Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MRCPsych Part A small > Clinical psychopharmacology > Flashcards

Clinical psychopharmacology Flashcards

1
Q

Manfred Joshua Sakel

(therapy, year)

A

Insulin Coma Therapy for schizophrenia

1934

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Ladislas Meduna

(therapy, year)

A

Convulsive Therapy for schizophrenia (using camphor and metrazol)

1934

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Egas Moniz

(therapy, year)

A

Frontal leucotomy for schizophrenia and depression

1935

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Cerletti and Bini

(therapy, year)

A

Introduced electroconvulsive therapy (ECT) for schizophrenia

1938

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Erik Jacobsen + Jens Hald

(drug, year)

A

Invented Disulfiram in 1948

Initially it was developed as an anthelmintic, then later its use in alcohol dependency was recognised.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

John Cade

(drug, year)

A

Discovered the antimanic effects of Lithium

1949

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Frank Berger

(drug, year)

A

Invented Meprobamate in the 1940s

This was hailed as the first ‘tranquiliser’ in 1954

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Paul Charpentier

(drug, year)

A

Invented Chlorpromazine

1950

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Jean Delay + Pierre Deniker

(drug, year)

A

First used Chlorpromazine to treat psychosis

1952

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Who coined the term ‘neuroleptic’

A

Pierre Deniker with reference to the drug Chlorpromazine, which he first used to treat psychosis in 1952 with Jean Delay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Mahlon Kline

(drug, year)

A

Isolated Reserpine from the rauwolfia plant in India

1954

Reserpine was prescribed more frequently than chlorpromazine in the 1950s, but its use decreased as it caused akathisia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Roland Kuhn

(drug, year)

A

Discovered the antidepressant effects of Imipramine - the first tricyclic antidepressant

1955

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Paul Janssen (drug, year)

A

Invented Haloperidol

1958

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Leo Sternbach

(drug, year)

A

Invented chlordiazepoxide (librium) - the first benzodiazepine

1955

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mahlon Kline

(antidepressant, year)

A

Iproniazid

- the first antidepressant

1957

(The antidepressant effects of isoniazid, an MAOI, had been noted in the 1950s while being used to treat tuberculosis. Iproniazid was invented in 1957 and used effectively to treat depression, but was later withdrawn due to its hepatotoxicity)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

John Kane

(drug, year)

A

Introduced Clozapine into clinical practice for treatment-resistant schizophrenia

1988

======================================================

Clozapine had been invented in 1958 by Fritz Hunziker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Arvid Carlssen

(drug, year)

A

Synthesised Zimeldine - the first SSRI - in the late 1970s/early 1980s.

This was withdrawn due to it causing hypersensitivity syndrome and demyelinating disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Blackwell

(key discovery, year)

A

First described the ‘cheese reaction’ seen in MAOI-associated hypertension

1963

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Who coined the term ‘antidepressant’?

A

Max Lurie 1953

  • with reference to Isoniazid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

SSRIs - common adverse effects (5)

A

GI effects (nausea, D+V, constipation)

Increased risk of GI bleeding

Dizziness

Sexual dysfunction

Hyponatraemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Which SSRI is preferred in the elderly?

A

Citalopram - associated with lower risk of drug interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which SSRI is preferred post-MI?

A

Sertraline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which SSRI is preferred in children/adolescents?

A

Fluoxetine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Tricyclic antidepressants - subdivision (2) + difference in mechanisms

A

1st gen - Tertiary amines

- boost serotonin and noradrenaline.

2nd gen - Secondary amines

- lower side effect profile and act primarily on noradrenaline.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Tricyclic antidepressants - tertiary amines (8)

A

Amitriptyline

Lofepramine

Imipramine

Clomipramine

Dosulepin (Dothiepin)

Doxepin

Trimipramine

Butriptyline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Tricyclic antidepressants - secondary amines (4)

A

Protriptyline

Amoxapine

Nortriptyline

Desipramine

‘PAND’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Tricyclic antidepressants - common side effects (5)

A

drowsiness

dry mouth

blurred vision

constipation

urinary retention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Monoamine Oxidase Inhibitors (MAOI) - subdivision (2)

A

Irreversible MAOIs (traditional) - ‘PIT’

  • Phenelzine
  • Isocarboxazid
  • Tranylcypromine

Reversible MAOIs

  • Moclobemide

(aka RIMA - Reversible Inhibitor of Monoamine oxidase type A)

- less likely to cause cheese reaction than the traditional MAOIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Serotonin-Noradrenaline Reuptake Inhibitors, SNRI (3)

A

Venlafaxine

Duloxetine

Milnacipran

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Noradrenaline Reuptake Inhibitors, NARI (2)

A

Reboxetine

Atomoxetine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Dopamine Reuptake Inhibitor, DARI (1)

A

Bupropion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Serotonin Antagonist and Reuptake Inhibitor, SARI (1)

A

Trazodone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Noradrenergic and Specific Serotonergic Antagonists, NaSSA (2)

A

Mirtazepine

Mianserin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Chlorpromazine, Promazine

(structural classification)

A

Phenothiazine (aliphatic side chain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Thioridazine, Pipothiazine

(structural classification)

A

Phenothiazine (piperidine side chain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Trifluoperazine, Fluphenazine

(structural classification)

A

Phenothiazine (piperizine side chain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Haloperidol, Benperidol, Droperidol

(structural classification)

A

Butyrophenone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Flupenthixol, Zuclupenthixol

(structural classification)

A

Thioxanthene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Pimozide

(structural classification)

A

Diphenylbutylpiperidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Clozapine

(structural classification)

A

Dibenzodiazepine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Risperidone (structural classification)

A

Benzoxasole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Olanzapine (structural classification)

A

Thienobenzodiazepine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Quetiapine (structural classification)

A

Dibenzothiazepine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Sulpride, Amisulpride (structural classification)

A

Substituted benzamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Aripiprazole (structural classification)

A

Arylpiperidylindole (quinolone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Tricyclic antidepressant considered least toxic in overdose

A

Lofepramine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Tricyclic antidepressants considered most toxic in overdose (2)

A

Amitriptylline

Dosulepin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Clozapine - indications

A

NICE guidelines recommend the use of clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs.

