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Flashcards in antidepressants Deck (67):
1

Imipramine (Tofranil, Janimine)

TCA, prototype
blocks reuptake of NE and 5-HT
treatment of enuresis and urinary incontinence, neuropathic pain
TCAs cheaper than newer drugs

2

Amitriptyline (Elavil)

TCA
more sedation and anticholinergic activity than imipramine

3

Fluoxetine (Prozac)

SSRI, prototype
OCD, GAD, PMDD, bulimia, anorexia nervosa
-less sedation antiACh and CV effects than TCAs
SEs: ha, anxiety, tremor, agitation, nausea, and sexual dysfunction in males. (suicide?)
-liver metab., req. 4-5 wks of tx to reach steady state/be cleared

4

Fluvoxamine (Luvox)

SSRI
Selective inhibitor of 5‐HT reuptake that is similar to fluoxetine
-used for OCD in US

5

Sertraline (Zoloft)

SSRI
selective inhibitor of 5‐HT reuptake, effects/SEs like fluoxetine, less drug interactions
-relatively slow elimination (T1⁄2 = ~24 hours)

6

Paroxetine (Paxil)

SSRI
selective inhibitor of 5‐HT reuptake, effects/SEs like fluoxetine, can have drug interations
-more rapidly metabolized (T1⁄2 = ~10 hours) and it does not form active metabolites.
*more weight gain than other SSRIs*

7

Citalopram (Celexa)

SSRI, newer
-similar to other SSRIs (esp. sertraline) -fewer drug interactions than fluoxetine.

8

Escitalopram (Lexapro)

SSRI, newer
-similar to other SSRIs (esp. sertraline) -fewer drug interactions than fluoxetine.

9

Venlafaxine (Effexor) and desvenlafaxine (Pristiq)

SNRI
Serotonin‐Norepinephrine Reuptake Inhibitors (and dopamine!)
-depression, GAD, social anxiety disorder, panic disorder, PTSD, OCD
-more rapid onset (1-2 wks?)
-less CV SEs than TCAs
-may have stimulant activity (used for ADHD in kids)
-may work when don't respond to SSRIs
SEs: nausea, nervousness, anxiety, sweating, HTN, tachycardia, palpitations, sexual dysfunction.
-

10

Duloxetine (Cymbalta)

SNRI, newer
neuropathic pain

other SNRIs: desvenlafaxine, levomilnacipran, milnacipran.

11

Trazodone (Desyrel)

Second generation antidepressant
FA:
Primarily blocks 5-HT2, α1-adrenergic, and H1 receptors; also weakly inhibits 5-HT reuptake.
use: mostly insomnia, as high doses are needed for antidepressant effects
-lower incidence antiACh and CV SEs than TCAs
SEs: priapism, sexual dysfunction in males, sedation (used at night)

12

Nefazodone (Serzone)

Second generation antidepressant
inhibit the reuptake of 5‐HT but also block 5‐HT‐2 receptors. (similar to trazadone)

13

Bupropion (Wellbutrin)

Second generation antidepressant
selectively inhibits DA reuptake (FA: inhibits dopamine>>NE uptake via unknown mechanism)
-has mild stimulant activity; “psychic energizer”
-more likely than other antidepressants to produce seizures
-tx of nicotine, cocaine and amphetamine dependence

14

Mirtazepine (Remeron)

Second generation antidepressant, chemically different from TCAs and SSRIs

-α2-antagonist (^release of NE and 5-HT), potent 5-HT2 and 5-HT3 receptor antagonist and H1 antagonist
SEs: like TCAs (mild ACh, hypotension, tachy)
FA: Sedation, ^serum cholesterol, ^appetite
-both antidepressant and anxiolytic activity

15

Atomoxetine (Strattera)

Selective Norepinephrine Reuptake Inhibitor
-ADHD, different than stimulants
SEs: suppression of appetite, decreased weight gain, increased blood pressure, tachycardia, sexual dysfunction in adult males

16

Phenelzine (Nardil)

MAO Inhibitors (both A and B)
contains a hydriazide group that can form covalent bonds with MAO-->can irreversibly inactivate MAO

17

Tranylcypromine (Parnate)

