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Paper A - MRCPsych > Psychopharmacology > Flashcards

Psychopharmacology Flashcards

1
Q

What is the name given to the range of doses at which a medication appeared to be effective in clinical trials for a median of participants without unacceptable adverse effects?

A

Therapeutic Index/ Therapeutic ratio

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2
Q

When does a drug have a narrow TI?

A

Less than 2x difference in minimum toxic conc, and minimum effective conc

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3
Q

Pharmacodynamics vs pharmacokinetics:

A

Pharmacokinetics = how the body affects the drug:
ADME (Absorption, Distribution, Metabolism, Excretion)

Pharmacodynamics - how the drug affects the body (mechanism of action, physiological effects)
D - Dynamics - Drug (affecting body)

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4
Q

Pharmacokinetic effects in elderly:
- Distribution

A

Increased body fat and decreased albumin and water = increased distribution of lipid sol drugs = prolonged half-life (prolonged side effects) PLUS increased conc of H2O sol drugs so lower doses needed
Increased VOL OF DISTRIBUTION for fat sol drugs

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5
Q

Pharmacokinetic effects in elderly:
- Absorption

A

Reduced gastric acid secretion and gastric motility - no huge effect clinically

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6
Q

Pharmacokinetic effects in elderly:
- Metabolism

A

Hepatic metabolism of drugs decreases with age as a consequence of reduced hepatic blood flow and reduced enzyme activity.

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7
Q

Pharmacokinetic effects in elderly:
- Excretion

A

By 65, 35% of renal function is lost, and by 80, 50% is lost - smaller doses needed of drgs primarily excreted by the kidney e.g lithium, sulpride

NB: Serum creatinine and urea is often used to estimate renal function but can be misleading in the elderly as they have less muscle and so produce less creatinine.

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8
Q

Pharmacodynamics in the elderly:

A

Increased receptor sensitivity = smaller doses required and more side effects
Reduced therapeutic response

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9
Q

4 types of EPSE
What causes EPSEs?

A

Dystonias (young men)
Akathisia - most resistent to treat
Parkinsonism (older females)
Tardive Dyskinesia (older females, affective illness)

Caused by antagonism of dopaminergic D2 receptors in the basal ganglia.
Threshold of approx 80% receptor occupancy = EPSEs occur

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10
Q

Tetrabenzine (a reversible inhibitor or vesicular monoamine transporter 2) is used to treat which EPSE?

A

Tardive Dyskinesia - happens down the line e.g months to years later

NB: Also discontinue anticholinergics (unlike the other ESPEs where these can be used as treatment)

Also, Ginkgo Bilboa

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11
Q

A subjective sense of restlessness, along with such objective evidence of restlessness as pacing or rocking is known as:
What are the treatments?

A

Akathisia - most resistant EPSE to treat

Can use Mirtazapine/ Mianserin in low doses
Propranolol
Benzos - clonazepam, diazepam as longer 1/2 life
Anticholinergics
Cyproheptadine (a H1 receptor blocker, and 5HT-2 receptor antagonist)
Clonidine

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12
Q

What is tardive dyskinesia?
Where?
When better or worse?
When does it happen?

A

Involuntary and repetitive body movements

Face affected in 75%
Limbs in 1/2
Trunk in 1/4

Fluctuates, worse with increased arousal and distraction, and anticholinergics
Better with sleep, relaxation and voluntary movements

Happen when pt has been on meds for long time

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13
Q

5 types of dystonia:

A

1) torticollis - cervical muscles spasms, resulting in a twisted posturing of the neck
2) trismus (lock-jaw)
3) opisthotonus - arched posturing of the head, trunk, and extremities.
4) laryngeal dystonia - difficulty breathing
5) occulogyric crises - involuntary contraction of one or more of the extraocular muscles, which may result in a fixed gaze with diplopia

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14
Q

Mechanism of action of Mirtazapine:

Mirtazapine acts by antagonism of these 5 receptors:

A

Noradrenaline and serotonin specific antidepressant (NaSSa)

5HT2
5HT3
H1 - most effective here at lower doses
Alpha 1
Alpha 2 - more effective at higher doses here, causes more wakefulness

(All of these enhance sleep except for alpha 2 which is a presynaptic receptor that inhibits the release of norepinephrine.)

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15
Q

In the P450 system, which enzyme shows the largest phenotypic variation amongst the cytochromes?

A

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

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16
Q

How do tobacco and grapefruit juice affect clozapine?

A

Tobacco induces CYP1A2 and so lowers clozapine levels. Grapefruit juice inhibits CYP1A2 and therefore can increase clozapine levels.

(CYP1A2 = primarily responsible for clozapine metabolism)

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17
Q

How do smoking, alcohol, barbiturates, carbamazepine, Phenytoin, and St John’s Wort affect the P450 system?

A

Inducers

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18
Q

How do chlorpromazine, SSRI’s, and grapefruit juice affect the P450 system?

A

Inhibitors

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19
Q

Which enzyme in the P450 system exhibits genetic polymorphism (it varies in its expression from person to person)?

A

CYP2D6 - Caucasians show less activity of CYP2D6 (6-10% poor metabolisers) than their Asian (2% poor metabolisers) counterparts.

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20
Q

5 key features of NMS:

A
  • mental status changes (first sign)
  • muscular rigidity
  • hyperthermia
  • autonomic instability (typically tachycardia)
  • elevated CK
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21
Q

which drug is a recognised cause of hypercalcemia and hyperparathyroidism?

A

Lithium

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22
Q

Suboxone vs Subutex

A

Suboxone = buprenorphine and naloxone (4:1)
Subutex = just buprenorphine

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23
Q

Which ADHD drug is a prodrug?

A

Lisdexamphetamine is absorbed by GI tract, converted to dexamfetamine which inhibits the reuptake of NA and DA.

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24
Q

What is the mechanism of action of dexamphetamine and methylphenidate?

A

Inhibit both DA and NA uptake - SODIUM-dependent

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25
Q

Naloxone vs Naltrexone:

A

Both opioid antagonists

Naloxone - pure (competitive) opioid antagonist at mu, delta, kappa - It reveals very high affinity for the opioid receptor sites and therefore displaces both opioid agonists and partial antagonists. Note: no mu efficacy, but high affinity.

Naltrexone - LONGER ACTING
Targets all receptors but mostly Mu

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26
Q

Which mood stabiliser has GABA modulation (increases GABA in the brain), sodium channel inhibition and NMDA antagonist?

A

Valproate

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27
Q

What is the mechanism of action of Carbamazepine and Phenytoin?

