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Antidepressants may be classified into three groups: the tricyclic antidepressants (TCAs),

depression results from a deficiency of biogenic amines in key areas of the brain; ( norepinephrine , dopamine, and serotonin).

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Antidepressants may be classified into three groups: the tricyclic antidepressants (TCAs),

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  1. depression results from a deficiency of biogenic amines in key areas of the brain; ( norepinephrine , dopamine, and serotonin). • Both NE and SER. are released throughout the brain by neurons that react with multiple receptors to regulate arousal, alertness,attention, moods, appetite, and sensory processing. • Deficiencies of these neurotransmitters may develop for three known reasons: • First, monoamine oxidase (MAO) may break them down to be recycled or restored in the neurons. • Second, rapid fire of the neurons may lead to their depletion. • third, the number or sensitivity of postsynaptic receptors may increase, thus depleting neurotransmitter levels. sh.alinia

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  3. First, they may inhibit the effects of MAO, leading to increased NE or 5HT(Ser)in the synaptic cleft. • Second, they may block reuptake by the releasing nerve, leading to increased neurotransmitter levels in the synaptic cleft. • Third, they may regulate receptor sites and the breakdown of neurotransmitters,leading to an accumulation of neurotransmitter in the synaptic cleft. sh.alinia

  4. Antidepressants may be classified into three groups: • the tricyclic antidepressants (TCAs), • the monoamine oxidase inhibitors (MAOIs), • the selective serotonin reuptake inhibitors (SSRIs). sh.alinia

  5. The tricyclic antidepressants (TCAs), reduce the reuptake of 5HT and NE into nerves. • TCAs that are available include: • amitriptyline , • amoxapine, • clomipramine (Anafranil), • doxepin(Sinequan), • imipramine (Tofranil), • and rimipramine(Surmontil); • the secondary amines desipramine(Norpramin), nortriptyline (Aventyl, Pamelor), and protriptyline(Vivactil); • and the tetracyclic drug maprotiline. sh.alinia

  6. The TCAs inhibit presynaptic reuptake of the neurotransmitters 5HT and NE, which leads to an accumulation of these neurotransmitters in the synaptic cleft and increased stimulation of the postsynaptic receptors. • for the relief of symptoms of depression. • The sedative effects of these drugs may make them more effective in patients whose depression is characterized by anxiety and sleep disturbances. sh.alinia

  7. The TCAs are well absorbed from the gastrointestinal (GI) tract, reaching peak levels in 2 to 4 hours. • They are highly bound to plasma proteins and are lipid soluble; this allows them to be distributed widely in the tissues, including the brain. • are metabolized in the liver and excreted in the urine, with long half-lives,ranging from 8 to 46 hours. • The TCAs cross the placenta and enter breast milk. sh.alinia

  8. One contraindication to the use of TCAs is the presence of allergy to any of the drugs in this class. • recent MI because of the potential occurrence of reinfarction or extension of the infarct with the cardiac effects of the drug, • myelographywithin the previous 24 hours or in the next 48 h. because of a possible drug–drug interaction with the dyes. • concurrent use of an MAOI because of the potential for serious adverse effects or toxic reactions. • In addition, pregnancy and lactation are contraindications sh.alinia

  9. The adverse effects of TCAs are associated with the effects of the drugs on the(CNS) and on the peripheral nervous system: • Sedation, sleepdisturbances, fatigue, hallucinations, disorientation,visual disturbances, difficulty in concentrating,weakness, ataxia, and tremors . • Use of TCAs may lead to GI anticholinergiceffects,such as dry mouth, constipation, nausea, vomiting,anorexia, increased salivation, cramps, and diarrhea. sh.alinia

  10. Resultant GU effects may include urinary retention and hesitancy, loss of libido, and changes in sexual functioning. • CV effects such as orthostatic hypotension,hypertension, arrhythmias, myocardial infarction,angina, palpitations, and stroke may also pose problems. • Miscellaneous reported effects include alopecia, weight gain or loss, flushing, chills, and nasal congestion. • Abrupt cessation of all TCAs causes a withdrawal syndrome characterized by nausea, headache, vertigo,malaise, and nightmares. sh.alinia