MAO Inhibitors (both A and B)- binds tightly

18

Selegiline (Emsam)

MAO Inhibitors
selective inhibitor of MAO‐B
-available as a patch preparations (EMSAM) for treatment of depression
-Parkinson’s disease
-does NOT undergo the classic interactions with tyramine and other sympathomimetics

19

Lithium carbonate (Eskalith and others)

mood stabilizer
-most effective drug for manic-depressive disorder (bipolar)
-ionic theory ‐ may alter the neuronal distribution or effect of Na+, K+ or Ca2+ in the CNS.
-biogenic amine theory may later the release, reuptake, or metabolism of NT amine.
-*phospholipid theory* ‐ may alter the metabolism of phospholipids that are involved in the phosphoinositide signaling pathway

20

Valproic Acid Analogs (Depakene/Depakote)

mood stabilizer
manic-depressive disorders/bipolar

21

Carbamazepine (Tegretol)

mood stabilizer
manic-depressive disorders/bipolar

22

Clonazepam (Klonopin)

mood stabilizer
manic-depressive disorders/bipolar

23

drugs that can induce depression

reserpine, B-blockers

24

pharm manangement for depression

(effective in 70-80% of pts)
1st line: SSRIs and 2nd gen
2nd/3rd: TCAs and MAO's (potential toxicity)
-benzos (alprazolam (Xanax)) for anxiolytic effects
-antipsychotics (2nd gen) for schizo symptoms


25

Manic-depressive disorder pharm management

(effective in 80%)
Lithium: reduce the fluctuation in mood swings.
Antipsychotics are used in severe phases of mania.
Antidepressants can help in some severely depressed patients, but may also trigger a switch to the manic phase

26

FA TCAs

Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, amoxapine.

27

FA TCA mechanism and use

Block reuptake of norepinephrine and less so 5-HT. (3o amines have a greater effect on 5‐HT than the 2o)

Major depression, OCD (clomipramine), peripheral neuropathy, chronic pain, migraine prophylaxis.

28

FA TCA SEs

Sedation, α1-blocking effects including postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth). 3° TCAs (amitriptyline) have more anticholinergic effects than 2° TCAs (nortriptyline). Can prolong QT interval.

*Tri-C’s: Convulsions, Coma, Cardiotoxicity* (arrhythmia due to Na+ channel inhibition); also respiratory depression, hyperpyrexia. Confusion and hallucinations in elderly due to anticholinergic side effects (use nortriptyline).
Tx: NaHCO3 to prevent arrhythmia.


29

FA SSRIs

Fluoxetine, paroxetine, sertraline, citalopram.

"Flashbacks paralyze senior citizens."

30

FA SSRI Mechanism and SEs

5-HT–specific reuptake inhibitors.

Fewer than TCAs. GI distress, SIADH, sexual dysfunction

31

FA SSRI uses


Depression, generalized anxiety disorder, panic disorder, OCD, bulimia, social anxiety disorder, PTSD, premature ejaculation, premenstrual dysphoric disorder.

32

CNS effects of TCAs/2nd gens

-sedation (tolerance develops: tricyclic tertiary amines > tricyclic secondary amines > second generation drugs)
-effect takes time (2-4 wks)
-may also tx OCD, panic attacks, GAD, social phobias
-CNS stim: 10%, may induce manic phase in bipolar pts
-decreased seizure threshold

33

Acute effect of TCAs/2nd gens

inhibition of the synaptic reuptake of NT amines (NE, 5‐HT, and DA)

34

Bupropion (Wellbutrin) SEs

stimulant effects (tachycardia, insomnia), headache, seizures in anorexic/bulimic patients. No sexual side effects.

35

Trazodone (Desyrel) SEs

sedation, nausea, priapism, postural hypotension. Called traZZZobone due to sedative and male-specific side effects.

