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MSPA- Neuropharmacology > Anti-psychotics and Anti-depressents > Flashcards

Anti-psychotics and Anti-depressents Flashcards

1
Q

What is the difference between anxiolytics and hypnotics ?

A
  • A single drug can induce both anxiolytic and hypnotic effects in a dose dependent fashion as a low does causes anxyolysis and a higher dose causes hypnosis.
  • Anxiolytics are taken in the morning and have long 1/2 life. Whereas, hypnotics are taken in the night and have short 1/2 life.
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2
Q

What are Benzodiazepines?

A

These are drugs with anxiolytic, hypnotic and anticonvulsant effects. They are safer than barbiturates.

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3
Q

What is the MOA of Benzodiazepines?

A

They bind to Benzodiazepines receptors, GABAa, and barbiturate receptors around common Cl- ion channel. Which enhance GABAA-mediated inhibition via increased frequency of Cl- channel openings. The affinities of benzodiazepines for benzodiazepine receptor correlate with clinical potency.

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4
Q

How does Benzodiazepines induce anxiolytic effects ?

A

By binding to alpha 2 sub unit of GABAa Receptor.

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5
Q

How does Benzodiazepines induce sedative or amenesic effects ?

A

By binding to alpha 1 sub unit of GABAa Receptor.

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6
Q

How does Benzodiazepines induce anti-convulsent effects ?

A

By binding to alpha 1,2,and 5 sub units of GABAa Receptor.

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7
Q

What is the first generation benzodiazepam developed by Roche in 1955?

A

chlordiazepoxide

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8
Q

What are the types and indications of benzodiazepams ?

A
  • Alprazolam: For generalized anxiety disorder.
  • Chlordiazepoxide: For alcohol withdrawal syndrome
    *Clonazepam: Panic disorder
  • Clobazam: For Lennox-Gastaut syndrome
    *Diazepam: severe alcohol withdrawal.
  • Estazolam and Flurazepam: Insomania
  • Lorazepam and Midazolam:convulsive status epilepticus.
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9
Q

What is the firstline SSRI for the treatment of generalised anxiety disorder ?

A

sertraline which can initially increase anxiety. Therefore, dosing should be gradual as anxiolytic effects require several weeks

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10
Q

What are the Sertaline alternatives in GAD?

A

Escitalopram or Paroxetine

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11
Q

What is the management of GAD if no response to first line Sertaline ?

A

*Increase dose or switch to an alternative SSRI / SNRI such as duloxetine/venlafaxine.
* If not tolerated, consider pregabalin.

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12
Q

What is the Tx of Severe disabling anxiety ?

A

Short term (2-4 weeks) BDZ with regular review

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13
Q

What are the side effects of Benzodiazepams ?

A
  • Unwanted sedation due to increased 1/2 life or older age.
  • Dangerous synergism with alcohol
  • Minimal respiratory depression relative to barbiturates
  • Decrease in REM sleep and rebound increase in REM sleep after discontinuation.
  • psyho-physiological dependence. Therefore dose should be gradually reduced.
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14
Q

What is the indication for Zolpidem ?

A

widely used non-benzodiazepine hypnotic acting at BZR1>BZR2. It is less anticonvulsant.

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15
Q

What is the indication and 1/2 life of Midazolam?

A

anaesthesia induction and the 1/2 life is 2 to 3 hours.

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16
Q

What is Flumazenil ?

A

benzodiazepine receptor antagonist to terminate benzodiazepine actions following surgery, overdose; precipitates withdrawal in dependent patients

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17
Q

What are the core symptoms of depression ?

A

*Depressed mood
*Anhedonia
*Lack of energy

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18
Q

What is the criteria for diagnosing depression ?

A

Mild - 4 symptoms must be detectable of which 2 should be core symptoms.
moderate- 6 with 2 core symptoms.
Severe- 7 with 3 core symptoms.

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19
Q

What are the most commonly used SSRIs in depression ?

A

Fluoxetine, paroxetine, citalopram, escitalopram, sertraline

20
Q

What are the advantages of SSRIs ?

A

*Low toxicity in overdose
*Better tolerated that TCAs due to less anti-muscarinic and cardiotoxic side effects.
* No need for dose titration
*Lack of addiction potential

21
Q

What is the MOA of SSRIs ?

A

SSRIs inhibit the serotonin transporter (SERT) at the presynaptic axon terminal, thereby increase the availability of Serotonin at the synaptic cleft by preventing the re-uptake of 5-HT. Unlike other classes of antidepressants, SSRIs have little effect on other neurotransmitters, such as dopamine or norepinephrine.

22
Q

What are the side effects of SSRIs ?

A
  • GIT bleeding, headaches, sexual dysfunction, movement disorders.
  • suicide risk under 30 years of age.
  • Hyonatremia in elderly and serotonin syndrome.
  • Withdrawal syndrome.
23
Q

What is the SSRI with long half life ?