They stipulated that at least one of the drugs should be a non-clozapine second-generation antipsychotic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Clozapine (levels)

A

The average clozapine dose in the UK is 450 mg/day.

A ‘therapeutic range’ has not been established. It is generally accepted that a level of 350 µg/L is necessary to achieve a therapeutic response.

Levels greater than 500 µg/L should be treated with caution as there is a risk of seizures.

Lower doses may be required in non-smokers, the elderly, females, and in patients using enzyme inhibitors (e.g. SSRI’s). Treatment should of course be guided by clinical response (treat the patient not the level).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Clozapine - common side effects (8)

A

Drowsiness/ sedation

Dizziness

Insomnia

Salivation

Nausea + Vomiting

Dyspepsia

Weight gain

Constipation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Clozapine - adverse effects (10)

A

Agranulocytosis

Myocarditis

Seizures

Severe orthostatic hypotension with or without syncope

Increased mortality in elderly patients with dementia related psychosis

Colitis

Pancreatitis

Thrombocytopenia

Thromboembolism

Insulin resistance and diabetes mellitus

==========================================

(Approx 33 percent developed diabetes mellitus over a ten year period (Henderson, 2005)) The BNF advices caution in the following circumstances: prostatic hypertrophy susceptibility to angle-closure glaucoma adult over 60 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Clozapine - agranulocytosis

(prevalence, timing, rechallenge)

A

Agranulocyotosis occurs in 1-2% of patients on clozapine

It is more common in the first 18 weeks of treatment

One-third of patients who stop clozapine due to neutropenia or agranulocytosis will develop a blood dyscrasia on rechallenge.

In most cases, the second reaction will occur more rapidly, be more severe, and will last longer than the first

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Clozapine - agranulocytosis (treatment)

A

Lithium has been shown to independently raise the white cell count and has been used in this way successfully in combination with clozapine. Use of this combination can enable patients to continue on treatment when they develop neutropenia.

Having said that there are case reports suggesting that the combined use of lithium and clozapine can result in toxicity and so this combination must be used with caution.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Clozapine - augmentation (favoured drugs)

A

Sulpride and amisulpride are the favoured antipsychotics for augmentation with clozapine as their selectivity for D2 dopamine blockade compliments clozapine (which lacks high potency dopamine blockade).

Lamotrigine has the best evidence of the mood stabilisers to support its use as an augmentation strategy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Atypical antipsychotics available in depot form (3)

A

Olanzapine

Aripiprazole

Risperidone - Risperdal Consta or Paliperidone

‘OAR’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Lithium (therapeutic index)

A

0.4 - 1.2 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Lithium - side effects (10)

A

Drowsiness

Dry mouth

Polyuria

Polydipsia

Metallic taste

Muscle weakness

GI - Nausea + Diarrhoea

Weight gain

Fine tremor

Worsening of psoriasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Lithium - long-term adverse effects (4)

A

Hypothyroidism

Irreversible nephrogenic diabetes insipidus

Reduced GFR (chronic kidney disease)

Hyperparathyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Drugs that increase lithium levels (3)

A

NSAIDs/COX-2 inhibitors

ACE inhibitors

Thiazide diuretics

====================================

NB: Loop diuretics (furosemide) generally have no effect on lithium levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Lithium

  • teratogenic effect
  • risk
  • increased risk from general population
A

Cardiac (Ebstein’s) anomalies

The risk of Ebstein’s in women taking lithium is 1 in 1000

(which is 20 times the normal level).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Carbamazepine (mechanism of action)

A

binds to sodium channels increases their refractory period

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Carbamazepine - adverse effects (8)

A

P450 enzyme inducer

dizziness and ataxia

drowsiness

headache

visual disturbances (especially diplopia)

Steven-Johnson syndrome

leucopenia and agranulocytosis

syndrome of inappropriate ADH secretion (hyponatraemia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Carbamazepine (teratogenic effect)

A

Fingernail hypoplasia, craniofacial defects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Valproate (mechanism of action)

A

GABA agonist

NMDA antagonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Valproate - forms (3, + indications)

A

1 - Semi-sodium valproate (Depakote) (licensed for acute mania associated with bipolar disorder)

2 - Valproic acid (licensed for acute mania associated with bipolar disorder)

3 - Sodium valproate (licensed for epilepsy)

[Note that the BNF 61 is not consistent with the Maudsley Guidelines 10th Edition which suggest valproic acid is not licensed for acute mania.]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Valproate (teratogenic effect)

A

Spina bifida, hypospadias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Valproate - key adverse effects (4)

A

Tiredness

Significant weight gain (30-50% of patients)

Tremor (up to 25% of patients)

Hair loss (5% to 10% of patients, with curly regrowth once valproate is stopped)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Topiramate (mechanism of action)

A

GABA agonist

NMDA antagonist

Na channel stabiliser

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Topiramate (use)

A

Refractory or rapid cycling bipolar affective disorder where lithium plus valproate has been ineffective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Phenytoin (mechanism of action)

A

binds to sodium channels increasing their refractory period

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Phenytoin (teratogenic effects - 4)

A

Craniofacial defects

limb defects

cerebrovascular defects

mental retardation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Phenytoin (chronic adverse effects - 7)

A

gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF)

hirsutism

coarsening of facial features

drowsiness

megaloblastic anaemia (2ndary to altered folate metabolism) peripheral neuropathy osteomalacia (enhanced vitamin D metabolism)

lymphadenopathy

dyskinesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Benzodiazepines (mechanism of action)

A

Potentiation of the GABA inhibitory effect on the CNS by increasing the number and frequency of chloride channel opening

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Benzodiazepines (pharmacokinetics)

A
  • absorbed well following oral administration
  • they show high plasma protein binding (95% for diazepam)
  • mainly metabolised in the liver
  • they tend to be highly lipophilic and rapidly cross the blood brain barrier and placental barrier
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Diazepam (half-life)

A

20-100 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Clonazepam (half-life)

A

18-50 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Chlordiazepoxide (half-life)

A

5-30 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Nitrazepam (half-life)

A

15-38 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Temazepam (half-life)

A

8-22 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Lorazepam (half-life)

A

10-20 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Alprazolam (half-life)

A

10-15 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Oxzazepam (half-life)

A

6-10 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Zopiclone (half-life)

A

5-6 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Zolpidem (half-life)

A

2 hours

(SPMM states 1-3 hours)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Zaleplon (half-life)

A

2 hours

(SPMM states 1 hour)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Buspirone (mechanism of action)

A

5HT1A partial agonist

Licensed for the short-term management of anxiety

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Who coined the term ‘placebo effect’?