A

Stabilising Na channels - increases refractory period

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28
Q

Which mood stabiliser is a GABA modulator, NMDA antagonist, and Na channel stabiliser?

2 side effects to be aware of:

A

Topirimate

Increased GABA levels, inhibits socium channels therefore reducing action potentials

Can develop kidney stones
Weight loss and anorexia

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29
Q

Which mood stabiliser has NMDA receptor modulation, stabilises Na channels, blocks calcium channels, and has some GABA modulation?
What is it licenced for?

A

Lamotrigine

Epilepsy
Bipolar - prevention of depression in bipolar I - not licenced for acute treatment of manic or depressive episodes)

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30
Q

Which 2 mood stabilisers bind to the alpha-2-delta subunit of voltage-gated calcium channels, which reduces the release of certain neurotransmitters, including glutamate and substance P, and can help reduce neuronal excitability?

A

Gabapentin and Pregabalin

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31
Q

Which addictions drug is a pure opioid antagonist (will reverse mu, delta, and kappa)
1/2 life?

A

Naloxone

Short 1/2 life - 30-120 mins

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32
Q

Which addictions drug is a partial agonist at the mu-opioid receptor?
What affinity does it have?
Halflife?

A

Buprenorphine

5X HIGHER AFFINITY THAN MORPHINE
Half life 24-42 hours (oral)

Also partial kappa agonist and weak delta agonist

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33
Q

Which drug binds irreversibly to enzyme aldehyde dehydrogenase (ALDH) and causes acetaldehyde to accumulate following ingestion of alcohol

A

Disulfiram

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34
Q

Which addictions drug is an NMDA glutamate receptor antagonist and positive allosteric modulator of GABA-A receptors (effect on both receptors is indirect)?

A

Acamprosate - reduces the excitatory actions of glutamate in the central nervous system via the NMDA receptors. This modulation helps in reducing the withdrawal symptoms associated with alcohol dependence.

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35
Q

Type A vs Type B adverse drug reactions:

A

A: Pharmacological reactions
80% of ADRs
Predictable based on drug pharmacology
Dose dependent and reversible

B: idiosyncratic reactions
Unrelated to drug’s intended pharmacological action
Includes allergic reactions (4 types)

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36
Q

Type 1 allergic reactions:

A

IgE-mediated

Immediate hypersensitivity reactions
e.g anaphylaxis

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37
Q

Type 2 allergic reactions:

A

Cytotoxic (TOTO = 2x = type 2)

involve the activation of complement proteins and destruction of cells by antibodies.
Examples include drug-induced haemolytic anaemia or thrombocytopenia.

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38
Q

Type 3 allergic reactions:

A

Immune Complex

Antigen-antibody aggregates (immune complexes), can form and deposit in tissues, leading to inflammation. This can manifest as conditions like serum sickness or drug-induced lupus. These usually occur 1 to 3 weeks after exposure.

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39
Q

Type 4 allergic reactions

A

Cell-mediated

These reactions are mediated by T cells and occur over a delayed period, often days to weeks after exposure to the drug. Contact dermatitis and some forms of drug-induced hepatitis are examples.

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40
Q

Mechanism of action of caffeine:

A

Caffeine primarily acts as an adenosine (an endogenous purine nucleoside) antagonist.
Antagonistic effect at all 4 g-protein coupled adenosine receptor subtypes, but mostly A2A - involved in wakefulness

Normally, when adenosine binds to its receptors, neural activity slows down and we feel sleepy. Caffeine blocks this.

NB: Inhibitor of CYP1A2 = clozapine levels can decrease by nearly half following a 5 day caffeine-free period in a regular user

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41
Q

4 secondary amines:

A

Protriptyline
Amoxapine
Nortriptyline
Desipramine

PAND

The PANDa is DESperate for AMOXicillin

So you know that Amoxapine (not Amitriptyline) and Desipramine (not dosulepin or doxepin)

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42
Q

What name is given to a compound that binds to a receptor and produces the biological response?

A

Agonist

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43
Q

What is a partial agonist vs a full agonist?

A

A partial agonist produces the biological response but cannot produce 100% of the response even at very high doses.

A full agonist displays full efficacy at a receptor

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44
Q

What does an antagonist do?

A

Antagonists block the effects of agonists. They have no effect on their own.

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45
Q

What is an inverse agonist?

A

Inverse agonists have opposite effects from those of full agonists. It binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. They are not the same as antagonists, which block the effect of both agonists and inverse agonists.

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46
Q

What is a competitive antagonist?

A

Competitive antagonists bind to the receptor in a reversible way without affecting a biological response. They make the agonist look less potent.

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47
Q

What is a non-competitive antagonist?

A

These ALTER the receptor in some way to make binding harder and can only be reversed by increasing the dose of the agonist drug
These reduce the potency and efficacy of agonists

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48
Q

Which anticonvulsant/ mood stabiliser can cause Stevens-Johnson Syndrome?

A

Lamotrigine

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49
Q

Which antidepressants are licenced for nocturnal eneuresis in children: (3)

A

Amitriptyline, Imipramine, Nortriptyline

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50
Q

Which antidepressants are licenced for panic disorder and agorophobia: (5)

A

CEPSV

Citalopram, Escitalopram, Sertraline, Paroxetine, Venlafaxine

(Moclobemide = for social anxiety/ phobia, citalopram = for panic disorder/ agorophobia) - citAlopram = pAnic

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51
Q

Which antidepressants are licenced for social anxiety/ phobia: (5)

A

EMPSV

Escitalopram, Paroxetine, Sertraline, Moclobemide, Venlafaxine

(Moclobemide = for social anxiety/ phobia, citalopram = for panic disorder/ agorophobia) - MOCLO = SOcial, PHObia

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52
Q

Which antidepressants are licenced for generalised anxiety disorder: (4)

A

DEPV

Escitalopram, Paroxetine, Duloxetine, Venlafaxine

(NOT SERTRALINE or FLUOXETINE)

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53
Q

Which antidepressants are licenced for OCD: (6)

A

CEFFPS

Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Clomipramine

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54
Q

Clomiprimine is licenced for: (3)

A

On its own:
Phobic and obsessional states
Adjunctive treatment of cataplexy associated with narcolepsy

OCD (with other meds as well)

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55
Q

Which antidepressant is licenced for bulimia?

A

Fluoxetine

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56
Q

Which 2 antidepressants are licenced for PTSD?