A

fluoxetine

24
Q

What is the SSRI with short half life ?

A

Paroxetine

25
Q

What are the most common TCAs in depression ?

A

Amitriptyline, nortriptyline, dosulepin, imipramine,clomipramine,

26
Q

What is the MOA of TCAs ?

A
  • Inhibit noradrenaline and serotonin uptake
  • Inhibit monamine re-uptake at M1, Alpha 1 and H1 receptors.
27
Q

What are the side effects of TCAs ?

A
  • Sedation due to H1 receptor inhibition.
  • Postural hyotention due to Alpha 1 receptor inhibition.
  • M1 receptor inhibition causes anti-chollenergic effects such as dry mouth, constipation, blurred vision etc.
  • Toxic doses causes prolongation of QT interval.
28
Q

What are the non selective Monoamine Oxidase Inhibitors (MAOIs)?

A

Isocarbozaxide, Phelenzine, Tranylcypromine. They increase the synaptic availability of 5-HT, Norepinephrine and dopamine.

29
Q

How does selective vs non selective MAOIs work ?

A
  • selective inhibit monamine oxidase B and the non-selective inhibit A and B.
30
Q

What are the selective Monoamine Oxidase Inhibitors (MAOIs)?

A
  • Selegiline and Rasagiline and they selectively increase dopamine. Therefore, they are used in the treatment of PD.
31
Q

What are the side effects of MAOIs ?

A

*hypertensive crises, arrhythmia, headaches and hypotension.
* Tyramine in food (cheese, wine, beer, bean) – acute hypertension, severe headache may lead to intracranial haemorrhage

32
Q

How does Venelafexine work ?

A

*Inhibits pre-synaptic uptake of serotonin and noradrenaline
*Lacks sedative and anti-muscarinic effects of TCAs
*Dose-related hypertension and nausea

33
Q

How does Mirtazepine work ?

A

Pre-synaptic α2-adrenoreceptor antagonist, increases central noradrenergic and serotonergic neurotransmission.

34
Q

How does Agomelatine work ?

A

It has favourable anti depressive effect due to its agonistic action on Melatonin receptor and selective action on serotonin receptors.

35
Q

What are the symptoms of bipolar disorder ?

A

*Elation
*Psychomotor hyperactivity
*Grandiosity

36
Q

What are the anti-maniac agents used in bipolar disorder ?

A

Mood stabilisers: lithium and anticonvulsants such as carbamazepine, valproate.

37
Q

What is the MOA of mood stabilizer Lithium ?

A

It exerts its mood swing prophylactic effect by increasing GABArgic transmission and modulate glutametergic transmission by down regulating NMDA receptor activation.

38
Q

What determines antipsychotic potency of first generation antipsychotics ?

A

Affinities for D2 [but not for D1, D3, D4, D5] receptors antagonism correlate with clinical antipsychotic potency.

39
Q

What are the commonly used first generation anti-psychotics ?

A

Chlorpromazine, fluphenazine, flupentixol, haloperidol.
All takes 2 to 4 weeks for full anti-psychotic effects.

40
Q

What is the antipsychotics for poor adherence ?

A

Liposomal haloperidol decanoate IM every 2 to 4 weeks for slow release.

41
Q

What are the side effects of First-generation antipsychotic drugs?

A
  • Extrapyramidal side effects
  • Tardive dyskinesia
  • Behavioral and CV side effects
  • Hyperprolactenemia
  • Neuroleptic malignant syndrome
42
Q

What are Second-Generation [Atypical] Antipsychotic Drugs?

A

These are drugs that exhibit greater affinity for 5HT2 receptors than D2 receptors with the exception of amisulphride. They cause fewer EPS and lesser side effects as compared to first generation.

43
Q

What is the main side effect of 2nd generation anti-psychotic Olanzapine and risperidone in elderly ?

A

Increased risk of stroke.

44
Q

What is the action and indication of Clozapine ?

A

It is a 2nd generation anti-psychotic that is a weak antagonist of D2 and strong antagonist of 5-HT2, M, alpha 1, H1. It is indicated for treatment resistant psychosis or with severe EPS/TD.

45
Q

What are the side effects of Clozapine ?

A
  • Increased risk of agranulocytosis which require mandatory weekly blood count monitorning.
  • Myocarditis and cardiomyopathy in the first 2 months.
  • Intestinal obstruction
  • Hyper-salivation which require Tx with hyoscine hydrobromide.
46
Q

What is the effect of smoking on Clozapine ?

A

Aromatic hydrocarbons in cigarette smoke induce cytochrome P450 enzymes which reduces serum levels of clozapine.

MSPA- Neuropharmacology (3 decks)

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