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Psychopharmacology Flashcards

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1
Q

Mirtazapine.

A

Noradrenaline and serotonin specific antidepressant (NaSSa)

5HT2 antagonist, 5HT3 antagonist, H1 antagonist, alpha 1 and alpha 2 antagonist, moderate muscarinic antagonist

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2
Q

Venlafaxine, Duloxetine.

A

SNRI Serotonin and noradrenaline reuptake inhibitor

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3
Q

Reboxetine

A

Noradrenaline reuptake inhibitor (NaRI)

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4
Q

St Johns Wort

A

Weak MAOI and weak SNRI (also considered by some to be a weak SSRI)

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5
Q

Trazadone

A

Weak antagonist and SARI (Serotonin antagonist and reuptake inhibitor)

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6
Q

Moclobemide

A

Reversible inhibitor of monoamine oxidase type A

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7
Q

Agomelatine

A

Melatonergic agonist (MT1 and MT2 receptors) and 5-HT2C antagonist

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8
Q

Bupropion

A

Norepinephrine-dopamine reuptake inhibitor (NDRI), and nicotinic acetylcholine receptor antagonist

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9
Q

Lofexidine

Clonidine

A

Used in symptoms of opiate withdrawal.

ALpha agonist.

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10
Q

The ‘other’ NASSA?

A

Mianserin.

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11
Q

Benzodiazepines are metabolised by?

A

Cytochrome 3A4

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12
Q

What is the ‘big’ NARI (noradrenalin reuptake inhibitor)?

What is the other one?

A

Reboxetine.

Atomexetine.

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13
Q

5 typical antipsychotics
5 atypical antipsychotics

Other classification systems?

A 
Typical:
Haloperidol
Clopixol (zupen)
Sulpride 
Chlorpromazine
Flupenthixol
Atypical:
Clozapine
Risperidone
Quetiapine
Olanzapine
Amisulpride
Butyrophenones- haloperidol
Dibenzodiazepines - clozapine
Dibenzothiazepines-  quetiapine
Thienodiazepines - olanzapine
Phenothiazines (Aliphatic side chain)	- chlorpromazine
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14
Q

Classification of Tricyclics?

A 
Secondary Amines
Desipramine
Nortriptyline
Protriptyline
Amoxapine
Tertiary Amines
Amitriptyline
Lofepramine
Imipramine
Clomipramine
Dosulepin (Dothiepin)
Doxepin
Trimipramine
Butriptyline
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15
Q

Common SEs of tricyclics

A 
drowsiness
dry mouth
blurred vision
constipation
urinary retention
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16
Q

Zero order kinetics.
What is it?
What drugs fit this?
Linear or non-linear?

A

Same amount of drug emitted per unit of time.
Alcohol, phenytoin.
Non-linear.

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17
Q

First order kinetics.
What is it?
What drugs fits this?
Linear or non-linear?

A

Same fraction of drug emitted per unit of time.
Most drugs.
Linear.

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18
Q

What drugs can you not have with MAOIs.

A

Tricyclics usually safe (other than CLOMIPRAMINE).
CAnnot have SSRIs.
Cannot have ephedrine.

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19
Q

What processes form part of pharmacokinetics?

A

Absorption.
Distributuon
Metabolism (involving reduction/hydrolysis, then conjugation)
Excretion

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20
Q

In which order of drug kinetics is the half life constant?

A

First order.
Linear kinetics.
ZOCFLAP

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21
Q

What are the three catecholeamines?

A

Dopamine.
Noradrenalin.
Adrenalin.

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22
Q

Bupropion.

A

Norepinephrine-dopamine reuptake inhibitor (NDRI), and nicotinic acetylcholine receptor antagonist

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23
Q

Name three pharmacodynamic drug interactions

A

Synergism
Inhibition of drug uptake and transport
Interaction at receptors

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24
Q

Name three pharmacokinetics 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

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25
Q

two key antipsychotics to avoid in renal impairment

A

sulpride and amisulpride

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26
Q

Acamprosate

A

Metabotropic glutamate receptor antagonist and GABA-A agonist

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27
Q

WHat is GABA made from?

A

Glutamate.

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28
Q

Antagonism of which receptor causes priapism

A

Alpha 1

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29
Q

Biological amine neurotransmitters?

aka biogenic amines

A

Biogenic amines are compounds derived from amino acids

Catecholamines (adrenaline, noradrenaline, and dopamine)
Serotonin
Histamine

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30
Q 
Benzo half lives
Diazepam
Lorazepam
Nitrazepam
Temazepam

Zopiclone
Zolpidem

A

Diazepam 20-100 hrs (36-200 hrs for active metabolite)
Lorazepam 10-20hrs
Chlordiazepoxide 5-30 hrs (36-200 hrs for active metabolite)
Nitrazepam 15-38 hrs
Temazepam 8-22 hrs

Zopiclone 4-6 hrs
Zolpidem 2-6 hrs

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31
Q

Frequent SE of carbamazepine

A

ataxia

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32
Q

Cytochrome enzyme most commonly found to metabolise antidepressants?