A

Henry K. Beecher (1955)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Active placebo (definition)

A

a drug which has its own inherent effects but none for the condition for which it is being given.

e.g. the use of atropine as the control drug in trials of antidepressants.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Factors that increase placebo response

A
  • Injections > oral
  • brighter coloured tablets
  • larger tablets
  • status of the treating professional
  • branded > unbranded
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Placebo response - pattern analyses

A

Pattern analyses have shown that the improvement as a result of placebo in depression tends to be abrupt, occurs early in treatment and is less likely to persist, whereas improvement in response to antidepressants tends to be gradual, occurs later and is more likely to persist.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Placebo sag (essence)

A

a situation where the placebo effect is diminished (attenuated) with repeated use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Placebo response rate (%) in - depression - schizophrenia

A

Depression - 60%

Schizophrenia - 30%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Drug approval process (5 steps)

A

Animal studies

Phase 1 clinical trials - safety

Phase 2 clinical trials - effectiveness

Phase 3 clinical trials - superiority

Phase 4 clinical trials - post-marketing surveillance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

… clinical trials involve only a small number of healthy people (possibly as few as 15-20). The focus is to evaluate the drugs safety, determine a safe dosage range, and identify side effects.

A

Phase 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

In … clinical trials the drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

A

Phase 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

In … trials the drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments (or placebos), and collect information that will allow the experimental drug or treatment to be used safely.

A

Phase 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

are done after the drug has been granted a license. They gather further information on the drug in areas not addressed in the previous trials (e.g. Safety in pregnancy) and also to find other potential uses for the drug.

A

Phase 4 (post-marketing trials)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

Pharmacokinetics - core components (4)

A

Absorption

Distribution

Metabolism

Elimination

‘ADME’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Absorption (definition)

A

The process by which a drug enters the bloodstream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

What route of administration yields the fastest absorption?

A

Inhalation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Bioavailability (definition)

A

the fraction of an administered dose of a drug that reaches the systemic circulation in an unchanged form

(by definition, when a medication is administered intravenously, its bioavailability is 100%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

Distribution (definition + two key factors)

A

the reversible transfer of a drug from one location to another within the body

2 important factors affecting this are:

  • tissue perfusion
  • drug lipophilicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Metabolism (definition)

A

the biotransformation of compounds into new compounds, in order that they are made more water-soluble and can be more easily excreted from the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Elimination (definition)

A

how a drug is removed from the body, whether unaltered or in the form of its metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

First-pass metabolism (aka, definition)

A

aka prehepatic/presystemic metabolism

the intestinal and hepatic degradation or alteration of a drug or substance taken by mouth, after absorption, that removes some of the active substance from the blood before it enters the general circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Plasma half-life (definition)

A

the time taken to eliminate 50% of the absorbed dose of a drug from a person’s plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

Biological half-life (definition)

A

the time taken for a drug to lose half of its pharmacologic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Clearance (definition)

A

the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time period

[aka renal clearance or renal plasma clearance where referring specifically to the kidneys]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

Blood brain barrier (definition, key facts)

A

a barrier separating the circulating blood flow in the human body from the extracellular fluid in the brain.

  • it consists of capillary endothelial cells tightly packed together
  • lipid soluble molecules pass through relatively easily whereas water soluble ones do not
  • Large molecules do not pass through the easily
  • Molecules that are highly charged struggle to pass through
  • The permeability of the BBB increases when it is inflamed
  • Nasally administered drugs can theoretically bypass the BBB
  • At several areas the BBB is fenestrated to allow neurosecretory products to enter the blood
    • Posterior pituitary
    • Area postrema
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

Cytochrome P450 system (essence)

A
  • an evolved mechanism that deals with exogenous toxins and is therefore essential in the metabolism of drugs
  • comprises about fifty separate enzymes
  • the enzymes are located on the endoplastic reticulum of cells and are mainly found in the liver and small intestine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

Which Cytochrome P450 enzyme is involved in the metabolism of clozapine?

A

CYP1A2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Grapefruit juice

(interaction with the Cytochrome P450 system, drugs affected)

A

Inhibits CYP3A4

Increases levels of:

  • carbamazepine
  • benzos: diazepam, nitrazepam
  • neuroleptics: aripiprazole, quetiapine
  • antidepressants: sertraline, trazodone

Inhibits CYP1A2

Increases levels of:

  • clozapine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

Caffeine

(interaction with the Cytochrome P450 system, drugs affected)

A

Inhibits CYP1A2

Increases levels of:

  • clozapine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

Tobacco

(interaction with the Cytochrome P450 system, drugs affected)

A

Induces CYP1A2

Reduces levels of:

  • clozapine
  • olanzapine
  • fluvoxamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

Steady state (essence)

A

This refers to the situation where the intake of a drug is at the same overall rate as its elimination from the body, so that there is no net change in the amount of drug in the person’s system.

It is usually reached after 4-5 times the half-life of the drug has elapsed after commencement of regular dosing.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

First-order kinetics

(aka, essence)

A

aka Linear kinetics

elimination of the drug takes place at a rate proportional to the plasma concentration

  • a constant fraction of the drug is eliminated per unit time, but the actual amount of drug eliminated per unit time varies (reduces with plasma concentration)
  • drugs that follow linear kinetics have a fixed half-life
  • most drugs undergo linear kinetics
117
Q

Zero-order kinetics

(aka, essence)

A

aka non-linear kinetics

elimination of the drug take place at a constant rate, regardless of the plasma concentration

  • the fraction of the drug eliminated per unit time varies, but the actual amount of drug eliminated per unit time stays the same
  • drugs that follow non-linear kinetics do not have a fixed half-life (the half-life will be longer at the beginning and get shorter as the total amount of drug in the body decreases)
118
Q

Pharmacokinetic changes with increasing age

(distribution)

A

More fat, less water

  • lipid-soluble drugs are more widely distributed, therefore decreased plasma levels
  • water-soluble drugs are less well-distributed, therefore increased plasma levels

Less albumin

  • greater unbound free fraction (increased amounts of active drug)
119
Q

Pharmacokinetic changes with increasing age (metabolism)

A

Reduced liver activity -> reduced first-pass metabolism

120
Q

Pharmacokinetic changes with increasing age (elimination)

A

More fat, less water

  • half-life of lipid-soluble drugs is increased
121
Q

Which cytochrome P450 enzyme displays the most phenotypic variation?

