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3153 Psychiatry > IC9 Pharmacology on MAOI, TCA, SSRI, SNRI, Typical and Atypical Antipsychotics > Flashcards

IC9 Pharmacology on MAOI, TCA, SSRI, SNRI, Typical and Atypical Antipsychotics Flashcards

1
Q

What are the 2 major forms of MAO? Which MAO breaks down what NTM?

A

*2 major forms:
o MAO-A and MAO-B
o 5-HT mainly broken down by MAO-A
o NA + dopamine broken down by both MAO-A and MAO-B

MAO-A breaks down
5-HT
NA
Dopamine

MAO-B breaks down
NA
Dopamine

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2
Q

What is a drug example of MAOI?

A

Phenelzine

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3
Q

What are the characteristics of Phenelzine? In terms of selectivity and reversibility.

A

Phenelzine

  • Non-selective for MAO-A + MAO-B
     Increase NA, DA & 5-HT
     increase toxicity too
  • Irreversible MAOI
     To recover MAO function, need to synthesize new MAO
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4
Q

What are the ADRs of MAOI?

A
  1. Postural Hypotension
  2. Restlessness & Insomnia (due to CNS stimulation)

DDI:

  • CNS depressant
  • Serotonergic drugs (increase serotonergic effects)
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5
Q

What is the precaution taken when taking MAOI?

A

Precautions:

  1. Should not be taken with other drugs that increases serotonergic functions e.g. pethidine (opioid pain reliever)
    a. Hyperexcitability, increase muscular tone, myoclonus (jerking, involuntary mvts), loss of consciousness
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6
Q

What is the MOA of TCAs?

A

Monoamine Reuptake Inhibitor Antidepressants

  • NTM stays longer in the synapse (NA & 5-HT)
    o T1/2 increase, thus longer effect
    o This is good since people with depression have a deficit of NTM
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7
Q

What are the drug examples of TCAs?

A
  • Non-selective for SERT / NET
    o Imipramine, amitriptyline, nortriptyline
  • Selective for NET
    o Desipramine
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8
Q

What are the advantageous of 2nd gen TCAs over 1st gen TCAs?

A

Nortriptyline

  • Milder SE compared to amitriptyline & imipramine
  • Improve compliance
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9
Q

What are the ADRs of TCAs?

A

ADR of TCAs (just know the ADR, no need know MOA):

  1. Sedation
    a. due to H1 receptor antagonism
    b. tolerance to sedation can develop in 1-2weeks
  2. postural hypotension
    a. due to alpha-adrenoceptor sympathetic block
  3. dry mouth, blurred vision, constipation
    a. due to muscarinic receptor antagonism
    –> shows that TCA is non-selective, binds to many receptors
    –> good to know the MOA so as to infer what ADRs a med has
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10
Q

What is the MOA of SSRIs? How is it better than TCAs?

A

(3) Selective Serotonin Reuptake Inhibitors

  • greater 5-HT reuptake selectivity than TCAs
  • more selective for 5-HT than NA
    o Fluoxetine 50x selective for 5-HT
    o Citalopram 1000x selective for 5-HT
  • Thus, fewer ADR than TCAs
  • Fluoxetine currently most widely used anti-depressant
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11
Q

What are the advantages of SSRIs? In terms of pharmacological features and thus SE?

A

*Advantages of SSRIs:
Pharmacological Features –> Clinical Benefits

Low affinity for alpha-adrenoceptors –> Lack of CVD effects, safer in overdose

Lack of effect at histamine receptors –> Reduce sedation

Low affinity for muscarinic cholinergic receptors –> Minimal anticholinergic SE e.g. dry mouth, constipation

  • Overall, SSRIs safer in overdose + less SE than TCAs –> thus better compliance than TCAs

Summary of benefits of SSRIs:

  • SSRIs are greater in terms of efficacy, safety, and tolerability
  • 1st line antidepressants but
    o Only got 2/3 get remission
    o ADR effects esp at start
    o Discontinuation can be a problem in some
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12
Q

What are the ADRs of SSRIs?

A

ADRs of SSRIs:

  1. Nausea
  2. Insomnia
    a. 1&2 –> may be due to discontinuation / rebound symptoms of withdrawal when plasma levels of drug drop btw doses
  3. Sexual dysfunction
  4. Sedation (Citalopram, since it still have Histamine receptor antagonism)
  5. Serotonin syndrome –> tremor, hyperthermia, cardiovascular collapse
    a. Too much serotonin
    b. Specifically due to SSRI effect with other drugs increasing serotoninergic activity e.g. MAOIs
    c. while for others e.g. MAOIs with other similar SE when taken with other drugs are not called serotonin syndrome
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13
Q

What is the MOA of SNRIs? When do people use SNRIs?