A

Paroxetine and Sertraline

P(t)S(d)

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57
Q

Side effects at which receptors cause:

Galactorrhoea, gynecomastia, menstrual disturbance, lowered sperm count, reduced libido, Parkinsonism, dystonia, akathisia, tardive dyskinesia

A

Dopaminergic

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58
Q

Side effects at which receptors cause:

Drowsiness

A

Histaminergic

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59
Q

Side effects at which receptors cause:
Postural (orthostatic) hypotension and ejaculatory failure, priapism, sedation

A

Antiandrenergic (Alpha 1)

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60
Q

Side effects at which receptors cause:

Dry mouth, blurred vision, urinary retention, constipation, narrow angle glaucoma, ataxia

A

Anticholinergic (antimuscarinic PERIPHERAL M1 blockade)

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61
Q

Antagonism at which receptors cause:
Agitation, delirium, memory impairment, confusion, seizures?

A

Muscarinic CENTRAL M1 blockade

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62
Q

5 criteria (Barrter and Schwartz) for SIADH:

A

Euvolemia

Decreased serum osmolality (<275 mOsm/kg)

Increased urine osmolality (>100 mOsm/kg) and urine sodium (>20 mmol/L)

No other cause for hyponatraemia (no diuretic use and no suspicion of hypothyroidism, cortisol deficiency, marked hyperproteinaemia, hyperlipidaemia or hyperglycaemia).

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63
Q

Benzos vs Barbiturates mechanism of action:

A

GABA-A drugs:

Benzodiazipines increase the frequency of chloride channels
Barbiturates increase the duration of chloride channel opening

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64
Q

4 sedatives recommended in hepatic impairment:

A

Lorazepam
Oxazepam
Temazepam
Zopiclone

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65
Q

Teratogenic effects of Valproate vs Carbamazepine:

A

V: spina bifida, hypospadias, cleft lip/ palate (1-10%). developmental delay (31-40%), autism, congenital heart abnormalities

C: fingernail hypoplasia, cranialfacial defects

IMPORTANT: They can synergistically increase the teratogenic effects from each other

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66
Q
A
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67
Q

5 facts about tricyclics (pharmacokinetics):

A

Highly protein bound
Highly lipid soluble
Smoking facilitates metabolism so reduces levels by 25-50%
May reduce own absorption as anticholinergic effects
Extensive hepatic breakdown

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68
Q

Mechanism of Lithium-Induced DI:

A

Lithium causes dysregulation of cells of collecting duct. Cells of collecting duct are less responsive to ADH = induces expression of water transport proteins in the late distal tubule and collecting duct to increase water reabsorption.

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69
Q

Treatment options for Lithium-induced DI include (4 main ones):

A

1) stop lithium
2) keep levels 0.4-0.8
3) Once daily dosing at bedtime - lower trough levels allows for renal repair
4) amiloride (K+ sparing diuretic
OTHER:
Thiazide diuretics, indomethacin, desmopressin

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70
Q

Absorption of controlled release drugs and depot anhtipsychotics follow which type of kinetics?

A

Zero Order - i.e constant AMOUNT rather than constant FRACTION

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71
Q

First Order vs Zero Order kinetics:

A

ZOC FLaP

Rate of reaction dependent on concentration of substance?
FO: Y
ZO: N

1/2 life:
FO: Constant
ZO: Decreases with decreased concentration i.e no fixed 1/2 life

Most drugs follow First Order Kinetics - rate of elimination proportional to level of drug in body

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72
Q
A
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73
Q

How long do benzos take to reach peak serum levels?
What is the protein binding level?

A

30mins-2hrs

High - 70-99%

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74
Q

What is the volume of distribution?

A

Quantity of drug divided by plasma concentration, at zero time

It is a theoretical volume that a drug would occupy if it were uniformly distributed throughout the body and is proportionate to the dose given

(Larger VoD in lipid sol drugs. Higher VoD = drug in tissues, more than plasma)

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75
Q

Steady-state plasma levels are usually achieved after how many half lives?

A

4-5

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76
Q

What receptors does Clozapine have effects at?

A

Antagonist at 5-HT2A, D1, D3, D4
(D4 = most effect, cortical and limbic dopamine pathways, less at striatal)
Also potent antagonist of M1, H1, Alpha-1
Low potency antagonist of D2 (occupies 40-50% D2 receptors = fewer EPS)
Partial agonist at 5HT1A = beneficial in reducing negative symptoms

Agonism at M4 = hypersalivation
(Also 5-HT2C = receptor responsible for weight gain)

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77
Q

D1-like vs D2-like receptors:

A

D1-like: D1, D5 - high density in striatum, NA, olfactory bulb, SN
D1 and D5 receptors couple to G stimulatory sites and activate adenylyl cyclase. The activation of adenylyl cyclase leads to the production of the second messenger cAMP, which leads to the production of protein kinase A (PKA), which leads to further transcription in the nucleus.

D2-like: D2, D3, D4 - high density in striatum, external GP, NA, hippocampus and cortex
D2 through D4 receptors couple to G inhibitory sites, which inhibit adenylyl cyclase and activate K+ channels

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78
Q

Ammonium chloride can be used for urinary acidification for overdose of which drug?

A

Amphetamines

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79
Q

Drug tolerance vs Drug sensitisation:

A

Opposites.

Tolerance = reduced response with repeated exposure
Sensitisation = increased response with repeated exposure

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80
Q

How is Amisulpride excreted?

A

Through the urine - 50% is excreted unchanged (compared to 95% of lithium)
Also excreted in urine = gabapentin, amisulpride, acamprosate, amantadine

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81
Q

What is the half life of lithium?
What is the protein binding?
How does sodium affect the renal clearance?

A

10-24 hours
Low protein binding
Clearance reduced when low sodium

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82
Q

Which SSRI exhhibits autoinhibition?

A

Paroxetine i.e doses can x2 when increased by 50% - non linear dosing

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83
Q

What is the 1/2 life of quetiapine?

A

Around 7 hours = short = may require multiple x per day dosing

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84
Q

Define clearance:

A

Volume of blood plasma cleared of drug per unit time (NOT AMOUNT OF DRUG)
Determines 1/2 life
Specific for each drug and does NOT depend on drug conc in plasma
Depends on renal and non-renal clearance e.g sweat, bile
Involves metabolism and excretion

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85
Q

What is the Steady State?

A

Once the drug intake equals the clearance it is referred to as a steady state. Steady state is usually achieved by 4.5 half lives. The time taken to reach steady state therefore depends on the half life.

