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MRCPsych Part A > Adverse Drug Reactions > Flashcards

Adverse Drug Reactions Flashcards

1
Q

Define tolerance

A

The need to use increased doses of a drug to maintain a clinical effect.

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2
Q

What can lead to tolerance of a drug?

A

Down-regulation
Up-regulation
Reduced responsitivity without alterations in receptor numbers

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3
Q

What is down-regulation?

A

Decreased sensitivity of target receptors due to decreased numbers due to agonists

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4
Q

What is up-regulation?

A

Increase in numbers of receptors due to antagonists

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5
Q

What is cross-tolerance?

A

When drugs with similar pharmacological actions can lead to tolerance of the other drug

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6
Q

What is reverse tolerance?

A

When sensitivity to a drug effect increases over time.

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7
Q

Give an e.g. of downregulation which leads to a therapeutic effect.

A

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.

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8
Q

Define withdrawl

A

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.

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9
Q

What type of drug leads to withdrawl symptoms?

A

Abrupt withdrawl of treatment for an agent with short eliminatino half-life

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10
Q

Which has longer half-life; methadone or heroin?

A

Methadone

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11
Q

Why does methadone lead to less withdrawl than heroin?

A

Methadone has a longer half-life

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12
Q

Why does Paroxetine lead to withdrawl?

A

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.

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13
Q

Why does Fluoxetine produce fewer withdrawl symptoms?

A

Its active metabolite, norfluoxetine, has a long half-life

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14
Q

What is the advice of benzodiazepine reducing regime?

A

10% dose reduction every 2 weeks.

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15
Q

Why must you wait 72 hours before prescribing naltrexone for an opioid detoxified patient?

A

Prescribing an antagonist can precipitate withdrawl symptoms.

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16
Q

Which cause more withdrawl; full or partial agonists?

A

Full

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17
Q

What kinetics do sustained release formulations affect?

A

Absorption kinetics

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18
Q

Do depot or oral preparations have more withdrawl potential?

A

Oral

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19
Q

Does XL or plan preparation of a drug lead to more withdrawl symptoms?

A

Neither; both same

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20
Q

Which receptors cause side effect of agitation?

A

Alpha 2 blockade
5HT2A/2C stimulation
DRI

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21
Q

Which receptors cause side effect of akathisia?

A

D2 blockade

5HT2A stimulation

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22
Q

Which receptors cause side effect of delirium?

A

Antimuscarinic

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23
Q

Which receptors cause side effect of EPSE?

A

D2 blockade reduces with 5HT2A antagonism

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24
Q

Which receptors cause side effect of hyperthermia?

A

Antimuscarinic action

In serotonin syndrome may be due to 5HT2A/2C.

