Antidepressant Pharmacology Flashcards
Antidepressant Classes
SSRIs SNRIs TCA MAOIs Others: mirtazapine, bupropion, trazodone
What is the first line treatment of depressive disorders?
SSRIs
Examples of SSRIs
Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Citalopram (Celexa) Fluvoxamine (Luvox) Escitalopram (Lexapro)
Psychiatric Conditions that SSRIs Treat
Depression Panic disorder OCD GAD Social anxiety disorder PTSD Body dysmorphic disorder Bulimia nervosa Binge eating disorder Premenstrual dysphoric disorder Somatoform disorders
MOA for SSRIs
Block the presynaptic serotonin re-uptake pump
Pharmacokinetics of SSRIs
Absorbed in GI tract
Bind to proteins
Metabolism & elimination occur in the liver
Which SSRIs inhibit liver enzymes less than other SSRIs?
Citalopram
Escitalopram
Why is inhibition of liver enzymes important?
Less drug interactions
What should you be caution with prescribing with SSRIs?
Azole antifungals
Macrolide antibiotics
Omeprazole
Hepatic impairment
What SSRIs are contraindicated with tamoxifen?
Paroxetine
Fluoxetine
SSRI SE
Sexual dysfunction Drowsiness Weight gain Dizziness Insomnia Anxiety Diaphoresis Diarrhea Hyperprolactinemia Headache Dry mouth Blurred vision Nausea Rash or pruritis Tremor Constipation SIADH Hyponatremia
Withdrawal Symptoms of SSRIs
Dysphoria Dizziness GI distress Fatigue Chills Myalgias
How long do SSRIs take to take effect?
Some few weeks
Others 4-6 weeks
Most Common SE of SSRIs Initially
Headache
Dizziness
Nausea
Diarrhea
What drug is good to use when concerned about drug interactions?
Citalopram (Celexa)
What risk is important in citalopram (Celexa)?
QT prolongation
Arrhythmia + hepatic impairment OR age >60 years OR on other CYP219 inhibitors
What is an isomer & similar to citalopram?
Escitalopram (Lexapro)
Which SSRI is more likely to cause activation and have the least problems with weight gain?
Fluoxetine (Prozac)
What is the most common SE of fluvoxamine (Luvox)?
Weight gain (2.6%)
Nausea
Sedation
Which SSRI is contraindicated with Tamoxifen & has a significant withdrawal symptoms?
Paroxetine (Paxil)
Which SSRI is more likely to cause diarrhea?
Sertraline (Zoloft)
More Intense SE of SSRIs
Increase risk of suicide as the patient recovers
Increase risk of abnormal bleeding
Possible increase in bone fractures
May affect male fertility
Examples of SNRIs
Venlafaxine (Effexor)
Duloxetine (Cymbalta)
Desvenlafaxine (Pristiq)
What do SNRI’s act on?
Serotonin
Norepinephrine
Uses for SNRIs
Depression Panic disorder GAD Social anxiety disorder OCD PTSD Body dysmorphic disorder Diabetic peripheral neuropathy Fibromyalgia Menopausal hot flashes
MOA of SNRIs
Inhibit the re-uptake of serotonin & norepinephrine
Pharmacokinetics of SNRIs
Food can decrease the rate of absorption but not the degree of absorption
Can eat with food if severe SE post dose
SNRI SE
Nausea Dizziness Diaphoresis Sexual dysfunction Sedation Agitation Fatigue Diarrhea Constipation Anorexia Insomnia Dry mouth Orthostatic hypotension
What are the most common SE of SNRIs?
Nausea
Dizziness
Diaphoresis
What needs to be monitored with the use of SNRIs?
Blood pressure
What is the most common SE of desvenlafaxine (Pristiq)
Nausea
Contraindications for Duloxetine (Cymbalta)
Uncontrolled angle closure glaucoma
Severe renal impairment (relative)
Severe liver impairment (relative)
What else is duloxetine (Cymbalta) used for?
Diabetic neuropathy
Fibromyalgia
Venlafaxine (Effexor)
Increase BP Upper GI bleed Adjust dose in hepatic & liver impairment Slow taper to avoid withdrawal symptoms QT prolongation
Examples of Tertiary Amines
Amitriptyline Clomipramine Doxepin Imipramine Trimipramine
What are tertiary amines more potent at blocking the uptake of neurotransmitter?
Serotonin
Examples of Secondary Amines
Desipramine
Nortriptyline
Protriptyline
What are secondary amines more potent at blocking the uptake of neurotransmitter?
Norepinephrine
TCA Uses
Insomnia
Neuropathic pain
Fibromyalgia
When are TCAs usually avoided?