A

CYP2D6

122
Q

Frequency of CYP2D6 poor metabolisers across ethnic groups

A

Asian < Caucasian < African American

123
Q

Which ethnic groups have the highest proportions of CYP2D6 ultrarapid metabolisers?

A

Middle Eastern and North African

124
Q

Pharmacokinetic changes in pregnancy (distribution, excretion)

A

D - increased water and fat content leads to dilution and hence lower plasma levels of drug

E - increased blood flow leads to increased renal clearance of many drugs

125
Q

Benzodiazepines are metabolised in the liver by which Cytochrome P450 enzyme

A

CYP3A4

126
Q

Drugs that have been removed from the UK market due to their effect on the QTc interval (2)

A

thioridazine

droperidol

127
Q

Kinetic homogeneity (essence)

A

An assumption made in therapeutic drug monitoring that plasma drug concentration is roughly equal to the concentration at the site of action.

128
Q

Therapeutic Index (definition)

A

TD50: ED50

The ratio of the median toxic dose (TD50) and the median effective dose of a drug (ED50)

129
Q

Therapeutic Window (definition)

A

The difference between the minimum effective concentration and the minimum toxic concentration of a drug

130
Q

Psychiatric drugs with narrow therapeutic index (3)

A

Carbamazepine

Lithium

Phenytoin

131
Q

Diazepam (active metabolite)

A

Desmethyldiazepam

132
Q

Dothiepin (active metabolite)

A

Dothiepinsulfoxide

133
Q

Fluoxetine (half-life)

(active metabolite + half-life)

A

Fluoxetine half-life - 4-6 days

Fluoxetine’s active metabolite is norfluoxetine

  • has a similar activity on 5-HT reuptake
  • half-life of 4-16 days
134
Q

Imipramine (active metabolite)

A

Desimipramine

135
Q

Risperidone (active metabolite)

A

9-Hydroxyrisperidone

136
Q

Amitriptyline (active metabolite)

A

Nortriptyline

137
Q

Codeine (active metabolite)

A

Morphine

138
Q

Amisulpride

(mechanism of action, profile)

A

D2/D3 selective antagonist

cause substantial increase in prolactin

less likely to produce EPSEs

lack sedative and anticholinergic properties

low affinity selective antagonist of ‘D2 like’ receptors (D2=D3>D4) - little affinity for D1 like receptors (D1 and D5) or non dopaminergic receptors (serotonin, histamine, adrenergic, and cholinergic)

139
Q

Aripiprazole

(mechanism of action, profile)

A

D2 partial agonist

5HT1A partial agonist

5HT2A antagonist

activating profile

prodopaminergic SEs - insomnia, nausea, vomiting

less likely to cause weight gain

140
Q

Arsenapine

(mechanism of action, profile)

A

D2 antagonist

5HT2A antagonist

alpha-2 adrenoceptor antagonist

requires sublingual administration in UK

licensed for mania but no schizophrenia

141
Q

Chlorpromazine

(mechanism of action, profile)

A

D2 antagonist

alpha-1 adrenoceptor antagonist -> hypotension

H1 antagonist -> sedating

muscarinic acetylcholin receptor antagonist -> dry mouth, urinary difficulties, constipation

142
Q

Clozapine

(mechanism of action)

A

D2 antagonist (weak)

D4 antagonist

5HT2 antagonist (high affinity)

5HT6 antagonist

H1 antagonist

Alpha-1 antagonist

Muscarinic cholinergic receptor antagonist

143
Q

Lurasidone

(mechanism of action, profile)

A

D2 antagonist (potent)

5-HT2 antagonist (potent)

Binds only weakly to H1 and and alpha-1 receptors, therefore less sedation, weight gain, and orthostatic hypotension

144
Q

Olanzapine

(mechanism of action, profile)

A

High 5HT2/D2 blocking ratio

Potent D4 and 5HT6 blockade

Significant anticholinergic and H1-antagonism, therefore strongly sedating

145
Q

Quetiapine

(mechanism of action, profile)

A

D2 antagonist (weak)

5-HT2 antagonist (weak)

H1 antagonist and anticholinergic

Highly sedating

146
Q

Risperidone

(mechanism of action, profile)

A

D2 antagonist (potent)

5-HT2 antagonist (potent)

alpha-1 antagonist

mild sedation and hypotension

in higher therapeutic doses can lead to EPSEs and hyperprolactinaemia similar to typicals

147
Q

Sulpiride

(mechanism of action, profile)

A

Selective D2 antagonism

causes substantial increase in prolactin

less likely to produce EPSEs

lack sedative and anticholinergic properties

148
Q

Ziprasidone

(mechanism of action, profile)

A

D2 antagonist

5HT2 antagonist

5HT1a agonist

Noradrenaline reuptake inhibitor

Not licensed in UK

QT interval prolongation

149
Q

Agomelatine

(mechanism of action)

A

Melatonergic receptor agonist (MT1 and MT2)

5-HT2C antagonist

150
Q

Bupropion

(mechanism of action, profile)

A

Norepinephrine-dopamine reuptake inhibitor (NDRI)

Nicotinic acetylcholine receptor antagonist

Used in smoking cessation and depression

=====================================

Class - Aminoketone

Increases seizure risk and is contraindicated in seizure disorders

151
Q

Buspirone

(mechanism of action, profile)

A

5HT1A partial agonist

Effective in generalised anxiety disorder but not panic disorder.

Unlike benzodiazepines, the anxiolytic effects take several days to develop.