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25
Which receptors cause side effect of insomnia?
Alpha 1 stimulation | 5HT2A stimulation
26
Which receptors cause side effect of amnesia?
Anticholinergic effect | GABAa stimulation
27
Which receptors cause side effect of hyperprolactinaemia?
D2 blockade | 5HT1A stimulation
28
Which receptors cause side effect of disrupted slow wave sleep?
Slow wave sleep is maintained by 5HT2A inhibition; hence 5HT2A stimulation disrupts this.
29
Which receptors cause side effect of sweating?
Cholinergic effect | Increases with noradrenaline reuptake inhibition
30
Which receptors cause side effect of postural hypotension?
Alpha 1 antagonism
31
Which receptors cause side effect of appetite loss?
5HT2A stimulation
32
Which receptors cause side effect of increased appetite?
Antihistamine
33
Which receptors cause side effect of GI discomfort/nausea?
5HT3 stimulation
34
Which receptors cause side effect of weight gain?
Antihistamine | 5HT2C antagonism
35
Symptoms of anticholinergic effects?
``` Blurred vision Delirium Constipation Tachycardia Dry secretions Decreased sweating Urinary retention Hyperthermia ```
36
What conditions do anticholinergics increase risk of?
Narrow-angle glaucoma | Photophobia due to mydriasis
37
Which receptors cause side effect of anorgasmia?
Alpha 1 antagonism | 5HT2A/C stimulation
38
Which receptors cause side effect of retrograde ejaculation?
Alpha 1 block Anticholinergic Antihistamine
39
Which receptors cause side effect of tardive dyskinesia?
Supersensitivity of dopamine receptors which develops due to prolonged therapy with dopamine blocking drugs
40
Which receptors cause side effect of impotence?
Alpha 2 blockade | 5HT2A/C stimulation
41
Which receptors cause side effect of priapism?
Alpha 1 blockade
42
Which receptors cause side effect of obsessions?
5HT1D stimuation
43
Which receptors cause reduced OCD?
5HT1A/2A
44
Which receptors cause side effect of pathological gambling?
Habituation of dopamine receptors on repeated use of dopamine agonists, leading to dopamine dysregulation syndrome
45
Which drugs cause insulin resistance?
Valproate | Olanzapine
46
Which polymorphism leads to weight gain?
Drugs with strong 5HT2C affinity used on patients with specific variant of polymorphism of 5HT2C receptor promotor regions
47
What types of antipsychotics cause weight gain more than others?
Low-potency produce more weight gain than high potency.
48
Give examples of EPSE
``` Acute dystonia Akathisia Parkinsonism Tarde dyskinesia Dystonia Perioral tremor ```
49
Which type of antipsychotics lead to EPSEs?
High potency
50
Which EPSEs are due to late SEs and chronic use of antipsychotics?
Tardive dyskinesia Dystonia Perioral tremor
51
What causes hyperprolactinaemia?
Blocking of D2 receptors on anterior pituitary mammotrophic cells that normally are tonically inhibited by dopamine produced in hypothalamic arcuate nucleus.
52
Which antipsychotics induce Parkinsonism?
``` Trifluoperazine Chlorpromazine Raclopride Haloperidol Fluphenazine Risperidone ```
53
Why do some antipsychotics cause Parkinsonism?
They bind more tightly than the endogenous ligand dopamine to D2
54
Which drugs are less likely to cause Parkinsonism and why?
Anticholinergics Quetiapine Clozapine Bind more loosely to D2 than dopamine
55
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
56
Which type of antipsychotics are more likely to lead to relapse?
Loosely bound antipsychotics as may dissociate from D2 receptor rapidly
57
When is drug-induced Parkinsonism seen?
Within 90 days of treatment
58
Which characteristic of Parkinsons is not seen in its drug-induced form?
Pill-rolling tremor | Coarse tremor seen instead
59
Who are at high risk of Parkinsonism from antipsychotics?
Elderly | Female
60
At what D2 receptor occupancy by antipsychotics leads to EPSE?
Higher than 80%
61
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)
62
What can you use to treat drug-induced Parkinsonism?
Anticholinergics for up to 6 weeks
63
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
64
What are dystonias?
Brief or prolonged contractions of specific groups of muscles
65
Give e.g. of dystonias
``` Oculogyric crises Tongue protrusion Trismus Torticolis Blepharospasm ```
66
When in the course of treatment do dystonias occur?
Early
67
Who is more likely to get dystonias?
Young men starting high-dose of high potency medications, especially IM.
68
What can be used to treat dystonias?
Reassurance | Anticholinergics
69
What causes akathisia?
Higher D2 occupancy in striatum
70
Symptoms of Akathisia?
Inability to relax Pacing Rocking with alternation of sitting and standing
71
What drugs can cause akathisia?
Neuroleptics Antidepressants Sympathomimetics
72
Treatment for Akathisia?
Dose reduction Changing drug Adding beta blocker/anticholinergic drug/benzo/cryoheptadine
73
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
74
When does tardive dyskinesia occur?
At least 6 months, often 1-2 years of treatment.
75
What is tardive dyskinesia?
Abnormal, involuntary, irregular choreaoathetotic movements of muscles of head, limbs and trunk.
76
Most common type of tardive dyskinesia?
Perioral movements
77
What exacerbates Tardive dyskinesia?
Stress | Absent on sleep
78