A

2D6

codes for debrisquine hydroxylase.

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33
Q

Which antipsychotics never alters EEG

Which alters it most

A 
Quetiapine
Clozapine (in 45% there is a change)
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34
Q

Valproate

A

GABA agonist and NMDA antagonist

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35
Q

Topiramate

A

GABA agonist, NMDA antagonist, and Na channel stabiliser

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36
Q

Carbamazepine

A

Stabilises Na channels

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37
Q

Phenytoin

A

Stabilises Na channels

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38
Q

Reduces contraceptive effect?

The drug not to take due to teratogenic effects is…

A 
St John's Wort
Carbamazepine
Phenytoin
Topiramate
Barbiturates

(B) Valproate [does not reduce contraceptive effect]

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39
Q

Side effects of stimulant drugs?

A

Sleep disturbance.
Appetite suppression.
Abdo pain.

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40
Q

3 stimulant drugs for ADHD and how they work

A

Dexamphetamine - Inhibits DA and NA uptake
Lisdexamfetamine - Prodrug, absorbed by GI tract, converted to dexamfetamine which inhibits the reuptake of NA and DA.
Methylphenidate - Inhibit DA and NA uptake

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41
Q

3 non-stimulant drugs for ADHD?

A

Clonidine - A2 receptor agonist
Atomexetine - inhibits NA (NARI)
Guanfacine - alpha receptor agonist

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42
Q

Name 6 changes in pregnancy pharmacokinetics.

A
  • Plasma volume increases.
  • Concentration of plasma albumin decreases.
  • Volume of distribution increases for lipophilic drugs.
  • Total plasma concentration of albumin-bound drugs decreases due to haemodilution.
  • Elevated progesterone –> delayed gastric emtpying and reduced small intestine motility
  • The activity of hepatic drug-metabolizing enzymes changes during pregnancy because estrogens and progesterone induce some CYP enzymes and inhibit others.
  • Renal blood flow and the glomerular filtration rate increase, leading to enhanced elimination of some drugs (GFR increases 50%).
43
Q

How do NASSA drugs work?

A

Mianserin and Mirtazapine.
Noradrenalin and serotonin specific antidepressants.
They antagonise receptors. Unlike other drugs they do not stop reuptake of serotonin.

44
Q

Memantine

A

Non-competetive NMDA receptor antagonist.

45
Q

Name 5 antidepressants that have active metabolites.

A 
Amitriptyline --> Nortryptyline.
Lofepramine --> Desipramine
Imipramine --> Desipramine
Clomipramine --> Desmethyl-clomipramine
Mirtazapine --> Demethyl-mirtazapine
Trazodone --> mCPP
Venlafaxine --> O-desmethyl-venlafaxine
Risperidone --> 9-Hydroxyrisperidone
Fluoxetine --> Norfluoxetine
46
Q

Name two drugs that avoid much first pass effect.

A

Lithium.

Pregabalin.

47
Q

Name five drugs that undergo significant first pass effect.

A 
Morphine.
Diazepam.
Imipramine.
Buprenorphine
fluphenazine
48
Q

SSRI Info:

  • Two preferred?
  • Most common SEs?
  • Which one post MI?
  • WHich one for kids?
  • Which two less drug interactions?
  • Interactions
  • After starting when review for >30, <30? Why?
  • How long should you gradually stop them over?
  • Which one do you not need to worry about this?
  • Which should you worry about discontiniuation?
  • Symptoms of discontinuation?
  • Which has shortest half life?
  • Which can, rarely, cause EPSEs?
A
  • Citalopram, Fluoxetine.
  • GI upset, paraxodical initial agitation, GI bleeding
  • Sertraline
  • Fluoxetine (but mostly avoid)
  • Two with less interactions are Citalopram, SErtraline (more suitable for elderly with lots of drugs)
  • Interactions with (i) warfarin/anticoagulants; avoid; consider Mirtazapine, (ii) NSAIDS/aspirin; avoid if possible but if prescribe then co-prescribe PPI, (iii) triptans - avoid
  • Review after 2 weeks for >30s and 1 week for <30s. Due to paradoxical agitaiton in first few weeks.
  • Symptoms of discontinuation: GI upset, paraesthesia, restlessness, difficutly sleeping, increased mood change
  • Shortest half life is Fluvoxamine
  • Paroxetine can rarely cause EPSEs
49
Q

