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Flashcards in Antidepressants Deck (24):
1

DSM criteria for major depression

-5 or more sxs from A present during a 2 weeks period
-cause significant impairment in cognitive, social & occupational fxn
-sxs not due to physiological effects of a substance or med condition

2

What causes depression: 3 hypothesis

1. Neurotrophic hypothesis: deficits in nerve growth factors (BDNF), atrophic structural changes & neuronal loss in brain, hippocampus & frontal cortex
2. Neuroendocrine Hypothesis: dysregulation of HPA axis, altered glucocorticoid fxn
3. Monoamine Hypothesis

3

Amine neurotransmitters, their effects and what targets then (3)

Dopamine: reward, motivation, euphoria, movement
-target of coke & speed

Norepinepherine: reward, arousal, alertness, decisions, flight or fright

Serotonin: mood, emotion, memory, sleep, cognition
-target of MDMA & LSD

4

Biogenic amine hypothesis of depression & evidence

abnormal amine (DA, NE & 5HT) neurotransmission

evidence: tx w/reserpine which depletes NE->depression
all antidepressants increase amine neurotransmission

Neuronal plasticity-delayed onset of effects (2-4 weeks)

5

Reuptake inhibitors: why the delayed effect?

Normal: 5-HT levels in synapse are modulated by reuptake & presynaptic inhibition

Uptake inhibitors: 5-HT levels in synapse increase BUT so does feedback inhibition, this balancing synaptic amine levels

Long-term: antidepressants down-regulate auto-receptors; increasing firing rate of 5-HT neuron

6

TCAs how do they work, what are they used for

-inhibit re-uptake of NE & 5-HT
-also block a-adrenergic, histamine & muscarinic receptors (so many SEs)
-no euphoria/low abuse potential

USES: depression, chronic pain (TMJ) [lower dose for TMJ], fibromyagia, enuresis

limited use due to toxicity & potential OK

7

Amitriptyline (Elavil): structure, action, SEs

Tertiary amine (TCA)
primarily INHIBITS 5-HT re-uptake
-high anticholinergic activity
-produce more seizures than secondary amines
-more sedating than secondary amines

8

Imipramine (Tofranil): structure, action, SEs

Tertiary amine (TCA)
primarily INHIBITS 5-HT re-uptake
-high anticholinergic activity
-produce more seizures than secondary amines
-more sedating than secondary amines

9

Nortriptyline (Pamelor): structure, action

TCA
secondary amines
primarily inhibit NE re-uptake

10

Desipramine (Norpramin): structure, action

TCA
secondary amines
primarily inhibit NE re-uptake

11

TCAs dosing, effectiveness

(U) start at low dose, then increased

all TCAs equally effective at tx depression

choice of TCA based on AEs

all antidepressants should be tapered gradually if possible

12

TCA PHK

well absorbed orally
long half-lives
gen given once per day at bedtime
METABOLIZED BY CYP2D6=drug intrxns are VERY common

13

TCA SEs & their causes

1. weight gain
2. histamine receptor blockade: drowsiness, fatigue, sedation
3.cholinergic blockade: blurry vision, tachycardia, constipation, urinary retention, dry mouth, palpitations, impairment of memory & cognition
4. alpha1 receptor blockade: cardiac depression & arrhythmias (Torsades de pointes), postural hypotension, dizziness & reflex tachycardia

14

TCA toxicity & OD can result in

TORSADES DE POINTES
cardiac arrhythmias
severe hypotension
agitation, delirium
seizures, hyperprezia
coma, shock, metabolic acidosis
respiratory depression

15

TCA toxicity & OD treatment

gastric lavage & activated charcoal

for TORSADES DE POINTES: magnesium, isoproterenol

manage arrhythmias &/or prevent seizures: lidocaine, propranolol, phenytoin

restore acid base balance: sodium bicarbonate & potassium chloride

16

more SEs of TCAs (4)

Analgesia results from activation of descending noradrenergic pathways in spinal cord

Syndrome of Inappopriate Antidiuretic Hormone secretion (SIADH): ↑ADH release, ↑water reabsorption, ↑Na excretion->may lead to water intoxication & hyponatremia, nausea, muscle aches, ataxia, tremor, confusion, seizures, coma, mental

Sexual dysfxn

↓seizure threshold

17

TCAs: tolerance (U) develops to which SEs

sedation, postural hypotension & anticholinergic effects

18

TCA drug intrxns

TCAs+MAOIs can=SEROTONIN SYNDROME
[d/c TCAs 2-4 weeks before admin of MAOIs]

TCAs compete for metabolism of SSRIs so SSRIs can cause TCAs to reach toxic levels

TCAs+amphetamines or other sympathomimetic drugs=HTN

TCAs potentiate the sedative actions of alcohol/CNS depressants

TCAs potential the effects of ANTICHOLINERGIC DRUGS

19

Serotonin syndrome

severe CNS toxicity manifested by hyperpyrexia, convulsions & coma

20

SSRI uses (7)

depression
panic disorder
OCD: paroxetine (Paxil)
social anxiety: paroxetine (Paxil)
bulimia
alcoholism
children & teens (SSRIs have least likelihood of ↑ suicidality in young people)

21

SSRIs: mechanism, pharmokinetics

selectively inhibits 5-HT reuptake
well absorbed by gut
metabolized by CYP450s (2D6)
-INHIBIT CYP2D6 (fluoxetine, paroxetine)
-many drug intrxns
t1/2=24-72 hrs

22

current DOC for depression

Citalopram (Celexa)

23

Fluoxetinie (Prozac): half life, unique features

t1/2 of 203 days; norfluoxetine, active metabolite, 7-9days
MOST LIKLEY TO INHIBIT CYP450 enzymes (CYP2D6 & CYP3A4)
MORE DRUG INTERACTIONS THAN OTHER SSRIs
impairs blood glucose levels in diabetics

24

Sertraline (Zoloft): half life, unique features

t1/2 26 hours; extensive first-pass elimination
least likely SSRI to interact w/other durgs
preferred in elderly