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Psychiatry > Pharmacodynamics > Flashcards

Pharmacodynamics Flashcards

1
Q

Which psychiatric drugs affect the storage of neurotransmitters?

A

Reserpine depletes NA and DA

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2
Q

Which psychiatric drugs cause partial agonism?

A

Aripiprazole - D2
Buspirone - 5HT1A
Clonazepam - BDZ receptor
Buprenorphine - opioid receptor mu

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3
Q

Which receptor does Buprenorphine cause partial agonism at?

A

Opioid receptor mu

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4
Q

Which psychiatric drugs cause full agonism?

A

Benzos - GABA-A complex

Bromocriptine - dopamine

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5
Q

E.g. of ionotropic receptors?

A

Acetylcholine
GABA-A
Glutamate
5HT-3

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6
Q

Examples of Metabotropic receptors?

A 
Dopamine - D1-5
Noradrenaline
5HT1-7 (except 5HT-3)
Muscarinic Acetylcholine receptors
Opioid receptors - mu
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7
Q

What is a ceiling effect?

A

Related to partial agonists; degree of response depends on availability of physiological neurotransmitter in the vicinity.

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8
Q

What is competitive antagonist?

A

Can be reversed by increasing dose of agonist drug.

Reduce potency but not efficacy of agonist.

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9
Q

What is potency?

A

Minimal dose needed to produce an efficacy

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10
Q

How do noncompetitive antagonists work?

A

Alter receptor site so increasing dose of agonist drug can reverse effects on partially.
Reduces both potency and efficacy of agonists.
Shift curve to right.

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11
Q

E.g. of noncompetitive antagonists.

A

Ketamine and phencyclidine are noncompetitive NMDA antagonists.

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12
Q

What is pharmacological antagonism?

A

Opposing action of 2 molecules acting via same receptor

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13
Q

What is physiological antagonism?

A

Opposing action of 2 molecules by acting via different receptors

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14
Q

What is the potency of a drug?

A

Amount of drug needed to produce particular effect compared to another standard drug with similar receptor profile (vigor)

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15
Q

What does efficacy depend upon?

A

Affinity
Potency
Duration of receptor action
Kinetic properties such as half-life

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16
Q

Mechanism of Amisulpride?

A

D2 and D3 antagonism
Dose-dependent
Limbic selectivity an 5HT7 activity

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17
Q

Mechanism of Aripiprazole?

A

Partial dopamine agonist at D2

5HT2A antagonist

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18
Q

Mechanism of Asenapine

A

D2 antagonist and 5HT2A blocker

Alpha-2 blockage

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19
Q

Mechanism of clozapine?

A 
High ratio of 5HT2 to D2 blockade
Blocks D4 and 5HT5
Alpha 1 antagonism
Anticholinergic and antihistaminic properties
Weak D1 and D2 affinity
Binds 5HT3
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20
Q

Mechanism of Lurasidone?

A 
D2 antagonist
5HT2A blocker
High affinity for 5HT7
Partial agonist at 5HT1A receptors
Minimal affinity for alpha-1 (less orthostatic effect) and histamine receptors (perhaps weight neutral)
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21
Q

Mechanism of Olanzapine

A

High 5HT2/D2 blockade ratio.
Potent D4 blockade and 5HT6 blockade
Significant anticholinergic and antihistaminic effects

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22
Q

Mechanism of Risperidone

A

Serotonin-Dopamine antagonist.
High 5HT2A antagonist.
Therapeutic doses: binds D2 similar to typicals -> EPSEs and prolactin SEs

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23
Q

Mechanism of Sulpride?

A

Pure D2 antagonist.
Low doses: presynaptic receptors blocked (helps with -ve symptoms).
Above 800mg/day; affects postsynaptic D2 - reducing +ve symptoms.

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24
Q

Mechanism of Zotepine

A 
Atypical antipsychotic
5HT2A, 5HT2C, D1-D4 antagonism
Potent noradrenaline reuptake inhibitor
Potent antihistaminic activity
Some NMDA antagonism
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25
Q

Mechanism of action of Agomelatine as an antidepressant

A

Enhances norepinephrine and dopamine neurotransmission through 5-HT2C antagonism.
Norepinephrine and dopamine disinhibitor via 5HT2C inhibition

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26
Q

How does Agomelatine cause inhibition of norepinephrine and dopamine via 5HT2C

A

GABA interneurons tonically inhibit noradrenergic circuits from locus coeruleus and dopaminergic ciriuts from ventral tegmentum, projecting to prefrontal cortex.
Serotonin via 5HT2C stimulation drives these GABA interneurons.