Disulfiram

A

Binds irreversibly to aldehyde dehydrogenase

50
Q

Diazepam:

  • Half life
  • Protein bound?
  • Cross BBB? Cross placenta?
  • Broken down by?
A
  • 20-100 hours
  • 95% protein bound
  • Being protein bound makes it lipophilic, so does cross BBB and palcenta
  • Mostly liver
51
Q

Acetylcholine:

  • How made?
  • Breakdown?
  • Two types of receptor?
A
  • Made from choline within neurons. The enzyme choline acetlytransferase transfers an acetyl group from acetyl coenzyme-A to choline resulting in acetylcholine.
  • Acetylcholine is inactivated and broken down to choline and acetate by acetylcholinesterase.
  • Nicotinic (inotropic, nicotine and acetylcholine activate), and muscarinic (metabotropic, acetylcholine and muscarine activate)
52
Q

Cytochromoe 3A4
What does it do?
What inhibits it?
What induces it?

Cytochrome 1A2
What does it do?
What inhibits it?
What induces it?

Which shows considerable polymorphism?

A
  • Involved in metabolism of certain antipsychotics and other psychotropic drugs
  • Grapefruit juice. Therefore increases levels of drugs
  • Barbiturates, st johns wort, carbamazepine, phenytoin
  • Responsible for getting rid of clozapine
  • Grapefruit inhibits. –> increases level of clozapine
  • Smoking induces –> reduces level of clozapine

Cytochrome 2D6

53
Q

Half lives of antipsychotics

  • What is the top three?
  • Bottom two?
A
  • Aripiprazole (75 hours), Olanzapine (30), Risperidone (20)

- Amisulpride (12 hours), Ziprasidone (7), Quetiapine (6)

54
Q 
Types of immune response.
I
II
III
IV
A

I- anaphylactic. fastest.
II- cytotoxic e.g. blood transfusion reaction
III- immune mediation e.g. RA, vasculitis (1-3 weeks)
IV- cell mediated e.g. allergic contact dermatitis (2-7 days)

55
Q

Tell me the two types of GABA receptor, what kind of receptor they are, and what agonists/antagonists they have?

A

GABA A
Ionotropic
Agonist: Z drugs, benzos, barbiturates, ethanol
Antagonist: Flumazenil

GABA B
Metabotropic
Agonist: GHB, Baclofen
Antagonist: Nil

56
Q

What two tricyclics are most dangerous in OD?

A

Amitriptyline and dosulepin (dothiepin) are considered the most dangerous TCAs in overdose.

57
Q

Where are the catecholeamines derived?

A

Tyrosine

TRY and get it right

58
Q

What foods are not allowed for those on MAOIs

A 
Bean Curd
Cheese (but cream cheese and cottage cheese is ok)
Chianti wine and vermouth
Fava beans
Banana peels 
Sauerkraut
Unfresh meat and liver
Yeasts inc marmite
59
Q

Buspirone
Used for?
Mechanism?

A
  • used for anxiety disorders (short term)

- 5HT1A partial agonist

60
Q

Aripiprazole

Mechanism

A

Partial agonist at 5HT1A and D2, and 5HT2A antagonist

seems to be the only antipsychotic with some agonist properties at a dopamine receptor

61
Q

Name 4 drugs that lower the seizure threshold

A

maprotiline, clomipramine, chlorpromazine, and clozapine lower the seizure threshold.
(all antipsychotics can, but chlorpromazine and clozapine in particular are the worst)

62
Q

Most antipsychotics take 2-3 days to reach steady state.

Name 3 important exceptions.

A

Aripiprazole - 2 weeks
Clozapine - 4 days
Olanzapine - 7 days

63
Q

Bupropion.
Buprenorphine.
Varenicline.

A

Bupropion - Norepinephrine-dopamine reuptake inhibitor (NDRI), and nicotinic acetylcholine receptor antagonist.
Buprenorphine - Partial agonist at the mu-opioid receptor
Varenicline - Nicotinic receptor partial agonist

64
Q

Calculation for volume of distribution?

A

Vd = amount of drug in body/conc in plasma

65
Q

What does MAO-A metabolise?

What does MAO-B metabolise?

A

MAO-A metabolises dopamine, noradenalin, adrenalin and serotonin.
MAO-B metabolises dopamine and phenethylamine

66
Q

Which antipsychotic has the shortest half life?

