes polyuria with Lithium?
Functional antagonism of ADH
What can help control polyuria due to Lithium?
K+ sparing diuretics
What can lead to renal failure from Lithium?
Cumulative lithium use
What renal damage is common with chronic lithium use?
> 10 years:
Interstitial fibrosis
How does Topiramate work?
Weak inhibitor of carbonic anhydrase
Can cause renal stones
What is Oxcarbazepine?
10-keto derivate of CBZ - less enzyme induction
SEs of Oxcarbazepine?
More likely to cause hyponatraemia than CBZ
ECG effects of Lithium?
Similar to low K+:
Flat T waves
Inverted T waves
Which cardiac problem is Lithium CI in and why?
Sick sinus syndrome;
Lithium can depress sinus node activity
Which thyroid problem can Lithium most commonly cause?
Benign hypothyroid state
Who is thyroid deficiency SE of when Lithium is used?
Those with high risk for pre-existing antithyroid antibodies (middle-aged women)
First two years of treatment
Rapid cycling patients
Which TFT dysfunction is seen in 1/3 of chronic Lithium patients, even in absence of symptoms?
High TSH
Explain use of thyroxine in subclinical hypothyroid and mood disorder?
In resistant depression and non-responsive rapid cyclers with bipolar, thyroxine treating hypothyroidism can be beneficial for the mood disorder
Which antimanic drug can increase risk of polycystic ovaries?
10%
Why does valproate cause polycystic ovaries?
Valproate increases ovarian androgen production.
Can lead to weight gain and insulin resistance; risk factors.
In liver, it can increase unbound testosterone.
When is oligomenorrhea likely to occur with valproate?
Within first year of treatment
Which antimanic drugs result in leucocytosis?
Lithium
Carbamazepine - first 3 months of treatment
Which antimanic drugs can lead to thrombocytopenia?
Valproate
Carbamazepine
Which tremor is a sign of toxicity in Lithium use?
Coarse tremor
Which tremor is a SE of lithium use?
fine tremor
SEs of Lamotrigine?
Dizziness Ataxia Headache Sedation Tremor
SEs of Topiramate
Renal stones
Anomia - word finding difficulties
Poor concentration
SEs of Vigabatrin
Visual field defects
What is Vigabatrin used for?
Anti-epileptic
Effect of Valproate on liver?
Induces hepatic enzymes
Elevation in liver transaminases - asymmptomatic
Which antimanic drugs can cause liver failure?
Valproate
Lamotrigine
Topirimate
Carbamazepine
What risk factors lead to liver failure if on antimanic drugs?
Young age
Combination therapy
What results in liver failure from antimanic drugs?
- Metabolic toxicity - due to 4-en valproate, a metabolite of valproate.
- Hypersensitivity - dose-independent effect is resulting in fulminant failure.
When is severe hepatic disease seen in (with valproate)?
Those with learning disability when undiagnosed urea cycle disorders present (often less than 2 years of age)
Which antimanic drug can cause acute pancreatitis?
Valproate
Can dose-reduction of valproate reduce risk of pancreatitis?
No - this is a hypersensitivity reaction, not dose-dependent
When can hyperammonaemia occur with antimanic drugs?
Carbamazepine
How does Hyperammonaemia present?
Coarse tremor
Treatment for hyperammonaemia?
L-carnitine
Most common teratogenic effect of Lithium?
Ebsteins anomaly of tricuspid valves
Risk of Ebsteins in lithium-exposed foetuses?
1 in 1,000 (20x risk of general population)
Is Lithium more or less teratogenic than valproate and carbamazepine?
Less
Which antimanic drug is excreted into breast milk?
Lithium
Signs of lithium toxicity in infants?
Lethargy
Cyanosis
Sluggish neonatal reflexes
Teratogenic effect of valproate?
Neural tube defects
Risk of neural tube defects in mothers using valproate?
1-4%
What can help reduce teratogenic risk of Valproate?
Folate-vitamin B complex supplementation
Most common teratogenic effect of Valproate?