36

Chronic effect of TCAs/2nd gens

alterations in the density and sensitivity of
receptors for NT amines

37

TCAs/2nd gens may directly interact with ??

certain NT receptors
-agonists or antagonists at muscarinic, serotonin, alpha adrenergic or dopaminergic receptors

may also INdirectly influence receptors

38

TCA/2nd gen Anticholinergic side effects

dry mouth, constipation, urine retention, loss of visual accommodation, etc
-Usually more severe than those of antipsychotic drugs.
-amitriptyline is the worst,
SSRI’s the least

39

TCA/2nd gen CV SEs

-postural hypotension ‐ due to alpha blockade and interference with hemostatic reflexes in the CNS
-tachycardia ‐ due to potentiation of the effects of NE and an anticholinergic effect in the heart.
-flattening or inversion of the T‐wave
-*arrhythmias*
-BBW: may increase suicidal ideation in children

40

TCA/2nd gen metabolism

-demethylation and aromatic hydroxylation in liver ‐ caution in
patients with liver disease and large potential for drug interactions
-conversion of some agents to active metabolites
-relatively narrow therapeutic windows (in general)

41

TCA/2nd gen Toxic Reactions and Side Effects

anticholinergic
CNS: tremor, agitation, manic phase, parkinsonism (rare), inc. seizure risk in epileptic pts
CV: hypotension, tachy, arrhythmias
-weight gain w. TCAs
-impotence due to alpha blockade; may have retrograde ejaculation
-possible teratogenic effects
-blood dyscrasias (rare but may be fatal)

42

TCA/2nd gen (atypicals) acute poisoning

fairly common ‐ serious toxicity at doses 5‐10 times normal therapeutic doses, life‐threatening emergency!
-CNS agitation-->grand mal seizures-->coma
-extreme hypotension, tachycardia, and arrhythmias progressing
to total CV collapse.
-classic “anticholinergic” symptoms
tx: supportive, NaHCO3 reduces cardiotoxic effects of TCAs (or antiarrhythmics, B-blockers, CCBs)

43

TCA/atypical drug interactions

anticholinergics
sedatives, alcohol
biogenic amines and adrenergic drugs ‐ potentiation
guanethidine ‐ antidepressants decrease its effect by blocking its uptake by nerve ending
drugs metabolized by microsomal system, many complex interactions
MAO inhibitors: “serotonin syndrome”
anticoagulants – complex effects through hepatic metabolism and through clotting mechanism (serotonin is involved in platelet aggregation and blood clotting)

44

serotonin syndrome

tremors, hypertension, hyperpyrexia and seizures

-At least 2‐4 weeks should elapse before switching from a tricyclic or second generation antidepressant to an MAO inhibitor and vice‐versa.

45

other antidepressant uses

-enuresis and urinary incontinence (imipramine)
-pain from neuropathies (tricyclics, duloxetine and others)
-adjuncts in the management of chronic pain
-cocaine and amphetamine dependence
-GAD and panic/phobia disorders
-OCD

46

MAO-inhibitors: acute and chronic effects

acute effect ‐ increased synaptic levels of NE, 5‐HT and DA
chronic effect ‐ decreased number and sensitivity of adrenergic and serotonergic
receptors

47

FA: MAO-inhibitors

Tranylcypromine, Phenelzine, Isocarboxazid, Selegiline (selective MAO-B inhibitor). (MAO Takes Pride In Shanghai).

48

FA: MAO-i mechanism and use

Nonselective MAO inhibitionlevels of amine NTs (NE, 5-HT, DA).
Atypical depression, anxiety, (bulimia, OCD, PTSD, narcolepsy)

49

FA: MAO-i SEs

HTN crisis (most notably with ingestion of *tyramine*, which is found in many foods such as aged cheese and wine), can be lethal, seen w. non-selectives-->HTN, fever, convulsions
CNS stimulation. Contraindicated with SSRIs, TCAs, St. John’s wort, meperidine, dextromethorphan (to prevent serotonin syndrome).

50

MAO-inhibitor CNS effects

little effect initially
antidepressant action usually takes several weeks to develop
normalization of sleep patterns
CNS stimulation in some patients (tremors, insomnia, hallucinations);
switch to manic phase in patients with bipolar phase.

51

MAO-i SEs (proz)

orthostatic hypotension ‐ normal effect at therapeutic doses
HTN ‐ in overdose or in interaction with sympathomimetic
GI effects (nausea, constipation)
headache, dizziness, vertigo
CNS stimulation
liver damage
allergic reactions, skin rashes, etc...

