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MRCPsych > Pharmacokinetics & pharmacodynamics > Flashcards

Pharmacokinetics & pharmacodynamics Flashcards

1
Q

What is the MOA of barbituates

A

Act on GABA receptors and increase the DURATION of chloride channel opening

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2
Q

MOA of cyproheptadine

A

H1 antagonist (it also has 5HT-2 antagonist action)

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3
Q

What can cyproheptadine be used for?

A

Treatment of sexual dysfunction caused by increased serotonin transmission, particularly anorgasmia
Some evidence it could be used to treat akathisia (unlicensed)

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4
Q

MOA of Aripiprazole

A

Partial D2 agonist
Partial 5-HT1A agonist
High affinity antagonist at 5-HT2A
Low/moderate affinity antagonist of H1 and alpha-1

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5
Q

Is lamotrigine advised for acute mania?

A

NO

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6
Q

What changes to receptors would you see with chronic administration of antidepressants?

A

Down regulation of beta receptors

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7
Q

Which antidepressant is a weak inhibitor of P450?

A

Citalopram (and escitalopram)

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8
Q

MOA of valproate

A

Complex - inhibits catabolism of GABA, reduces turnover of arachidonic acid, reduces levels of protein kinase C, promotes brain derived neurotrophic factor expression

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9
Q

What is the active metabolite of trazodone?

A

mCPP

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10
Q

What does mCPP do?

A

Agonist at 5HT2C receptors

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11
Q

Bruxism is most associated with which class of drugs?

A

Stimulants

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12
Q

MOA of Varenicline

A

Partial nicotinic agonist

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13
Q

What is efficacy?

A

How well the drug produces the expected response

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14
Q

What does efficacy depend on?

A

Affinity
Potency
Duration of receptor action
Half life

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15
Q

Which medications are effective for premature ejaculation?

A

Fluoxetine & sertraline

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16
Q

What does mirtazapine preferentially block at lower doses?

A

H1

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17
Q

Which receptors does mirtazapine act on?

A

Alpha 2 blocker - increases serotonergic activity - antidepressant
Alpha 2 autoreceptor blocker - increases noradrenergic activity - antidepressant
H1 blocker - sedation, weight gain, dry mouth
5HT3 blocker - antiemetic
5HT2C blocker - antidepressant
5HT2A blocker - reduces akathisia

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18
Q

Which receptors does Risperidone act on?

A

Antagonist of 5-HT2A, D2, alpha-1, alpha-2 and H1

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19
Q

Which drug has high D2/high 5Ht2A activity?

A

Risperidone

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20
Q

Which drug has low D2 and high 5HT2A activity?

A

Clozapine

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21
Q

Which drug has high D2 and low 5HT2A activity?

A

Haloperidol

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22
Q

Which antipsychotic is a predominant D2 antagonist at therapeutic doses?

A

Sulpride (minimal D3 antagonist/partial agonist action)

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23
Q

MOA of Amisulpride

A

D2/D3 antagonist

Blocks autoreceptors, increasing synaptic dopamine levels

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24
Q

Which are the most sedative TCAs?

A

Dothiepin and amitriptyline

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25
Q

What can cause anorgasmia?

A

Alpha 1 antagonism

Raised prolactin

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26
Q

Which antipsychotic is best tolerated in Parkinson’s disease?

A

Quetiapine

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27
Q

What is the suggested pharmacological basis for clozapine-related hypersalivation?

A

M4 agonism

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28
Q

Half life of methadone

A

24 hours

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29
Q

Effect of non-competitive antagonists on receptor sites

A

Alter the receptor site so that the effects can reversed only partially by increasing dose of agonist drug

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30
Q

Effect of non-competitive antagonists on agonists

A

Reduces potency and efficacy of agonists

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31
Q

Which TCA has the largest evidence base in ADHD?

A

Desipramine

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32
Q

Which TCA has stimulant effect?

A

Desipramine

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33
Q

How does tyramine enter the presynaptic neuron?

A

Amine uptake pumps

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34
Q

4 main mechanisms of absorption

A
  1. Passive diffusion
  2. Facilitated diffusion
  3. Active transport
  4. Endocytosis
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35
Q

Where does most absorption from the gut take place and why?

A

Small intestine
Less acidic than stomach
Large surface area
Long transit time

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36
Q

Where does the absorption of most MR formulations take place?

