Pharmacology Psychotherapeutic Drugs: Antidepressants And Antimanic Drugs Iiid-F

Front 1

What drugs are norepinephrine/dopamine reuptake inhibitors (NDRIs)

Back 1

Bupropion

Front 2

Describe the structure of NDRIs

Back 2

Aminoketone structure; unrelated to other known antidepressant drugs

Front 3

Describe the use of NDRIs

Back 3

Used for smoking cessation as well as an antidepressant, efficacy in treatment of smoking possibly related to the prevention of nicotine withdrawal.

Front 4

Describe the pharmacological effects of NDRIs

Back 4

-Significantly inhibits the neuronal reuptake of dopamine. Also blocks NE uptake but is weaker than the tricyclics
-Moderate anticholinergic effects

Front 5

What is the oral bioavailability of NDRIs? How long does it take to reach a steady state concentration? When does the antidepressant effect occur?

Back 5

Oral bioavailability: 5-20%
Steady State: 5-8 days
Antidepressant effect: 1-3 weeks

Front 6

Describe the metabolism of NDRIs

Back 6

Metabolized in the liver by CYP2D6 to active metabolites. This enzyme is partly inhibited by the drug. Over 60% of these metabolites are then excreted in the urine. Buproprion inhibition of 2D6 may cause increase in serum levels of substances metabolized by this enzyme.

Front 7

Describe the adverse effects of NDRIs

Back 7

-Headache/migraine
-Insomnia
-Anxiety
-Irritability
-Weight loss
-Anticholinergic Effects
-Changes in sexual function are reported infrequently
-Bupropion exhibits a potential for causing seizures

Front 8

Describe buproprions potential for causing seizures

Back 8

The occurrence of this is dose dependent (2.2% at doses >450 mg/day). The typical dose is 300mg/day. This may be of particular concern in patients with bulimia as the purging can result in electrolyte imbalance predisposing to seizures.

Front 9

What drugs are serotonin/norepinephrine reuptake inhibitors (SNRIs)?

Back 9

Venlafaxine

Front 10

What are the pharmacologic effects of SNRIs?

Back 10

-Inhibits serotonin reuptake and NE reuptake in central nerve endings. Potency is greater for inhibition of serotonin than NE. Weak inhibition of dopamine uptake, which only occurs at high doses (>450 mg). The side effect profile is very similar to SRIs since its most potent effect is on serotonin.
-No activity at muscarinic, histaminergic or alpha receptors.

Front 11

Describe the absorption, metabolism, and elimination of SNRIs

Back 11

-Well absorbed from the GI tract
-Metabolized by liver to an active metabolite, O-desmethylvenlafaxine
-Metabolites eliminated in the urine

Front 12

What are the adverse effects of SNRIs?

Back 12

-Drowsiness
-Dose related hypertension (doses > 225 mg/d)

Front 13

What drugs are serotonin 2A receptor (5-HT2A) antagonists + SRI?

Back 13

Nefazodone

Front 14

Describe nefazodone

Back 14

It is a phenylpiperazine derivative

Front 15

What are the pharmacological effects of nefazodone?

Back 15

-Potent antagonist at 5-HT2 post-synaptic receptors
-Inhibits pre-synaptic reuptake of serotonin
-Minimal inhibiton of norepinephrine uptake
-Blocks alpha-1 receptors peripherally
-No effects on muscarinic or histaminic receptors

Front 16

Describe the absorption, metabolism, and excretion of nefazodone

Back 16

-Completely absorbed from the GI tract.
-Large first pass liver metabolism (20% in plasma).
-Liver metabolism by CYP2A4 to active metabolites
-Excretion of metabolites in the urine

Front 17

What are the drug-drug interactions of nefazodone?

Back 17

Inhibits activity of CYP3A4 which can lead to drug interactions with drugs such as calcium channel blockers, clozapine, triazolam. q

Front 18

What are the adverse effects of nefazodone?

Back 18

-Drowsiness
-Changes in sexual function are reported infrequently

Front 19

What is the mainstay of antimanic drugs?

Back 19

Lithium

Front 20

Describe the mechanism of lithium action

Back 20

While the exact mechanism of the mood-stabilzing effect is unknown, it is thought that lithium acts on second-messenger systems within the post-synaptic neuron.

Front 21

What drugs are antimanic drugs?

Back 21

Lithium
Antiepileptic drugs

Front 22

Describe the absorption, time to peak plasma levels, elimination, and time to steady state of lithium

Back 22

-Readily absorbed from the GI tract
-Peak plasma levels in 2-4 hours after an oral dose
-95% of the oral dose is eliminated in the urine
-Steady state occurs in about 5 days

Front 23

What affects lithium levels?

Back 23

-Anything which impacts renal excretion (primarily proximal tubule) will effect lithium levels: dehydration, sodium loss, diuretics, and NSAIDS may increase lithium levels
-Aminophylline, osmotic diuretics, acetazolamide can decrease lithium levels by increasing renal excretion

Front 24

What are the adverse effects of lithium?

Back 24

-Diarrhea
-Nausea
-Tremor
-Sedation

Toxic effects:
-GI effects
-seizures
-ataxia
-coma
-A small number of patients develop thyroid dysfunction, with a goiter, hypothyroidism is uncommon
-Polydipsia and polyuria

Front 25

Describe the polydipsia and polyuria side effects of lithium

Back 25

This can be a disturbing side effect. A small number of patients may develop chronic inflammatory change in the kidney. Maintenance treatment with lithium includes regular serum monitoring of lithium levels and monitoring of plasma creatinine and creatinine clearance.