Learning disability
Low IQ
Effect of Lithium on the skin
Acne
Psoriases
Alopecia - 5-10%
Effect of Valproate on Endocrinology system?
Obesity
Hyperandrogenism
PCOD - hirutism
Which drugs are most likely to cause anticonvulsant hypersensitivity syndrome?
Aromatic compounds: Lamotrigine Carbamazepine Phenytoin Phenobarbitone
Common SE of aromatic compunds?
Rash
Risk factors leading to skin reactions/rash with aromatic compounds?
Rapid initial dose escalation
Concurrent VPA
Age <16 years
What happens if a rash occurs with aromatic compounds?
Stop drug - cannot tell if benign from serious
Which antimanic drug can lead to Steven Johnson syndrome?
Lamotrigine - especially if combined with Valproate
Why do valproate + lamotrigine together increase risk of Steven Johnson Syndrome?
Valproate has enzyme inhibiting effects which increase lamotrigine levels
Initial signs of Steven Johnson syndrome?
Rash
Pharyngitis
Fever
Systemic involvement if drug not stopped
Dose-related effects of Carbamazepine
Visual disturbances GI disturbance Cognitive impairment Vertigo Dizziness
Dose-related effects of Valproate
Hyperammonaemia
Teratogenicity
Sedation
Thrombocytopenia
Idiosyncratic reactions of Carbamazepine
Haematological reactions: agranulocytosis/aplastic anaemia, Steven Johnson, fulminant liver damage, pancreatitis
SIADH - elderly
Idiosyncratic reactions of Valproate
Hepatotoxicity
Pancreatitis
Rash
Acute dermatitis (rare)
Which antimanics cause weight gain?
Valproate - 70%
Carbamazine - 40%
What causes weight gain with valproate?
Impaired beta-oxidation of fatty acids
Which antimanic drug can be used to counteract weight gain caused by psychotropic drugs?
Topiramate
Common SE of cholinesterase inhibitors
Nausea/vomiting
Diarrhoea
Insomnia
Muscle cramps
What type of drug is Tacrine?
Cholinesterase inhibitor
Why is Tacrine no longer used?
Fatal hepatotoxicity
Important SEs of cholinesterase inhibitors due to increased cholinergic stimulation?
UGIB (esp if peptic ulcer/NSAIDS) Bradycardia Exacerbate COPD Urinary retention Increase seizure risk
In which patients is there a higher risk of bradycardia if on cholinesterase inhibitor?
Supraventricular conduction delay
Which types of drugs can cholinesterase inhibitors prolong the risk of?
Succinylcholine-type muscle relaxants
Where is Memantine excreted?
Mainly urine
Is Rivastigmine metabolised by liver?
Rarely
Does Memantine affect liver enzymes?
No
SEs of stimulants used in ADHD
Anxiety Irritability Insomnia Tachycardia Cardiac arrhythmias Dysphoria Decreased appetite - tolerance develops
Less common SE of stimulants used in ADHD?
Self-limited exacerbation of movement disorders (tics, dyskinesias)
Linked to growth suppression
What is Pemoline?
Stimulant used in ADHD
Why is Pemoline no longer used?
Associated with Hepatic failure
Which drug used in ADHD can cause dependence (rare)?
Methylphenidate
SEs of Atomoxetine?
Appetite loss
Sexual dysfunction
Dizziness
Severe liver injury
Signs of Benzo OD?
Slurred speech Incoordination Unsteady gait Nystagmus Impairment in attention + memory Stupor/coma Inappropriate sexual/aggressive behaviour Mood lability
Which benzos cause anterograde amnesia?
High-potency
Why is Triazolam banned in UK since 1991?
Disinhibition and aggression
When can paradoxical disinhibition present with benzo use?
If patients have pre-existing brain damage
Which type of patients can have respiratory impairment from benzo use?
COPD
Sleep apnoea
Which patients should Benzos be avoided in due to risk of respiratory impairment?
Myasthenia Gravis
Head injury
Porphyria
SE of Alprazolam?
