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Post  counselor on Mon Oct 15, 2012 12:08 pm


Major depression
E 'a chronic disabling disease, which manifests itself in a periodic applicant. E 'characterized by:
• Symptoms of emotional-affective sphere (anhedonia, sadness, guilt, etc.).
• vegetative disorders (sleep disorders)
• Altered psychomotor activity
• Impaired ability to concentrate and impaired memory

Bipolar Disorder
E 'characterized by alternating phases of depression and manic access (with excitement, sense of security, ideas of grandeur).

May contribute to depression genetic causes, but depression can be generated by viral infections and trauma. Stress is recognized a very important role in the etiopathogenesis of depression.

Monoaminergic hypothesis
The historical observations made with the antihypertensive reserpine (which inhibits monoamine storage intravescicolare and induces depression) led to the hypothesis of monoaminergic depression. According to this hypothesis depression stems from a reduced serotonergic neurotransmission operation, noradrenergic and, to a lesser extent, dopamine.

But the hypothesis monoaminergic has problems:
• Some drugs with antidepressant activity does not alter the synaptic levels of monoamine
• Some drugs that modify monoamine antidepressants are not always
• the antidepressant effect appears after 2-3 weeks, while the block reuptake is observed to the first dose of medication.

It 'has been suggested that the delay in onset of effect is due to adaptive responses to slow development, such as:
• desensitization of presynaptic autoreceptors for monoamine
• gradual increase in brain levels of the neurotrophic factor BDNF (Brain Derived Factor Neutropic) in the hippocampus. BDNF is reduced by stress.
The chronic (but not acute) treatment with antidepressants increases levels of BDNF.
• Occurrence of other molecular effects induced by antidepressants such as:
-Decreased expression of tyrosine kinases,
-Decreased expression of beta adrenergic receptors, modified-expression of the transcription factors CREB and ARC,
-Increased neurogenesis

The experimental model of "Chronic mild stress" seems to be the most predictive for the effects of a potential antidepressant drug in humans. In this model rats are exposed to different types of stress is not predictable (inversion of the day-night cycle, temporary removal of food or water, etc.); after 5-6 weeks manifest reduced intake of 10% sucrose (anhedonia), which Antidepressant drugs may revert.



Are derivatives of dibenzazepina, the dibenzocicloeptadiene and similar structures.
Belong to this class of drugs imipramine, desipramine, amitriptyline, clomipramine, etc..

Increase synaptic levels of serotonin and norepinephrine through a blocking their neuronal reuptake. Have little effect on the reuptake of dopamine (as does the cocaine).
• The antidepressant effect is istaura after 2-3 weeks of treatment.
• Tricyclic antidepressants may be useful in insomnia in depressed patients, but they do increase the step 4 and reduce the duration of REM sleep. It is not advised to use them as hypnotic subjects without depression.
• Initially tricyclic antidepressants decrease the turnover of noradrenaline and the firing of noradrenergic neurons (perhaps autoreceptor stimulation).
• Then the turnover of norepinephrine returned to normal (maybe autoreceptor desensitization) and increases the synaptic availability of norepinephrine and 5-HT.

The tricyclics have antagonistic action on muscarinic receptors, beta1 adrenergic, H1, H2 for histamine.

Cardiovascular system
Induce tachycardia by blocking the reuptake of norepinephrine and antimuscarinic action.

A toxic doses evoke respiratory depression.

• Good oral absorption.
• Usually used with a single daily dose at bedtime.
• You are trying to limit the dose to the minimum to avoid creating problems of absorption due to anticholinergic actions.
• It is distributed in the CNS being very lyophilized. Large volumes of distribution (20-50 liters). Bind strongly to plasma proteins.

Tricyclic antidepressants are metaboilizzati by hepatic microsomal enzymes.

a) antimuscarinic effects: dry mouth, blurred vision, urinary retention, constipation, tachycardia.
b) Effects of central: weakness and fatigue. Transition from depression to bipolar manic-depressive psychosis.
c) Confusion and delirium.
d) Increased risk of tonic-clonic convulsive fits.
e) Problems cardiovascular risk of orthostatic hypotension for -adrenergic blockade (desipramine is a poor beta blocker). Effects on the heart, the tricyclic antidepressants should not be used in patients with heart disease.
f) Miscellaneous Issues: jaundice, agranulocytosis, orgasmic impotence. Avoid in pregnancy.

Acute intoxication.
Subjects with suicidal tendencies may take toxic doses of tricyclic antidepressants.
Never give the patient amounts to more than 1 week of therapy.

Gastric lavage, physostigmine measures to maintain vital functions. May be indicated as phenytoin for its anti-arrhythmic action and to reduce the incidence of convulsive attacks.

