Pharmacology Of Affective Disorders (Antidepressants)

Front 1

Depression symptoms

Back 1

"SIG E CAPS D" 5 symptoms in 2 wks
1) Sleep disruption
2) Interest wanes
3) Guilt
4) Energy loss
5) Concentration loss
6) Appetite change
7) Psychomotor retardation
8) Suicidal tendencies
9) Depression

Front 2

Mania symptoms

Back 2

"DIG FAST" (need 3 of 7)
1) Distractability
2) Irresponsibility
3) Grandiosity
4) Flight of ideas
5)Activity (increase in goal-oriented)
6) Sleep (decreased need)
7) Talkativeness/pressured speech

Front 3

Monoamine Theory of Depression

Back 3

Depression: functional DEFICIT of aminergic neurotransmitters

Mania: functional EXCESS of aminergic neurotransmitters
(Functional Excess or Depression: not actual numbers changed - just upregulation somewhere in pathway producing equivalent effect (increase or decrease)

Front 4

Neuroadaptation to MAOI

Back 4

Acute: MAOI increase availability and release of aminergic transmitters
Chronic:
a) REDUCE post-synaptic density of receptors;
b) UPREGULATE 2nd messenger signaling

Front 5

MAOI

Back 5

NON-selective: Isocarboxazid, Phenelzine, Tranylcypromine (irreversible, Hydrazine deriv -> hepatotoxic)

Selective: Selegiline "Select one amine to B oxidized" (MAO-B inhib); reversible

Front 6

MAOI Adverse effects

Back 6

"MAOI give you a Heavy Hit"
Heavy = weight gain
H: HTN (hypertension)
I: Insomnia
T: Tyramine effects (avoid w/ TCA, SSRI & food w/ Tyramine)
increase Tyramine -> increase BP

Front 7

TCA 2nd Amine

Back 7

Amoxapine, Desipramine, Notriptyline, Protriptyline
"Amo Des Not Protect for a Second"
2nd Amines - inhibit NE transporters only (no 5-HT transporter)

Front 8

TCA 3rd Amine

Back 8

Amitriptyline, Clomipramine, Doxepin, Imipramine, Trimipramine
"3rd TRI I'M CLOMsier than AMI's DOX"
3rd amines - inhibit NE transporters AND 5-ht transporter

Front 9

TCA effects

Back 9

Effects: Block reuptake of NE and/or 5-HT
a) Acute: Block reuptake -> autoreceptor activated -> ↓ NE synth & ↓ NE release -> NET RESULT = Homeostasis
b) Chronic: Desensitize (NE synthesis & release returns/exceeds basal levels), Post-synaptic response increased -> NET RESULT = ↑ activity at NE synapses

Front 10

TCA Additional use

Back 10

Enuresis (Musc. Antag - can prolong Q-T, no more than 2.5mg/day)
Panic
OCD
Pain syndromes

Front 11

TCA Adverse effects

Back 11

"TCAS"
T: Thrombocytopenia
C: Cardiac (prolong Q-T, Hypotension, Vasodilate)
A: Anticholinergic (Anti-SLUD, blurred vision, tachycardia)
S: Seizures, Serotonin Syndrome (w/ Antipsychotics)
Also: wt gain, withdrawal, 2 wks btwn MAOI, leukopenia

Front 12

Alpha 1 vs Alpha 2 receptor location

Back 12

Alpha1: POSTsynaptic (if were sensitized -> lose effect)
Alpha2: PREsynaptic (autoreceptor - becomes sensitized)

Front 13

CYP Inhibitors

Back 13

"Fluvox is virst (1A2) to Burp up PARt of FLUox (2D6)"
Fluvoxamine (SSRI): 1A2
Buproprion (other antidep): 2D6
Fluoxetine (SSRI): 2D6
Paroxetine (SSRI): 2D6

Front 14

SSRI MOA

Back 14

MOA: like TCA but more selective for 5-HT
a) Acute: Blocks 5-HT reuptake -> Stim 5-HT autoreceptors -> ↓5-HT synth & release -> NET RESULT = Homeostasis
b) Chronic: 5-HT1-R Desensitize -> 5-HT synth & release return to basal levels -> Increased 5-HT output at synapses

Front 15

Fluoxetine

Back 15

SSRI:
Depression, OCD, Panic, Bulimia
Metab to S-norfluoxetine (active metabolite -> INHIBITS CYP2D6)
ONCE A DAY DOSING (T1/2: 50h)