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86
Q

What happens to drugs that move from first order to zero order kinetics in supratherapeutic doses? (e.g fluoxetine)

A

Saturation of enzymes
Switch to ZO kinetics - regardless of how much drug in body, fixed amount cleared = no real 1/2 life any more and clearance becomes DEPENDENT on the dose

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87
Q

The active metabolite of
a) imipramine
b) amitriptyline

A

Desipramine
Nortriptyline

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88
Q

Mechanism of action of clonidine and guanfacine (ADHD meds)

A

Pre-synaptic alpha-2 receptor agonists = cause vasodilation of blood vessels, and reduce amount of norepinephrine released from presynaptic nerve terminals

Can cause orthostatic hypotension

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89
Q

What is the mechanism of mebolism of lorazepanm, temazepam and oxazepam?

A

metabolised by non CYP-450 pathways i.e phase 2 metabolism directly without undergoing phase 1 reactions

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90
Q

Which SSRIs are most selective for serotonin uptake?

A

Citalopram and escitalopram

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91
Q

High D2 affinity/ high 5HT2 activity is characteristic of:

A

Risperidone, olanzapine, loxapine

NB: Haloperidol = high D2, LOW 5-HT2
Risperidone = higher for 5-HT2A than D2

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92
Q

Most of the body’s dopamine is metabolised by:

A

MAO-B and COMT

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93
Q

MAO-A preferentially deaminates:

A

Serotonin and norepinephrine

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94
Q

Two drugs metabolised by both MAO A and MAO B:

A

Dopamine
Tyramine

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95
Q

What is the mechanism of action of methadone?

A

Full agonist at mu opioid receptors
Long 1/2 life (15-22 hours)
(some action against kappa and delta)

M = Most = Mu = Methadone

Compared to bupernorphine which is a PARTIAL agonist at mu opioid receptors

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96
Q

Mechanism of action of galantamine: (2)

A

Competitive, reversible ACh-i
Also binds allosterically to the nicotinic acetylcholine receptor (agonist)

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97
Q

Mechanism of action of mamantine

A

NMDA receptor antagonist (non-competitive) - may protect neurones from glutamate-mediated excitotoxicity
Also 5-HT3 receptor antagonist

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98
Q

How does DisulfIram work?

A

Irreversible inhibitor of ALDEHYDE DEHYDROGENASE = accumulation of acetaldehyde
Dose dependent

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99
Q

Which TCA has the most evidence for use in ADHD due to its stimulant effect?

A

Desipramine

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100
Q

Which receptor is implicated in the weight gain caused by clozapine?

A

5HT2-C

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101
Q

Which channels are blocked by antidepressants e.g TCAs?

A

Catacholamine reuptake channels - how tyramine enters the presynaptic neurones

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102
Q

What is the mechanism of action of buspirone?

A

5HT1A partial agonist - chemically distinct from other psychotropic agents

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103
Q

Mechanism of action of Varenecycline:
What is its metabolism?

A

Partial, selective nicotinic receptor agonist
= reduces dopaminergic reward if patient smokes (competes with nicotine)
but also reduces withdrawal symptoms by stimulating some neurotransmission

High affinity for Alpha 4 Beta 2 nicotinic receptor

Only undergoes 10% hepatic metabolism = safe in liver dysfunction

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104
Q

Mechanism of action of trazodone:

A

Mixed serotonin agonist/ antagonist (SARI - serotonin antagonist and reuptake inhibitor) - blocks SERT (serotonin reuptake pump) and antagonist at 5HT2A and 5HT2C - these are the receptors that cause the most side effects, so antagonism here is helpful

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105
Q

Sedation, increased appetite, dry mouth with Mirtazapine are caused by effects at which receptor?

A

H1 blockade - NB: lower doses only. Noradrenergic (alpha-2 blockade) effect is higher at higher doses = stimulating effect

106
Q

Which antidepressants are effective for patients with premature ejaculation?

A

Fluoxetine, sertraline - anorgasmic effects

107
Q

Mechanism of action of Reboxetine:

A

NA reuptake inhibitor (NARI)

It has little or no affinity for 5-HT, dopamine, histamine, muscarinic and alpha-adrenergic receptors. This makes it unique among antidepressants as it specifically targets the reuptake of noradrenaline.

108
Q

Mechanism of action of aripiprazole:
1/2 life:

A

Partial D2 agonist, also 5HT1A agonist and 5HT2A (high affinity) antagonist. NO anticholinergic effect, but low/mod affinity antagonist for H1 and Alpha 1

75hrs 1/2 life - 2 weeks to steady state

109
Q

Mechanism of action of bupropion (Zyban):

A

NDRI (norepinephrine-dopamine reuptake inhibitor) and nicotinic receptor antagonist
Licenced outside UK for smoking cessation

Note: dose-related risk of seizures

110
Q

Bupropion vs Varenicline mechanism of action:

A

Both used as smoking cessation

Bupropion is a norepinephrine-dopamine reuptake inhibitor and a nicotinic receptor antagonist

Varenicline is a partial agonist at nicotinic acetylcholine receptors, specifically binding to the alpha4-beta2 subunit. This action helps reduce cravings and withdrawal symptoms associated with smoking cessation by partially stimulating these receptors, but with a lower intrinsic activity compared to nicotine.

111
Q

What does the ASEX scale measure?

A

Arizona Sexual Experiences Scale - sexual side effects of psychotropic medications

112
Q

Which 2 antipsychotics cause the most sexual side effects?

A

Risperidone and Haloperidol - 70%
Both cause ++ prolactin

NB: amisulpride and sulpride also cause increased prolactin

113
Q

6 contraindications for lithium treatment:

A
  • Addison’s disease
  • Brugada syndrome
  • Cardiac disease associated with rhythm disorders
  • Clinically significant renal impairment
  • Untreated or untreatable hypothyroidism
  • Low sodium levels, including people that are dehydrated and those on low-sodium diets
114
Q

What drug is first line to treat Lithium-induced DI?

A

Amiloride - K-sparing diuretic
Can also use indomethacin or desmopressin

115
Q

What is the rating scale for Lithium toxicity?

A

AMDISEN (0-3 SCALE)

116
Q

Lithium monitoring requirements:

A

Levels weekly until stable then 3-monthly
(12 hours post-dose) - NICE (6 months, Maudsley)

TFTs and U&Es every 6 months

117
Q

Which antidepressants can be given IV?

A

Citalopram
Escitalopram
Amitriptyline
Clomipramine
(Ketamine and allopregnanolone)

118
Q

Which FGA is most effective in preventing relapses?

A

Zuclopentixol

119
Q

3 atypical antipsychotics available in depot form:

A

Aripiprazole
Risperidone
Olanzapine

120
Q

Who discovered lithium’s beneficial effect in Mania? (1949)

A

Cade

121
Q

Who discovered the antidepressant effects of imipramine? (1957)

A

Kuhn

NB: Clozapine first synthesised from imipramine in 1958

122
Q

Who discovered the use of iproniazid (MAOI) in 1951?