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27
Q

Structure of Amoxapine

A

Tetracyclic with dibenzoxazepine structure

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28
Q

Mechanism of Amoxapine

A

Both dopamine antagonistic and serotonin-noradrenaline reuptake inhibition effects.
Antipsychotic + antidepressant.
EPSEs.

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29
Q

Mechanism of Buspirone?

A

Partial agonist on 5HT1A
Presynaptic - full agonist, inhibits release of serotonin which leads to antianxiety.
Postsynaptic - partial agonist to account for antidepressant activity.

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30
Q

Mechanism of Desipramine

A

Tricyclic with least anticholinergic action but lethal on OD.

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31
Q

Mechanism of Milnacipran

A

SNRI

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32
Q

Mechanism of Mirtazapine

A

5HT2A antagonism
Alpha 2 antagonism
Antihistaminic
Anti 5HT3

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33
Q

Mechanism of Moclobemide

A

Reversible inhibitor of MAO-A electively.

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34
Q

Mechanism of Nefazadone

A

5HT2A antagonist with serotonin ruptake inhibition and mild norepinephrine reuptake inhibition.
Alpha 1 antagonism

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35
Q

Mechanism of Pindolol

A

Beta blocker with intrinsic symapthomimetic activity.

5HT1A antagonism - possibly enhances action of SSRI by this

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36
Q

Mechanism of action of Selegiline

A

MAOI - selective for B at normal dose.

Selectivity lost when applied at higher doses

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37
Q

Mechanism of action of Tranylcypromine

A

MAOI - irreversible, non-selective.

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38
Q

Mechanism of Vilazodone

A

Selective serotonin reuptake inhibition

Partial agonist at 5HT1A

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39
Q

Mechanism of Vortioxetine

A

SSRI-like effect
5HT3 antagonism
5HT1-A agonism

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40
Q

Mechanism of Carbamazepine

A

Prolongs Na channel inactivation, so that ca channel inactivation is prolonged.
Reduces glutamate neurotransmission,

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41
Q

Mechanism of Lamotrigine

A

Neuronal stabilization

Block Na channel–>decrease glutamate release

42
Q

Mechanism of Levetiracetam

A

Indirectly enhances GABA system

43
Q

Mechanism of Tiagabine

A

Potent and selective reuptake inhibitor of GABA.

44
Q

Mechanism of Topiramate

A

Enhances GABA

Blocks glutamate at NMDA

45
Q

Mechanism of Valproic acid

A

Enhances GABA
Inhibits GABA aminotransferase
Increases GABA binding sites

46
Q

Mechanism of Benzos

A 
Act via omega site in GABA-A
all agonists (except clonazepam - partial)
47
Q

Mechanism of Ramelteon

A

MT1 and MT2 agonist with high affinity

Decreases sleep latency, increases sleep time.

48
Q

Mechanism of alcohol

A

Intercalates into fluid cell membrane
Decreases NMDA sensitivity
Increases GABA sensitivity

49
Q

Mechanism of amphetamine

A

Acts via releasing stored monoamines - noradrenaline and dopamine.

50
Q

Mechanism of clonidine and lofexidine

A

Presynaptic alpha 2 agonist - reduces central sympathetic tone.

51
Q

Mechanism of disulfiram

A

Inhibits aldehyde dehydrogenase

Leads to accumulation of acetaldehyde if alcohol is consumed.

52
Q

Mechanism of LSD

A

5HT2A partial agonism - produces hallucinogenic effect

53
Q

Mechanism of methadone

A

Opioid receptor agonist
Longer acting than heroin
Pure mu agonist

54
Q

Mechanism of varenicline

A

Alpha 4 beta 2 partial agonist

55
Q

Rivastigmine

A

Rivastigmine inhibits both acetyl and butyl-cholinesterase.

56
Q

Galantamine

A

Galantamine - nicotine agonist

57
Q

Which drug is approved for use in MND?

A

Riluzole

58
Q

What does Riluzole do for MND?

A

Prolongs survival by 10% for more than a year of treatment

59
Q

Riluzole’s mechanism of action?

