Pharmacology Antidepressants Flashcards by Katya Angoua

What is depression

Affective disorder with persistently low mood and loss of interest or pleasure in almost all the persons usual activities or pastimes

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What are the two types of symptoms in depression

Emotional symptoms

biological symptoms

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What are the emotional symptoms of depression

Misery 
Apathy
pessimism 
low self-esteem 
feelings of guilt 
inadequacy 
ugliness 
loss of motivation 
indecisiveness

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What are the biological symptoms of depression

Retardation of thoughts and action
loss of libido
sleep disturbance
Loss of appetites

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You have depressed mood or loss of interest or pleasure if you have five or more of the following symptoms presenting during the same two week periods and represented change from previous States

Depressed mood most of the day nearly every day
diminished interest or pleasure in all or almost all activities most of the day

significant weight loss when not dieting or weight gain
increase or decrease appetite
insomnia, hypersomnia
psycho motor agitation or retardation
feelings of worthlessness
excessive or inappropriate guilt nearly every day
diminished ability to think or concentrates or indecisiveness
recurrent thoughts of death
Recurrent suicidal ideation without a specific plan or
Suicide attempt or specific plans for committing suicide

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What are the different types of depressive disorders

Major depressive disorder

persistent depressive disorder dysthymia

disruptive mood dysregulation disorder

premenstrual dysphoric disorder

depressive disorder due to another medical condition

substance medication induced depressive disorder

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What is major depressive disorder

No manic or hypomanic episodes and can be recurrent or single episode

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What is the persistent depressive disorder

No how do faces last longer than major depressive disorder but is not severe enough to be called an episode of major depressive disorder

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What is the disruptive mood dysregulation disorder

Found mostly in children and the modest persistently negative between frequent severe explosions of temper

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What is the premenstrual dysphoric disorder

Occurs a few days before menses

woman experiences symptoms of depression and anxiety

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What is a depressive disorder due to another medical condition

Depressive symptoms due to medical or neurological

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What is a substance medication induced depressive disorder

Depression due to alcohol or other substances leading to intoxication or withdrawal

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What is responsible for disturbances in depression

Brainstem and hypothalamus

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Part of the brain responsible for appetite and energy changes in depression

Hypothalamic areas

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Part of the brain responsible for anhedonia or mania in depression

Limbic structure

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Part of the brain responsible for anxiety in depression

Amygdala

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Part of brain responsible for alteration in thought content in depression

Cortex

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What is the cortisol neurobiology of depression

Stress leads to release of corticotropin releasing factor from hypothalamus

Leads to ACTH hormone released from pituitary gland

Leads to cortisol released from adrenal cortex

Cortisol leads to detrimental gene transcription response which leads to neural apoptosis and neurogenesis inhibition leading to depressive symptoms

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What is the glutamate neurobiology of depression

Stress leads to release of glutamate
Glutamate activates NMDA receptors
NMDA receptors leads to neural apoptosis hence depressive symptoms

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How does noradrenaline ,serotonin and brain derived neurotrophic factor help in reducing depressive symptoms

Noradrenaline activate a2 receptors
serotonin activates 5HT1a receptors
BDNF activate TRKB receptors

They all induce signal transduction pathways which inhibit detrimental gene transcription and promotes beneficial gene transcription response

Leads to inhibition of neural apoptosis and promotion of neurogenesis

Depressive symptoms are inhibited

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What is the monoamine theory of depression

Due to depletion in levels of serotonin norepinephrine and dopamine in CNS

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What is the neurotrophic hypothesis of depression

Neuronal plasticity is key factor in development of depression

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What are the anti-depressant classes

Tricyclic antidepressant 
monoamine oxidase inhibitors
 selective serotonin reuptake  inhibitors 
serotonin noradrenaline reuptake inhibitors 
noradrenaline reuptake inhibitors 
noradrenaline dopamine inhibitors 
atypical antidepressants 
herbal Saint johns wort 
melatonin receptor agonist

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Examples of tricyclic antidepressants

Imipramine
Amitriptyline
Trimipramine
Doxepine 
Clomipramine
Nortriptyline
Desipramine
Protriptyline

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MOA of TCAs

Block reuptake of NA and 5HT by competing at the binding site of protien transport

What is the consequence of 5HT reuptake block

Improvement of emotional symptoms

What is the consequence of NA reuptake block

Improvement of biological symptoms

What are the unwanted effect of tricyclic antidepressants

Antimuscarinic effect ( Dry mouth ,blurred vision ,constipation ,urinary retention ) antihistaminergic effect ( sedation ,drowsiness ,difficulty concentrating ,weight gain) anti-adrenergic alpha1 effect ( postural hypotension) Sedation, confusion and motor incoordination when non depressed

Does TCA at therapeutic dose increase risk of sudden cardiac death, Or lower seizure threshold

Yes

What can TCA cause in overdose

Ventricular dysrhythmias with prolongation of QT interval Life-threatening seizures

What happens in TCA overdosage

Initial effect -> excitement ,delirium , convulsions then-> coma, respiratory depression over days

Are TCAs absorbed well orally ?