152
Q

Citalopram

(mechanism of action, profile)

A

Selective Serotonin Re-uptake Inhibitor (SSRI)

Associated with QT interval prolongation

153
Q

Clomipramine

(mechanism of action, profile)

A

5HT reuptake inhibitor (most potent of the tricyclics)

Its metabolite desmethylclomipramine is an effective noradrenaline reuptake inhibitor

Only tricyclic effective in OCD

154
Q

Duloxetine

(mechanism of action)

A

Serotonin and noradrenaline reuptake inhibitor (SNRI)

155
Q

Mirtazapine

(mechanism of action, profile)

A

Noradrenaline and serotonin specific antidepressant (NaSSa)

5HT2 antagonist

5HT3 antagonist

H1 antagonist

alpha 1 and alpha 2 antagonist

muscarinic antagonist (moderate)

Sedating profile

156
Q

Venlafaxine

(mechanism of action, profile)

A

Serotonin and noradrenaline reuptake inhibitor (SNRI)

  • potent 5HT reuptake inhibition
  • noradrenaline reuptake inhibition only apparent at higher doses
  • negligible affinity for other receptors, therefore lacks sedative and anticholinergic properties*
157
Q

Reboxetine

(mechanism of action, profile)

A

Selective Noradrenaline Re-uptake Inhibitor (NARI)

No clinically significant effects on other receptors

158
Q

St John’s Wort

(mechanism of action, profile)

A

Weak MAOI

Weak SNRI

(also considered by some to be a weak SSRI)

159
Q

Trazodone

(mechanism of action, profile)

A

SARI (Serotonin antagonist and reuptake inhibitor)

5HT2 antagonism

5HT reuptake inhibition (weak)

alpha-1 antagonism

Distinct sedating profile

160
Q

Moclobemide

(mechanism of action, profile)

A

Reversible inhibitor of monoamine oxidase type A

No tyramine reaction, making it advantages compared with conventional MAOIs. However, therapeutic efficacy not well established.

161
Q

Donepezil

Rivastigmine

Galantamine

(mechanism of action)

A

Reversible acetylcholinesterase inhibitor (all)

Rivastigmine is additionally a butyrylcholinesterase inhibitor

Galantamine is additionally a nicotinic acetylcholine receptor agonist

162
Q

Memantine

(mechanism of action)

A

NMDA (glutamate) receptor antagonist

163
Q

Valproate

(mechanism of action, profile)

A

Unknown. However, according to MRCPsych mentor:

GABA agonist

NMDA antagonist

164
Q

Gabapentin

(mechanism of action, profile)

A

Mechanism unclear - known to inhibit voltage activated calcium channels but it is not clear if this is how it exerts its therapeutic effect

  • Sedating*
  • Not licensed for the treatment of mood disorders*
165
Q

Topiramate

(mechanism of action)

A

GABA agonist

NMDA antagonist

Na channel stabiliser

166
Q

Carbamazepine

(mechanism of action)

A

Stabilises Na channels

167
Q

Phenytoin

(mechanism of action)

A

Stabilises Na channels

168
Q

Lamotrigine

(mechanism of action, profile)

A

Blocks voltage-dependent sodium channels

Reduces excitatory neurotransmitter release - esp. glutamate

  • not licensed in UK for mood disorders.*
  • some evidence of benefit in bipolar depression, but not mania*
169
Q

Pregabalin

(mechanism of action, profile)

A

Inhibition of the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system

licensed for generalised anxiety disorder and neuropathic pain

170
Q

Benzodiazepines

(mechanism of action)

A

Facilitate GABA transmission by acting as agonists on the omega site within the GABA-A complex

(all are agonists except clonazepam which is a partial agonist)

They therefore facilitate inhibitory neurotransmission via chloride ions - they increase the frequency and duration (not number) of chloride channel openings

171
Q

Z-drugs

(mechanism of action)

A

GABA-A agonists

(but act on different parts of the GABA-A complex to benzodiazepines)

172
Q

Ketamine

(mechanism of action)

A

NMDA antagonist

173
Q

Phencyclidine

A

NMDA antagonist

174
Q

Lofexedine

(mechanism of action, use)

A

(presynpatic) Alpha 2 adrenoceptor agonist

historically used to treat high blood pressure, but more commonly used to help with the physical symptoms of opioid withdrawal

175
Q

Clonidine

(mechanism of action, uses)

A

(presynaptic) Alpha 2 adrenoceptor agonist

Hypertension

Prevention of recurrent migraine,

Prevention of vascular headache,

Menopausal symptoms, particularly flushing and vasomotor conditions

176
Q

Buprenorphine

(mechanism of action, use)

A

Partial agonist at the mu-opioid receptor

Adjunct in the treatment of opioid dependence

177
Q

Naloxone

(mechanism of action)

A

Short-acting mu opioid antagonist

178
Q

Methadone

(mechanism of action, use)

A

Mu opioid receptor agonist

Adjunct in treatment of opioid dependence

Longer acting than heroin

179
Q

Atomoxetine

(mechanism of action, use)

A

Noradrenaline reuptake inhibitor (NARI)

used in ADHD

180
Q

Varenicline

(mechanism of action, use)

A

selective nicotine-receptor partial agonist.

used in smoking cessation

181
Q

Disulfiram

(mechanism of action, use)

A

Irreversibly inhibits aldehyde dehydrogenase

Adjunct in the treatment of alcohol dependence

182
Q

Acamprosate

(mechanism of action, use)

A

Metabotropic glutamate receptor antagonist

GABA-A agonist

a synthetic taurine analogue

Maintenance of abstinence in alcohol-dependent patients

183
Q

Selegiline

(mechanism of action, use)

A

selective, irreversible inhibition of monoamine oxidase type B

(also inhibits MAO-A at higher doses)

Parkinson’s disease

184
Q

Drugs that inhibit tricyclic antidepressant metabolism (6)

A

Phenothiazines

SSRI: fluoxetine, paroxetine

Disulfiram

Methylphenidate

Quinidine

Cimetidine

185
Q

Drugs that induce tricyclic antidepressant metabolism (5)

A

Smoking

Phenytoin

Carbamazepine

Contraceptive pill

Barbiturates

186
Q

Tricyclics and Phenothiazines - interaction

A

Mutual inhibition of metabolism

-> increase in levels of both antipsychotic and TCA

187
Q

Tricyclics and warfarin - interaction

A

TCAs increase warfarin levels - high risk of bleeding

188
Q

Tricyclics and clonidine - interaction

A

TCAs reduce clonidine levels - risk of hypertensive crisis

189
Q

Tricyclics and MAOIs - interaction

A

Synergistic serotonergic enhancement (especially with clomipramine)

-> increased risk of serotonin syndrome

TCAs reduce tyramine entry via monoamine reuptake channels

-> lower risk of cheese reaction

190
Q

Fluoxetine and Paroxetine - pharmacokinetics

A

Both are capable of inhibiting their own clearance at clinically relevant doses

  • they therefore have nonlinear pharmacokinetics
  • changes in dose can produce proportionately large changes in plasma level
191
Q

Most selective SSRI

A

Citalopram

(and escitalopram)

192
Q

Citalopram

  • half-life
  • interactions
A

33 hours

Not a potent inhibitor of most cytochrome enzymes

193
Q

Escitalopram

  • half-life
  • interactions
A

30 hours

Not a potent inhibitor of most cytochrome enzymes

194
Q

Fluoxetine

  • half-life
  • interactions
A

4-6 days

Inhibits CYP2D6, CYP3A4.