A

Large bowel

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37
Q

Drugs which are 95-99% protein bound

A

Diazepam
Chlopromazine
Amitriptyline
Imipramine

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38
Q

Drugs which are 90-95% protein bound

A

Phenytoin
Valproate
Clomipramine

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39
Q

Principle plasma protein responsible for binding to acidic drugs

A

Albumin

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40
Q

Principle plasma protein for binding to basic drugs

A

Alpha-1 acid glycoprotein

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41
Q

Are most psychotropic drugs acid or base?

A

Basic

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42
Q

Equation for volume of distribution

A

Vd = Quantity of drug/plasma conc. at time of administration

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43
Q

What does high volume of distribution suggest?

A

Drug concentrated in cells or fatty tissues and not the blood

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44
Q

What is a high figure for Vd?

A

500-1000

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45
Q

What is the BBB made up of?

A

Capillary endothelium which have tight junctions

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46
Q

What type of molecules can cross BBB easily?

A

Unionized molecules that are less protein bound

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47
Q

Which parts of the brain lack BBB?

A

Area postrema of the medulla
Median eminence
Subfornical organ

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48
Q

Where is the blood-CSF barrier found?

A

Choroid plexus

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49
Q

What are tight junctions located between in blood-CSF barrier?

A

Adjacent epithelial cells

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50
Q

What is bioavailability?

A

How much of an administered drug reaches its target

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51
Q

How do you determine the bioavailability fraction?

A

Area under the curve obtained for orally administered drug divided by area under the curve for IV administered drug

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52
Q

Give an example of a TCA that undergoes high degree of first pass metabolism

A

Imipramine - only 30-80% of the oral dose enters the systemic circulation

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53
Q

What is bioequivalence?

A

Measure of comparability of plasma levels of 2 different formulations of the same active compound when given at the same dose and same route of administration

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54
Q

What does xenobiotics refer to?

A

The mechanism by which a foreign agent such as a drug molecule is metabolised and eliminated from the body

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55
Q

Where is the principal site of drug metabolism?

A

Liver

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56
Q

What are the 4 major metabolic routes?

A

Oxidation
Reduction
Hydrolysis
Conjugation

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57
Q

What happens in phase 1 metabolism?

A

Oxidation, reduction and hydrolysis

A molecule suitable for conjugation is produced

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58
Q

What happens in phase 2 metabolism?

A

Conjugation by reactions such as glucueonidation

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59
Q

Where is a molecule generally excreted if it has a relative molecular mass of less than 300?

A

Kidneys

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60
Q

Where is a molecule generally excreted if it has a relative molecular mass of more than 300?

A

Bile

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61
Q

What % and what race of people lack the CYP2D6 enzyme?

A

5-10% of Caucasian people

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62
Q

What class of drug and which drugs in this class particularly inhibit CYP system?

A

SSRIs

Particularly fluoxetine and fluvoxamine

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63
Q

Which drugs can induce their own metabolism?

A

Carbamazepine

Phenobarbitone

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64
Q

Which food/lifestyle factors are CYP inducers?

A

Alcohol
Smoking
Brussel sprouts

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65
Q

Which food/lifestyle factors are CYP inhibitors?

A

Grapefruit juice

Caffeine

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66
Q

Which major psychotropics are metabolised by CYP2D6?

A 
All TCAs
All neuroleptics
Fluoxetine 
Paroxetine 
Valproate
Risperidone
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67
Q

Which major psychotropics are metabolised by CYP3A4?

A

Most benzos
Mirtazapine
Fluvoxamine

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68
Q

Via which enzyme do smoking and caffeine affect glucuronidation?

A

UGT (and also by CYP1A2)

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69
Q

What is risperidone metabolised by?

A

CYP2D6

CYP3A

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70
Q

What is aripiprazole metabolised by?

A

CYP2D6 CYP3A

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71
Q

What is Quetiapine metabolised by?

A

CYP3A

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72
Q

What is clearance?

A

Term used to describe the rate of elimination of a drug

The volume of blood cleared of a particular drug in a unit of time

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73
Q

What is clearance directly proportional to?

A

Volume of distribution

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74
Q

Which drugs are excreted renally without significant liver breakdown?

