Anti-depressant and bipolar disorder drugs Flashcards
What are the drug interaction of SSRIs- Selective Serotonin Reuptake inhibitors?
- increase 5HT: Serotonin syndrome» with drugs ( MAOs, TCAs and meperidine)
- most inhibit cytochrome P450 enzymes (partially fluvoxamine and fluoxetine)
- increase level of benzodiazepines for anxiety disorder
- Safer drug is Citalopram for interactions
Which is a safer SSRIs antidepressant for interactions?
Citalopram
When will you use SSRIs (selective serotonin reuptake inhibitors?
To treat major depression, OCD, Bulimia, anxiety disorders and PMDD- premenstral dyspeptic disorder.
Two examples of SSRIs.
**Fluoxetine, **Citalopram, **Sertraline, (Escitalopram, Paroxetine, Fluvoxamine, Vilazodone)
(either two)
What is the mechanism for SSRIs?
SSRIs: selective blockade of 5HT reuptake
- cause increase in extra cellular serotonin that initially activate 5HT(1A) autoreceptors, which inhibits serotonin release and reduce extra cellular serotonin to its previous level.
Most of the antidepressants inhibit uptake of ____ and ____.
Norepinephrine (NE) and serotonin (5HT)
What are the five main categories of antidepressants?
SSRIs- selective serotonin reuptake inhibitors- FIRST LINE DRUG
TCAs- tricyclic antidepressants- SECOND LINE DRUG
SNRIs- Serotonin/ Noradrenaline Receptor Inhibitors
MAOIs- Monoamine Oxidase Inhibitors
MA receptor antagonists
All antidepressants may provoke ____.
Seizure ( and no particular drug is safe for depressed epileptic patients)
Antidepressants need at least 2-3 weeks to work because ______.
To gradually change the sensitivity of central 5HT and/ or adenoceptors.
A second augmenting drug is normally added with antidepressant. What is it? It is also used in ____ and ____ for mood stabilising action.
Lithium (and needs to continue for at least 4-6 months)
Mania and bipolar affective disorders.
Abrupt withdrawal of antidepressant drugs (esp MAOIs) may cause ______.
Nausea, vomiting, panic, anxiety and motor restlessness.
What is monoamine theory?
Depression resulted from a decrease in activity of central noradrenergic and/or serotonergic systems.
Name three drugs that are used for mood - stabilising properties.
Lithium
Carbamazepine
Valproate
Serotonin cleared from synapse by ____, and subsequently breakdown by ____.
5-HT re-uptake transporter
intracellular monoamine oxidase A
What are the side effects of taking SSRIs?
nausea, agitation, insomnia, drowsiness, sexual dysfunction.
What do you need to be cautious when taking SSRIs?
Avoid taking with monoamine oxidase inhibitors (with at least 2 weeks gap). However low overdose risk.
*SSRIs should not be given to patients under 18 years old because this will increase the risk of suicidal behaviour.
What is TCAs (Tricyclic antidepressants)?
TCAs (Tricyclic antidepressants) refers to compounds based on dibenzazepine (eg. imipramine) and dibenzo-cycloheptadiene (eg. amitriptyline) ring structure.
It has similar blocking actions at cholinergic muscarinic receptor, alpha- adrenoreceptors and histamine receptors.
Explain the mechanism of TCAs and SNRIs (Serotonin/ Noradrenaline Reuptake Inhibitors).
> TCAs: non-specific blockade of 5HT and NE reuptake.
Serotonin and noradrenaline are cleared from synapse by 5HT and NA reuptake transporters, and subsequently breakdown by intracellular monoamine oxidase A (MAO) for both** and catechol-O-methyltransferase (COMT) only for NA**.
SSRIs have (more/less) effective than TCAs, but have worse side effect.
more
What are the side effects of TCAs?
S/E: muscurinic and alpha-blockade,
sedation, seizures, anticholinergic S/E
What do you need to be cautious about taking TCAs?
- high risk from overdose (ventricular arrhythmia)
- interact with other CNS depressants (i.e. alcohol)
- avoid taking with MAOIs
Give two examples of TCAs.
- ** Amitriptyline (most used TCA; for neuropathic pain),
- Desipramine,
- Nortriptyline,
- Clomipramine (Dosulepin, Doxepin, Lofepramine- least dangerous but leads to hepatotoxicity, Trimipramine, Imipramine)
Give an example of SNRIs that are not NA-selective inhibitors, and give some details about these drugs.
** Venlafaxine- inhibits the reuptake of both 5HT and norepinephrine, is weak and non-selective (may be 5-HT selective), metabolite desvenlafaxine inhibits NA uptake, low risk of overdose.
Duloxetine- use for anxiety disorder. Non-selective and also inhibits DA uptake. Fewer S/E than Venlafaxine, and low risk of overdose.
Give some examples of SNRIs that are NA-selective inhibitors, and it’s side effects.