A

Kline

First antidepressant

123
Q

Who Introduced chlorpromazine as a treatment for schizophrenia and coined the term ‘neuroleptic’? (1952)

A

Delay and Deniker

Charpentier

124
Q

First described the ‘cheese effect’ seen in MAOI use in the 1960s?

A

Blackwell

125
Q

Who reintroduced clozapine into clinical practice in 1988?

A

Kane

Was removed from markets in 1975 due to agranulocytosis deaths

126
Q
A
127
Q

Who synthesised chlorpromazine in 1950?

A

Charpentier

Note: Delay and Deniker first demonstrated its effectiveness in 1952

128
Q

Which lab synthesised Haloperidol from pethidine in 1958 and then risperidone in 1989?

A

Janssen

129
Q

3 risk factors for developing neutropenia on clozapine:

A

Afrocarribean ethnicity
Low WCC to start with
Younger age
(NOT DOSE DEPENDENT)

130
Q

What was the first SSRI synthesised?
Why was this discontinued?

A

Zimelidine - 1972
(Carlsson)

Caused demyelinating disease, and hypersensitivity syndrome

131
Q

What did Kline study in the 1950’s?

A

Iproniazid - for TB
An MAOI

132
Q

Mechanism of action of cariprazine

A

Partial D2/D3 agonist

D3 activity = particularly useful to treat neg symptoms of schizophrenia

133
Q

Which Alzheimer’s drug is neuroprotective?

A

Memantine

134
Q

Mechanism of action of memantine:

A

Non-Competitive NMDA antagonist
Reduces NMDA receptor sensitivity to gutamate

135
Q

What class of drugs are:
Diphenhydramine
Cetirizine
Chlorpheniramine
Cyclizine
Hydroxyzine

A

H1 receptor blockers - used for sedation and allergies

136
Q

What class of drugs are:
Cimetidine
Ranitidine

A

H2 receptor blockers - used for excess stomach acid

137
Q

What class of drugs:
Diphenhydramine
Promethazine
Hydroxyzine
Chlorpheniramine
Cyproheptadine
Cyclizine
Ketotifen

A

First generation antihistamines

138
Q

What class of drugs:
Loratadine
Cetirizine
Fexofenadine
Acrivastine

A

Second generation antihistamines - less sedating as don’t cross BBB as much.
Receptor-specific and don’t show anticholinergic effects

139
Q

3 contraindications to first gen antihistamines:

A

Benign prostatic hyperplasia
Angle-closure glaucoma
Pyloric stenosis (in infants)

140
Q

3 reasons for First gen antihistamines use in psychiatry

A

Cross the BBB
Sedating
Anticholinergic properties

141
Q

Mechanism of action of atomoxetine:

A

Selective NA reuptake inhibitor - used in ADHD

142
Q

How do guanfacine and clonidine work in ADHD?

A

Agonists of alpha-2 adrenergic receptors, mimicking NA

143
Q

2 active metabolites of clozapine:

A

N-desmethylclozapine (norclozapine)
clozapine N-oxide

144
Q

Why was Pemoline removed from the market for ADHD?

A

Severe liver disease

Note: still used in Japan

145
Q

Which antidepressant is most associated with priapism and can prolong the QTc interval in normal doses?
Which antipsychotics?

A

Trazodone - AD
Chlorpromazine and thioradazine - AP

146
Q

3 types of opioid receptors and effects at each: (all G-protein coupled)

A

Mu - analgesia, euphoria, constipation, resp depression, dependence

Kappa - analgesia, diuresis, dysphoria

Delta - analgesia, anxiolysis

(MU = MOST
All = Analgesia)

147
Q

Serotonin syndrome:
Mechanism
Symptoms
Caused by

A

Excess serotonergic activity in the CNS

  • The symptoms of hyperreflexia, rigidity, and clonus tend to be more prominent in the lower extremities (clonus is nearly always present)

Rapid onset, within 24hrs
Often due to multiple agents but CAN be caused by single agent
(antidepressants (main group)
lithium
opioids
olanzapine
risperidone)

Triad to remember: neuromuscular abnormalities, altered mental state, autonomic dysfunction

148
Q

Differentiating NMS from SS:

A

SS: hyper-reflexia, clonus, occular clonus, tremors
NMS: lead-pipe rigidity and hypo-reflexia
(NMS = bradykinesic, SS = “faster”, aggitation)

SS: faster onset but also faster recovery

Both (4):
Hyperthermia
Tachycardia
Tachypnoea
Hypertension

149
Q

1/2 life of: (5)
Aripiprazole
Olanzapine
Risperidone
Clozapine
Quetiapine

A

A - 75hrs - 2 weeks to SS
O - 30hrs - 1 week to SS
R - 20hrs
C - 12hrs
Q - 6hrs

RCQ = 2-3 days to SS

150
Q

Drug interactions:
Pharmacokinetic vs Pharmacodynamic:

A

Pharmacokinetic drug interactions take place when one drug interacts with another at the level of metabolism, absorption or excretion.

Pharmacodynamic interactions occur when one drug directly alters the effect of another

151
Q

5 examples of pharmacokinetic drug interactions:

A

Enzyme induction/ inhibition (interference with metabolism)
Changes in gastrointestinal tract motility and pH (interference with absorption)
Chelation
Competition for renal tubular transport (interference with excretion)
Changes in protein binding

152
Q

3 examples of pharmacodynamic drug interactions:

A

Synergism
Antagonism
Interaction at receptors (allosteric modulation)

153
Q

Phenothiazines:
3 types of side chain
Examples for each (1, 2, 2)

A

1) Aliphatic side chain - Chlorpromazine
2) Piperidine side chain - Thioridazine, pipothiazine
3) Piperizine side chaine - Trifluoperazine, fluphenazine

Notes:
(AliphatiChlorpromazine)
DINE with Thio and Pip
FLU…zine - FLU-Z

154
Q

What class of antipsychotics?
Haloperidol

A

Butyrophenones

155
Q

What class of antipsychotics?
Flupentixol, Zuclopenthixol

A

ThioXanthines
(X)

156
Q

What class of antipsychotics?
Pimozide

A

DiPhenylbutylPiPeridines

All the “P”s

157
Q

What class of antipsychotics?
Clozapine

A

Dibenzodiazepines

Call DIBs on Clozapine
(Diaz, not THIAZ - DibenzoTHIAZEPINE = Quetiapine)

158
Q

What class of antipsychotics?
Risperidone

A

Benzoxasoles

159
Q

What class of antipsychotics?
Olanzapine

A

Thienobenzodiazepines

ThienOLANZAPINE

160
Q

What class of antipsychotics?
Quetiapine

A

Dibenzothiazepines

2 x benzos makes a Quetiapine
(THIAZ not DIAZ
DibenziDIAZEPINE = clozapine)

161
Q

Which 2 antipsychotics are substituted benzamides?