Treatment of depression due to anticholinergic SE
MOA of TCAs
Inhibit re-uptake of serotonin & norepinephrine
Block muscarinic, histamine & alpha-adrenergic receptors
Pharmacokinetics of TCAs
Rapid/near complete absorption
First pass metabolism
Binds to proteins
Active metabolites
Cardiac SE of TCAs
Heart block
Ventricular arrhythmias
Sudden death
TCAs
Lower seizure threshold Increase bone fractures Block histamine receptors Block acetylcholine receptors Dangerous in overdose
What does blocking histamine receptors with TCAs cause?
Sedation
Increased appetite
Confusion
Delirium
What does blocking acetylcholine receptors with TCAs cause?
Blurred vision
Constipation
Dry mouth
Urinary retention
Why are TCAs not well tolerated in the elderly?
Orthostatic hypotension
Anticholinergic SE
Heavily sedating
Cardiac SE
Examples of MAOIs
Phenelzine (Nardil)
Tranylcypromaine (Parnate)
What can MAOI drug-drug interactions cause?
Serotonin syndrome
HTN crisis
What dietary restrictions are necessary with MAOIs?
No tyramine containing foods
Why are MAOIs poorly tolerated?
Side effects
Other Antidepressant Medications
Trazodone (Desyrel) Bupropion (Wellbutrin) Mirtazapine (Remeron) Vilazodone (Viibryd) Vortioxetine (Brintellix)
MOA of Trazodone (Desyrel)
Serotonin antagonists & re-uptake inhibitors
What is trazodone (Desyrel) usually used for?
Sleep
SE to watch for with trazodone (Desyrel)
Sedation
Orthostasis
Priapism
Uses for Bupropion (Wellbutrin)
Major depressive disorder
ADHD
Smoking cessation
MOA of Bupropion (Wellbutrin)
Inhibits the re-uptake of dopamine
Effects of Bupropion
Anxiety
Lowers seizure threshold
Avoid in bulimia due to possible electrolyte disturbances
Who is Bupropion good for?
Patients with fatigue, hypersomnia, or poor concentration
What can Bupropion be added on to for the treatment of sexual SE?
SSRIs
Bupropion Considerations
No sexual SE Smoking cessation Co-morbid ADHD Often used with SSRIs Consider with sleepy, slowed down patients Preg. Cat. C
MOA of Mirtazapine (Remeron)
Blocks adrenergic receptors leading to an increased release of norepinephrine & serotonin
Blocks sertonergic receptors & increases serotonin mediated neurotransmission
SE of Mirtazepine (Remeron)
Sedation
Weight gain
Less sexual SE
Good for patients with nausea
2 New Antidepressant Drugs
Vilazodone (Viibryd)
Vortioxetine (Brintellix)
Serotonin Syndrome
Simultaneous administration of two serotonergic agent
Sometimes after invitation of a single sertonergic drug or increasing the dose
Drugs that can cause serotonin syndrome
Psych: SSRIs, SNRIs, TCA, MAOI, nefazadone, trazadone, bupropion, buspirone, lithium
Pain: pentaxocine (Talwin), meperidine (Demerol), tramadol, fentanyl, cyclobenzaprine (Flexeril)
Migraine: triptans, ergots
Neuro: levodopa, carbidopa-levodopa, valproate, carbamezepine
OTC: dextromethorphan (Robitussin), St. John’s wort
Antiemetics: odansetron (Zofran), ganisetron (Kytril)
Street drugs: cocaine, meth, MDMA (ecstasy), LSD
ADHD: amphetamine derivatives, dextroamphetamine
Weight loss drugs
Metaclopramide (Reglan)
Serotonin Syndrome PE
Hyperthermia Agitation Ocular clonus Tremor Akathisia Deep tendon hyperreflexia Clonus, muscle rigidity Dilated pupils Dry mucus membranes Increased bowel sounds Flushed skin Diaphoresis
HARM from Serotonin Syndrome
H: hyperthermia
A: autonomic instability
R: rigidity
M: myclonus
Signs/Symptoms of Serotonin Syndrome
Anxiety
Agitated delirium
Restlessness
Disorientation
Autonomic Manifestations of Serotonin Syndrome
Diaphoresis Tachycardia Hyperthermia HTN Vomiting Diarrhea
Types of Neuromuscular Hyperactivity
Tremor Muscle rigidity Myclonus Hyperreflexia Bilateral Babinski sign
Hunter Criteria for Serotonin Syndrome
Serotoniergic agent PLUS spontaneous clonus OR inducible clonus & agitation or diaphroesis OR ocular clonus & agitation or diaphoresis OR tremor & hyperreflexia OR hypertonia & temp >38C & ocular clonus or inducible clonus
Treatment for Serotonin Syndrome
DC sertonergic agents Sedate using lorazepam Supplemental O2 IV fluids Cardiac monitor Benzo's don't work, use cyproheptadine Temp >41.1C (106F), immediate intubation & sedation Avoid acetaminophen
Which drugs carry the greatest risk for serotonin syndrome?
MAOIs