A

Quetiapine (2-3 days till steady state; half life of 6 hours)

67
Q

Clozapine.
More effect at striatal or limbic?
Effect on what receptors?
Prolactin effect?

A

More effect on limbic than striatal; thought to represent why clozapine causes less EPSEs.
Antagonist at D1,2,3,4,5. Particular affinity for D4. Also antagonistic at adrenergic, cholinergic, histaminergic and serotonergic receptors.
Little or no prolactin elevation.

68
Q

Name the 4 treatments for restless legs.

A

Benzos.
SSRIs.
Opiates.
Dopamine agonists.

69
Q

What is GABA synthesised from?

A

Glutamate.

70
Q

What receptor action of Mirtazapine makes people sleepy?

A

All of mirtazapine’s effects enhance sleep except alpha 2 antagonism

71
Q

Name the two types of drug reaction.

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.

72
Q

Name some
Inhibitors of CTP450
Inducers of CTP450

A

Inducers - smoking, alcohol, barbiturates, carbamazepine, Phenytoin, and St John’s Wort.

Inhibitors - chlorpromazine, SSRI’s, and grapefruit juice.

73
Q

Smoking will

  • increase or decrease clozapine levels
  • what other commonly done thing could theoretically INCREASE levels
A
  • decrease

- coffee

74
Q

What is normal, borderline and prolonged times for QTc in men and women

when is action needed?

A

Both <440 is normal
borderlien 440-450 in men and 440-460 in women
prolonged is >450 in men and >460 in women

action is needed;
>500 for both.
consdier reducing dose when >440 in men and >470 in women

75
Q

Which antipsychotics have

  • highest effect on QTc
  • lowest effect on Qtc
A

highest: haloperidol
lowest: aripiprazole

76
Q

When should you take post lithium levels

A

12 hours post dose

77
Q

What drug do you use to treat clozapine induced seizures?

A

Valproate

78
Q

recreational drugs which

  • interefere with ionotropic receptors?
  • metabotropic receptors?
  • target monoamine transprotesr?
A

Mechanism

Examples

Drugs which interfere with ionotropic receptors or ion channels Alcohol, nicotine, benzodiazepines, ketamine
Drugs which interfere with G coupled receptors Opioids, cannabinoids, y-hydroxybutyrate (GHB)
Drugs that target monoamine transporters Amphetamine, ecstasy, cocaine

79
Q

Effect of the following on clozapine levels

SSRIs
Erythromycin
Caffeine

Carbamazepine
Phenytoin
Tobacco

A

Drug

Effect on plasma clozapine levels

SSRI's Increased 
Erythromycin Increased 
Caffeine Increased 
Carbamazepine Decreased 
Phenytoin Decreased 
Tobacco Decreased
80
Q

in liver patients
what 3 antipsychotics can you use
what 3 antidepressants can you use

A 
Antipsychotics Haloperidol
Amisulpride
Sulpiride 
Antidepressants Imipramine
Paroxetine
81
Q

Hyperprolactinaemia
What drugs offend?
What drugs are not associated?

A
  • all typical APs, risperidone, amisulpride, zotepine

- clozapine, aripiprazole, quetiapine, olanzapine

82
Q 
What are the following names associated with:
- Kane
- Carlsson
- Blackwell
- Cade
- Kline
- Charpentier
- Delay and Denniker
- Kuhn
Cerletti
- Lurie
- Sakel
- Moniz
- Meduna
A
  • Kane - introduced clozapine into clinical practice
  • Carlsson - developed the first SSRI
  • Blackwell - first described the ‘cheese effect’ seen in MAOI use
  • Cade - discovered lithium’s beneficial effect in mania
  • Kline - discovered use of iproniazid (MAOI)
  • Charpentier - synthesised chlorpromazine
  • Delay and Deniker - introduced chlorpromazine as a treatment for schizophrenia
  • Kuhn - discovered the antidepressant effects of imipramine
  • Cerletti (and Bini) - first use of ECT
  • Lurie - coined the term ‘antidepressant’
  • Sakel - insulin shock therapy
  • Moniz - frontal leucotomy for psychosis
  • Meduna - metrazol therapy
83
Q

Antipsychotic

  • most sedating
  • may actually help weight gain
  • worst for hypotension
  • best for hypotension
A
  • most sedating: clozapine
  • may help weight gain: aripiprazole
  • worst for hypotension: clozapine
  • best for hypotension: aripiprazole
84
Q

which drugs cause people to drop dead adn therefore removed from UK market

A

Both thioridazine and droperidol have been removed from the UK market due to their effect on the QTc interval.