** Reboxetine- safe in overdose. [S/E: dizziness, insomnia, anticholinergic effect]
Maprotiline- [S/E: as TCAs]
State the major use of TCAs.
- major depression
- phobic and panic anxiety state
- OCDs (obsessive-compulsive disorders)
- neuropathic pain
- enuresis (involuntary vibration)
State the toxicity of TCAs
3 ‘C’s: coma, convulsions, and cardiotoxicity
State the drug interaction of TCAs
- hypertensive crisis with MAO inhibitors
- Serotonin syndrome with SSRIs, MAO inhibitors, and meperidine
- prevent antiHT action of alpha-2 agonists
State the types of Monoamine receptors (in depression).
1) Adrenergic alpha-2 receptors (Gi- linked GPCR) decrease cAMP
2) 5-HT2 receptors (Gq- linked GPCR) IP3- mediated Ca2+ release
3) 5-HT3 receptors (Ligand gated cation channel)
Examples of monoamine receptor antagonists/ blocker (MARA) as anti-depressant.
1) ** Mirtazepine:
- Blocks adrenergic a2, 5-HT2C & 5-HT3 receptors, increases 5HT and nor-adrenaline release.
- S/E: Dry mouth, increased appetite & weight gain, drowsiness, insomnia
2) Trazodone
- Blocks 5-HT2A, 5-HT2C, Histamine H1, increases 5HT release.
- S/E: Sedation, hypotension, nausea, cardiac dysrhythmias, dizziness
Others: mianserin
What is monoamine receptor antagonists/ blocker (MARA)?
- they are sedative antidepressants, which have little or no activity on amine uptake.
- they are less cardiotoxic, thus less S/E
State the mechanism of MAO inhibitors
irreversible inhibition of MAO(A) and MAO(B)
Details:
- Serotonin cleared from synapse by 5-HT & NA re-uptake transporters
- Subsequent breakdown by intracellular monoamine oxidase A, and catechol-O-methyltransferase (NA only)
- Some MAOIs nonselective; also inhibit MAO-B
Use of MAO inhibitors
atypical depression
Drug interactions of MAO inhibitors
1) serotonin syndrome: SSRIs, TCAs, meperidine
2) Increase Norepinephrine: HT crisis
- Symptoms: increase BP, arrhythmias, excitation, hyperthermia
- Drugs: TCAs, alpha-1 agonists, levodopa, releaser (i.e. tyramine)
Examples of MAO inhibitors as anti-depressant.
1) Moclobemide:
> Selective MAO-A inhibitor. Short acting, reversible
S/E: Safer than older MAOIs; hypotension, nausea, insomnia, agitation.
2) Phenelzine:
> Non-selective MOA inhibitor.
S/E: “Cheese reaction”. Hypotension, insomnia, weight gain, anticholinergic effects, liver damage
3) Other: Isocarboxazid, tranylcypromine
Give an example of selective MAO inhibitor.
Moclobemide
In bipolar disorder, what drugs are given for treatment?
- Conventional antidepressants controversial
- usually given with additional anti-mania drug
> Lithium, Antiepileptics, Antipsychotics
What is a typical medication use to treat biopolar? and state the mechanism, S/E and notes for this medication.
> Lithium
> Mechanism: selectively via certain Na+ channels (e.g. brain, kidneys). It accumulates, and not pumped out by Na+/K+ exchanger.
> S/E: Renal impairment, tremor, cognitive deficits
> Note: More effective against manic episodes than depressive.
What is a typical medication more preferred to use over lithium to treat biopolar? and please give two examples.
Antiepileptics, as a mood stabaliser
e.g. Carbamezepine, valproate, lamotrigine
Note:
- Valproate and carbamazepine effective against manic phases, less against depression
- Lamotrigine effective against mania and depression
Examples of Antipsychotics for treating bipolar disorder.
e.g. Olanzapine, rispereridone, quietapine, aripiprazole
Highly effective against mania, but not depression.
Pharmacology of depression is based on increasing _____ and _____ signalling in the brain.
serotinergic and noradrenergic signalling
What is the first choice of drug types as antidepressant?
SSRIs are usually first choice;
then TCAs, SNRIs, Monoamine receptor antagonists.
Bipolar disorder is normally treated via ____ or ____.
lithium or anticonvulsants.
State the mechanism of lithium to treat Bipolar disorder.
1) prevent recycling of inositol (decrease PIP2) by blocking inositol monophosphatase
2) decrease cAMP
State the S/E of Lithium to treat Bipolar disorder.
- narrow therapeutic index
- tremor, flu-like symptoms, life-threatening seizures
- Hypothyroidism with goitre (decrease TSH effects and inhibition of 5’-deiodinase)
- Nephrogenic Diabetes Insipidus (decrease ADH effect)
State the teatogenicity of Lithium to treat Bipolar disorder.
Ebstein’s anomaly (malformation of tricuspid valve)