• They enhance the effects of alcohol and sedatives
• Interact with anticholinergic drugs
• They enhance the activity of biogenic amines with indirect action.
• Together with MAO inhibitors: risk of hyperpyrexia, convulsions, coma.
• Pharmacokinetic interactions with phenothiazines and aspirin, which reduce the protein binding.
• Interactions with other drugs because the tricyclics inbiscono various isoforms of cytochrome P450 enzymes.

• Tricyclic antidepressants drugs are still widely used. Their cost is definitely lower than that of newer antidepressants.
• In addition to the major depression are used to:
- Syndromes with anxious reactions paniche
- Syndrome anxious that require long-term treatment
- Obsessive-Compulsive Disorder
- Neurogenic pain (amitriptyline)

2) selective inhibitors of serotonin reuptake inhibitors (SSRIs)
Belong to this class fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram

• They have selective action on serotonin reuptake. Affect less reuptake of NA and DA.
• The intensity of the antidepressant effect is similar to that of tricyclic
• Less sedative effects
• Lower antimuscarinic effects and antiadrenergic
• Reduced cardiovascular effects

Are administered per os
Inhibit CYP2D6 generating possible interactions.

-Nausea and diarrhea
-Sexual Disorders
-Increased risk of seizures in epileptics
-Serotonergic syndrome with tremor, muscle rigidity, mood changes. This syndrome can be caused by overdosing or by interaction with antiMAO.

-Major Depressive Disorder
Obsessive-Compulsive Disorder

3) DRUGS THAT INTERACT WITH THE TRANSMISSION serotonergic and noradrenergic (SNRI)

• Representatives of this class include venlafaxine and duloxetine.
• The action on norepinephrine and serotonin transporters gives high efficacy of these compounds.
• Lower antimuscarinic effects
• Lower antiadrenergic effects
• Reduced cardiovascular effects
• Reduced sexual dysfunction compared with the SSRIs

4) SELECTIVE INHIBITORS norepinephrine reuptake (NARI)

• A member of the class is the reboxetine
• Influence selectively only the reuptake of norepinephrine
• It has a low incidence of antimuscarinic effects
• little effect antiadrenergic

5) SPECIFIC ANTIDEPRESSANTS serotonergic and noradrenergic (NASSA)
• An exponent of this class is mirtazapine.
• Blocks  2 receptors that control the release of norepinephrine (autoreceptors) and serotonin (eterocettori)
• E '5HT2 and 5HT3 receptor antagonist, for which the action of serotonin is based mainly on 5HT1 receptors
• It has antimuscarinic side effects

Are members of the class nefazodone and trazodone
• Increase serotonergic transmission by blocking the reuptake, and more
• inhibit the 5HT2A receptor
• Damage low incidence of antimuscarinic effects and
antiadrenergic effects of

7) ANTIDEPRESSANTS INTERACTING WITH dopaminergic transmission
• A member of the class is the amisulpride
• It increases the release of dopamine by blocking presynaptic D2 receptors.
• At higher doses blocks the postsynaptic D2 and serves as antipsychotic

Cool Monoamine oxidase inhibitors (MAOIs)

• By inhibiting MAO, blocking the oxidative deamination of monoamines natural, although this activity does not explain all of their pharmacological actions.
• They are irreversible inhibitors of MAO: tranylcypromine, phenelzine and isocarboxazid.
• E 'reversible inhibitor moclobemide (RIMA)

a) They antidepressant action that appears to be related to increased availability of monoamines in the CNS.
b) They correct the sleep disturbances associated with depression. But they are potent suppressors of REM sleep.
c) They enhance the effects of other CNS depressants

1) The MAO flavin-containing enzymes are localized on the mitochondrial membranes of nerve tissue, liver and other organs.
Regulate the metabolic degradation of serotonin, dopamine, norepinephrine, epinephrine and tyramine from the intestine and absorbed into the portal circulation.

There are two forms of MAO, both present in the CNS:
a) MAO-A: sensitive to clorgilina and which has as its preferred substrate 5-HT.
b) MAO-B: sensitive to deprenyl and phenylethylamine as the substrate of choice.

Suspended the use of MAO inhibitors are required 2-3 weeks for amine metabolism back to normal (synthesis of new enzyme molecules).

• Excellent oral absorption.
• It is believed that the first split is isocarboxazid to hydrazine.
• The elimination of these drugs occurs mainly by acetylation (attention to "slow acetylators"). These individuals have strong response to MAO inhibitors.

• Reactions of overdose: agitation, hyperthermia, hypo-or hypertension, seizures.
• hepatotoxicity. The compounds idrazinici cause serious damage to the liver parenchyma.
• Orthostatic hypotension.
• Constipation and difficulty in urination, inhibition of ejaculation.