A

(4) Serotonin & Noradrenaline reuptake inhibitors (SNRIs):

  • Similar dual 5-HT & NA reuptake inhibition profiles to non-selective TCAs
  • E.g. Venlafaxine, desvenlafaxine (synthetic metabolite of venlafaxine) & duloxetine
  • When people are not improving with SSRIs, then switch to SNRIs
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14
Q

What are some drug examples of SSRIs?

A

Fluoxetine, Citalopram

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15
Q

What are some drug examples of SNRIs?

A

Venlafaxine, Desvenlafaxine, Duloxetine

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16
Q

What are the advantages of SNRIs vs other antidepressants?

A

Advantages of Venlafaxine:

  • Different structure to TCAs –> thus fewer SE
  • Work slightly faster than other antidepressants
  • Work better in treatment-resistant pts (to SSRIs)
17
Q

What are drug classes categorized as antidepressants?

A

MAOIs, TCAs, SSRIs, SNRIs

18
Q

What are the ADRs of SNRIs?

A

ADRs of SNRIs:

  1. Nausea
  2. Insomnia
  3. Sexual dysfunction
  4. Serotonin syndrome (when add with other serotonergic drugs & MAOIs)
  5. Withdrawal effects (more common & stronger than for SSRIs and TCAs)
19
Q

What are the other drug examples of antidepressants? (not under the 4 main categories)

A
  1. Mirtazapine
  2. Bupropion
  3. Agomelatine
  4. Ketamine
  5. Vortioxetine (Multimodal serotonergic antidepressants)
20
Q

What are the 4 dopamine pathways?

A

Dopamine pathways:

  1. Nigrostriatal (part of extrapyramidal motor system)
  2. Mesolimbic (reward & emotions)
  3. Mesocortical (cognition & attention)
  4. Tuberoinfundibular (from hypothalamus to anterior pituitary regulates prolactin secretion into blood)
21
Q

What is the MOA of typical antipsychotics?

A

(5) Typical Antipsychotics (1st gen)

  • Control positive symptoms of schizophrenia (by blocking dopamine receptors)
22
Q

What are the drug examples of typical antipsychotics?

A

chlorpromazine, haloperidol

23
Q

What are the ADRs of chlorpromazine?

A

ADR of chlorpromazine (need to know which receptor it blocks):

  1. M1 receptor
    a. Dry mouth, constipation, blurred vision
  2. H1
    a. Sedation, weight gain
  3. Alpha 1 adrenergic
    a. Postural hypotension, dizziness
  4. Dopamine pathway
    a. extrapyrimidal side effects
24
Q

What is the ADR of haloperidol?

A

ADR of haloperidol:

  1. Alpha 1 adrenergic
    a. Postural hypotension, dizziness
  2. Dopamine pathway
    a. extrapyrimidal SE
25
Q

How does typical antipsychotics produce EPSE? What are the symptoms of EPSE?

A
  • Produce extrapyramidal SE (EPSE)
    o Block nigrostriatal pathway
    o Stimulating a PD process, decrease dopamine activity on the pathway controlling motor functions

For extrapyramidal SE:

  • The extrapyramidal pathway involves the basal ganglia, including the striatum and substantia nigra
  • At any one point the primary motor cortex is sending all sorts of signal
  • Every moment all signals are sent out, but the basal ganglia will cancel out all the mvts but only allow one signal and thus release the inhibition and allow the person to do one action
  • But if this is not working properly, then everything happen at once
  • When have breakdown/inhibition of the nigrostriatal pathway, will then lead to these extrapyramidal SE
  1. Acute dystonias
    a. Stiffening and contraction of the muscles
    b. Parkinsonism-like syndrome e.g. cogwheel rigidity, tremor at rest
    c. Occurs within 1st few weeks of treatment
    d. Reversible when drug is stopped
    e. Caused by D2 antagonism in nigrostriatal pathway (from substantia nigra to striatum)
  2. Tardive dyskinesia (movement)
  3. Akathisia (inability to remain still)
26
Q

What is the MOA of atypical antipsychotics?

A

Atypical Antipsychotics (2nd gen)

  • Control positive symptoms of schizophrenia
  • Produce less EPS (thus defining it as atypical)
  • Main action is serotonin-dopamine antagonism but have mixture of actions (but do not define it as atypical)
    o Greater affinity at 5-HT2 receptor
    o Greater affinity at D4 receptors
    o Mixed antagonism at alpha-adrenoceptors, H1 receptors, muscarinic acetylcholine receptors and 5-HT2 receptors
27
Q

What are some drug examples of atypical antipsychotics?

A

Amisulpride, clozapine, olanzapine, risperidone

28
Q

What are the ADRs of clozapine?

