Lecture 76: Antidepressants Flashcards
MAOIs (key, 3)
Phenelzine, tranylcypromine, selegiline
What is special about selegline?
Patch delivery
Are MAOIs first line? What population might they be used?
No–after trying other anti-depressants first; atypical depression: sleep/eat a lot
MAOI mechanism
MAO located in presynaptic neuron and degrades monoamines –> MAOIs inhibit enzyme, inhibiting degradation of monoamines
Important MAOI mechanism notes
More NT in both presynaptic neuron AND cleft; irreversible (MAOIs take 2 weeks to recover)
Describe types of MAOs and targeted catecholamines. Which one is in the gut? Which one degrades tyramine? Which are targeted by MAOIs?
MAOa: 5-HT, NE, Epi, DA; MAOb: DA; MAOa; both; both
2 MAIN (scary) side effects of MAOI and mechanism
- Also inhibit breakdown of Tyramine –> NE release (hypertensive crisis) if combined with tyramine diet or adrenergic agonists; 2. Serotonin syndrome if combined with other serotonergic drugs
Other SEs of MAOIs (5)
Orthostatic hypotension, weight gain, insomnia, sexual dysfunction, rare hepatoxicity
Describe symptoms serotonin syndrome (11)
Abdominal pain, diarrhea, sweating, hyperthermia, tachycardia, hypertension, myoclonus, tremor, irritability, delirium, death
What can you NOT take with MAOIs because of serotonin syndrome (3)
Other antidepressants, dextromethorphan (cough medicine) and opiates
What else can you NOT take with MAOIs? Why?
Decongestants, stimulants because they can cause hypertensive crisis (BP > 120 mm Hg) due adrenergic agonists
What food items must be avoided with MAOIs? Why?
Tyramine inhibition in GUT via MAOa but if tyramine gets access to NE sympa neurons, these MAOa are ALSO blocked leading to NE release; soy, beer, red wine, aged cheese, dried sausage, liver, smoked fish, sauerkraut
How long must a patient wait to resume normal diet after stopping MAOI?
2 weeks
Describe Selegiline’s hope
At low doses only inhibits MAOb, but turns out at antidepressant levels, also inhibits MAOa so STILL requires dietary restriction
TCAs (key, 1) and secondary amines (key, 2)
Amitriptyine; nortriptyline, desipramine
Mechanism of TCAs (?)
Inhibit re-uptake of NE and 5-HT
TCA therapeutic uses (4)
Depression, neuropathic pain, anixety, migraine
How are tertiary amines different?
Also inhibit 5-HT reuptake
TCA SEs via receptor
H1 blocker: sedation, weight gain; Alpha1 blockers: orthostatic hypotension; M1 blocker (anticholinergic) constipation/urinary retention, dry mouth, blurred vision; Na channel blockers: type 1 antiarrythmic effects; Serotonin Reuptake inhibitors (same as SSRIs)
Problem with TCAs being a NA channel blocker (2)
- If you have bad ischemic heart disease, TCA can CAUSE arrythmias; 2. Can lead to overdose
Which TCAs are the LEAST anticholinergic and alpha1 blockers
Secondary amines
TCA: avoid in…
People with narrow angle glaucoma, recent cardiac events, children, elderly (orthostatic hypotension –> falling)
TCA is active in what liver system?
Metabolized BY cytochrome p450
SSRIs (key, 5)
Fluoxetine, sertraline, paroxetine, citalopram, escitalopram
SSRIs major indications (4)
MDD, anxiety, OCD, bulimia
SSRI mechanism (main)
Inhibit reuptake of 5-HT into presynaptic neuron –> more 5-HT in synapse
SSRI secondary effects. Important?
Some NE and DA reuptake effects; potential SEs
Paroxetine secondarily
Inhibits NE reuptake
Sertraline secondarily; why important
Inhibits DA reuptake –> activating good for tired patients
SSRIs common SE
GI, weight gain, tremor, headache, sweating, sexual
SSRIs less common SE
Dry mouth, bruising/bleeding (important for surgery), hyponatremia, vivid dreams, serotonin syndrome, mania if underlying BP disorder
Fluoxetine has the most…What else is special about this drug (2)?
Drug:drug interactions due to p450 inhibition; longest half-life (once weekly formula, best for people who don’t take drugs daily); “activating” –> insomnia
Citalopram and Escitalopram has the fewest…importance?
Drug:drug interactions; perhaps fewest SEs
Paroxetine half-life is…causing…What else is noteworthy about this drug?
Short; withdrawal symptoms; NE reuptake blockade and anticholinergic activity; more sedation, dry mouth, weight gain
Describe SSRI withdrawal and how long. Drug least and most likely
Abrupt discontinution of SSRI –> dizziness, nausea, paresthesias, flu-like, muscle aches, headaches; 3 weeks; fluoxetine = least and paroxetine = most
SSRI advantages
Standard dosing, clinical response at starting dose, not lethal in OD, no arhythmias, no changes in BP, no seizures, fewer drug-drug interactions
Problem with SSRIs and new drugs?
Perhaps SSRIs are not effective enough because of the lost of NE, but trying to be less dirty (= SNRIs)
SNRIs (key, 2)
Venlafaxine, duloxetine
SNRI therapeutic use (3)
Neuropathic pain, depression, anxiety
SNRI SEs
Increases diastolic BP at higher doses, otherwise similar to SSRIs
Duloxetine (describe and 2 SEs)
Affinity for 5HT and NE at all doses with many pain and psych indiactions; small amount get hepatoxicity and elevated BP is possible
Advantage of Buproprion and therapeutic use. Mechanism? Avoid in what 3 patients?
No weight gain/sex issues; MDD, smoking cessation, ADHD; weak NE and DA inhibitor AND inhibits nACh but NOT 5-HT; avoid in anxious patients, alcoholics (seizure), eating disordered
Buproprion SEs (scary one and others)
Seizures at high doses; anxiety, rare psychosis
Mirtazapine mechanism. Avoids what SEs but not?
Alpha2 antagonist (presynaptic) –> more NE and 5-HT NT but blocks 5-HT subtypes that causes SEs (GI, sexual); avoids sexual and GI SEs but STILL causes sedation/weight gain
Mirtazapine should be used in what patients…
People who are NOT eating or sleeping
Trazadone is too…so now just used for? SEs?
Sedating; insomnia; priapism
Anti-depressant response rate (%)
60%
Four theories for antidepressant action
- Therapeutic delay –> downregulation of receptors; 2. Enhance neuronal regeneration; 3. Restore cortical dendrites; 4. Increase expression of neurotrophic factors
Comorbid pain, think…
SNRIs