Increases levels of some antipsychotics, some benzodiazepines, carbamazepine, ciclosporin, phenytoin, tricyclics

Never use with MAOIs

Avoid selegiline and St John’s Wort

195
Q

Fluvoxamine

  • half-life
  • interactions
A

17-22 hours

Inhibits CYP1A2/2C9/3A4.

Increases levels of some benzodiazepines, carbamazepine, ciclosporin, phenytoin, some tricyclics, methadone, olanzapine, clozapine, propanolol, theophylline, warfarin

196
Q

Paroxetine

  • half-life
  • notable side effects
  • interactions
A

24 hours

antimuscarinic effects and sedation more common

Potent inhibitor of CYP2D6/3A4.

Increases levels of some antipsychotics and tricyclics

Never use with MAOIs. Avoid St John’s Wort

197
Q

Sertraline

  • half-life
  • interactions
A

26 hours

Inhibits CYP2D6.

Increases levels of some antipsychotics and tricyclics

Avoid St John’s Wort

198
Q

irreversible MAOIs

  • how long to wait after stopping before starting drugs with potential interactions
A

2 weeks

199
Q

MAOI - combinations

A

The combination of MAOIs and TCAs, appears safe if both treatments are initiated in low doses simultaneously and are gradually increased together.

The combination of MAOIs and SSRIs (or clomipramine) is generally contraindicated, because it can cause potentially fatal reactions such as serotonin syndrome.

200
Q

Lithium (pharmacokinetics)

  • absorption
  • distribution
  • metabolism
  • elimination
A

rapidly absorbed following oral administration

does not bind to plasma proteins

it is not metabolised so does not have an active metabolite

it is almost exclusively excreted by the kidneys unchanged

========================

Blood samples for lithium should be taken 12 hours post dose (for people prescribed a single daily dose).

201
Q

Lithium - monitoring

A

Lithium blood level should ‘normally’ be checked every 3 months

Thyroid and renal function should be checked every 6 months

202
Q

Adverse drug reactions

  • type A
  • type B
A

Type A (pharmacological) can be predicted from the pharmacology of the drug involved. They are dose dependent and so are reversible on withdrawal of the drug.

Type B reactions (idiosyncratic) cannot be predicted from the known pharmacology of the drug. Type B reactions include allergic reactions.

=======================

Type A accounts for 80% of all ADRs

203
Q

Antidopaminergic side effects (8)

A

Galactorrhoea, gynecomastia,

menstrual disturbance,

lowered sperm count,

reduced libido,

Parkinsonism,

dystonia,

akathisia,

tardive dyskinesia

204
Q

Anticholinergic (central M1) side effects (2)

A

Memory impairment,

confusion

205
Q

Anticholinergic (peripheral M1) side effects (7)

A

Dry mouth,

blurred vision,

glaucoma,

tachycardia,

urinary retention,

constipation,

ataxia

206
Q

Histaminergic H1 side effects (2)

A

Weight gain,

sedation

207
Q

Adrenergic alpha 1 antagonism side effects (4)

A

Orthostatic hypotension,

sedation,

sexual dysfunction,

priapism

208
Q

Antipsychotics recommended in hepatic impairment (3)

A

Haloperidol
Amisulpride
Sulpiride

209
Q

Antidepressants recommended in hepatic impairment (3)

A

Imipramine
Paroxetine
Citalopram

210
Q

Mood stabilisers recommended in hepatic impairment (1)

A

Lithium

211
Q

Sedatives recommended in hepatic impairment (4)

A

Lorazepam
Oxazepam
Temazepam
Zopliclone 3.75mg (with care)

212
Q

Receptors implicated in weight gain (2)

A

Histamine H1 antagonism

Serotonin 5-HT2C antagonism

213
Q

CNS side effects like anxiety and agitation in the initial few weeks of treatment with SSRIs are proposed to be due to —

(receptors, location)

A

Over stimulation of 5HT2 receptors in the limbic system

214
Q

Clozapine-related hypersalivation

  • suggested mechanisms (3)
A

muscarinic M4 agonism

adrenergic alpha 2 antagonism

inhibition of the swallowing reflex

215
Q

Which SSRI is present in high concentrations in breast milk?

A

Fluoxetine

216
Q

Tetrabenazine

  • use
A

Licensed in UK for treatment of moderate to severe tardive dyskinesia

217
Q

Terazosin

  • mechanism
  • use
A

alpha 1 adrenoceptor antagonist

effective in reducing excessive sweating caused by antidepressant treatment, especially venlafaxine and SSRIs

218
Q

Psychostimulants

(Dexamfetamine, Methylphenidate)

  • common side effects (3)
A

appetite suppression

sleep disturbance

abdominal pain

219
Q

Psychostimulants

(Dexamfetamine, Methylphenidate)

  • uncommon side effects (6)
A

weight loss

restricted growth

headache

worsening of tics

behavioural rebound

significantly raised blood pressure

220
Q

QTc prolongation

  • cardiac risk factors (6)
A

Long QT syndrome
Bradycardia
Ischaemic heart disease
Myocarditis
Myocardial infarction
Left ventricular hypertrophy

221
Q

QTc prolongation

  • metabolic risk factors (3)
A

Hypokalaemia
Hypomagnesaemia
Hypocalcaemia

222
Q

QTc prolongation

  • risk factors (other) - 5
A

Extreme physical exertion
Stress or shock
Anorexia nervosa
Extremes of age (old or young)
Female gender