A 
Lithium 
Amisulpride
Sulpride 
Gabapentin 
Acamprosate
Amantadine
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75
Q

What is half life defined as?

A

Time taken for the plasma concentration of a drug to halve

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76
Q

Rate of elimination in zero order kinetics

A

Constant

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77
Q

Rate of elimination in first order kinetics

A

Directly proportional to drug concentration

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78
Q

Which drugs undergo zero order kinetics?

A

Modified release preparations and depots
Ethanol
Phenytoin

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79
Q

What happens to gastric pH in elderly?

A

Increases

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80
Q

Physiological changes in neonates

A

Higher body water
Lower adipose tissue
BBB more permable
Low conc of albumin

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81
Q

Physiological changes in pregnancy

A

Delayed gastric emptying
Increase Vd
Decreased albumin
Increased GFR and renal clearance

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82
Q

Which class of psychotropic drugs should be used with caution in renal disease?

A

Benzos

83
Q

Why should you use diazepam with caution in end stage renal disease?

A

Diazepam half life unchanged but its metabolite desmethyldiazepam may accumulate

84
Q

Effect of TCAs on l-dopa

A

Reduce absorption of l-dopa

85
Q

Half life of fluoxetine and norfluoextine

A

Fluoxetine 4-6 days

Norfluoxetine 4-16 days

86
Q

Which SSRIs do not have active metabolites?

A

Fluvoxamine and paroxetine

87
Q

Which is the most selective SSRI?

A

Citalopram (and escitalopram)

88
Q

What is the most potent SSRI?

A

Paroxetine

89
Q

Which SSRI can reduce the clearance of diazepam and therefore should not be given together?

A

Fluvoxamine

90
Q

What is citalopram metabolised by?

A

CYP2C19 and then by CYP2D6

91
Q

How does fluvoxamine affect theophylline?

A

Reduces clearance of theopyhlline by around 3 fold via CYP1A2 inhibition

92
Q

Half life of citalopram

A

33 hours

93
Q

Fluvoxamine half life

A

17-22hrs

94
Q

Paroxetine half life

A

22 hours

95
Q

Sertraline half life

A

26 hours

96
Q

What is the advice for starting drug that can fatally interact with MAO?

A

Wait at least 2 weeks after stopping MAOI

97
Q

Half life of venlafaxine

A

3.5hrs

98
Q

Which drug should never be started when on MAOIs?

A

Pethidine - can cause excitatory reaction which can result in death

99
Q

Half life of duloxetine

A

12 hours

100
Q

Trazodone half life

A

5-9 hours

101
Q

Buspirone half life and subsequent effect on dosing

A

2-11 hours

3x daily dosing

102
Q

St John’s Wort MOA

A

Acts via multiple monoamine reuptake inhibition

103
Q

How long does it take for mirtazapine to reach peak plasma concentration?

A

2 hours

104
Q

Bioavailability of mirtazapine

A

50%

105
Q

Metabolism of mirtazapine

A

CYP2D6 CYP3A4

106
Q

What type of metabolism does Agomelatine undergo extensively?

A

First pass

107
Q

Metabolism of Agomelatine

A

CYP1A2 (90%)

CYP2C9 (10%)

108
Q

Time taken for lithium to achieve steady state

A

4-5 days

109
Q

Initial half life of lithium and what does it increase to/

A

Initially 18 hours then increases to 36 hours after 1 year of chronic use

110
Q

Where is lithium excreted?

A

Proximal tubules

111
Q

Which drugs increase lithium levels?

A 
ACE inhibitors 
Loop diuretics 
Fluoxetine 
NSAIDs
Thiazides
112
Q

Which drugs decrease lithium?

A 
Osmotic diuretics
Caffeine 
Aminophylline 
Theophylline 
Carbonic anhydrase inhibitors
113
Q

Half life of valproate

A

9 to 16 hours

114
Q

Bioavailability of valproate

A

100%

115
Q

Which drugs can increase carbamazepine levels?

A

Verapamil
Diltiazem
Valproate - displaces carbamazepine from plasma protein therefore increased carbamazepine levels

116
Q

Which depot drugs are esterified in sesame oil?

A

Fluphenazine, haloperidol and perphenazine

117
Q

Which depots are esterified in coconut oil?

A

Flupenthixol, piptiazine, zuclopenthixol

118
Q

When is the peak level generally following depot injection?

