1.3.3 Pharmacodynamics Flashcards
A new drug A is a non-competitive antagonist at NMDA receptors. If availability of glutamate at the receptor sites is increased experimentally after administering drug A, which of the following can happen?
- Effect of drug A increases
- Effect of drug A is partially reversed
- Effect of drug A is reversed fully
- Glutamate levels decrease
- No change takes place
Effect of drug A is partially reversed.
Noncompetitive antagonists alter the receptor site in some way so the effects can be reversed only partially by increasing the dose of the agonist drug. Non-competitive antagonism reduces both the potency and the efficacy of agonists.
Drug X produces improvement in depression when given at a dose of 10mg. Drug Y which acts via same mechanism as X produces the same improvement when given at a dose of 20mg. When X and Y are given together Y binds to more receptors in a quicker and stronger fashion than X. Which of the following is true?
- X and Y are equally efficacious
- X and Y have equal affinity but different potency
- X and Y have equal potency but different affinity
- X is less potent than Y
- Y has lesser affinity then X
X and Y are equally efficacious.
Efficacy refers to how well the drug produces the expected response i.e. the maximum clinical response produced by a drug (‘productivity’).
Efficacy depends on:
- affinity,
- potency,
- duration of receptor action in some cases and
- kinetic properties such as half life, among other factors
Which of the following has atypical antipsychotic activity?
- Amisulpiride
- Amoxapine
- Chlorpromazine
- Fluphenazine
- Promazine
Amisulpride has atypical antipsychotic activity as it:
- produces very low EPSEs,
- is more D2/3 selective compared to other typicals.
- But it does not have 5HT2A blockade like other newer atypicals
Which one of the following has antiepileptic activity?
Bupropion Buspirone Buspirone Fluoxetine Gabapentin
Gabapentin
Which of the following increases the risk of withdrawal reactions to therapeutic drugs?
- Drugs being a partial agonist instead of full agonist
- Having multiple active metabolites with slow clearance
- Slow withdrawal of the drug
- Taking the drug after food
- The drug having anticholinergic properties
The drug having anticholinergic properties.
Paroxetine has anticholinergic properties; withdrawal causes cholinergic rebound symptoms.
Which of the following actions can cause anorgasmia?
- Alpha 1 agonism
- Alpha 1 antagonism
- Antihistaminergic property
- Beta agonism
- GABA-A agonism
Alpha 1 antagonism
This and 5HT2A/2C stimulation (delayed ejaculation in SSRIs) can cause anorgasmia.
Retrograde ejaculation due to Alpha 1 block, anticholinergic and antihistaminic effects
The enzyme/s that metabolise/s most of the body dopamine:
- COMT only
- MAO-A and COMT
- MAO-A and MAO-B
- MAO-A and Tyrosine hydroxylase
- MAO-B and COMT
MAO-B and COMT
Dopamine is metabolized in the liver, kidney, and plasma by MAO and COMT. Therefore, inhibition of one or both of these enzymes would decrease dopamine metabolism and result in increased levels of dopamine in the brain.
How much Zuclopenthixol depot is equivalent to 50mg of haloperidol given every 4 weeks?
- 100mg every 2-4 weeks
- 20 mg every 2-4 weeks
- 200mg every 2-4 weeks
- 20mg every 3 weeks
- 400mg every 2 weeks
200mg every 2-4 weeks.
Using antipsychotic depot conversion chart from POMH (Prescribing Observatory for Mental Health), 200mg / 2 weeks or 400mg/4 weeks of zuclopentixol depot is equivalent to 50mg of haloperidol depot every 4 weeks.
Hal 10 = Zuc 80
A patient with Parkinson’s disease experiences visual hallucinations on levodopa/carbidopa therapy. The most appropriate intervention would be to initiate treatment with which ofthe following medications?
- Amisulpride
- Aripiprazole
- Olanzapine
- Quetiapine
- Risperidone
Quetiapine.
Atypical antipsychotic, especially quetiapine, have a reduced likelihood of causing adverse drug-induced parkinsonism and therefore a possible role in treating psychotic symptoms in patients with Parkinson’s, including the hallucinations induced by levodopa/carbidopa.
Aripiprazole has no evidence base yet for this use.
Excitotoxicity secondary to glutaminergic overstimulation results in neuronal damage. This is the basis of treating patients with neurodegenerative disorders with which of the following medications?
- Donepezil
- Galantamine
- Memantine
- Risperidone
- Selegiline
Memantine.
The hypothesis that glutamate-mediated neurotoxicity is involved in the pathogenesis of AD is increasingly being favoured;
Glutamate receptors are overactive, and N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential for the treatment of AD and other neurological disorders.
Memantine is a noncompetitive NMDA antagonist that is considered a neuroprotective drug.
Endogenous substrates for monoamine oxidase (MAO) isoenzymes include
- Acetylcholine,dopamine,and epinephrine.
- Epinephrine, dopamine, and serotonin.
- Histamine, acetylcholine, and serotonin.
- Tyramine, acetylcholine, and dopamine.
- Tyramine, serotonin, and histamine
serotonin, dopamine and norepinephrine are broken down by MAO enzymes.
MAO A is more selective for serotonin while
MAO B is more so for dopamine.
Which of the following is a 5HT1A partial agonist?
- Amisulpride
- Aripiprazole
- Buspirone
- Pramipexole
- Risperidone
Buspirone
This is an azaspirondecandione, a non-benzodiazepine anxiolytic.
Buspirone’s mechanism of action is related to 5HT partial agonism.
Which of the following is a partial D2 agonist?
- Amisulpride
- Aripiprazole
- Buspirone
- Pramipexole
- Risperidone
Aripiprazole is a dopamine D2 receptor partial agonist with
partial agonist activity at serotonin 5HT1A receptors and
antagonist activity at 5HT2A receptors
Which of the following is a noradrenaline reuptake inhibitor?
- Agomelatine
- Fluoxetine
- Paroxetine
- Reboxetine
- Risperidone
Reboxetine = the first selective norepinephrine reuptake inhibitor used in the treatment of depression, mainly acts by binding to the norepinephrine transporter and blocking the reuptake of extracellular norepinephrine
Which of the following statements best describes the receptor profile of trazodone?
- It is a mixed serotonin antagonist/agonist.
- It is a serotonin agonist
- It is a serotonin antagonist
- It is a serotonin, dopamine and norepinephrine agonist
- It is a serotonin, dopamine and norepinephrine antagonist
It is a mixed serotonin antagonist/agonist.
Trazodone is a multifunctional drug:
it is a hypnotic at low doses and an antidepressant at high doses due to the manner in which different multifunctional binding properties apply at different doses.
Trazodone’s most potent binding property is 5-HT2A antagonism. Its ability to block Serotonin reuptake transporters (SERT) is 100 fold less potent than its ability to block 5- HT2A receptors.
Trazadone is categorized as “serotonin antagonist-reuptake inhibitor”.
At lower doses it acts as 5HT2A antagonist; though at higher doses it acts as SERT blocker.
