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42 Cards in this Set

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  • Back
What is the mechanism of action of most antidepressants?
*inhibition of uptake of 5-HT and/or NE
*Act at the neurotrophic hypothesis
*Think genetic reason for delay
What is the mechanism of action of the TCA drugs?
*NE/5-HT uptake blockers with strong muscarinic, histaminergic, and a1-adrenergic antagonist properties
*Also block some ion channels (inc. V-activated NA channels)-cardiac SE
What are the TCA drugs?
1st generation antidepressants
What are the properties of TCA drugs?
Lipid soluble
tight to Plasma proteins
metab. by liver
*Some metabolites are active:
ex: amitryptyline-> nortriptyline, imipramine-> desipramine
**Takes 2-3 wks to develop
What are the CNS effects of TCA drugs?
1. sedation (a1 &/0r H1-antag effects)
2. insomnia, restlessness
3. fine tremor
***At high doses:
1. Mania in depressed pt with really bipolar
2. Seizures with epilepsy hx
3. toxic psychosis (anticholin)
What are the periperal SE of TCA drugs?
1. Cardio: orthohypotension with reflex tach; direct cardiac toxicity: quinidine-like effect
2. Autonomic: Cholinergic Blockade; weight gain (volume retention)
What are the toxicities assoc. with TCA drugs?
1. OD causes: arrythmias, hypotension, seizure ans coma, death from cardiotox
2.Lethal doese =~ 10-20x daily does
What are the therapeutic uses of TCAs?
1. Unipolar (major) depression and panic disorder
2. Adjunctive tx of chronic pain
3. Tx of sleep disorders needing REM-sleep suppression
4. OCD (only clomipramine)
What are the names of the TCA drugs?
amitriptylline (elavil, endep)
nortriptylline (Aventyl)
clomipramine(used OCD only)
What are the major drugs of the SSRI class?
fluoxetine (Prozac)
sertaline (zoloft)
paroxetine (paxil)
What is the mechanism of action for SSRIs?
Selective (not complete) 5-HT blocker. No a1adrenergic, muscarinic and histamine and no cardiac SE
What are the properties of SSRIs?
CNS active lipid soluble
94% bound to plasma protein c large volume of distribution
all hepatic metabolism
t0.5= 2days
What are the SE of SSRIs?
Common: Nausea, Insomnia and sexual SE other: nervousness, ha, fatigue, anorgasmia
Occn'l: mania, rash, fever, leukocytosis, arthralgia, respiratory distress
Rare: suicidal attempts/ideations
What is the major drug interaction of SSRIs?
With MAOIs because of "serotonin syndrome"
What are the clinical uses of SSRIs?
1. Major depression
2. anxiety disorders
3. panic disorder
4. OCD
Compare SSRIs to TCA
1. SSRI larger therapeutic index
2. SSRI little-no ortho hypot, no weight gain, no sedation no anticholinerg, no cardiac
3.SSRIs are less effective overall than TCAs with severe depression
What are NRIs?
selective norepinephrine-reuptake inhibitors
EX: Robextine
What are SNRI?
Serotonin and NE-reuptake inhibitors
EX: Venlafaxine (effexor)-may cause slight HTN
What are the atypical Anti-depressants (list)?
Bupropion (wellbutrin, zyban)
What is the mechanism of action of buproprion?
Related structurally to amphetamines, and releases DA, stimulant, effective in depression assoc. with psychomotor retardation
What are the advantages of buproprion over TCA
No cardiac problem, hypoT, or anti-cholin, but HIGHLY prone to seizures and can cause HTN
What is another use of buproprion?
lower doses to attenuate discomfort of nicotine withdrawal
What are the non-selective MAOIs (list)?
What is the mechanism of action of MAOIs?
MAO inhibition increases synaptic levels of 5-HT and NE, esp. 5HT. slight effect on DA transmission
***Antidepressant from MAOA
What are MAOI-A?
Subtype not in US as an antidepressant moclobemide with fewer SE
What are MAOI-B?
NOT ANTIDEPRESSANT! used to treat parkinson's disease
What are the SE of MAOI?
euphoria, overactive behavior; weakness, drymouth, blurred vision, inhibit ejact, orthoHypo, dizziness and suppress REM sleep
What are the signs of OD with MAOI?
excessive central stimulation (tremors, insomnia, agitation, hypomanic behavior), hyperreflexia, hyperthermia
What are the drug interactions with MAOIs?
1. Sympathmimetic amines: wine and cheese syndrome: food with tyramine or drugs like ephedrine, amphetamines:::HTN crisis
2.SSRIs: Serotonin syndrome::Hyperthermia, muscle rigidty, myoclonus. excess extracellular 5HT
3. Levo-dopa: produces agitation (central) and HTN (peripheral)
4. Meperidine (Demerol): fatal interactions need to wait 2wks to admin.
What are the Clinical uses of MAOIs?
1. 2nd/3rd line in unipolar depression
2. Cases where TCA failed or ECT rejected, useful in atypical derpessions
What do you do if on MAOI from an MD perspective?
Need to moniter level of MAOI to make sure you adjust to optimal does, need > 85% inhibition
What is the mechanism of action of Lithium?
1. berridge hypoth: inhibits inositol monophosphate, produces a depletion of PIP2, so it decreases reactions that use PLC pathway. Ex: NE at a1 adrenergic R and 5ht at 5ht1c and 5ht2 R, ach at Muscarinic R.
***Peripheral organs less effected
What are the pharmacokinetics of lithium?
*Oral only
*eliminated by kidney and 80% reabsorbed by proximal tubule
*Low therapeutic index need to keep about 1.2 meq
What are the signs of OD of Lithium?
Early: ataxia, drowsy, choreathetoric move, hyperreflexia, incontinence, cardiac arrythmias, slurred speech, seizre coma***can reverse by inc. the renal exretion
What are the SE of Lithium?
GI distress, N/v/d; fine hand tremor, muscle ewakness, polyuria, edema
What are the toxic effects of Lithium?
1.Cardiac: produce QRS widening and T wave flatt
2. Thyroid effect: lower t3 and t4; inc. risk of goiter, builds up in thyroid the most and can decrease stim of TSH of throid adenylate cyclase
3. Renal tox: rare, polyuria is massive
What are the drug interactions of lithium?
1. Diuretics
2. For polyuira: TCAs b/c anti-cholinergics
What are the uses of Lithium?
1. Acute treatment of manic episode
2.chronic prophylactic treatment of manic episodes
**Takes 5-6days to accumulate before antimanic effect, boost antidepressant effect of TCA
What is Carbamazepine?
Anticonvulsant that blocks the NA channel
What is Carbamazepine used for?
*alterntive to lithium
works in subpopulation of bipolar patients, takes 1-2wks to work to reduce freq. of manic episodes
What is Valproate?
Broad-spectrum anticonvusant
Alternative therapy (to lithium) in txof biplar depression
-impairs several voltage dependent ion channels=fast NA and low threshold CA channels
What is gabapentin?
Broad spectrum anticonvulsant
Alternative tx fro bipolar depression (other than lithium)