What is particularly striking in Tardive Dyskinesia patients?
Absence of insight
79
Treatment of Tardive Dyskinesia?
``` Spontaneously resolve - unlikely in elderly. Clozapine Dose reduction Withdrawl of drug Switch to atypicals Add clonazepam ```
80
When can neuroleptic malignant syndrome occur?
Anytime during treatment
81
Symptoms of NMS?
``` Extreme hyperthermia Severe muscular rigidity Confusion Autonomic fluctuations (BP, HR) Akinetic/mute ```
82
Blood test values of NMS
High WCC, CK, LFTs, plasma myoglobin | Myoglobinuria
83
Onset of NMS?
24-72 hours
84
How long does NMS last if untreated?
10-14 days
85
When is NMS more common?
Young men After agitation Using high potency drugs, especially rapid tranq Dopaminergic drugs on withdrawl
86
Mechanism underlying NMS?
Dopamine blockade or hypothalamic sympathetic dysregulation
87
Mortality rate of NMS?
20-30% if untreated | Higher if depot used
88
Management of NMS?
Fluid replacement & prevent renal failure secondary to myoglobinuria Prevent aspiration pneumonia Stop antipsychotic
89
Which drugs can be used to treat NMS?
Dantrolene Bromocriptine Amantadine
90
What antipsychotics need to be considered after NMS occurs?
Low potency or atypical
91
How many patients on clozapine develop agrunulocytosis?
1 in 100
92
When is risk of agrunulocytosis at maximum on clozapine?
Between 4-18 weeks
93
Main SE of clozapine related to dose?
``` Salivation Sedation Weight gain Fatigue Lowering of seizure threshold ```
94
Which SE of clozapine are not dose realted?
Arganulocytosis | Myocarditis
95
What happens if yellow result occurs on someone on clozapine?
Monitoring frequency must increase until green signal obtained
96
Which drug may precipitate clozapine-associated neutropenia?
Paroxetine
97
Effect of increased dopaminergic transmission on sexual function?
Enhances sexual arousal | Penile erection
98
Effect of hyperprolactinaemia on women?
Amenorrhoea Reduced sexual desire Hirsutism
99
How do antipsychotics lead to reduced sexual function?
Reduce dopamine transmission | Inducing hyperprolactinaemia
100
Which drugs cause ejaculatory problems?
Neuroleptics
101
Which drugs are linked to priapism?
``` Risperidone Chlorpromazine Clozapine Olanzapine Thioridazine Trazodone ```
102
Is priapism drug-dependent or duration-dependent?
Neither
103
What can priapism lead to if untreated?
Permanent impotance
104
What is used to treat sexual dysfunction in men due to hyperprolactinaemia?
Bromocriptine
105
How does Bromocriptine work?
Dopamine agonist
106
What drugs lower seizure threshold?
Low potency antipsychotics | Dose-dependent
107
Which antipsyshotic is the most sedating?
Chlorpromazine - due to H1 antihistamine
108
Which drugs are more likely to cause anticholinergic syndrome; high or low potency drugs?
Low
109
Impact of neuroleptics on cardiac function?
Reduce cardiac contractility Increase circulating catecholamines Prolong atrial and ventricular conduction time
110
Which drugs are more cardio-toxiac; low or high potency?
Low potency
111
ECG changes with neuroleptics?
QT and PR prolongation Blunting of T waves ST depression
112
Which psychiatric medications can cause Torsades de Pointes?
Thioridazine | Droperidol
113
What leads to antipsychotic related sudden death?
Cardiac arrhythmias Seizures Asphyixation Malignant hyperthermia
114
Which types of drugs cause postual drop?
Low potency drugs
115
Skin side effects on antipsychotics?
Allergic dermatitis and photosensitivity on low-potency drugs.
116
What is the skin SE of Chlorpromazine?
Blue-gray discoloration in areas exposed to light - reversible.
117
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.
118
Effect of Chlorpromazine on eyesight?
Pigmentation of anterior lens and posterior cornea; white-brown stellate granular deposits. Benign.
119
Which antipsychotic can lead to cholestatic jaundice?
Chlorpromazine
120
When does drug-induced obstructive jaundice occur?
First month of treatment
121
What is associated with drug-induced jaundice?
Rash | Eosinophilia
122
Treatment for drug-induced jaundice?
Immediately stop antipsychotic | Avoid rechallenge
123
Signs of Haloperidol OD on EEG?
Diffuse slowing and low voltage
124
Which typical antipsychotic is safest in an OD?q
Haloperidol isone
125
What mediates QTc?
Blockade of rapid component of delayed rectifier potassium current responsible for repolarisation of cardiac Purkinje cells and myocardial cells.
126
How do drugs cause prolonged QTc?
Bind to delayed rectifier K+ channgel and thereby decrease outward movement of K+
127
Which antipsychotics have greater risk of causing prolonged QTc?
Droperidol Pimozide Sertindole Thioridazine
128
What are the symptoms of inadvertent intravascular injection event/postinjection delirium sedation syndrome?
``` Sedation Confusion Dizziness Dysarthria Somnolence ```
129
When does inadvertent intravascular injection event/postinjection delirium sedation syndrome occur?
20min - 3 hours after injection of olanzapine pamoate (long-acting depot)
130
Treatment for inadvertent intravascular injection event/postinjection delirium sedation syndrome?
Supportive medical care; symptoms alleviate within 3-72 hours
131
What is inadvertent intravascular injection event/postinjection delirium sedation syndrome linked to?