Yes

Do TCAs experience extensive first fast metabolism

Yes

Half life of TCAs

8 to 89

dosing of TCAs

Once Daily

What is the metabolism of TCAs

Hydroxylation of tricyclic nucleus | Conjugation of hydroxylated products to glucuronide

What drugs can inhibits metabolism of TCAs

Antipsychotics oral contraceptives some SSRIs

What drugs compete with protein binding of TCAs

Phenytoin aspirin phenothiazines

Can TCAs potentiates effects of alcohol and anesthetic agent

Yes

What happens if you combine TCAs with MAO inhibitors

CNS toxicity with hyperpyrexia convulsions and coma

Do you have to monitor patient with hypertension when administering TCAs due to toxicity

Yes

What is the clinical indication for tcas

``` mood disorders anxiety disorders eating disorders personality disorders neurological disorders like ADHD Parkinson’s disease chronic pain neuropathic pain Narcolepsy insomnia pathological crying or laughing chronic hiccups ciguatera poisoning schizophrenia adjunct fibromyalgia headache migraine Smoking cessation Tourette’s syndrome irritable bowel syndrome interstitial cystitis nocturnal enuresis ```

Examples of selective serotonin reuptake inhibitors

``` Fluoxetine sertraline citalopram paroxetine fluvoxamine ```

Are SSRIs supported by poeple with cardiac conditions and old people

Yes

Mechanism of action of SSRIs

Inhibition of 5HT reuptake by nurse terminals | desensitization of autoreceptors 5HT1E because of increased serotonin level leads to More serotonin release

What are the unwanted effects of SSRIs

``` Agitation and anxiety in beginning insomnia nausea loose stools sexual dysfunction decreased libido delayed ejaculation anorgasmia ```

Why is fluoxetine only given in the morning

Because of potential for insomnia

Metabolism of fluoxetine

Demethylated in the liver and become active metabolites | Inactive metabolites excreted by kidney

Should you reduce dose of patients with liver failure taking fluoxetine

Yes

How long does elimination of fluoxetine take

4 to 6 weeks after discontinuation of medication

Why should you not give fluoxetine with medication metabolized by cytochrome P4 50 2D6

Because inhibits this enzyme

Is there some issue with giving fluoxetine with TCAs and type 1C anti-arrhythmic like flecainide and propafenone

Yes

How do you administer setraline

Once a day | In the morning to avoid insomnia

Metabolism of sertraline

hepatic metabolism so should be reduced in liver disease patient

Is sertraline highly bound to protein and hence prevent binding of other medication to protein

Yes at 98%

If you’re on sertraline and want to start MAOIs what should you do

14 day washouts

Is sertraline and paroxetine a weak inhibitor of cytochrome P450 2D6

Yes So should be attention when giving drugs with narrow therapeutic index metabolized by this route

Why should you pay attention when giving paroxetine with warfarin

Elimination half-life long 21 hours | highly bound to plasma proteins

With which SSRIs is weight gain the most important

Paroxetine

Which SSRIs has the least effect on the cytochrome P4 50 system and less drug drug interactions

Citalopram

What is the clinical indication of SSRIs

``` Major depressive disorder anxiety disorders like social anxiety panic disorder OCD, PTSD Eating disorders depersonalization disorder chronic pain ```

What are examples of mono amine oxidase inhibitors hydrazide

Phenelzine | Isocarboxazid

What are example of monoamine oxidase inhibitors non-hydrazides

Tranylcypromine

Phenelzine metabolism

Acetylated in the liver | Polymorphism

What life-threatening threatening events can MAOIs cause

Hepatotoxicity | dietary tyramineinduced hypertensive crisis

When should you give MAOIs

When there is resistant treatment for depression

What is the mechanism of action of monoamine oxidase inhibitors like isocarboxazid, phenelzine and tranylcypromine

They are irreversible nonselective inhibitors of both MAO-A (NA, HT5, Dopamin) and MAO-B ( dopamine)

What are some selective MAO-A inhibitors

Clorgyline | Moclobemide

What are the adverse effects of MOAIs

Hepatotoxicity Tyramine-induce hypertensive crisis -> increased blood pressure ``` tremors orthostatic hypotension ejaculatory delay dry mouth fatigue weight gain ```

What happens if you give over-the-counter cough and cold medication with MAOIs

Serious hypertension

How long should you wait between switching from MAOIs to another antidepressants

2 weeks

What is serotonin syndrome

``` Symptoms occur when coadministrating SSRI with MAOIs Symptoms like Confusion elevated or dysphoric mood tremor myoclonus in coordination hyperthermia cardiovascular collapse ```

What is the treatment of serotonin syndrome

Discontinue serotonergic agents Treat symptoms give serotonin antagonist like cyproheptadine or methysergide Dantrolene

What are some example of second generation antidepressant

Trazodone amoxapine Maprotyline bupropion

What are some example of third generation atypical antidepressant

Nefazodone mirtazapine venlafaxine vortioxetine

What are examples of serotonin noradrenaline reuptake inhibitors

``` Venlafaxine desvenlafaxine duloxetine Milnacipran Levomilnacipran Sibutramine (obesity ) Tramadol (weak agent ) ```

Active metabolites of venlafaxine

O-desmethyl-venlafaxine

Dosage of venlafaxine

2x per day

Dosage of duloxetine

1 per day