85
Q

what SSRI can be added to venlafaxine to reduce discontinuation symptoms

A

There is some evidence to support the use of fluoxetine for discontinuation symptoms associated with stopping venlafaxine and clomipramine. It use here probably stems from its long half-life.

86
Q

Which antidepressants are avaialble IV? IM?

A
  • citalopram is the only SSRI available as an intravenous preperation
  • mirtazapine (a NaSSa)
  • amitriptyline (available as both IV and IM)
  • clomipramine
87
Q

What changes to ECG do tricyclics do?

A

PR prolongation
QRS Prolongation
QTc prolongation

Brugada syndrome (genetic abnormality manifest only by aberrant cardiac conduction)

88
Q

What is the most common antipsychotic that has no effect on QTc?

A

Aripiprazole.

89
Q 
What is the trend for clozapine for:
Sedation	
Weight gain	
Diabetes	
EPSE	
Anticholinergic	
Hypotension	
Prolactin elevation
A

Bad for all, other than:

  • EPSE
  • prolactin
90
Q

Which one antipsychotic may be better for weight gain?

A

Aripiprazole

91
Q

What meds are used for

  • Nocturnal enuresis in children
  • Phobic and obsessional states
  • Adjunctive treatment of cataplexy associated with narcolepsy
  • Panic disorder and agoraphobia
  • Social anxiety/ phobia
  • Generalised anxiety disorder
  • OCD
  • Bulimia nervosa
  • PTSD
A

Nocturnal enuresis in children Amitriptyline, Imipramine, Nortriptyline
Phobic and obsessional states Clomipramine
Adjunctive treatment of cataplexy associated with narcolepsy Clomipramine
Panic disorder and agoraphobia Citalopram, Escitalopram, Sertraline, Paroxetine, Venlafaxine
Social anxiety/ phobia Escitalopram, Paroxetine, Sertraline, Moclobemide, Venlafaxine
Generalised anxiety disorder Escitalopram, Paroxetine, Duloxetine, Venlafaxine
OCD Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline
Bulimia nervosa Fluoxetine
PTSD Paroxetine, Sertraline

92
Q

What antidepressant would you use in a diabetic?

A

SSRIs are first line (most data support fluoxetine)

93
Q

List of antidepressants to try when postural hypotension is a problem?

A 
Amisulpride
Aripiprazole
Haloperidol
Sulpiride
Trifluoperazine
94
Q

Name 4 drugs that worsen psoriasis

A

Lithium
SSRI’s
Beta blockers
ACE inhibitors

95
Q

Name 7 SEs of lithium

A 
Drowsiness
Dry mouth
Polyuria
Polydipsia
Nausea
Weight gain
Fine tremor
Metallic taste
Diarrhoea
Muscle weakness
96
Q

name 4 long term effects of lithium

A

Hypothyroidism
Irreversible nephrogenic diabetes insipidus
Reduced GFR (chronic kidney disease)
Hyperparathyroidism

97
Q

What two classes are surprisingly okay with lithium?

A 
Loop diuretics (Furosemide) 
K sparing diureitcs (Amiloride, Spironolactone)
98
Q

general scheme for monitoring bloods in clozapine ?

A

Monitoring guidelines vary slightly. The general consensus is that weekly bloods should be be taken for the first 18 weeks, then fortnightly until 52 weeks and then monthly for the duration of treatment.

99
Q 
SSRI discontinuation symptoms?
onset within how many days of stopping?
Duration of symptoms? 
Particularly bad drugs for it? 
Particularly good for it?
A 
Flu-like symptoms
Dizziness
Insomnia
Vivid dreams
Irritability
Crying spells
Sensory symptoms (e.g. sensations resembling electric shocks)

The onset is usually within 5 days of stopping but varies depending on half life. Most antidepressant discontinuation reactions are of short duration, resolving spontaneously between 1 day and 3 weeks after onset. The mean duration of SSRI discontinuation symptoms is 5 days.

Paroxetine. Venlafaxine.
Adding Fluoxetine can be helpful (long half life)

100
Q

What does the following mean in Clozapine monitoring:
Green result
Amber result
Red result

A

A green result indicates that the WBC and neutrophil count is satisfactory and Clozaril may be dispensed.

An amber result means that the patient can continue with treatment but must have another blood test within a day or two and must have twice weekly blood tests until the result improves.

A red result means that the patient must stop taking Clozaril immediately.

101
Q

What was the first TCA?

A

Imipramine

102
Q

What four things is duloxetine licensed for?

A

Generalised anxiety disorder
Diabetic neuropathy
Stress urinary incontinence
depression

103
Q

which antidepressant can be used sublingually

A

Fluoxetine liquid has been shown to be effective when used subligually.

Genetics (11 decks)

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