A

Sulpride and Amisulpride

162
Q

What class of antipsychotics?
Aripiprazole

A

Arylpiperidylindole (quinolone)

Ar = Ar

163
Q

Who coined the term psychopharmacology?

A

Macht and Mora - 1915, while studying opioid alkaloids on rats

164
Q

Sen and Bose in 1931 in India discovered what?
Linked to which drug in 1954?

A

Antipsychotic properties of Rouwolfia Serpentine

Klein - Reserpine

165
Q

What did Cerletti and Bini do in 1930?

A

Induced elective seizures - antidepressant effects

166
Q

Who first undertook frontal lobotomy?

A

Moniz (1937)

167
Q

Librium (chlordiazapoxide) was discovered in 1954 by:

A

Leo Sternbach

168
Q

Which drugs are known as:
a) major
b) minor
tranquilisers?

A

Major: antipsychotics
Minor: Benzos and barbituates

169
Q

Who discovered the use of Carbamazepine to treat mania in 1971?

A

Takezaki and Hanaka

170
Q

What was the RCT done by Kane in 1988?

A

Clozapine vs Chlorpromazine for TR schizophrenia
30% responded to Cloz
4% to chlorpromazine

171
Q

Who discovered the use of Valproate in Mania?

A

Bowden in 1994

172
Q

What causes erectile dysfunction in antipsychotic use?

A

Cholinergic receptor antagonism

173
Q

Which drug is licenced for narcolepsy, obstructive sleep apnoea, and chronic shift work, and is also suggested as an adjunctive treatment for depression (in the Maudsley)

A

Modafenil - a psychostimulant which 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.

174
Q

5 examples of drugs that undergo significant first pass effect:

A

imipramine
fluphenazine
morphine
diazepam
buprenorphine

175
Q

2 examples of drugs that do not undergo significant first pass effect:

A

Lithium
Pregabalin

176
Q

Which TCAs are associated with discontinuation syndrome?

A

Amitriptyline
Imipramine

177
Q

What are 3 symptoms of TCA discontinuation syndrome?

A

Flu-like symptoms
Insomnia
Excessive dreaming

178
Q

Which mechanism of action is most associated with psychedelic hallucinogens?

A

5HT2A agonism

Psilocybin, LSD, DMT are potent agonists of serotonergic receptors, in particular 5HT2A

Note: only DMT and LSD have potent effects at 5HT1A as well, NOT psilocybin

179
Q

What is the mechanism of action of:
Amphetamine, ecstasy, cocaine

A

Target monoamine transporters

180
Q

What is the mechanism of action of:
Dissociatives - ketamine, PCP (phencyclidine, angel dust), dextromethorphan (DXM), nitrous oxide (N2O

A

NMDA antagonists - impacting glutamate system

181
Q

Which drug has the following side effects:
Liver injury
Vomiting / diarrhoea
Gingival hyperplasia
Memory impairment / confusional state
Somnolence
Weight gain
Anaemia / thrombocytopenia
Alopecia (with curly regrowth)

A

Valproate

NB:
Increased liver enzymes are common, particularly at the beginning of therapy, and are usually transient.
V&D Tend to occur at start of treatment and remit after a few days

SEVERE LIVER IMPAIRMENT IS RARE but most cases occur in first 6 months of therapy (max risk 2-12 weeks) - risk also declines with advancing age

182
Q

What is the prevalence of:
Dystonia
Pseudoparkinsonism
Akathisia
Tardive Dyskinesia

A

D: 10%
P: 20%
A: 25%
TD: 5%

183
Q

Why do atypical antipsychotics have a lower risk of ESPEs and a better reduction of negative symptoms than typicals?

A

5-HT2A serotonin receptor antagonism
Also, their lower affinity for D2 receptors (antagonism)

184
Q

Why does Clozapine have a reduced incidence of ESPEs?

A

It appears more active at the limbic than at striatal dopamine receptors

185
Q

Which cytochrome P450 enzymes metabolise benzodiazepines?

A

Most benzodiazepines are metabolized extensively by hepatic CYP3A4 and CYP2C19

NB: Not lorazepam - so more suitable with liver impairment

186
Q

1/2 life of different benzos:
DCNCTLAOZZZT

A

Diazepam 20-100
Clonazepam 18-50
Nitrazepam 15-38
Chlordiazepoxide 5-30
Temazepam 8-22
Lorazepam 10-20
Alprazolam 10-15
Oxazepam 6-10
Zopiclone 5-6
Zolpidem 2
Zaleplon 2
Triazolam 2

187
Q
A
188
Q

Approximate equivalent doses of other benzos to diazepam 10mg:
LLNTCO

A

Lorazepam 1mg
Lormetazepam 1mg
Nitrazepam 10mg
Temazepam 20mg
Chlordiazepoxide 25mg
Oxazepam 30mg

189
Q

2 contraindications for carbamazepine therapy:

A

Hx of bone marrow depression
Combination with MAOIs

190
Q

What is the most common side effect of discontinuing benzos?

A

Insomnia

Also: stiffness, weakness, GI sx, flu-like sx, anxiety, delusions

191
Q

Use and mechanism of action of lofexidine:

A

Alpha-2 agonist, used to help withdrawal sx in opioid discontinuation. Not available in UK since 2018.

192
Q

3 main medication causes of cleft lip and palate in babies:

A

Benzodiazepines, steroids, anticonvulsants

193
Q

What is a biogenic amine?

A

A compound derived from amino acids.

Neurotransmitters in this class include:
Catecholamines (adrenaline, noradrenaline, dopamine)
Serotonin
Histamine

(HANDS)

194
Q

What is the treatment for SIADH?

A

Fluid restriction
Democlocycline

195
Q

How long do the following drugs take to reach steady state?
Lithium
Aripiprazole
Carbamazapine
Olanzapine
Risperidone depot
Paliperidone depot

A

L: 4-5 days
A: 14-16 days (2 weeks approx)
C: 14 days
O: 7 days (1 week)
RD: 6-8 weeks
PD: 2 months

196
Q

How does Lurasidone work?