  11. The combination of TCAs with MAOIs leads to a risk of severe hyperpyretic crisis with severe convulsions, hypertensive episodes, and death. • This combination should be avoided. sh.alinia

  12. Maintain the initial dose for 4 to 8 weeks to evaluate the therapeutic effect. • Administer parenteral forms of the drug only if oral forms are not feasible or available. • Administer a major portion of the dose at bedtime . • Instruct the patient about the need for periodic monitoring and evaluation to enhance patient knowledge about drug therapy and to promote compliance. sh.alinia

  13. Monoamine oxidase inhibitors (MAOIs) irreversibly inhibits MAO, an enzyme found in nerves and other tissues (including the liver), to break down the biogenic amines NE, dopamine, and 5HT and relieve depression. • isocarboxazid (Marplan), phenelzine(Nardil), and tranylcypromine (Parnate). sh.alinia

  14. The MAOIs are well absorbed from the GI tract, reaching peak levels in 2 to 3 hours. • They are metabolized in the liver primarily by acetylation and are excreted in the urine. • The MAOIs cross the placenta and enter breast milk. sh.alinia

  15. The MAOIs are associated with more adverse effects, • more of which are fatal, than most other antidepressants. • The effects relate to the accumulation of NE in the synapticcleft. • Dizziness, excitement, nervousness, mania,hyperreflexia, tremors, confusion, insomnia, agitation,and blurred vision may occur. • MAOIs can cause liver toxicity. sh.alinia

  16. Limit drug access to a potentially suicidal patient to decrease the risk of overdose. • Monitor the patient for 2 to 4 weeks to ascertain the onset of the full therapeutic effect. • Monitor blood pressure and orthostatic blood pressure carefully . • Monitor liver function before and periodically during therapy . • Discontinue drug and monitor the patient carefully at any complaint of severe headache to decrease the risk of severe hypertension and cerebrovascular effects. • Have phentolamine or another adrenergic blocker on standby as treatment in case of hypertensive crisis. • Provide a diet that is low in tyramine-containing foods: • Aged cheeses: cheddar cheese, blue cheese, Swiss cheese, fish, or poultry: chicken paté, beef liver paté, caviar Brewer’s yeast Fava beans Red wines: Chianti, burgundy,sherry, vermouth Smoked or pickled meats, fish, or poultry: herring, sausage, corned beef, salami, pepperoni sh.alinia

  17. Selective serotonin reuptake inhibitors (SSRIs), the newest group of antidepressant drugs,specifically block the reuptake of 5HT, with little to no known effect on NE. • Because SSRIs do not have the many adverse effects associated with TCAs and MAOIs,they are a better choice for many patients. • SSRIs include: • fluoxetine (Prozac), the first SSRI; citalopram (Celexa); escitalopram (Lexapro); fluvoxamine (Luvox); paroxetine • (Paxil); sertraline (Zoloft); and vilazodone (Viibryd). sh.alinia

  18. Because of the risk of serotonin syndrome if SSRIs are used with MAOIs, this combination should be avoided,and at least 2 to 4 weeks should be allowed between use of the two types of drugs if one is switching from one to the other. sh.alinia

  19. Establish suicide precautions for severely depressed patients and limit the quantity of the drug dispensed to decrease the risk of overdose to cause harm. • Administer the drug once a day in the morning to achieve optimal therapeutic effects. • If dose is increased or if the patient is having severe GI effects,the dose can be divided. • Serious name confusion has been reported with some of the SSRIs . • Suggest that the patient use barrier contraceptives to prevent pregnancy while taking this drug because serious fetal abnormalities can occur. sh.alinia

  20. Increased CNS depression results if these agents are taken with other CNS depressants, including alcohol, antihistamines,and other tranquilizers. • Nursing Care as banzodiazepines. • Anxiolytics, or minor tranquilizers, are drugs used to treat anxiety by depressing the CNS. When given at higher doses, these drugs may be sedatives or hypnotics. sh.alinia

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