223
Q

Non-psychotropic drugs causing QTc prolongation

  • antibiotics (2)
  • antiarrthythmics (2)
  • antimalarials (2)
  • Others (3)
A

Antibiotics

  • Ampicillin
  • Erythromycin

Antiarrthythmics

  • Amiodarone
  • Sotalol

Antimalarials

  • Chloroquine
  • Quinine

Others

  • Methadone
  • Tamoxifen
  • Amantadine
224
Q

QTc interval (men)

  • normal
  • borderline
  • prolonged
A

normal <440

borderline 440-450

prolonged >450

225
Q

QTc interval (women)

  • normal
  • borderline
  • prolonged
A

normal <440

borderline 440-460

prolonged >460

226
Q

QTc interval

<440ms (men)

<470ms (women)

(Recommended action)

A

No action required unless T-wave morphology

227
Q

QTc interval:

>440ms (men)

>470ms (women)

(recommended action)

A

Consider reducing dose

or switching to drug of lower QTc effect,

repeat ECG and refer to cardiology

228
Q

QTc interval:

>500ms (men and women)

(recommended action)

A

Stop causative drug,

switch to drug of lower effect

refer to cardiology

229
Q

Antipsychotics with high effect on QTc interval (2)

A

Haloperidol

Pimozide

230
Q

Antipsychotics with moderate effect on QTc interval (4)

A

Quetiapine

Chlorpromazine

Zotepine

Ziprasidone

231
Q

Antipsychotics with low effect on QTc interval (4)

A

Amisulpride

Clozapine

Olanzapine

Risperidone

232
Q

Antipsychotics with no effect on QTc interval (2)

A

Aripiprazole

Paliperidone

233
Q

Adverse drug reactions

  • Type A
  • Type B
A

Type A (pharmacological) reactions can be predicted from the pharmacology of the drug involved. They are dose dependent and so are reversible on withdrawal of the drug.

Type B (idiosyncratic) reactions cannot be predicted from the known pharmacology of the drug. Type B reactions include allergic reactions.

====================================
Type A account for up to 80% of all ARDs.

234
Q

Affinity

(definition)

A

how avidly the drug binds to the receptor

235
Q

Potency

(definition)

A

the concentration or dose of a drug required to produce 50% of the drug’s maximal effect.

Potency depends on both the affinity of a drug for its receptor, and the efficiency with which drug-receptor interaction is coupled to response

236
Q

Efficacy

(aka, definition)

A

also referred to as ‘intrinsic activity’

the ability of the drug to elicit a response when it binds to the receptor

237
Q

EPSEs (4)

A

Parkinsonism - characterized by the triad of tremor, rigidity (lead pipe or cogwheel), and bradykinesia

Akathisia - a subjective sense of restlessness, along with such objective evidence of restlessness as pacing or rocking

Dystonias - prolonged and unintentional muscular contractions of voluntary or involuntary muscles

Tardive dyskinesia - involuntary, repetitive body movements. This may include grimacing, sticking out the tongue, or smacking the lips

‘PAD-T’

238
Q

EPSEs - Dystonia

  • prevalence
  • more common in (3)
  • time taken to develop
  • treatments (4)
A

10%

More common in:

  • young males
  • neuroleptic-naive
  • high potency drugs (e.g. haloperidol)

develops within minutes or hours of starting antipsychotics

Treatments:

  • anticholinergic drugs
  • switch antipsychotic
  • botulinum toxin
  • rTMS
239
Q

EPSEs - Dystonia

  • examples (5)
A

Torticollis - cervical muscles spasms, resulting in a twisted posturing of the neck.

Trismus - contraction of the jaw musculature and can result in lockjaw.

Opisthotonus - arched posturing of the head, trunk, and extremities.

Laryngeal dystonia - difficulty in breathing

Oculogyric crises - involuntary contraction of one or more of the extraocular muscles, which may result in a fixed gaze with diplopia

240
Q

EPSEs - Parkinsonism

  • prevalence
  • more common in (2)
  • time taken to develop
  • treatments (2)
A

20%

more common in

  • elderly females
  • those with pre-existing neuro damage (e.g. stroke)

Days to weeks after antipsychotic started or dose increased

Treatments

  • reduce dose/switch
  • anticholinergic drugs
241
Q

EPSEs - Akathisia

  • prevalence
  • time taken to develop
  • treatments (8)
A

25%

Hours to weeks

Treatments:

  • reduce dose/switch
  • propranolol
  • clonazepam
  • mirtazepine
  • trazodone
  • mianserin
  • cyproheptadine
  • diphenhydramine
242
Q

EPSEs - Tardive dyskinesia

  • prevalence
  • more common in (3)
  • time taken to develop
  • treatments (3)
A

5% of patients per year of antipsychotic exposure

More common in

  • elderly women
  • those with affective illness
  • those who have had EPSE early on in treatment

develops over months to years

Treatments

  • stop anticholinergic
  • reduce dose/switch to an atypical (clozapine/quetiapine)
  • tetrabenazine
243
Q

Antidepressants - alternative routes of administration

  • liquid (1)
  • patch (1)
A

liquid - Fluoxetine

patch - Selegeline

244
Q

Antidepressants available as IV preparations (4)

A

Citalopram

Mirtazepine

Amitriptyline

Clomipramine

245
Q

SIADH

  • risk factors (9)

Hyponatraemia caused by SIADH is associated with both antidepressants and antipsychotics

A

Being elderly

Being female

Being a smoker

Having medical co-morbidity

Polypharmacy

Low body weight

Low baseline sodium concentration

Reduced renal function

Warm weather

246
Q

Absorption

  • where does it occur?
A
  • Absorption by oral administration occurs primarily in the small bowel
  • Absorption of many slow or sustained release drugs occurs in the large bowel.
  • There is poor absorption in the acidic stomach but conversely good absorption in the alkaline jejunum, ileum, colon and rectum.
247
Q

Serotonin syndrome

  • cause
  • onset
  • clinical presentation
A

excess serotonergic activity in the CNS

most frequent cause of severe reaction is the co-administration of an MAOI with an SSRI

typically acute and rapidly progressive, following shortly after one or two doses of the offending medication.

clinical triad:

  • neuromuscular abnormalities
    • clonus
    • hyperreflexia
    • muscular rigidity
  • altered mental state
  • autonomic dysfunction
    • hyperthermia
248
Q

Neuroleptic malignant syndrome (NMS)

  • cause
  • onset
  • presentation
A

almost exclusively caused by antipsychotics (but is also associated with antidepressants and lithium).