A

Full D2 and 5-HT2A ANTAGONIST
High affinity at 5HT-7 (antagonist) - unique to Lurasidone
Partial agonist at 5-HT1

High affinity for D2
Minimal to no effect at H1 or N1 = better side effect profile, less metabolic syndrome

Food increases its absorption

197
Q

What causes sexual side effects in SSRIs?

A

5-HT2 agonism

Note: can be reversed by 5-HT2 antagonists like cyproheptadine, or 5-HT1A agonists like buspirone

198
Q

Which 2 antipsychotics have the highest risk of postural hypotension?

A

Clozapine
Quetiapine

199
Q

Contraindications for chlorpromazine include: (5)

A

Bone marrow depression
Myasthenia gravis
History of agranulocytosis
Dopaminergic antiparkinsonism agents
Citalopram, escitalopram

NB: risk of photosensitivity

200
Q

Which 2 TCAs have the most toxicity in OD (MOST SEDATING)?
Which has a lower incidence?

A

Highest - Dothiepin (Dosulepin) and then Amitriptyline

Lowest: lofepramine

201
Q

Define bioavailability:

A

The fraction of an administered dose of unchanged drug that reaches the systemic circulation when given intravenously

202
Q

Which drug is licenced for:
Generalised anxiety disorder
Diabetic neuropathy
Stress urinary incontinence
Depression?

A

Duloxetine

203
Q

MAOIs examples:
Reversible (RIMA) x1
Irreversible x 4

A

RIMA: Moclobemide
Irreversible:
Selegiline
Tranylcypromine
Phenelzine
Isocarboxazid

204
Q

Which Alzheimer’s drug is a butyrylcholinesterase inhibitor?
(it also undergoes no hepatic breakdown)

A

Rivastigmine

205
Q

A drug which is inactive until converted to its active metabolite is known as what?

A

Prodrug

206
Q

What term describes the process by which a drug moves from its administration site to the systemic circulation?

A

Absorption

207
Q

Methylphenidate vs amfetamine:

A

Both result in increased synaptic levels of monoamines (principally dopamine and noradrenaline)
Both block the reuptake of the monoamines from the synapse back into the presynaptic neurone (blocking DAT and NAT)

Amfetamine only:
- promotes release of monoamines from the presynaptic neurone into the synapse by disrupting the function of VMAT
- Blocks SERT

Methylphenidate only:
- binds to α-adrenergic receptors linked to cognitive effects and increased peripheral resistance (α1 agonism)
- agonist at 5-HT1A

208
Q

How does Sidenafil work?

A

Inhibits cGMP-specific phosphodiesterase type 5 (PDE5) i.e prolongs effects of cGMP (phosphodiesterase would terminate it)

209
Q

Which 2 antipsychotics were removed from the UK market due to their effect on the QTc interval and risk of sudden death?

A

Thioridazine and droperidol

210
Q

What were Phase 1 and Phase 2 of the CATIE study?

A

Phase I compared typical and atypical antipsychotics - compared 4 new meds (OQRZ) to each other, and an older medication (perphenazine)

Phase II sought to provide guidance on which antipsychotic to try next if the first failed (either due to ineffectiveness or intolerability).

211
Q

Opioids, cannabinoids and GHB (gamma hydroxybutyrate) interfere with which type of receptors? (ionotropic or g-protein coupled?)

A

G-protein coupled

212
Q

Alcohol, benzos, nicotine and ketamine interfere with which type of receptors? (ionotropic or g-protein coupled?)

A

Ionotropic

213
Q

Mechanism of action of agomelantine:

A

Agomelatine is a relatively new drug used for treating depression. It acts as an agonist at melatonin M1 and M2 receptors and as an antagonist at 5HT2C receptors.

NOTE: Not associated with discontinuation syndrome

214
Q

What is torsades du point?

A

A type of polymorphic ventricular tachycardia, often transient, associated with prolonged QTc, often asymptomatic but associated with syncope and death (deteriorates into VF)

215
Q

What is the issue with the Bazett formula for QTc?

A

The Bazett formula over-corrects at heart rates > 100 bpm and under-corrects at heart rates < 60 bpm, but provides an adequate correction for heart rates ranging from 60 - 100 bpm.

216
Q

5 independent risk factors for prolonged QTc:

A

Female sex
Hypokalemia
Hypomagnesaemia
Hypocalcemia
Anorexia nervosa

217
Q

Which cytochrome P450 subfamily is most abundant in the human liver?

A

The CYP3A subfamily is the most abundant in the human liver, accounting for nearly 30% of the total cytochrome P450 content.

218
Q

What is the main difference between Phase I and phase II biotransformation reactions?

A

Phase I metabolism converts a parent drug to polar, water soluble ACTIVE metabolites while phase II metabolism converts a parent drug to polar INACTIVE metabolites.

219
Q

3 processes involved in Phase I biotransformation reactions:

A
  • Oxidation with cytochrome P450 (most common) - membrane-bound enzymes primarily found within the endoplasmic reticulum of hepatocytes
  • Reduction
  • Hydrolysis
220
Q

3 antipsychotics LEAST likely to cause orthostatic hypotension:

A

Lurasadone, Asenapine, Amisulpride

Also Haloperidol, Sulpride, Aripiprazole. Trifluoperazine

221
Q

Which D2/D3 antagonist is preferentially used in PET scans?

A

Raclopride - it can be radiolabelled, binds reversibly, is relatively selective for D2, shows low internalisation (does not induce internalisation / degradation of the D2 receptors), and has limited therapeutic effects.

222
Q

Of the commonly used antipsychotics, which has the most and the least effect on EEG?

A

Most: Clozapine - 47.1%
Least: Quetiapine - 0%

223
Q

5 types of medication that can precipitate mood changes, particularly in the elderly:

A
  • Centrally-acting antihypertensives (e.g. methyldopa, reserpine, and clonidine) can cause depressive symptoms.
  • Interferon-a is capable of inducing depressive symptoms.
  • Digoxin is capable of inducing depressive symptoms.
  • Corticosteroids can cause depressive, manic, and mixed symptoms with or without psychosis.
  • Antidepressants can precipitate mania.
224
Q

Which Alzheimer’s drug is best for those with liver disease or those on multiple medications?

A

Rivastigmine - undergoes minimal metabolism through P450 system, primarily being metabolised through hydrolysis by esterases = fewer drug interactions

225
Q

Nandrolone, Stanozolol, Oxandrolone, Trenbolone are examples of:

What psychiatric disorders are associated (4)?