A

Around 1 week

119
Q

Half life of aripiprazole

A

90 hours

120
Q

Half life of olanzapine

A

30 hours

121
Q

Half life of quetiapine

A

6 hours

122
Q

half life of clozapine

A

16hours

123
Q

Half life of risperidone

A

15 hours

124
Q

What does risperidone undergo extensive first pass metabolism to form?

A

9-hydroxyrisperidone

125
Q

What catalyzes the hydroxylating of risperidone to 9-hydroxyrisperidone

A

CYP2D6

126
Q

What length of oral tapering is required for aripiprazole depot?

A

2 weeks

127
Q

Oral bioavailability of donepezil

A

100%

128
Q

Half life of donepezil

A

70 hours

129
Q

Half life of rivastigmine

A

1.5 hours

130
Q

Half life of methylpenidate

A

2-3 hours

131
Q

How can SSRIs affect atomoxetine levels?

A

SSRIs can raise levels

132
Q

At supratherapeutic doses, what happens to fluoxetine metabolism?

A

Goes from first order to zero order kinetics

133
Q

What happens in zero order kinetics?

A

Constant amount of drug cleared per unit of time

134
Q

3 main compartments that drugs are distributed in

A
  1. Vascular
  2. Extra-cellular
  3. Intracellular
135
Q

Which part of CYP system does fluoxetine inhibit?

A

2D6 and 3A4

136
Q

Which drugs does fluoxetine increase the concentration of?

A

Haloperidol
Carbamazepine
Phenytoin

137
Q

Which enzyme is responsible for oxidative metabolism of most psychotropic drugs?

A

Cytochrome P450

138
Q

Does venlafaxine have high or low binding to plasma proteins?

A

Low

139
Q

How long between stopping ssri and starting mao should you wait?

A

5-6 weeks

140
Q

How are 95% of drugs eliminated (kinetics)?

A

First order

141
Q

Examples of zero order kinetics

A 
Ethanol 
Phenytoin 
High dose salicylates
High dose fluoxetine 
High dose omeprazole
142
Q

How can you treat amphetamine overdose?

A

Urinary acidification

143
Q

After how many half lives should you assume that a drug is eliminated?

A

4-5

144
Q

Zaleplon half life

A

1 hour

145
Q

Which drug can be given as loading dose in acute mania?

A

Valproate

146
Q

Effect of NSAIDs on lithium

A

Decreases excretion

147
Q

How do NSAIDs cause decreased lithium excretion?

A

Inhibit the synthesis of renal prostaglandins, reducing renal blood flow and increasing renal re-absorption of sodium and therefore lithium

148
Q

Which are the least sedative TCAs?

A

Lofepramine

Nortriptyline

149
Q

Which TCA is safest in overdose?

A

Lofepramine

150
Q

Which psychiatric drugs are CYP3A4 inducers?

A

Carbamazepine
St John’s Wart
Phenytoin
Topiramate

151
Q

Is bioavailability affected by gender?

A

No

152
Q

Zolpidem half life

A

2.6 hours

153
Q

What is sensitisation?

A

Enhancement of drug effects following repeated administration of the same dose of drug

154
Q

Which drugs skip phase 1 metabolism and go straight to phase 2?

A

Lorazepam
Oxazepam
Temazepam

155
Q

What is fluvoxamine a potent inhibitor of?

A

CYP1A2

156
Q

MOA of clonidine

A

Presynaptic alpha-2 receptor agonist

Decrease the amount of noradrenaline released

157
Q

In which condition would drugs that alter protein binding become important?

A

Renal disease where proteinuria can occur

158
Q

Which antidepressant exhibits autoinhibition?

A

Paroxetine

159
Q

What needs to be balanced to allow high permeability across a membrane?

A

Hydrophillic and lipophillic properties

160
Q

Active metabolite of imipramine

A

Desipramine

161
Q

What metabolises imipramine to desipramine?

A

CYP2C19

162
Q

Example of a partial agonist at the benzodiazepine receptor

A

Clonazepam

163
Q

What is an ionotropic receptor?

A

Ligand-gated ionic channels

164
Q

Examples of ionotropic receptors

A

5HT3
NMDA
GABA-A
Glutamate

165
Q

What is a metabtropic receptor?

A

Slower response involving G-proteins which bind to the intracellular portion of the receptor and activate a second messenger

166
Q

Examples of metabotropic receptors

A 
D1-5
NA 
Serotonin 5HT1-7 (except 3)
Muscarinic
Opioid - mu
167
Q

Which type of receptor binding produces maximal response?

A

Full agonist

168
Q

What type of binding has a ceiling effect?

A

Partial agonist

169
Q

What is an inverse agonist?

A

Agent that binds to the same receptor but produces the opposite pharmacological effect - no drugs work this way

170
Q

How can a competitive antagonist be reversed?

A

By increasing the agonist dose

171
Q

What is potency?

A

Minimum dose needed to produce an effect

172
Q

What is efficacy?

A

Maximal response produced

173
Q

How do non-competitive antagonists work?

A

Alter the receptor site

174
Q

Effects of non-competitive antagonist on potency and efficacy?

A

Reduces both potency and efficacy

175
Q

What is affinity?

A

Ability of drug to bind to its appropriate receptor

176
Q

Difference in Sulpride MOA at low and high doses

A

Pure D2 antagonist
Low dose - presynaptic receptors blocked
High dose - post synaptic receptors blocked

177
Q

MOA Lurasidone

A

D2 Antagonist
5HT2A blocker
High affinity for 5HT7

178
Q

MOA Ziprasidone

A

5-HT2A and D2 antagonist

Also antagonises 5-HT1D, 5-HT2C, D3 and D4

179
Q

MOA Zotepine

A

5HT2A, 5hT2C, D1, D2, D3, D4 antagonist

Potent NA reuptake inhibitor

180
Q

MOA Agomelatine

A

5HT2C antagonist - enhances NA and dopamine neurotransmission
Direct agonist at melatonin MT1 and MT2

181
Q

MOA Amoxapine

A

Dopamine antagonist and serotonin-noradrenaline reuptake inhibition

182
Q

MOA Buproprion

A

Dopamine and noradrenaline reuptake inhibitor

183
Q

Which TCA is most potent?

A

Clomipramine

184
Q

TCA with least anticholinergic action

A

Desipramine

185
Q

MOA of carbamazepine

A

Prolongs sodium channel inactivation

186
Q

MOA of Gabapentin

A

Binds to alpha 2 delta subunit of the voltage-dependent calcium channel in the CNS

187
Q

MOA of lamotrigine

A

Blocks voltage-gated sodium channels leading to modulation of glutamate

188
Q

MOA of levetiracetam

A

Indirectly enhances GABA system

189
Q

MOA of pregabalin

A

GABA analogue structurally but binds to alpha2delta subunit of voltage-dependent calcium channel

190
Q

MOA of topiramate

A

Selective inhibitor of glutamate ampa receptors, blocks Na+ receptors and has indirect GABAergic activity

191
Q

MOA of Vigabatrin

A

GABA transaminase inhibitor

192
Q

Which is the least selective Z drug?

A

Zopiclone

193
Q

MOA of amphetamine

A

Releases stored monoamines especially NA and dopamine

194
Q

MOA of LSD

A

5HT2A partial agonist producing hallucinogenic effect

195
Q

MOA of MDMA

A

2 isomers:
R- isomer - LSD-like effect
S+ isomer - amphetamine-like property

196
Q

What inactivates acetylcholine?

A

Acetylcholinesterase

Butylcholinesterase

197
Q

Non-competitive inhibitor of both AChE and BChE

A

Tacrine

198
Q

MOA of modafinil

A

Activates hypocretin producing neurons possibly though alpha 2 or alpha 1 adrenergic agonist properties

199
Q

4 groups of CYP2D6 variations

A
  1. Poor metabolisers
  2. Intermediate metabolisers
  3. Extensive metabolisers
  4. Ultrarapid metabolisers
200
Q

Which group of CYP2D6 variations do most Caucasians fit into?

A

Poor metabolisers

201
Q

Which group of CYP2D6 variations do most Asians fit into?

A

Intermediate metabolisers

202
Q

Which group of CYP2D6 variations do most North Africans fit into?

A

Ultrarapid metabolisers

203
Q

In which gender group is antipsychotic response shown to be superior?

A

Women

204
Q

Which enzyme appears to be less active in women than men?

A

CYP1A2

MRCPsych (19 decks)

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