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Flashcards in Antidepressants and Stimulants Deck (27)
1

amitriptyline

Tricyclic Antidepressant

Nonspecific blocker of monoamine reuptake
- Block 5-HT and NE reuptake

Also block muscarinic, adrenergic, and histamine receptors: SIDE EFFECTS

Choice depends on tolerance to side effects and duration of action

2

amoxapine

Tricyclic Antidepressant

Nonspecific blocker of monoamine reuptake
- Block 5-HT and NE reuptake

Also block muscarinic, adrenergic, and histamine receptors: SIDE EFFECTS

Choice depends on tolerance to side effects and duration of action

3

imipramine

Tricyclic Antidepressant

Nonspecific blocker of monoamine reuptake
- Block 5-HT and NE reuptake

Also block muscarinic, adrenergic, and histamine receptors: SIDE EFFECTS

Choice depends on tolerance to side effects and duration of action

Prototypical TCA

4

nortriptyline

Tricyclic Antidepressant

Nonspecific blocker of monoamine reuptake
- Block 5-HT and NE reuptake

Also block muscarinic, adrenergic, and histamine receptors: SIDE EFFECTS

Choice depends on tolerance to side effects and duration of action

5

citalopram

Serotonin Reuptake Inhibitor (SSRIs)
- Block against SERT

Most widely used antidepressants in the US

Fewer SE then TCAs

Choice of SSRI depends on side-effect profile

Long Term EFFECT:
- Neurogenesis: Takes two weeks to see changes (desired effect) although drug has been absorbed.
- Activateds BDNF (brain derived growth factor)

Orally Active

Absorbed by small intestine

HIgh FIRST PASS Metab

Therapeutic effect: 2 wks

Long half life: 1-3 days

HIGH BINDING to PLASMA PROTEINS

Block several liver p450 enzymes

Eliminated by KIDNEYS

Side Effects:
- Early: Nausea, Anxiety, Sleep Disturbance/insomnia
- Late: Anorexia, sexual dysfunction, mania in bipolar patients

6

SSRI Drug Interactions

Block several liver p450 enzymes: CYP2D6, CYP1A2, CYP3A4

Interact with:
- TCAs
- Neuroleptic Drugs: HALPERIDOL
- Antiarrhythmic Drugs
- Beta-adrenergic antagonists

7

escitalopram

Serotonin Reuptake Inhibitor (SSRIs)
- Block against SERT

Most widely used antidepressants in the US

Fewer SE then TCAs

Choice of SSRI depends on side-effect profile

Long Term EFFECT:
- Neurogenesis: Takes two weeks to see changes (desired effect) although drug has been absorbed.
- Activateds BDNF (brain derived growth factor)

Orally Active

Absorbed by small intestine

HIgh FIRST PASS Metab

Therapeutic effect: 2 wks

Long half life: 1-3 days

HIGH BINDING to PLASMA PROTEINS

Block several liver p450 enzymes

Eliminated by KIDNEYS

Side Effects:
- Early: Nausea, Anxiety, Sleep Disturbance/insomnia
- Late: Anorexia, sexual dysfunction, mania in bipolar patients

8

fluoxetine (HAS IMPORTANT METABOLITE)

Serotonin Reuptake Inhibitor (SSRIs)
- Block against SERT

Most widely used antidepressants in the US

Fewer SE then TCAs

Choice of SSRI depends on side-effect profile

Long Term EFFECT:
- Neurogenesis: Takes two weeks to see changes (desired effect) although drug has been absorbed.
- Activateds BDNF (brain derived growth factor)

Orally Active

Absorbed by small intestine

HIgh FIRST PASS Metab

Therapeutic effect: 2 wks

Long half life: 1-3 days

HIGH BINDING to PLASMA PROTEINS

Block several liver p450 enzymes

Eliminated by KIDNEYS

Side Effects:
- Early: Nausea, Anxiety, Sleep Disturbance/insomnia
- Late: Anorexia, sexual dysfunction, mania in bipolar patients

DEMETHYLATED to ACTIVE METABOLITE:
- NORFLUOXETINE (half life 30 days)