A

Na channel blockade
High voltage Ca channel blockade
NMDA glutamate receptor antagonism

60
Q

Mechanism of dextroamphetamine and methylphenidate

A

induce release of dopamine and noradrenaline from presynaptic neurons.
Weak inhibitors of catecholamine reuptake

61
Q

Mechanism of atomoxetine

A

Selective inhibitor of presynaptic noradrenaline reuptake

62
Q

Cyproheptadine -

A

antihistamine and 5HT2 antagonist.

63
Q

What was Cyproheptadine used as?

A

Treat delayed ejaculation associated with SSRI use

64
Q

Mechanism of Modafinil

A

Activates hypocretin-producing neurons through alpha 2 and alpha 1 adrenergic agonist properties and noradrenaline reuptake blocking effects.

65
Q

Mechanism of pramipexole, ropinirole, aopmorphine

A

Dopamine agonists - bind 20x more selectively to D3 than D2.

Pramipexole - nonergot dopamine agonis

66
Q

Mechanism of sumatriptan

A

5HT1D and 1F agonist

67
Q

Mechanism of yohimbe

A

Alpha 2 antagonist

Used to treat erectile dysfunction

68
Q

Relationship between ECT and kindling?

A

ECT is anti-kindling

69
Q

How does ECT lead to neurogenesis?

A

Mediated by increased expression of brain-derived neurotrophic factor and its receptor

70
Q

What happens to blood brain barrier permeability in ECT?

A

Acutely increases, returns to normal within 24 hours

71
Q

EEG activity in ECT

A

Delta and theta activity afterwards - returns to normal after 3 months

72
Q

Impact of ECT on neurotrophic factors

A

Increase in NGF, BDNF, NF3

73
Q

Impact of ECT on hormones

A

Increased cortisol, prolactin and TSH coincides with good response.

74
Q

Impact of ECT on 5HT2 receptors?

A

Increase

75
Q

Which ethnicity are poor metabolizers of CYP2D6?

A

Caucasians - 7%
East asians - 1%
These lack this enzyme so are poor metabolizers of TCAs and risperidone

76
Q

Etnicity with intermediate metabolization of CYP2D6?

A

Higher in asians - higher SE but good drug efficacy

77
Q

Which ethnicity are ultrarapid metabolizers of CYP 2D6?

A

33% of north africans - they have multiple copies of CYP 2D6
5% cauccasians
1% east asians
25% indians

78
Q

weight gain caused by antipsychotics

A

5HT2C block

79
Q

GI side effects caused by SSRIs

A

5HT3 stimulation

80
Q

Newborn with spina bifida

A

Valproate

81
Q

What should ideally not administered with Fluvoxamine

A

Diazepam
Theophylline
Warfarin

82
Q

Acidification of urine helps eliminate what drugs

A

Amphetamine

PCP

83
Q

OD with amitryptiline

A

Diazepam to prevent seizures

84
Q

treatment for excessive salivation with clozapine

A

Hyoscine 300micrograms

85
Q

Therapeutic blood level for clozapine

A

350-500 micrograms/L

86
Q

Therapeutic blood level for amitrtriptyline

A

100-200 micrograms/L

87
Q

Mechanism of atomoxetine

A

Inhibits NE transporter

88
Q

Treatment of NMS

A

Dantrolene

Bromocriptine

89
Q

what is a heteroreceptor

A

A receptor that mediates the synthesis of mediators other than its own ligabd

90
Q

Blockade of postsynaptic alpha-1 Receptor

A

Orthostatic hypotension

Sedation

91
Q

Tolerance to LSD

A

downregulation of 5HT2

92
Q

Clozapine induced hypersalivation

A

M4 agonism

93
Q

Low incidence of EPSE

A

5HT2 blockade

94
Q

Mechanism of vigabatrin

A

irreversibly inhibits GABA transaminae

95
Q

Side effect of reboxetine in 10% males

A

Urinary hesitency

96
Q

Hydralazine MAOi

A

Phenelzine

isocarboxizid

97
Q

Non-hydralazine MAOi

A

Tranycypromine

98
Q

Mechanism of dry mouth TCAs

A

M3 antagonism

99
Q

Most important side effect with anti- dementia drugs

A

Bradycardia

100
Q

Competitive antagonist

A

reversed completely by increasing dose of agonist

Reduce potency but not efficacy

101
Q

Mechanism of GHB

A

GABA-B agonist

102
Q

1/2 life of temazepam

A

10 hours

Psychiatry (10 decks)

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