Rapid and large dose increases often trigger it, along with rapid dose reductions, and abrupt withdrawal of anticholinergics.

typically develops within 2 weeks of initial treatment but may occur at any time the drug is being taken.

Presentation

  • hyperthermia
  • muscle rigidity -> rhabdomyolysis, elevated CPK
  • altered consciousness
249
Q

Serotonin syndrome vs Neuroleptic malignant syndrome

  • commonalities
  • differences
A

Common features include alteration in consciousness, sweating, autonomic instability, hyperthermia, and elevated CPK levels.

Serotonin syndrome typically has an acute onset (within 24 hours of drug administration), whereas that of NMS is more insidious (typically taking up to 2 weeks to appear).

250
Q

Nocturnal enuresis in children

  • licensed antidepressants (3)
A

Amitriptyline

Imipramine

Nortriptyline

251
Q

Phobic and obsessional states

  • licensed antidepressants (1)
A

Clomipramine

252
Q

Adjunctive treatment of cataplexy associated with narcolepsy

  • licensed antidepressants (1)
A

Clomipramine

[Cataplexy - ‘C’ for ‘Clomipramine’]

253
Q

Panic disorder and agoraphobia

  • licensed antidepressants (5)
A

Citalopram

Escitalopram

Sertraline

Paroxetine

Venlafaxine

254
Q

Social anxiety / phobia

  • licensed antidepressants (5)
A

Escitalopram

Paroxetine

Sertraline

Moclobemide

Venlafaxine

255
Q

Generalised anxiety disorder

  • licensed antidepressants (4)
A

Escitalopram

Paroxetine

Duloxetine

Venlafaxine

256
Q

OCD

  • licensed antidepressants (5)
A

Escitalopram

Fluoxetine

Fluvoxamine

Paroxetine

Sertraline

257
Q

Bulimia nervosa

  • licensed antidepressants (1)
A

Fluoxetine

258
Q

PTSD

  • licensed antidepressants (2)
A

Paroxetine

Sertraline

259
Q

Modafinil

  • class
  • properties
  • uses
A

psychostimulant

enhances wakefulness, attention, and vigilance. It is similar to amphetamines apart from that it tends to lack the euphoric effects, does not seem to be associated with dependence or tolerance, and does not tend to precipitate psychosis.

licensed for:

  • narcolepsy
  • obstructive sleep apnea
  • chronic shift work
  • also suggested as an adjunctive treatment for depression (in the Maudsley).

More recently it has also been used as a ‘smart drug’ in the hope that it will boost normal cognitive functioning.

260
Q

Schizophrenia (Duration of treatment)

A

Inform the service user that there is a high risk of relapse if they stop medication in the next 1-2 years.

(NICE guidelines)

261
Q

Cannabis (heavy use)

  • Length of time detectable in urine
A

14-28 days

262
Q

Cannabis (single use)

  • Length of time detectable in urine
A

3 days

263
Q

Phencyclidine

  • Length of time detectable in urine
A

8 days

264
Q

Methadone

  • Length of time detectable in urine
A

3 days

265
Q

Morphine

  • Length of time detectable in urine
A

3 days

266
Q

Benzodiazepine

  • Length of time detectable in urine
A

3 days

267
Q

Heroin

  • Length of time detectable in urine
A

3 days

268
Q

Cocaine

  • Length of time detectable in urine
A

1-3 days

269
Q

Amphetamine

  • Length of time detectable in urine
A

1-3 days

270
Q

LSD

Length of time detectable in urine

A

1-3 days

271
Q

Codeine

Length of time detectable in urine

A

2 days

272
Q

Alcohol

Length of time detectable in urine

A

12 hours

273
Q
A
274
Q

What proportion of people prescribed Clozapine experience silarrhoea?

A

31% of patients using clozapine develop hypersalivation (silarrhoea)

275
Q

Suboxone

  • constituents
A

Suboxone is a combination of four parts buprenorphine to one part naloxone.

The latter is added to prevent addicts from injecting the tablets, as this was common when addicts were given pure buprenorphine tablets. Because it contains naloxone it is likely to produce intense withdrawal symptoms if injected, this does not occur when the tablet is swallowed as naloxone is not absorbed by the gut.

276
Q

Subutex

  • active ingredient
A

buprenorphine

277
Q

Time to steady state:

Amisulpride
Clozapine
Quetiapine
Risperidone (oral)
Tricyclics
Valproate

A

2-3 days

278
Q

Time to steady state:

Lithium

A

4-5 days

279
Q

Time to steady state:

Aripiprazole

A

14-16 days

280
Q

Time to steady state:

Carbamazapine

A

14 days

281
Q

Time to steady state:

Olanzapine

A

7 days

282
Q

Time to steady state:

Risperidone (depot)

A

6-8 weeks

283
Q

Time to steady state

Paliperidone (depot)

A

2 months

284
Q

Clozapine - neutropenia

  • risk factors (3)
A

Race - Afro-Caribbean 77% increase in risk

Age - risk decreases as age increases

Low baseline white cell count

285
Q

Clozapine - agranulocytosis

  • definition
  • risk factors (2)
A

absolute neutrophil count (ANC) of less than 0.5 * 10^9/L

Ethnicity - Asians are 2.4 times more likely than Caucasians to develop agranulocytosis on clozapine

Age - risk increases with age

286
Q

Tardive dyskinesia

  • risk factors (7)
A

Advancing age

Female

Ethnicity - higher rates in African Americans

Affective disorder

1st gen > 2nd antipsychotics

Mental retardation

Substance abuse

287
Q

Drugs unsuitable for compliance aids e.g. dosette box (8)

A

Sodium valproate

Zopiclone

Venlafaxine

Topiramate

Methylphenidate

Mirtazapine

Olanzapine

Amisulpride

Aripiprazole

288
Q

CYP2D6 is inactive in —% of white people, and —% of Asians

(i.e. they are poor metabolisers)

A

CYP2D6 is inactive in 6-10% of white people, and 2% of Asians.

MRCPsych Part A small (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions