Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
42 Cards in this Set
- Front
- 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) imipramine desipramine clomipramine(used OCD only) |
|
|
What are the major drugs of the SSRI class?
|
fluoxetine (Prozac)
sertaline (zoloft) paroxetine (paxil) fluvoxamine |
|
|
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)?
|
phenelzine
tranylcypromine |
|
|
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?
|
Selegiline
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 3.Narcolepsy |
|
|
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?
|
anticonvulsant
*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) |