Weight gain via appetite stimulation
Teratogenic effects of Benzos?
Cleft palate and lips
When is benzo withdrawl syndrome seen in neonates?
If used in third trimester
SEs of Z-hypnotics?
Diarrhoea
Abdominal pain
Unique SE of eszopiclone?
Unnpleasant taste
What does benzo withdrawl syndrome depend on?
Half-life
Rate of tapering
Dose
Duration
Signs of benzo withdrawl
Anxiety Diaphoresis Kinaesthetic hallucinations Restlessness/irritability Tremor Insomnia Autonomic hyperactivity Weakness
Severe SEs of benzo withdrawl?
Paranoia
Delirium
Grand mal seizures
When does benzo withdrawl syndrome occur with long-acting benzos?
1-2 weeks after long-acting benzos stopped
Which benzos are associated with immediate and severe withdrawl syndrome?
Alprazolam
Lorazepam
At what point are prescribed benzos unlikely to cause withdrawl?
<4 weeks use
Withdrawl rate in benzo use for 6-8 years?
75%
Withdrawl rate in benzo use for 2 years?
25-45%
Withdrawl rate for benzo use in 4 months?
5-10 mnoths
How to taper benzos?
Rate of 25% per week
Use of longer acting agents when tapering
Avoid long-term use of short-acting benzos
Use carbamazepine to assist discontinuation
Psych SEs of beta-blockers
Sedation
Nightmares
Dysphoria
Depression
In which type of beta-blockers are psych SEs seen in?
Lipophilic compounds
e.g. metoprolol, propranolol
Psych SEs of ACE inhibitors
Increased arousal Anxiety Fatigue Insomnia Increased psychomotor activity
Psych SEs of Clonidine
Sedation Anxiety Agitation Depression Insomnia
Psych SEs of nitrates?
Delirium Psychosis Anxiety Restlessness/agitation Hypomanaia
Psych SEs of digoxin?
Depression
Delirium
Psych SEs of statins?
Depression
Psych SEs of corticosteroids?
Mania>depression
Agitation
Lethargy
What makes corticosteroid-induced psych SEs more likely?
Dose-dependent
If >80mg/day
Symptoms start within 2 weeks
More common in females + those with past psych history
Psych SEs of anabolic androgenic steroids?
Acute parnoia Delirium Mania Homicidal rage Aggression Extreme mood swings Increase in libido Agitation Anger
What makes psych SEs more likely with anabolic androgenic steroid use?
Dose-dependent
Psych SEs of GNRH agonists (e.g. leuprolide)?
Depression
Psych SEs of interferon-alpha?
Depression - seen in first 12 weeks
Psych SEs of penicillin?
Sedation
Anxiety
Hallucinations
Psych SEs of cephalosporins?
Delirium
Psych SEs of ciprofloxacin and ofloxacin?
Restlessness Lethargy Tremors Insomnia Mania Depression Psychosis Delirium Seizures Catatonia
Psych SEs of Isoniazid?
Delirium
Mania
Depression
Psychosis
Psych SEs of Tetracyclines?
Depression
Insomnia
Irritability - at high doses
Psych SEs of antihistamines and decongestants?
Atropine-like psychosis
Psych SEs of PPIs & H2 antagonists?
Confusion
Agitation
Depression
Hallucinations
Who are Psych SEs of PPIs and H2 antagonists more common in?
Elderly patients with impaired hepatic-renal function
Psych SEs of Ondansetron?
Anxiety
Psych SEs of Isotretinoin?
Severe depression and suicidal behaviour
Psych SEs of aminophylline and salbutamol?
Agitation
Insomnia
Euphoria
Delirium
Name some depressogenic drugs
Beta blocks Ca channel blocks Interferons (alpha>beta) Steroids Cyproterone, progesterone Varenicline Isotretinoin Ezetimibe
How does Rimonabant work?
CB1 receptor antagonist
What is Rimonabant used for?
Anti-obesity; blockig central cannabinoid activity may reduce food intake
Concerns regarding Rimonabant use?
Severe psychiatric SEs; 2.5x more depression, 3x more anxiety
What do animal studies show about blockade of CB1 receptor?
Impairs anti-depressant reducing and anxiety-reducing actions of endocannabinoids
Name some Class A drugs
Ecstacy LSD Heroin Cocaine Crack Magic mushrooms Merthylamphetamine Other amphteamines if prepared for injection
Penalty for possession of class A drug?
Upto 7 years in prison, unlimited fine or both
Penalty for dealing Class A drug?
Upto lif in prison, unlimited fine or both
Name some Class B drugs
Amphetamines
Methylphenidate
Pholcodine
Penalty for possession of Class B drugs
Upto 5 years in prison or unlimited fine or both
Penalty for dealing of Class B drugs
Upto 14 years in prison or unlimited fine or both
Name some Class C drugs
Cannabis Tranquilisers Some pankillers GHB Ketamine
Penalty for possession of class c drug
Upto 2 years in prison, unlimited fine or both
Penalty for dealing Class C drug
Upto 14 years in prison, unlimited fine or both
Class A, B, C drugs are under which Act?
2001 Misuse of Drugs Act UK
Schedule 1, 2,3, 4 and 5 drugs are under which Act?
2001 Misuse of Drugs Regulations
Examples of Schedule 1 drugs
Coca lef
Cannabis
LSD
Mescaline
Regulations of Schedule 1 drugs?
No medicinal use.
Supply limited to research or other special purposes judged to be in public interest; requires home office license to possess
Give some e.g. of Schedule 2 drugs
Diamorphine Morphine Dipipanone Remifentanil Pethidine Secobarbital Glutethimide Amphetamine Cocaine
Regulations of Schedule 2 drug use?
Subject to special prescription requirements and safe custody requirements - except for secobarbital.
Stock drugs must be recorded in a register.
Regulations and drug stock must only be destroyed in presence of an appropriately authorized person.
Name some examples of Schedule 3 drugs
Barbituates - except secobarbital Buprenorphine Diethylpropion Mazindol Meprobamate Pentazocine Phenter,ine Temazepam
Regulations of Schedule 3 drugs
Subject to special prescription requirements - except for temazepam, but not to safe custody requirements (except for buprenorphine, diethylpropion, flunitrazepam and temazepam) or to keep register.
Requirements for retention of invoices for 2 years.
Give examples of some Schedule 4, Part 1 drugs
Benzos - except temazepam
Zolpidem
Regulations for schedule 4 drugs?
Not subject to special prescription requirements or safe custody requirements.
No need to keep register
requirement for retention of invoices for 2 years
Give examples of Schedule 4, Part 2 drugs
Androgenic and anabolic steroids Clenbuterol HCG Non-human chorionic gonadotrophin Somatotropin Somatrem Somatropin
Name some examples of Schedule 5 drugs
Weak preparations of drugs usually in other schedules - e.g. morphine, codeine
Regulations of Schedule 5 drugs?
Exempt from all controlled drug regulations except the need to keep invoices for at least 2 years
Which drugs cannot be prescribed on repeat prescriptions?
Schedule 2 and 3 drugs
How should patients collect controlled drugs?
In person, show ID on first occasion and sign back of prescription form
Which drugs must be prescribed in daily instalments?
Substitute opioids
What must prescription of instalments specify?
Number of instalments
Interval between instalments
Instructions for supplies at weekends/BH
Total quantity to provide treatment for a period (not exceeding 14 days)
Quantity to be supplied in each instalment along with duration of instalment to be set out on prescription
Purpose of reporting adverse drug reactions?
Reduce hazards of medical prescribing
Trigger regulatory action to ensure patient safety
Should adverse reaction be reported if reaction is well known?
Yes
Should adverse reaction be reported if you are unsure whether the drug caused this reaction?
Yes
Should adverse reaction be reported if it was a result of an overdose?
Yes
Should an adverse reaction be reported if other drugs were given at the same time?
Yes
Who can use the yellow card scheme to report adverse reactions?
Prescribers
Patients
Carers
Pharmacists
What does the black triangle symbol mean?
Preparation is newly licensed and requires additional monitoring by the European Medicines agency
What is the requirement for adverse reaction reporting if there is a black triangle symbol?
MHRA requires all suspected reactions, including those that are not serious, be reported.
For drugs w/o the black triangle symbol, when are you expected to use the yellow card reporting system?
To report SE that are serious, medically significant or result in harm.
Also those reactions that occur due to a medication error
For SEs, what does very common mean?
Greater than 1 in 10
For SEs, what does common mean?
1 in 100 to 1 in 10
For SEs, what does uncommon or less commonly mean?
1 in 1000 to 1 in 100
For SEs, what does rare mean?
1 in 10,000 to 1 in 1000
For SEs, what does very rare mean?
Less than 1 in 10,000
What is the WHO Collaborating Centre for International Drug Monitoring?
International system for monitoring ADRs developed by WHO in 1971
Located in Uppsala Monitoring Centre, Sweden
Which drugs cause EPSEs?
All neuroleptics - less for anticholinergic neuroleptics e.g. CPZ
Higher dose atypicals
Which drugs cause delirium?
Anticholinergic TCAs
Anticholinergic antipsychotics
Which drugs cause seizures?
Bupropion
Clozapine
Which drugs cause tics?
Stimulants
Which drugs cause hepatic damage?
Nefazodone
VPA
Tacrine
Which drugs cause hepatic enzyme induction?
CBZ
Phenytoin
Barbituates
Which drugs cause acute pancreatitis?
VPA
Which drugs cause paralytic ileus?
Clozapine
Which drugs can cause UGIB?
SSRIs
Acetylcholinesterase inhibitors
Which drugs can cause weight gain?
All antipsychotics - less of Aripiprazole, ZPD TCAs Lithium VPA CBZ
Which drugs cause weight loss?
Topiramate
Bupropion
Which drugs cause renal damage?
Lithium
Which drugs cause renal stones?
Topiramate
Which drugs cause Priapism?
Trazadone
Risperidone
Which drugs cause polycystic ovaries?
Valproate
Which drugs cause erectile dysfunction?
All TCAs
Antipsychotics
Which drugs caused anorgasm or delayed ejaculation?
SSRIs
Which drug can lead to a rash?
CBZ
Lamotrigine
Which drug can cause thrombocytopenia?
Valproate
Which drug can cause sweating?
Particularly Venlafaxine
TCAs
SSRIs
Which drug can cause psoriasis and acne?
Lithium
Which drugs cause worsening of glaucoma?
Paroxcetine
Quetiapine
TCAs
Which drug can cause retinitis pigmentosa?
Thioridazine
Which drug can cause hypersalivation?
Clozapine
Most common SE of clozapine?
Hypersalivation
Which drug can cause corneal deposits?
CPZ
Which drug can cause visual field defects?
Vigabatrin
Which drugs can cause bruxism?
Stimulants
Which drugs can cause hypothyroidism?
Lithium
Which drugs can cause PE or myocarditis?
Clozapine
Which drugs can cause prolonged QT?
All antipsychotics - especially thioridazine, pimozide, droperidol
Which drugs can cause arrhythmias?
High dsoe TCAs
Which drug s can cause hypertension?
VFX
TCAs
Which drugs can cause fine tremors?
Therapeutic dose of Lithium, TCAs
Which drugs can cause coarse tremors?
Lithium toxicity
Antipsychotic Parkinsonism
Which drugs can cause osteoporosis?
Hyperprolactinaemic antipsychotics
Which drugs can cause WCC suppression?
Clozapine Olanzapine Mirtazapine Carbamazapine Mianserin
Which drugs can cause haemolytic anaemia?
Nomifensine
Which drugs can cause Guillian Barre?
Zimeldine
Which drug can cause pedal oedema?
MAOIs
Which drugs can cause cramps?
Acetylcholinesterase inhibitors
Which drugs can cause othostatic hypotension?
All TCAs
All antipsychotics