Pharmacology Antidepressants Flashcards
What is depression
Affective disorder with persistently low mood and loss of interest or pleasure in almost all the persons usual activities or pastimes
What are the two types of symptoms in depression
Emotional symptoms
biological symptoms
What are the emotional symptoms of depression
Misery Apathy pessimism low self-esteem feelings of guilt inadequacy ugliness loss of motivation indecisiveness
What are the biological symptoms of depression
Retardation of thoughts and action
loss of libido
sleep disturbance
Loss of appetites
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
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
What is major depressive disorder
No manic or hypomanic episodes and can be recurrent or single episode
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
What is the disruptive mood dysregulation disorder
Found mostly in children and the modest persistently negative between frequent severe explosions of temper
What is the premenstrual dysphoric disorder
Occurs a few days before menses
woman experiences symptoms of depression and anxiety
What is a depressive disorder due to another medical condition
Depressive symptoms due to medical or neurological
What is a substance medication induced depressive disorder
Depression due to alcohol or other substances leading to intoxication or withdrawal
What is responsible for disturbances in depression
Brainstem and hypothalamus
Part of the brain responsible for appetite and energy changes in depression
Hypothalamic areas
Part of the brain responsible for anhedonia or mania in depression
Limbic structure
Part of the brain responsible for anxiety in depression
Amygdala
Part of brain responsible for alteration in thought content in depression
Cortex
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
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
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
What is the monoamine theory of depression
Due to depletion in levels of serotonin norepinephrine and dopamine in CNS
What is the neurotrophic hypothesis of depression
Neuronal plasticity is key factor in development of depression
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
Examples of tricyclic antidepressants
Imipramine Amitriptyline Trimipramine Doxepine Clomipramine Nortriptyline Desipramine Protriptyline
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