TREATMENT FOR BIPOLAR DISORDER
- Fluoxetine combined bith olanzapine

9

sertraline

Serotonin Reuptake Inhibitor (SSRIs)
- Block against SERT

Most widely used antidepressants in the US

Fewer SE then TCAs

Choice of SSRI depends on side-effect profile

Long Term EFFECT:
- Neurogenesis: Takes two weeks to see changes (desired effect) although drug has been absorbed.
- Activateds BDNF (brain derived growth factor)

Orally Active

Absorbed by small intestine

HIgh FIRST PASS Metab

Therapeutic effect: 2 wks

Long half life: 1-3 days

HIGH BINDING to PLASMA PROTEINS

Block several liver p450 enzymes

Eliminated by KIDNEYS

Side Effects:
- Early: Nausea, Anxiety, Sleep Disturbance/insomnia
- Late: Anorexia, sexual dysfunction, mania in bipolar patients

10

duloxetine

Serotonin-Norepinephrine Reuptake Inhibitor (SNRIs)

Treat patients who are Refractory to SSRIs

Fewer side effects than TCAs

Orally Active

Half life: 11-12 hours

HIGHLY BOUND TO PLASMA PROTEINS (97%)

Metabolized by Liver:
- CYP1A2
- CYP2D6
- Contraindication for patients with hepatic insufficiency

Elimination: KIDNEY

Side Effects:
- Nausea, Anxiety, Sleep disturbance, Sexual Dysfunction
- HIGH DOSES: increase in BP and HR (due to NE)

11

venlafaxine

Serotonin-Norepinephrine Reuptake Inhibitor (SNRIs)

Treat patients who are Refractory to SSRIs

Fewer side effects than TCAs

Orally Active

Half life: 11-12 hours

MILDLY BOUND TO PLASMA PROTEINS (27%)

Metabolized by Liver:
- CYP2D6

Elimination: KIDNEY

Side Effects:
- Nausea, Anxiety, Sleep disturbance, Sexual Dysfunction
- HIGH DOSES: increase in BP and HR (due to NE)

12

bupropion

Atypical Antidepressant

Inhibits Dopamine Reuptake

Useful also for:
RAPID-CYCLING BIPOLAR DISORDER

Therapeutic Efficacy similar to that of TCAs/SSRIs

Less toxic than TCAs

Increase NE and 5-HT in synaptic transmission

Side Effects:
- Headache, nausea, tinnitus, insomnia, nervousness

13

mirtazapine

Atypical Antidepressant

Increases NE and Serotonin release by blocking alpha 2 receptors

Therapeutic Efficacy similar to that of TCAs/SSRIs

Less toxic than TCAs

Increase NE and 5-HT in synaptic transmission

Side Effects:
- Headache, nausea, tinnitus, insomnia, nervousness

14

nefazodone

Atypical Antidepressant

Inhibits reuptake of 5-HT and blocks 5-HT2 receptor
- Anti Psychotic

Therapeutic Efficacy similar to that of TCAs/SSRIs

Less toxic than TCAs

Increase NE and 5-HT in synaptic transmission

Side Effects:
- Headache, nausea, tinnitus, insomnia, nervousness

15

phenelzine

MAO inhibitor (MAOIs)

Third line drug for depression in patients who don't respond to SSRIs or TCAs

LIMITED DUE TO SEVERE and UNPREDICTABLE side effects

Increase presynaptic concentration of monoamines

Irreversible and Long Lasting inhibitor of Monoamine Oxidase
- MAO-A deaminates NE, 5-HT, and DA
- MAO-B deaminates DA

Inhibits MAO-A and MAO-B

Orally active

Therapeutic Effect: 2-4 weeks

Eliminated: KIDNEYS

Block MAO irreversibly
- Loss of activity lasts long after drug is metabolized and eliminated
- New MAO enzymes must be synthesized to function normally (7 weeks)

SIDE EFFECTS:
CNS
- RESTLESSNESS, AGITATION, PSYCHOSES
Cardiovascular:
-Orthostatic Hypotension
- Tachycardia

Drug Interaction:
- Serotonin Syndrome cause by combining with SSRIs:
- Potentially fatal : cognitive, autonomic, and somatic effects
COGNITIVE (delirium, coma)
Autonomic (hypertension, tachycardia)
Somatic (hyperthermia, hyperreflexia, Tremor)

Tyramine: Metabolized by MAO
- IF MAO inhibited Tyramine causes release of large amounts of Catecholamines
- Headaches, tachycardia, hypertension, seizures, stroke (cheese effect)

16

selegiline

MAO inhibitor (MAOIs)

Third line drug for depression in patients who don't respond to SSRIs or TCAs

LIMITED DUE TO SEVERE and UNPREDICTABLE side effects

Increase presynaptic concentration of monoamines

Irreversible and Long Lasting inhibitor of Monoamine Oxidase
- MAO-A deaminates NE, 5-HT, and DA
- MAO-B deaminates DA

Inhibits: MAO-B (MAO-A at high concentrations)

Orally active

TRANSDERMAL PATCH AVAILABLE

Therapeutic Effect: 2-4 weeks

Eliminated: KIDNEYS

Block MAO irreversibly
- Loss of activity lasts long after drug is metabolized and eliminated
- New MAO enzymes must be synthesized to function normally (7 weeks)

SIDE EFFECTS:
CNS
- RESTLESSNESS, AGITATION, PSYCHOSES
Cardiovascular:
-Orthostatic Hypotension
- Tachycardia

Drug Interaction:
- Serotonin Syndrome cause by combining with SSRIs:
- Potentially fatal : cognitive, autonomic, and somatic effects
COGNITIVE (delirium, coma)
Autonomic (hypertension, tachycardia)
Somatic (hyperthermia, hyperreflexia, Tremor)

Tyramine: Metabolized by MAO
- IF MAO inhibited Tyramine causes release of large amounts of Catecholamines
- Headaches, tachycardia, hypertension, seizures, stroke (cheese effect)

17

tranylcypromine

MAO inhibitor (MAOIs)

Third line drug for depression in patients who don't respond to SSRIs or TCAs

LIMITED DUE TO SEVERE and UNPREDICTABLE side effects

Increase presynaptic concentration of monoamines

Irreversible and Long Lasting inhibitor of Monoamine Oxidase
- MAO-A deaminates NE, 5-HT, and DA
- MAO-B deaminates DA

Inhibits MAO-A and MAO-B

Orally active

Therapeutic Effect: 2-4 weeks

Eliminated: KIDNEYS

Block MAO irreversibly
- Loss of activity lasts long after drug is metabolized and eliminated
- New MAO enzymes must be synthesized to function normally (7 weeks)

SIDE EFFECTS:
CNS
- RESTLESSNESS, AGITATION, PSYCHOSES
Cardiovascular:
-Orthostatic Hypotension
- Tachycardia

Drug Interaction:
- Serotonin Syndrome cause by combining with SSRIs:
- Potentially fatal : cognitive, autonomic, and somatic effects
COGNITIVE (delirium, coma)
Autonomic (hypertension, tachycardia)
Somatic (hyperthermia, hyperreflexia, Tremor)

Tyramine: Metabolized by MAO
- IF MAO inhibited Tyramine causes release of large amounts of Catecholamines
- Headaches, tachycardia, hypertension, seizures, stroke (cheese effect)

18

lithium

Bipolar Treatment

Carbonate and Citrate (prophylatic)

Significantly decreases frequency of manic and depressive attacks (70% patients)

Combined with antidepressant drugs, neuroletpic and antiepileptics

Onset takes several weeks

Substitute Na and produce undesirable effects

VERY TOXIC: EXTREMELY low therapeutic Index

MECHANISM:
- Blocks hydrolysis of inositol phosphate to free inositol therefore preventing formation of phosphatidylinositol

Blocks GSK-3B kinase

Inhibits 5-HT1 and 5-HT1B receptors

Enhances glutamate reuptake

Inhibits IMPase: inositol monophosphatase

Pharmacokinetics:
- Carbonate and citrate salts
- Oral administration
- Rapidly absorbed from GI tract
- Soluble ion
- Peak Plasma level reached at 2-4 hours
- Half Life: 20-24 hours

Elimination: Kidneys
- Reduced kidney function is associated with greater lithium toxicity

Side Effects:
- Low Therapeutic Index: 0.6 -1.4 meq/L therapy
1.6-2.0 meq/L toxic
- Substitutes Na
- CNS: tremors, confusion, convulsions, coma
- Cardiovascular: Arrthymias
- Thyroid: Decreased function
- Renal: Polydipsia, polyuria, induced diabetes insipidus (due to disabling vasopressin)
- Teratogenic Effects
- Drug Interaction with thiazize diuretics and NSAIDS
- Contraindication due to low lithium excretion



19

carbamazepine

Treat Bipolar Disorder

Anticonvulsant given with lithium


20

olanzapine

Bipolar Treatment

Given with Lithium Salts

Antipsychotic
(risperidone, this drug and quetiapine)

Antidepressant (fluoxetine with this drug)

21

risperidone

Bipolar Treatment

Given with Lithium Salts

Antipsychotic
(risperidone, olaznapine and quetiapine)

22

valproic acid

Bipolar Treatment

Given with Lithium Salts

Anticonvulsants (valproic acid, carbamazepine and
lamotrigine)

23

Dextroamphetamine

Stimulant

Psychomotor stim (fights fatigue)

Prevent narcolepsy
- Mechanism: Unclear but might involve DA and NE systems

Treat ADHD

Oral Admin, absorbed completely by GI

Mechanism:
- Increase release of DA and NE by brain
- Increasing DA and NE release form synaptic vesicles into presynatpic cytoplasm via Vesicular Monoamine Transporter (VMAT)
- Inhibit MAO
- Increase actions of presynatpic cytoplasmic conc of DA and NE

Increases vesicular and nonvesicular release of DA and NE (reversal of DA/NE transporters)

Metabolized: liver

Excreted: Kidney

Smoking or via via IV by abusers

Side Effects:
- Euphora
- Anxiety
- Insomnia
- Confusion
- Vertigo
- Paranoia, psychoses, suicidal/homicidal impulses

Cardiovascular: Arrthymias, hypertension

GI: nausea, diarrhea

Potential for addiction

24

amphetamine

Stimulant

Psychomotor stim (fights fatigue)

Prevent narcolepsy
- Mechanism: Unclear but might involve DA and NE systems

Treat ADHD

Oral Admin, absorbed completely by GI

Mechanism:
- Increase release of DA and NE by brain
- Increasing DA and NE release form synaptic vesicles into presynatpic cytoplasm via Vesicular Monoamine Transporter (VMAT)
- Inhibit MAO
- Increase actions of presynatpic cytoplasmic conc of DA and NE

Increases vesicular and nonvesicular release of DA and NE (reversal of DA/NE transporters)

Metabolized: liver

Excreted: Kidney

Smoking or via via IV by abusers

Side Effects:
- Euphora
- Anxiety
- Insomnia
- Confusion
- Vertigo
- Paranoia, psychoses, suicidal/homicidal impulses

Cardiovascular: Arrthymias, hypertension

GI: nausea, diarrhea

Potential for addiction

25

atomoxetine

Treatment of ADHD

NE reuptake Inhibitor
- NOT a STIMULANT

Not habit forming and is not a controlled substance

26

methylphenidate

Stimulant

Psychomotor stim (fights fatigue)

Prevent narcolepsy
- Mechanism: Unclear but might involve DA and NE systems

Treat ADHD

Oral Admin, absorbed completely by GI

Mechanism:
- Increase release of DA and NE by brain
- Increasing DA and NE release form synaptic vesicles into presynatpic cytoplasm via Vesicular Monoamine Transporter (VMAT)
- Inhibit MAO
- Increase actions of presynatpic cytoplasmic conc of DA and NE

Increases vesicular and nonvesicular release of DA and NE (reversal of DA/NE transporters)

Metabolized: liver

Excreted: Kidney

Smoking or via via IV by abusers

Side Effects:
- Euphora
- Anxiety
- Insomnia
- Confusion
- Vertigo
- Paranoia, psychoses, suicidal/homicidal impulses

Cardiovascular: Arrthymias, hypertension

GI: nausea, diarrhea

Potential for addiction

27

modafinil

Treatment of Narcolepsy

Mech unclear but involves NE and DA systems

Fewer psychoactive and euphoric effects as well as effects on the mood and thinking