Moclobemide presents little risk of hypertensive crisis

1) organic amine precursors: levodopa and 5-hydroxytryptophan + antiMAO signs of central excitation.
2) sympathomimetic amines. You have greater effects of amines with indirect action, with the risk of hypertensive crisis and bleeding. Dangerous to assume cheeses are high in tyramine, other foods rich in yeast.
3) Interaction with tricyclic antidepressants (convulsions, delirium, sometimes hypertension)
4) The antiMAO reduce the detoxification of several drugs: general anesthetics, sedatives, analgesics, antihistamines, anticholinergics.

Moclobemide presents little risk of interaction with tyramine diet.

1) Treatment of depression: MAO inhibitors generally are lower than reuptake inhibitors. Using antiMAO when they did not give good results.
2) Forms neurotic characterized by phobias and anxiety
3) Treatment of bulimia
4) Obsessive-compulsive disorder
5) Narcolepsy

Their toxicity and the risk of drug interactions with many other drugs, they recommend its use only when other medications have proved to be inactive.



Lithium salts
In 1949 the observation that lithium salts had a specific effect in the treatment of mania.

• Subject normal does not exert psychotropic effects: it does not either euphoria or depression and it is not a sedative.
• Subjects mania: a strong stabilizing effect on mood. Also, if the subject suffers from insomnia lithium corrects sleep disturbance. It 'documented markedly reduced REM sleep.

We formulate several hypotheses:
1) has a gradient distribution to the two sides of the membrane decidedly small. Is not transported significantly by the sodium pump.
2) The lithium inhibits the release of dopamine, while inhibiting the reuptake of serotonin into nerve endings.
3) The lithium ion decreases the content of fosfatidilinositidi in neurons of the CNS.
4) It has recently been shown that lithium increases the expression of bcl-2 in the frontal cortex. The bcl-2 protects neurons from neurotoxic agents.
5) The lithium increases the BDNF and reduces the protein p53, which has proapoptotic action.

Good gastrointestinal absorption.
Lithium carbonate slow release gives blood levels more constant, but more frequent gastrointestinal disorders.
It 'distributed fairly evenly in the body.
Well through the blood-brain barrier.

95% is excreted in the urine. Elimination is slow because 89% of the filtered lithium is reabsorbed by the tubule. A sodium depletion reduces the elimination of Li (attention to the concomitant use of diuretics).
In the sweat removes 5% of battery.

• After 3-5 days of therapy can be observed edema, due to increased secretion of aldosterone.
• The Lithium inhibits the activation of adenilatociclasi by TSH. You have benign thyroid in response to functional impairment.
• Polyuria and polydipsia. Perhaps blocking renal effects of ADH by inhibiting the renal adenilatociclasi ADH sensitive.
• Allergic reactions.

Acute intoxication
• It is characterized by vomiting, diarrhea, tremor, coma, convulsions. You can have cardiac arrhythmias.
• The intoxication is treated using osmotic diuresis, administration of sodium bicarbonate to accelerate elimination of lithium
• Caution: low therapeutic index, monitoring of plasma levels

• Treatment of acute mania in adults or adolescents, who did not have heart or kidney disease. For moderate to severe manic attacks begin with antipsychotics. The Lithium is used after 5-10 days.
• For prevention of recurrence of manic-depressive bipolar.
• Can also be used as an alternative to tricyclic antidepressants in the treatment of severe recurrent depression.
• Helps in the treatment of acute major depression.
• Mood disorders in childhood.


Are antiepileptic drugs that can be a viable alternative to the use of lithium salts

• Its stabilizing action is due to prolongation of the phase of inactivation of the channel for the voltage-dependent Na +
• This medicine can improve mood and cognitive processes
• Individuals who do not respond to lithium, may respond to carbamazepine
• How has side effects sedation, nausea, ataxia, increased farm
• E 'a strong inducer of hepatic microsomal enzymes, where he presents a pharmacokinetic interactions.
• The oxcarbazepine is better tolerated and has no pharmacokinetic interactions.

Valproic acid
• Its stabilizing action is due to increased GABAergic transmission, but also to inhibition of channels for Na +, K + and Ca + +.
• Increases the expression of bcl-2, as does the battery.
• How has gastrointestinal side effects, sedation, hand tremors, hair loss, teratogenicity
• You enzyme inducer

• E 'especially effective in the depressive phase, rather than the manic bipolar disorder.
• He stabilizing action on the neuron for inhibition of channels for Na + and Ca + +
• Has the following side effects such as headaches, insomnia, tremors, diarrhea.

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