52

other MAO-i potentiations (like tyramine effect)

pheochromocytoma
amphets, cocaine, DA
TCAs and other antideps (wait 3-4 wks)
-may slow metab of other drugs

53

lithium metabolism

excreted by kidneys
-caution in patients with impaired renal function
-enhanced reabsorption in sodium depleted patients
-any drugs (i.e. NSAIDs, diuretics, etc..) that after renal function can
influence the renal excretion of lithium
-low therapeutic index (2-3): therapeutic range 0.8‐1.4 mEq/l; severe toxicity above 2.0 mEq/l

54

symptoms of acute lithium intoxication

GI: N/V/D
NM: fatigue, weakness, fine tremor, ataxia, hyperirritability
neurosens: blurred vision, tinnitus
CNS: slurred speech, dizziness, confusion,
restlessness, grand mal seizures, stupor, coma
CV: arrhythmias, hypotension, circulatory collapse
*may appear drunk*

55

tx of lithium intoxication

remove drug, symptomatic support: maintain fluids and electrolytes, administer
anticonvulsants, antiarrhythmics, and CV drugs as needed.
induce diuresis
hemodialysis

56

other lithium toxic effects

a. EKG changes; arrhythmias
b. hypothyroidism*
c. polydipsia, polyuria
d. kidney damage* ‐ nephrogenic diabetes insipidus
e. weight gain
f. dermatological problems
g. teratogenic effects*

*avoid in these pts

57

lithium has been tried for these conditions

cluster headache, premenstrual syndrome, tardive dyskinesia, hyperthyroidism and post partum affective psychosis.

58

lithium drug reactions

-^^ levels by NSAIDs and diuretics (interfere with renal excretion of lithium)
-Carbamazepine, antidepressants, antipsychotics, and methyldopa can enhance the neurotoxic effects of lithium.
-Lithium can enhance the effects of antidepressants and other CNS drugs.

59

FA: lithium SEs

tremor, hypothyroidism, polyuria (causes nephrogenic diabetes insipidus), teratogenesis. Causes Ebstein anomaly in newborn if taken by pregnant mother. Narrow therapeutic window requires close monitoring of serum levels. Almost exclusively excreted by kidneys; most is reabsorbed at PCT with Na+. Thiazide use is implicated in lithium toxicity in bipolar patients.

60

LMNOP—Lithium side effects:

Movement (tremor)
Nephrogenic diabetes insipidus
HypOthyroidism
Pregnancy problems

61

moderate‐severe endogenous depression

SSRI's: first choice
TCAs and other second generation antideps may be preferred in some pts
MAO inhibitors are alternative drugs ‐ remember to clear TCAs before starting

62

mild acute depression with anxiety

antianxiety drugs, especially alprazolam (Xanax)

63

bipolar
manic‐depressive disorders

lithium
antipsychotic drugs (for severe acute manic phase)
antidepressants (for severe depressed phase)
valproic acid analogs (Depakene/Depakote) is also gaining in use
carbamazepine (Tegretol) – is becoming more widely used

64

A withdrawal syndrome that includes ?? can occur when antidepressant drugs are abruptly discontinued after long term usage. Accordingly, the dose of the drug should be gradually tapered off over a period of ??Discontinuation problems are more severe with shorter acting drugs like ? and less severe with longer acting drugs like ?.

lethargy, chills, neurologic disturbances and muscle aches

2‐4 weeks.

paroxetine
fluoxetine

65

only FA: buspirone

Stimulates 5-HT1A receptors.
GAD. Does not cause sedation, addiction, or tolerance. Takes 1–2 weeks to take effect. Does not interact with alcohol (vs barbiturates, benzodiazepines).

"I’m always anxious if the bus will be on time, so I take buspirone"

66

FA: serotonin syndrome

3 A’s: neuromuscular Activity (clonus, hyperreflexia, hypertonia, tremor, seizure), Autonomic stimulation (hyperthermia, diaphoresis, diarrhea), and Agitation. Treatment: cyproheptadine (5-HT2 receptor antagonist).

67

only FA: varenicline

Nicotinic ACh receptor partial agonist. Used for smoking cessation. Toxicity: sleep disturbance.