Accidental punctures of vessel or injects into capillary bed leaking
132
What is Metabolic syndrome composed of?
``` Obesity Dyslipidaemia Glucose intolerance Insulin resistance HTN ```
133
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
134
Prevalence of Diabetes on schizophrenics?
Twice as prevalent than in general population
135
Drugs that are most linked with metabolic syndrome/
``` Olanzapine Clozapine Quetiapine Risperidone Aripiprazole (worst at top) ```
136
Which gender have higher risk of metabolic syndrome if schizophrenic?
Females
137
What type of study was the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)?
Double-blind pragmatic RCT
138
What drugs were looked at in CATIE?
``` Olanzapine Quetiapine Risperidone Ziprasidone Perphenazine ```
139
Which antipsychotic has lowest discontinuation rate?
Olanzapine
140
What type of study was CUtLASS (Cost utility of latest antipsychotic drugs in schizophrenia study)?
Unblinded RCT comparing first-generation and second-generation antipsychotics
141
Which 2nd-generation antipsychotics were used in CUtLASS?
``` Amsulpride Olanzapine Quetiapine Risperidone Clozapine (in second phase) ```
142
Outcome of CUtLASS?
Those on 1st generation antipsychotics did relatively better. Advantage of clozapine in symptom improvement over 1 year and patients preferred it.
143
Long-term SE of Lithium
Hypothyroidism Irreversible nephrogenic diabetes insipidus Reduced GFR (chronic kidney disease) Hyperparathyroidism
144
Which diuretic has no effect on Lithium levels?
Loop diuretics
145
What score is used to assess severity of Lithium toxicity
``` AMDISEN 0 - no signs 1 - mild 2 - moderate 3 - severe ```
146
Which antipsychotic is best to treat negative symptoms?
Amisulpride
147
Which SSRIs cause prolonged QTc?
Citalopram
148
Which TCA is the most selective inhibitor of serotonin?
Clomipramine
149
Which TCA is the most selective inhibitor of noradrenaline?
Desipramine
150
Which TCAs have the least anticholinergic activity?
Amoxapine Nortriptyline Desipramine Maprotiline
151
Which TCAs have the most antihistaminic activity?
Doxepin
152
Which TCA is associated with weight gain
Amitriptyline
153
Cardiac SE of TCAs?
QT prolongation Tachycardia Flattened T waves Depressed ST segment
154
Effect of TCAs on overdose?
Cardiac arrhythmias Anticholinergic delirium May occur 3-4 days after due to long half-life
155
Treatment for TCA overdose?
Lavage QRS monitoring No antidose
156
Symptoms of anticholinergic delirium?
``` Confusion Visual hallucinations Hyperpyrexia Loss of visual accommodation Peripheral vasodilatation Drying of mucous membranes ```
157
Which TCA can cause hyperprolactinaemia?
Amoxapine
158
SEs of all TCAs?
``` SIADH Hyponatraemia Fine rapid tremor Dysarthria Precipitate angle closure glaucoma ```
159
What happens if TCAs are reduced too quickly?
Cholinergic rebound
160
What is the best way to reduce TCAs?
Reduce 25-50mg per 2-3 days
161
When can discontinuation reaction occur with TCAs?
48 hours - 2 weeks after
162
Mechanism of serotonin syndrome
Excessive serotonergic transmission in brain. Most CNS symptoms due to 5HT 2A stimulation
163
Features of serotonin syndrome
``` Diarrhoea Myoclonus Diaphoresis Hyperactive reflexes Ataxia Hypomania/labile mood Disorientation ```
164
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
165
What is oxazolidinone antibacterial linezolid?
Reversible non-selective MAOI
166
What is Tetrabenazine?
Acts via dopamine and serotonin depletion at nerve endings
167
What is entacapone?
COMT inhibitor
168
Treatment of serotonin syndrome?
Stop agent Correct vital signs Benzos 5HT2A antagonists
169
Name some 5HT2A antagonists that can be used in the treatment of serotonin syndrome
Cyproheptadine Atypical antipsychotics Chlorpromazine
170
Why do SSRIs cause anorexia when starting, then weight gain late during therapy?
Desensitization and down-regulation of receptors.
171
What is fluoxetine associated with in particular?
Change in duration of menstrual period
172
Effect of SSRIs on platelets?
Thrombasthenia - functional impairment of platelet aggregation
173
Impact of Thrombasthenia?
Easy bruising Prolonged bleeding (in those with gastric ulcers or bleeding diathesis)
174
In which patients is SIADH more likely who are on SSRIs?
Alcoholics | Elderly
175
SEs of SSRIs
``` Nausea Diarrhoea Anorexia (initially) Thrombasthenia SIADH Severe sweating Nocturnal myoclonus Restless legs Acute angle-closure glaucoma ```
176
Treatment for severe sweating from SSRI?
Terazosin
177
What is nocturnal myoclonus?
Repetitive leg movement every 2-60 seconds; extension of large toe and flexion of angle, knee and hips.
178
Treatment of nocturnal myoclonus?
Benzo | Levodopa
179
Treatment for restless legs
Ropinirole Benzo Levodopa
180
Which SSRIs/SNRIs cause acute angle closure glaucoma?
``` Duloxetine Venlafaxine Citalopram Fluoxetine Paroxetine ```
181
Which SSRIs are associated with SSRI discontinuation syndrome?
Paroxetine - additional cholinergic rebound | Fluvoxamine - short half-life
182
When does SSRI discontinuation syndrome occur?
If someone is on SSRI for 4-6 weeks at least, and it is stopped abruptly.
183
Which SSRI is least likely to cause discontinuation syndrome?
Fluoxetine - long half-life
184
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 ```
