Antidepressants: DRUGS AFFECTING THE CNS

Lesson 3 of midterms part 2

Brain amines (NE, Serotonin, Dopamine)

Are important neurotransmitters in pathways for mood.

DEPRESSION

Functional decrease of activity:

• Overuse of neurotransmitters (Norepinephrine, Dopamine, and Serotonin)

• Increase the  effect of the Monoamine Oxidase (MAO) enzyme

• Increase reuptake of neurotransmitter back to presynaptic neuron

• Venlafaxine

• Desvenlafaxin

• Duloxetine

SNRI (Serotonin-Norepinephrine Reuptake Inhibitor):

• ___________

• ___________

• ___________

• Imipramine

• Clomipramine

• Desipramine

• Amitriptyline

• Nortriptyline

• Protriptyline

TCA (Tricyclic Antidepresants):

MOA of SNRIs and TRICYCLIC ANTIDEPRESSANTS (TCA)

inhibits the reuptake of 5HT and NE into nerves

Indications for SNRIs and TCA

Depression, anxiety, sleep disturbances, enuresis in children > 6yo, chronic pain, Clomipramine for OCD

• A: Well absorbed in GIT (peak levels in 2-4 hrs)

• D: Widely distributed in the tissue including the brain. They cross the placenta and the breast milk.

• M: Liver

• E: Urine

Pharmacokinetics of SNRI and TCA:

• Absorption: ___________

• Distribution: ___________

• Metabolism: ___________

• Excretion: ___________

Contraindications and Cautions of TCA and SNRIs

Contraindicated to those with known allergy to TCA, clients with recent myocardial infarction because of its cardiovascular effects, and pregnancy and lactation. Caution should be used in clients with Gastrointestinal and Genitourinary tract disorders. The presence of hepatic and renal impairment increases the toxicity of the drugs.

Adverse Effects of SNRIs and TCA

sedation, hallucinations, fatigue, cardiovascular effects, unstable blood pressure, abnormal rhythms, myocardial infarction, anticholinergic effects like drying of the mouth, constipation, urinary retention

C – Cardiovascular effects

A – Anticholinergic effects

S – Sedation

H – Hypotension or Hypertension

Mnemonics (CASH) for the adverse effects of TCA and SNRIs:

• ______________

• ______________

• ______________

• ______________

• Coma

• Convulsions

• Cardiotoxicity

TCA Toxicity: the three Cs

• Isocarboxazid

• Selegiline (MAO-B Selective)

• Phenelzine

• Tranylcypromine

MONOAMINE OXIDASE INHIBITORS (MAOi) DRUGS:

• _____________

• _____________

• _____________

• _____________

MOA of MAOi

inhibits MAO thereby inhibiting break down of NE, dopamine, and 5HT

Indication of MAOi

Depression unresponsive to other drugs

• A: absorbed in the GIT (peak levels in 2 – 3 hours)

• D: Crosses the placenta and breastmilk, making them unsable for pregnant adults

• M: Metabolized in the liver

• E: Excreted in the urine

Pharmacokinetics of MAOi:

• A: _____________

• D: _____________

• M: _____________

• E: _____________

Contraindication of MAOi

Contraindicated in clients with pheochromocytoma, cardiovascular disease, hepatic and renal disease. Caution should be used in psychiatric patients

Adverse effect of MAOi

More adverse effects than other antidepressant drugs. Dizziness, excitement, nervousness, mania, hyperreflexia, tremors, confusion, insomnia, agitation and blurred vision. Liver toxicity, Cardiovascular toxicity. Anticholinergic effects

Tyramine–rich foods

_______________ (aged cheese, fermented meat and vegetables, wine) which are normally broken down by MAO enzymes in the GIT may be absorbed in high concentration in the presence of MAOi and may cause hypertensive crisis

• Fluoxetine

• Paroxetine

• Citalopram

• Escitalopram

• Sertraline

• Fluvoxamine

Drugs of SELECTIVE SERITONIN REUPTAKE INHIBITOR (SSRI)

• ________

• ________

• ________

• ________

• ________

• ________

MOA of SSRI

Specifically blocks the reuptake of serotonin

Indication of SSRI

Depression, OCDs, panic attacks, bulimia, premenstrual dysphoric disorder (PMDD), PTSD, social phobias, and social anxiety disorders

Pharmacokinetics of SSRI:

• A: well absorbed from the GI tract

• D: widely distributed throughout the body, including the brain, due to their lipid solubility.

• M: metabolized in the liver

• E: excreted in the urine and feces

Contraindication of SSRI

Contraindicated to those with allergy to SSRIs, pregnancy and lactation. Caution to patients with impaired renal or hepatic function

Adverse effects of SSRI

CNS effects like headache, drowsiness, dizziness, insomnia, anxiety, tremor, agitation and seizures. Anticholinergic effects on the gastrointestinal tract and genitourinary tract, increased risk of suicidal ideation in those <25yo except with fluoxetine (BLACK BOX WARNING)

SEROTONIN SYNDROME

caused by excess serotonin in the synapse leading to severe muscle rigidity, hyperthermia, cardiovascular instability, and marked CNS stimulatory effects

Sedate (with BZDs), intubate, ventilate; block 5-HT2 with cyproheptadine

Treatment for Serotonin Syndrome

TRAZODONE

OTHER ANTIDEPRESSANTS:

• blocks 5-HT2 receptors

• For hypnosis, anxiety disorders, used as sleeping aid

MIRTAZAPINE

OTHER ANTIDEPRESSANTS:

• antagonism of presynaptic a2 adrenoceptors; blocks 5HT2 receptors

• Used of sedation/sleeping aid

BUPROPION

OTHER ANTIDEPRESSANTS:

• weakly blocks reuptake of NE, 5HT, and dopamine

• Used for smoking cessation at lower doses

• Limit drug access to potentially suicidal patients to decrease the risk of overdose

• Monitor the patient for 2 – 4 weeks to ascertain the onset and full effects

• Monitor blood pressure and orthostatic blood pressure carefully

• Monitor liver function

• Withhold medication dose in client with severe headache that may be due to severe hypertension and cerebrovascular effects

• Have phentolamine or another adrenergic blocker for hypertensive crisis

• Provide comfort measures to help the client tolerate drug effects

• Provide list of food that is low or no tyramine to clients on MAOI therapy

• Offer support and encouragement to help patients cope with the disease and drug regimen

NURSING CONSIDERATIONS

• Limit drug access to ____________ to decrease the risk of overdose

• Monitor the patient for ____________ to ascertain the onset and full effects

• Monitor ____________ and ____________ carefully

• Monitor ____________

• Withhold medication dose in client with ____________ that may be due to severe hypertension and cerebrovascular effects

• Have ____________ or another adrenergic blocker for hypertensive crisis

• Provide ____________ to help the client tolerate drug effects

• Provide list of food that is low or no ____________ to clients on MAOI therapy

• Offer ____________ and ____________ to help patients cope with the disease and drug regimen