A

ADR of Clozapine

  1. M1 receptor
    a. Dry mouth, constipation, blurred vision
    b. Esp. for clozapine and olanzapine
  2. H1
    a. Sedation, weight gain
    b. Esp. for clozapine and olanzapine
  3. Alpha 1 adrenergic
    a. Postural hypotension, dizziness, reflex tachycardia
    b. Esp. for risperidone
  4. Clozapine-induced agranulocytosis
    a. Monitoring regular blood counts is required
    b. Thus, use olanzapine instead (don’t have this SE)
  5. Drug-induced diabetes e.g. hyperglycemia, diabetes
  6. Drug-induced weight gain
29
Q

What is amisulpride considered “atypical” compared to the other atypical antipsychotics?

A

Amisulpride

  • Selective D2/D3 antagonist (and possibly 5-HT7 antagonist)
  • It has an atypical pattern for receptor affinities (vs other atypical antipsychotics)
  • less mixed antagonism
30
Q

What is the unique ADR associated with Amisulpride?

A

ADR of amisulpride:

  • Fewer SE due to selectivity for D2/D3 receptors
  • Absence of alpha-adrenoceptor block, antihistaminergic, anticholinergic SE
  1. Hyperprolactinemia (due to dopamine receptor blockade in anterior pituitary gland)
    a. Breast swelling, pain, lactation (even when not pregnant), gynaecomastia in males (tuberoinfundibular pathway is affected)
    b. Tuberoinfundibular pathway –> Have more D3 receptors
31
Q

What are the other ADRs of atypical antipsychotics?

A

Other ADRs of atypical antipsychotics:

  1. Drug induced diabetes e.g. hyperglycemia, diabetes
    a. Esp. for clozapine, olanzapine, risperidone
    b. Amisulpride is an exception
    c. Diabetes can be irreversible
    d. FDA require that there is labelling on all atypical antipsychotics on risk of hyperglycemia and diabetes
  2. Drug induced weight gain
    a. Esp. clozapine, olanzapine, risperidone
32
Q

*Why does atypical antipsychotics produce less EPSE?

A
  1. Potent 5-HT2A receptor antagonism vs weak D2 antagonism –> lower EPSE & higher efficacy against negative symptoms
    a. Esp. clozapine, olanzapine
  2. High D3 to D2 antagonism ratio –> favours actions on nucleus accumbens (involved in motivation and action) over striatum (striatum have D1 and D2, very little D3)
    a. Esp. amisulpride
  3. High D4 to D2 antagonism ration –> favours actions in the prefrontal cortex (higher cognition, emotions, thus wanna target this) over the striatum
    a. Esp. clozapine
  4. High D2 to D1 antagonism ratio reduces impact of antagonism in striatum
    a. Esp. amisulpride, risperidone
    b. D1 is worse compared to D2, wrt to causing EPSE –> so hierarchy of causing is D1 > D2 > D3 > D4
    c. D2 antagonism will increase dopamine release –> becos other than binding to the D2 receptors on the post-synaptic neuron, it binds to D2 auto-receptors on the presynaptic neuron (thus more release of NTM)
32
Q

*Why does atypical antipsychotics produce less EPSE?

A
  1. Potent 5-HT2A receptor antagonism vs weak D2 antagonism –> lower EPSE & higher efficacy against negative symptoms
    a. Esp. clozapine, olanzapine
  2. High D3 to D2 antagonism ratio –> favours actions on nucleus accumbens (involved in motivation and action) over striatum (striatum have D1 and D2, very little D3)
    a. Esp. amisulpride
  3. High D4 to D2 antagonism ration –> favours actions in the prefrontal cortex (higher cognition, emotions, thus wanna target this) over the striatum
    a. Esp. clozapine
  4. High D2 to D1 antagonism ratio reduces impact of antagonism in striatum
    a. Esp. amisulpride, risperidone
    b. D1 is worse compared to D2, wrt to causing EPSE  so hierarchy of causing is D1 > D2 > D3 > D4
    c. D2 antagonism will increase dopamine release  becos other than binding to the D2 receptors on the post-synaptic neuron, it binds to D2 auto-receptors on the presynaptic neuron (thus more release of NTM)
33
Q

What are the additional benefits of atypical antipsychotics vs typical?

A

Additional Benefits of Atypical antipsychotics vs typical:

  1. More effective against negative symptoms of schizophrenia
    o Clozapine, olanzapine, risperidone
  2. Ameliorate cognitive dysfunction in schizophrenia
    o Clozapine, risperidone
  3. Better at mood stabilization
    o Clozapine, olanzapine, risperidone

BUT atypical antipsychotics effects on these 3 above are generally still weak

34
Q

What are the ADRs of olanzapine?

A
  1. Dry mouth, constipation, blurred vision (anti-M)
  2. Sedation, weight gain (anti-H)
  3. Postural hypotension, dizziness (not much)
  4. Drug-induced diabetes e.g. hyperglycemia, diabetes
  5. Drug-induced weight gain
35
Q

What is the ADRs of risperidone?

A
  1. Postural hypotension, dizziness
  2. Drug-induced diabetes e.g. hyperglycemia, diabetes
  3. Drug-induced weight gain

3153 Psychiatry (10 decks)

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