A

Anabolic steroids - Class C controlled drug

Aggression / irritability / moods swings (‘roid rage’ refers to frenzied violent behaviour during the high-dose cycles of steroid use)
Psychosis, Mania/hypomania, Depression / anxiety

226
Q

Compare the mechanism of action of amphetamines and cocaine:

A

Amphetamines act primarily by inducing the release of dopamine, a neurotransmitter associated with pleasure and reward, from presynaptic neurons into the synaptic cleft. This results in increased concentrations of dopamine in the synapse and prolonged stimulation of post-synaptic neurons.

Cocaine DOES NOT STIMULATE the release of dopamine but instead works by blocking the reuptake of dopamine at the synaptic cleft (competes at DAT). By inhibiting its reuptake, cocaine increases the concentration of dopamine in the synapse, resulting in an enhanced and prolonged stimulatory effect on post-synaptic neurons.

227
Q

Which drug is known to increase lamotrigine levels?
How does the use of oestrogen in the COCP affect lamotrigine?
2 MAJOR side effects of lamotrigine to be aware of:

A

Valproate

Decreased lamotrigine - lamotrigine doses may need to be doubled

SJS - in first 8 weeks
suicidal ideation

228
Q

Which TCA is considered the LEAST cardiotoxic?

A

Lofepramine

229
Q

Which TCA has a stimulant effect and can be used in ADHD?

A

Desipramine

230
Q

4 types of drugs that can cause porphyria:

A

Barbiturates
Benzodiazepines
Sulpiride
Certain mood stabilizers

231
Q

Which mood stabilizer causes hypospadias, neural tube defects, cleft lip/palate when used during pregnancy?

A

Valproate

Also can cause: cardiovascular abnormalities, developmental delay, endocrinological disorders, limb defects, and autism

232
Q

The reduction in drug concentration that occurs when a drug is absorbed before it reaches the systemic circulation is termed:

A

First Pass Effect

233
Q

Most sedating SSRI:
SSRI with most activation:
SSRI most likely to cause sexual side effects:
SSRI least likely to cause sexual side effects:
Most protein bound SSRI:

A

Paroxetine
Fluoxetine
Paroxetine - includes issues with lubrication
Vortioxetine
Sertraline

234
Q

What is the mechanism of action of Iecanemab in the treatment of Alzheimer’s Disease?

A

Binds to soluble amyloid-beta protofibrils. This facilitates their removal from the brain before they can accumulate into larger, insoluble plaques, which are characteristic features in Alzheimer’s disease pathology.

235
Q

What receptor is responsible for the following side effect of psychotropic medications:
Weight gain caused by antipsychotics (2)

A

H1 and 5HT2C antagonism

236
Q

What receptor is responsible for the following side effect of antipsychotics:
Hyperprolactinaemia

A

D2 blockade in the tuberoinfundibular pathway

237
Q

What receptor is responsible for the following side effect of psychotropic medications:
Postural Hypotension:

A

Alpha 1 adrenergic receptors

238
Q

What receptor is responsible for the following side effect of psychotropics:
Parkinsonism

A

D2 blockade in the nigrostriatal pathway

239
Q

What receptor is responsible for the following side effect of psychotropic medication:
Gastrointestinal distress caused by SSRIs

A

5HT3 receptor stimulation

240
Q

What receptors do Sulpride and Amisulpride work on?

A

Sulpride: Predominant D2 antagonist, minima D3 antagonist/partial agonist actions (known as a “pure D2 antagonist”)
Amisulpride: D2/D3 antagonist - reduces positive symptoms by affecting dopamine in the limbic system

241
Q

The chronic administration of tricyclics results in:

A

Down-regulation of beta adrenergic receptors

242
Q

What effect does D2 blockade have at the:
1) mesocortical pathway
2) mesolimbic pathway
3) tuberoinfundibular pathway
4) nigrostriatal pathway

A

1) production or worsening of negative symptoms
2) improvement of positive symptoms
3) hyperprolactinaemia - pituitary stuff
4) EPSEs

243
Q

What class of drugs can cause bruxism?

A

Stimulants

244
Q

What is the treatment for amphetamine or PCP overdose?

A

Acidification of the urine

245
Q

What is the treatment for severe lithium toxicity (>3)?

A

Haemodynamic dialysis

246
Q

What is the treatment for the tyramine-induced Cheese Reaction caused by MAOIs?

A

Alpha-adrenergic agents e.g phentolamine or chlorpromazine

247
Q

What is the range for target plasma levels for:
1) Lithium
2) Carbamazepine
3) Clozapine
4) Phenytoin
5) Amitriptyline
6) Valproate

A

1) 0.6-1 mmol/L
2) >7 mg/L
3) 350-500mg mg/L
4) 10-20 mg/L
5) 100-200 mcg/L
6) 50-150 mg/L

248
Q

When would you see the following side effects:
Headache, halitosis, metalic taste in mouth, dermatitis, sedation

A

Disulfaram - in the ABSENCE of alcohol

249
Q

What is the rate limiting step in Dopamine metabolism?

A

Tyrosine to DOPA (using tyrosine hydroxylase)

(DOPA is then converted into Dopamine)

250
Q

When switching from MAOIs to SSRIs how long is the crossover?

A

Withdraw and wait 2 weeks (to prevent serotonin syndrome)

251
Q

Which antidepressant has the same sexual side effects as the placebo?

A

Agomelantine

252
Q

What is the annual risk of a patient on clozapine for developing agranulocytosis?

A

0.01% - usually seen in first 18 weeks of treatment

253
Q

What are the risk factors for agranulocytosis on clozapine:

A

Female sex, being older, Asian or Ashkenazi Jewish

254
Q

How do caffeine, acetazolomide and theophylline affect lithium levels?

A

Can reduce lithium levels

255
Q

How do furosemide, NSAIDs, ACEi’s and thiazides affect lithium levels?

A

They increase lithium levels

256
Q

What is the most likely explanation for SSRI discontinuation syndrome?

A

Temporary deficiency in the brain of one or more essential neurotransmitters associated with mood

257
Q

Clozapine can cause myocarditis - what ECG changes would be seen?

A

Saddled ST elevation
Diffuse T-wave inversion
Other non-specific ST changes

258
Q

What is the main active metabolite of diazepam?
What are the 2 minor metabolites?

A

Major - desmethyldiazepam
Minor - oxazepam, temazepam

259
Q

How does Vortioxetine work?

A

SERT inhibition
Antagonist at 5-HT3 and 5HT7
Agonist at 5-HT1A
(some weak action at 5-HT1B/D)

260
Q

How does carbidopa work?

A

Inhibits DOPA-decarboxylase (which metabolises L-dopa into dopamine) outside the CNS = more L-DOPA is able to enter the CNS and become dopamine

It does not itself cross the BBB

Paper A - MRCPsych (6 decks)

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