185
What is the link between SSRI and suicide risk?
Only in those up to age 24 if used between 4-16 weeks.
186
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.
187
What increases risk of UGIB if on SSRI?
Elderly NSAIDs H. Pylori
188
Which SSRIs are at higher risk of causing UGIB?
``` Those with high inhibition of serotonin reuptake: Clomipramine Paroxetine Sertraline Fluoxetine ```
189
Which SSRIs are at lower risk of causing UGIB?
Those with low inhibition f serotonin reuptake; Nortriptyline Doxepin Trazadone
190
Which antidepressants are associated with lower risk of sexual dysfunction?
``` Bupropion Mirtazapine Moclobemide Nefazodone Reboxetine ```
191
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
192
Which patients must Sildenafil be avoided in?
Patients with arrhythmias, unstable angina / uncontrolled HTN
193
In which antidepressant is sweating most common?
Venlafaxine
194
SEs of Venlafaxine?
``` Sweating Increase in diastolic BP if >300mg/day Mydriasis Exacerbation of ange closure glaucoma Disctoninuation reaction (short half life) ```
195
SEs of Duloxetine?
Similar to Venlafaxine but less likely to affect BP
196
How to stop Venlafaxine?
Over 2-4 weeks
197
How to treat priapism?
Intracavernosal injection of an alpha1 agonist
198
E.g. of alpha1 agonist used in priapism?
Metaraminol | Epinephrine
199
When is there risk of priapism?
Starting Trazadone (high risk) - early phases of treatment
200
How does Nefazodone work?
Inhibits CYP3A4
201
Why is Nefazodone not used as often?
Can cause serious hepatic damage
202
Who is Trazadone and Nefazodone best for?
Elderly | Those with cardiac illness
203
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 ```
204
Why can Bupropion cause psychotic symptoms?
Dopaminergic
205
Which antidepressants can cause agranulocytosis?
Mirtazapine
206
Which combinations of Buspirone do you need to be careful with?
Haloperidol - increases conc of haloperidol | MAOI - causes serotonin syndrome
207
Which drugs increase buspirone plasma conc?
``` CYP3A4 inhibitors: Erythromycin Itraconazole Nefazodone Grapefruit juice ```
208
SEs of Mianserin and Mirtazapine
Drowsiness first few weeks of treatment | Increased weight gain and appetite
209
Why is Mirtazapine preferred option to treat depression in chemotherapy?
5HT3 blockade - reduced vomiting and nausea
210
What type of antidepressant is Reboxetine?
NARI
211
Which patients is Reboxetine good for?
Elderly | Cardiac history
212
What type of drug is Atomoxetine?
NARI
213
What illness is Atomoxetine used in?
ADHD
214
SEs of Reboxetine
Due to noradrenergic effect: | urinary hesitancy in males
215
What can help with urinary hesitancy SE
Tamsulosin - peripheral alpha1 blocker | Doxazosin
216
What type of drug is phenelzine?
MAOI
217
SEs of MAOIs?
``` Orthostatic hypotension Pedal oedema Insomnia Cheese reaction Serotonergic syndrome - with SSRIs Weight gain Sexual dysfunction ```
218
Why is it best to give MAOIs such as Phenelzine and Tranylcypromine at 6pm?
Can have stimulating effects leading to insomnia
219
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.
220
Signs of cheese reaction
``` Nausea Apprehension Chills Sweating Restlessness Hypotension - with occipital headache, palpitations and vomiting Dilated pupils Fever ```
221
Severe effect of cheese reaction?
Cerebral haemorrhage
222
Which MAOIs are safest for severity of hypertensive crisis?
Reversible MAOIs
223
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 ```
224
How to treat MAOI-induced hypertensive crisis?
Alpha-adrenergic antagonists
225
Give eg. of alpha-adrenergic antagonists for hypertensive crisis treatment?
Phentolamine | Chlorpromazine
226
What can help reduce polyuria in Lithium use?
Once daily rather than twice daily dosing
227
What causes polyuria with Lithium?
Functional antagonism of ADH
228
What can help control polyuria due to Lithium?
K+ sparing diuretics
229
What can lead to renal failure from Lithium?
Cumulative lithium use
230
What renal damage is common with chronic lithium use?
>10 years: | Interstitial fibrosis
231
How does Topiramate work?
Weak inhibitor of carbonic anhydrase | Can cause renal stones
232
What is Oxcarbazepine?
10-keto derivate of CBZ - less enzyme induction
233
SEs of Oxcarbazepine?
More likely to cause hyponatraemia than CBZ
234
ECG effects of Lithium?
Similar to low K+: Flat T waves Inverted T waves
235
Which cardiac problem is Lithium CI in and why?
Sick sinus syndrome; | Lithium can depress sinus node activity
236
Which thyroid problem can Lithium most commonly cause?
Benign hypothyroid state
237
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
238
Which TFT dysfunction is seen in 1/3 of chronic Lithium patients, even in absence of symptoms?
High TSH
239
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
240
Which antimanic drug can increase risk of polycystic ovaries?
10%
241
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.
242
When is oligomenorrhea likely to occur with valproate?
Within first year of treatment
243
Which antimanic drugs result in leucocytosis?
Lithium | Carbamazepine - first 3 months of treatment
244
Which antimanic drugs can lead to thrombocytopenia?
Valproate | Carbamazepine
245
Which tremor is a sign of toxicity in Lithium use?
Coarse tremor
246
Which tremor is a SE of lithium use?
fine tremor
247
SEs of Lamotrigine?
``` Dizziness Ataxia Headache Sedation Tremor ```
248
SEs of Topiramate
Renal stones Anomia - word finding difficulties Poor concentration
249
SEs of Vigabatrin
Visual field defects
250
What is Vigabatrin used for?
Anti-epileptic
251
Effect of Valproate on liver?
Induces hepatic enzymes | Elevation in liver transaminases - asymmptomatic
252
Which antimanic drugs can cause liver failure?
Valproate Lamotrigine Topirimate Carbamazepine
253
What risk factors lead to liver failure if on antimanic drugs?
Young age | Combination therapy
254
What results in liver failure from antimanic drugs?
1. Metabolic toxicity - due to 4-en valproate, a metabolite of valproate. 2. Hypersensitivity - dose-independent effect is resulting in fulminant failure.
255
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)
256
Which antimanic drug can cause acute pancreatitis?
Valproate
257
Can dose-reduction of valproate reduce risk of pancreatitis?
No - this is a hypersensitivity reaction, not dose-dependent
258
When can hyperammonaemia occur with antimanic drugs?
Carbamazepine
259
How does Hyperammonaemia present?
Coarse tremor
260
Treatment for hyperammonaemia?
L-carnitine
261
Most common teratogenic effect of Lithium?
Ebsteins anomaly of tricuspid valves
262
Risk of Ebsteins in lithium-exposed foetuses?
1 in 1,000 (20x risk of general population)
263
Is Lithium more or less teratogenic than valproate and carbamazepine?
Less
264
Which antimanic drug is excreted into breast milk?
Lithium
265
Signs of lithium toxicity in infants?
Lethargy Cyanosis Sluggish neonatal reflexes
266
Teratogenic effect of valproate?
Neural tube defects
267
Risk of neural tube defects in mothers using valproate?
1-4%
268
What can help reduce teratogenic risk of Valproate?
Folate-vitamin B complex supplementation
269
Most common teratogenic effect of Valproate?
Learning disability | Low IQ
270
Effect of Lithium on the skin
Acne Psoriases Alopecia - 5-10%
271
Effect of Valproate on Endocrinology system?
Obesity Hyperandrogenism PCOD - hirutism
272
Which drugs are most likely to cause anticonvulsant hypersensitivity syndrome?
``` Aromatic compounds: Lamotrigine Carbamazepine Phenytoin Phenobarbitone ```
273
Common SE of aromatic compunds?
Rash
274
Risk factors leading to skin reactions/rash with aromatic compounds?
Rapid initial dose escalation Concurrent VPA Age <16 years
275
What happens if a rash occurs with aromatic compounds?
Stop drug - cannot tell if benign from serious
276
Which antimanic drug can lead to Steven Johnson syndrome?
Lamotrigine - especially if combined with Valproate
277
Why do valproate + lamotrigine together increase risk of Steven Johnson Syndrome?
Valproate has enzyme inhibiting effects which increase lamotrigine levels
278
Initial signs of Steven Johnson syndrome?
Rash Pharyngitis Fever Systemic involvement if drug not stopped
279
Dose-related effects of Carbamazepine
``` Visual disturbances GI disturbance Cognitive impairment Vertigo Dizziness ```
280
Dose-related effects of Valproate
Hyperammonaemia Teratogenicity Sedation Thrombocytopenia
281
Idiosyncratic reactions of Carbamazepine
Haematological reactions: agranulocytosis/aplastic anaemia, Steven Johnson, fulminant liver damage, pancreatitis SIADH - elderly
282
Idiosyncratic reactions of Valproate
Hepatotoxicity Pancreatitis Rash Acute dermatitis (rare)
283
Which antimanics cause weight gain?
Valproate - 70% | Carbamazine - 40%
284
What causes weight gain with valproate?
Impaired beta-oxidation of fatty acids
285
Which antimanic drug can be used to counteract weight gain caused by psychotropic drugs?
Topiramate
286
Common SE of cholinesterase inhibitors
Nausea/vomiting Diarrhoea Insomnia Muscle cramps
287
What type of drug is Tacrine?
Cholinesterase inhibitor
288
Why is Tacrine no longer used?
Fatal hepatotoxicity
289
Important SEs of cholinesterase inhibitors due to increased cholinergic stimulation?
``` UGIB (esp if peptic ulcer/NSAIDS) Bradycardia Exacerbate COPD Urinary retention Increase seizure risk ```
290
In which patients is there a higher risk of bradycardia if on cholinesterase inhibitor?
Supraventricular conduction delay
291
Which types of drugs can cholinesterase inhibitors prolong the risk of?
Succinylcholine-type muscle relaxants
292
Where is Memantine excreted?
Mainly urine
293
Is Rivastigmine metabolised by liver?
Rarely
294
Does Memantine affect liver enzymes?
No
295
SEs of stimulants used in ADHD
``` Anxiety Irritability Insomnia Tachycardia Cardiac arrhythmias Dysphoria Decreased appetite - tolerance develops ```
296
Less common SE of stimulants used in ADHD?
Self-limited exacerbation of movement disorders (tics, dyskinesias) Linked to growth suppression
297
What is Pemoline?
Stimulant used in ADHD
298
Why is Pemoline no longer used?
Associated with Hepatic failure
299
Which drug used in ADHD can cause dependence (rare)?
Methylphenidate
300
SEs of Atomoxetine?
Appetite loss Sexual dysfunction Dizziness Severe liver injury
301
Signs of Benzo OD?
``` Slurred speech Incoordination Unsteady gait Nystagmus Impairment in attention + memory Stupor/coma Inappropriate sexual/aggressive behaviour Mood lability ```
302
Which benzos cause anterograde amnesia?
High-potency
303
Why is Triazolam banned in UK since 1991?
Disinhibition and aggression
304
When can paradoxical disinhibition present with benzo use?
If patients have pre-existing brain damage
305
Which type of patients can have respiratory impairment from benzo use?
COPD | Sleep apnoea
306
Which patients should Benzos be avoided in due to risk of respiratory impairment?
Myasthenia Gravis Head injury Porphyria
307
SE of Alprazolam?
Weight gain via appetite stimulation
308
Teratogenic effects of Benzos?
Cleft palate and lips
309
When is benzo withdrawl syndrome seen in neonates?
If used in third trimester
310
SEs of Z-hypnotics?
Diarrhoea | Abdominal pain
311
Unique SE of eszopiclone?
Unnpleasant taste
312
What does benzo withdrawl syndrome depend on?
Half-life Rate of tapering Dose Duration
313
Signs of benzo withdrawl
``` Anxiety Diaphoresis Kinaesthetic hallucinations Restlessness/irritability Tremor Insomnia Autonomic hyperactivity Weakness ```
314
Severe SEs of benzo withdrawl?
Paranoia Delirium Grand mal seizures
315
When does benzo withdrawl syndrome occur with long-acting benzos?
1-2 weeks after long-acting benzos stopped
316
Which benzos are associated with immediate and severe withdrawl syndrome?
Alprazolam | Lorazepam
317
At what point are prescribed benzos unlikely to cause withdrawl?
<4 weeks use
318
Withdrawl rate in benzo use for 6-8 years?
75%
319
Withdrawl rate in benzo use for 2 years?
25-45%
320
Withdrawl rate for benzo use in 4 months?
5-10 mnoths
321
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
322
Psych SEs of beta-blockers
Sedation Nightmares Dysphoria Depression
323
In which type of beta-blockers are psych SEs seen in?
Lipophilic compounds | e.g. metoprolol, propranolol
324
Psych SEs of ACE inhibitors
``` Increased arousal Anxiety Fatigue Insomnia Increased psychomotor activity ```
325
Psych SEs of Clonidine
``` Sedation Anxiety Agitation Depression Insomnia ```
326
Psych SEs of nitrates?
``` Delirium Psychosis Anxiety Restlessness/agitation Hypomanaia ```
327
Psych SEs of digoxin?
Depression | Delirium
328
Psych SEs of statins?
Depression
329
Psych SEs of corticosteroids?
Mania>depression Agitation Lethargy
330
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
331
Psych SEs of anabolic androgenic steroids?
``` Acute parnoia Delirium Mania Homicidal rage Aggression Extreme mood swings Increase in libido Agitation Anger ```
332
What makes psych SEs more likely with anabolic androgenic steroid use?
Dose-dependent
333
Psych SEs of GNRH agonists (e.g. leuprolide)?
Depression
334
Psych SEs of interferon-alpha?
Depression - seen in first 12 weeks
335
Psych SEs of penicillin?
Sedation Anxiety Hallucinations
336
Psych SEs of cephalosporins?
Delirium
337
Psych SEs of ciprofloxacin and ofloxacin?
``` Restlessness Lethargy Tremors Insomnia Mania Depression Psychosis Delirium Seizures Catatonia ```
338
Psych SEs of Isoniazid?
Delirium Mania Depression Psychosis
339
Psych SEs of Tetracyclines?
Depression Insomnia Irritability - at high doses
340
Psych SEs of antihistamines and decongestants?
Atropine-like psychosis
341
Psych SEs of PPIs & H2 antagonists?
Confusion Agitation Depression Hallucinations
342
Who are Psych SEs of PPIs and H2 antagonists more common in?
Elderly patients with impaired hepatic-renal function
343
Psych SEs of Ondansetron?
Anxiety
344
Psych SEs of Isotretinoin?
Severe depression and suicidal behaviour
345
Psych SEs of aminophylline and salbutamol?
Agitation Insomnia Euphoria Delirium
346
Name some depressogenic drugs
``` Beta blocks Ca channel blocks Interferons (alpha>beta) Steroids Cyproterone, progesterone Varenicline Isotretinoin Ezetimibe ```
347
How does Rimonabant work?
CB1 receptor antagonist
348
What is Rimonabant used for?
Anti-obesity; blockig central cannabinoid activity may reduce food intake
349
Concerns regarding Rimonabant use?
Severe psychiatric SEs; 2.5x more depression, 3x more anxiety
350
What do animal studies show about blockade of CB1 receptor?
Impairs anti-depressant reducing and anxiety-reducing actions of endocannabinoids
351
Name some Class A drugs
``` Ecstacy LSD Heroin Cocaine Crack Magic mushrooms Merthylamphetamine Other amphteamines if prepared for injection ```
352
Penalty for possession of class A drug?
Upto 7 years in prison, unlimited fine or both
353
Penalty for dealing Class A drug?
Upto lif in prison, unlimited fine or both
354
Name some Class B drugs
Amphetamines Methylphenidate Pholcodine
355
Penalty for possession of Class B drugs
Upto 5 years in prison or unlimited fine or both
356
Penalty for dealing of Class B drugs
Upto 14 years in prison or unlimited fine or both
357
Name some Class C drugs
``` Cannabis Tranquilisers Some pankillers GHB Ketamine ```
358
Penalty for possession of class c drug
Upto 2 years in prison, unlimited fine or both
359
Penalty for dealing Class C drug
Upto 14 years in prison, unlimited fine or both
360
Class A, B, C drugs are under which Act?
2001 Misuse of Drugs Act UK
361
Schedule 1, 2,3, 4 and 5 drugs are under which Act?
2001 Misuse of Drugs Regulations
362
Examples of Schedule 1 drugs
Coca lef Cannabis LSD Mescaline
363
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
364
Give some e.g. of Schedule 2 drugs
``` Diamorphine Morphine Dipipanone Remifentanil Pethidine Secobarbital Glutethimide Amphetamine Cocaine ```
365
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.
366
Name some examples of Schedule 3 drugs
``` Barbituates - except secobarbital Buprenorphine Diethylpropion Mazindol Meprobamate Pentazocine Phenter,ine Temazepam ```
367
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.
368
Give examples of some Schedule 4, Part 1 drugs
Benzos - except temazepam | Zolpidem
369
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
370
Give examples of Schedule 4, Part 2 drugs
``` Androgenic and anabolic steroids Clenbuterol HCG Non-human chorionic gonadotrophin Somatotropin Somatrem Somatropin ```
371
Name some examples of Schedule 5 drugs
Weak preparations of drugs usually in other schedules - e.g. morphine, codeine
372
Regulations of Schedule 5 drugs?
Exempt from all controlled drug regulations except the need to keep invoices for at least 2 years
373
Which drugs cannot be prescribed on repeat prescriptions?
Schedule 2 and 3 drugs
374
How should patients collect controlled drugs?
In person, show ID on first occasion and sign back of prescription form
375
Which drugs must be prescribed in daily instalments?
Substitute opioids
376
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
377
Purpose of reporting adverse drug reactions?
Reduce hazards of medical prescribing | Trigger regulatory action to ensure patient safety
378
Should adverse reaction be reported if reaction is well known?
Yes
379
Should adverse reaction be reported if you are unsure whether the drug caused this reaction?
Yes
380
Should adverse reaction be reported if it was a result of an overdose?
Yes
381
Should an adverse reaction be reported if other drugs were given at the same time?
Yes
382
Who can use the yellow card scheme to report adverse reactions?
Prescribers Patients Carers Pharmacists
383
What does the black triangle symbol mean?
Preparation is newly licensed and requires additional monitoring by the European Medicines agency
384
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.
385
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
386
For SEs, what does very common mean?
Greater than 1 in 10
387
For SEs, what does common mean?
1 in 100 to 1 in 10
388
For SEs, what does uncommon or less commonly mean?
1 in 1000 to 1 in 100
389
For SEs, what does rare mean?
1 in 10,000 to 1 in 1000
390
For SEs, what does very rare mean?
Less than 1 in 10,000
391
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
392
Which drugs cause EPSEs?
All neuroleptics - less for anticholinergic neuroleptics e.g. CPZ Higher dose atypicals
393
Which drugs cause delirium?
Anticholinergic TCAs | Anticholinergic antipsychotics
394
Which drugs cause seizures?
Bupropion | Clozapine
395
Which drugs cause tics?
Stimulants
396
Which drugs cause hepatic damage?
Nefazodone VPA Tacrine
397
Which drugs cause hepatic enzyme induction?
CBZ Phenytoin Barbituates
398
Which drugs cause acute pancreatitis?
VPA
399
Which drugs cause paralytic ileus?
Clozapine
400
Which drugs can cause UGIB?
SSRIs | Acetylcholinesterase inhibitors
401
Which drugs can cause weight gain?
``` All antipsychotics - less of Aripiprazole, ZPD TCAs Lithium VPA CBZ ```
402
Which drugs cause weight loss?
Topiramate | Bupropion
403
Which drugs cause renal damage?
Lithium
404
Which drugs cause renal stones?
Topiramate
405
Which drugs cause Priapism?
Trazadone | Risperidone
406
Which drugs cause polycystic ovaries?
Valproate
407
Which drugs cause erectile dysfunction?
All TCAs | Antipsychotics
408
Which drugs caused anorgasm or delayed ejaculation?
SSRIs
409
Which drug can lead to a rash?
CBZ | Lamotrigine
410
Which drug can cause thrombocytopenia?
Valproate
411
Which drug can cause sweating?
Particularly Venlafaxine TCAs SSRIs
412
Which drug can cause psoriasis and acne?
Lithium
413
Which drugs cause worsening of glaucoma?
Paroxcetine Quetiapine TCAs
414
Which drug can cause retinitis pigmentosa?
Thioridazine
415
Which drug can cause hypersalivation?
Clozapine
416
Most common SE of clozapine?
Hypersalivation
417
Which drug can cause corneal deposits?
CPZ
418
Which drug can cause visual field defects?
Vigabatrin
419
Which drugs can cause bruxism?
Stimulants
420
Which drugs can cause hypothyroidism?
Lithium
421
Which drugs can cause PE or myocarditis?
Clozapine
422
Which drugs can cause prolonged QT?
All antipsychotics - especially thioridazine, pimozide, droperidol
423
Which drugs can cause arrhythmias?
High dsoe TCAs
424
Which drug s can cause hypertension?
VFX | TCAs
425
Which drugs can cause fine tremors?
Therapeutic dose of Lithium, TCAs
426
Which drugs can cause coarse tremors?
Lithium toxicity | Antipsychotic Parkinsonism
427
Which drugs can cause osteoporosis?
Hyperprolactinaemic antipsychotics
428
Which drugs can cause WCC suppression?
``` Clozapine Olanzapine Mirtazapine Carbamazapine Mianserin ```
429
Which drugs can cause haemolytic anaemia?
Nomifensine
430
Which drugs can cause Guillian Barre?
Zimeldine
431
Which drug can cause pedal oedema?
MAOIs
432
Which drugs can cause cramps?
Acetylcholinesterase inhibitors
433
Which drugs can cause othostatic hypotension?
All TCAs | All antipsychotics

MRCPsych Part A (22 decks)

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