Front 16

Citalopram

Back 16

SSRI
Use: MDD, GAD
Metab: CYP3A4 and CYP2C19
INHIBITS CYP2D6
1x/day Dosing
Contraindicated w/ MAOI, thioridazine, pimozide

Front 17

Escitalopram

Back 17

SSRI
Use: MDD, GAD
Metab: CYP3A4 and CYP2C19
INHIBITS CYP2D6
60% Plasma bound
1x/day Dosing
Contraindicated w/ MAOI

Front 18

Fluovoxamine

Back 18

SSRI
Use: OCD
Metab: CYP3A4 & CYP2C19 (decrease if old or liver impaired)
INHIBITS CYP1A2
Contraindicated: MAOI, thioridazine, Pimozide

Front 19

Paroxetine

Back 19

SSRI
Use: Depression, Social Anxiety, GAD, OCD, Panic, PTSD
Metab: CYP2D6 (decrease dose in elderly)
INHIBITS CYP2D6
contraindicated w/ MAOI, thioridazine, pimozide

Front 20

Sertraline

Back 20

SSRI
Use: MDD, OCD, Panic, PTSD, PMDD, Social Anxiety
1x/day dosing
INHIBITS CYP1A2

Front 21

SSRI Adverse Effects

Back 21

"SSRI"
S: Serotonin Syndrome (causes HARM: Hyperthermia, Autonomic instability (delerium), Rigidity, Myoclonus)
S: Stimulate CNS
R: Repro dysfunction
I: Insomnia
also:
SIADH excessive ADH
risk of PPHN: Persistent Pulmonary Hypertension of the Newborn
Platelet function inhibit

Front 22

Serotonin Syndrome symptoms

Back 22

HARM:
H: Hyperthermia
A: Autonomic instability (delerium)
R: Rigidity
M: Myoclonus

Front 23

Buproprion

Back 23

Misc "Bupro punishes Brain" (contra indic: sz, head trauma)
Use: MDD, ADHD
MOA: Unk - inhib uptake of NE, 5-HT, DA (no MAOI), CNS stim
Metab: CYP2B6
INHIBITS CYP2D6
SE: Decrease Seizure threshold (cannot use if Head trauma or hx of seizures), insomnia, anxiety

Front 24

Maprotiline

Back 24

Misc "mapro makes pyramids real"
Use: MDD
MOA: inhib NE Reuptake, and H1 antag
Metab: CYP2D6 (active metabolite)
1x/day dosing
SERIOUS: increase risk of EPS

Front 25

Mirtazapine

Back 25

Misc ("Mirt (like Bert) HAS antag your WBC (H1, Adren, Serotonin)")
Use: MDD
MOA: Antag: Adrenergic, 5-HT, H1
Adverse: Sedation (H1); AGRANULOCYTOSIS, NEUTROPENIA

Front 26

Nefazodone

Back 26

Misc
Use: MDD
MOA: Antag HAS (H1, Alpha1, 5-HT/Serotonin); weak inhib 5-HT & NE reuptake
Metab: CYP1A2, CYP2D6
INHIBITS CYP3A4
Adverse: Hepatotoxic, Orthostatic hypo (alpha1), priapism, sz

Front 27

Desvenlafaxine

Back 27

SNRI
Metab: CYP3A4 (CYP2D6 not involved)
Excrete: Renal & Fecal
Adverse: Nausea/constip, dizzy, insomn, sexual dysfunction
Contraindicated w/ MAOI

Front 28

Venlafaxine

Back 28

Use: MDD, GAD, Panic, Social Anx
Metab: Conjugated (some CYP3A4)
Adverse: Cholest & Triglyceride Elevation
Contraindicated w/ MAOI

Front 29

Duloxetine

Back 29

SNRI
Metab: CYP1A2, CYP2D6
INHIBITS CYP2D6
Excrete: Renal
Adverse: AntiSLUD
Contraindicated w/ MAOI, narrow angle glauc

Front 30

Trazodone

Back 30

SNRI, 5-HT AGONIST!!!, Alpha1 Antag, H1 antag
Metab: CYP3A4
Adverse: anti SLUD, Sedation

Front 31

Pediatric MDD: Only drug explicitly approved

Back 31

Fluoxetine (Prozac)

Front 32

Pediatric OCD: Only drug explicitly approved

Back 32

Fluvoxetine & Sertaline

Front 33

Lithium Carbonate/Citrate

Back 33

Use: Manic episodes of bipolar & maintenance
MOA: Reduce Catecholamine concentration (↓ release; ↑ reuptake); Increase 5-HT levels
Advers: LITH
L: leukocytosis
I: Insipidus (diabetes insipidus; tied to polyuria)
T: Tremor/Teratogenic
H: Hypothyroidism (disrupts cAMP in TSH pathway)

Front 34

Carbemazepine

Back 34

Use: Manic & mixed episodes of BD, V & IX neuralgia
MOA: Stabilize V-Gated Na channels (Closed -> open -> inactive); Increase GABA receptor potency
Adverse: BBW: Rash (SJS), Agranulocytosis
"Carbs from EtOH in my Part Gin/Tonic gave me a headache (Trigem Neuralgia), made me a crazy (Mania) red faced asian (SJS rash, test in Asians) w/ glasses (diplopia) eating bones and up and kill my liver (agranulocytosis & induce enzymes also kill liver)"

Front 35

Drugs used to Treat Bipolar

Back 35

Lithium, Carbemazepine, Valproic Acid, Lamotrigine, Gabapentin

Front 36

Valproic acid

Back 36

1) "Val was Absent minded 2yo c/o too many Gin/Tonic at MLB got a migraine so ate a steak even though not hungry -> got fat & EtOH kills kids & liver"
Use: mood stabilizer if Refractory to Lithium, anti-convuls
MOA: inhib T-type Ca channel
Adverse: Hepatotoxic, Teratogenic, Pancreatitis

Front 37

Lamotrigine

Back 37

Use: mood stabilizer if refractory to lithium
MOA: Blocks NA channels
Adverse: Rash (SJS): DO NOT USE IF UNDER 16!!!
"Lamotrigine: "Absence of Myo Sugar (glucuronidation) enzymes made me fall asleep on llama whose rough fur gave me a rash -> wake up with cross eyes & rash looking like zit-faced 16yo"

Front 38

Gabapentin

Back 38

1) MANIC, Fat & tired, can't walk, Says GAGA c/o CNS distress, drinks Part Gin/tonic for neuropathic pain but does not affect his liver
Use: mood stabilizer if REFRACTORY TO LITHIUM; also anticonvulsant
MOA: Unclear - GABA agonist, Binds Ca channels,
Adverse: tumorogenic, withdrawal -> seizures

Front 39

Drugs if Bipolar refractory to lithium

Back 39

Valproic acid
Lamotrigine
Gabapentin

Front 40

Treatment of Anxiety Disorders (3 general classes

Back 40

Benzodiazepines (BZD)
Amine Reuptake Inhibitors (SSRI)
Others (Buspirone, Hydroxyzine)

Front 41

Benzodiazepine Half-lives

Back 41

"Diaz made a CLONe: Clora, a clone of LORA who climbed ALPs with CHLORine instead of OXYgen"
a) Diazepam - 43h
b) Clonazepam - 20-50h
c) Clorazepate - 8 - 24h
d) Lorazepam - 14h
e) Alprazolam - 12h
f) Chlordiazepoxide - 10h
g) Oxazepam - 8h

Front 42

Other Misc drugs to treat Anxiety

Back 42

Buspirone
Hydroxyzine

Front 43

Buspirone

Back 43

can give w/ EtOH (unlike BZD)
Use: GAD, Anxiety, PMDD
MOA: Partial 5-HT agonist, D2 antag
T1/2: 2h
Metab: CYP3A4 (active metabolite)
Contraindications: MAOI, Severe renal impairment (excreted via renal)
Advantages: NO sedation, NO EtOH interaction, dependence or withdrawal

Front 44

Hydroxyzine

Back 44

"Hydroxycut if you're WORRIED about getting fat during 1st trimester (kills baby so won't get fat)"
Use: Anxiolytic, antipruritic, antiemetic, weak analg
MOA: H1 antagonist
T1/2 20h
Contraindicated 1st trimester of pregnancy

Front 45

Suicide Risk Assessment

Back 45

"SADPERSONS"
S: Sex
A: Age
D: Depression
P: Previous attempt
E: Excessive EtOH/Drugs
R: Rational thinking loss
S: Separated/divorced/widowed
O: Organized plan
N: No social support
S: Sickness/chronic disease