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Sunday, August 31, 2008

Mcqs-pharmacology

The resident on call decides to start the patient on a medication to control this disease. The patient refuses the medication, stating that she has taken it in the past and it causes her to be constantly thirsty and break out in pimples and makes her food taste funny. Which of the following medications is being discussed?

  1. Valproic acid
  2. Haloperidol
  3. Carbamazepine
  4. Lithium
  5. Sertraline

The answer is 4, Lithium.

explanation:

Lithium is still the treatment of choice for acute mania and maintenance,

Lithium carbonate is often referred to as an "antimanic" drug, but in many parts of the world it is considered a "mood-stabilizing" agent because of its primary action of preventing mood swings in patients with bipolar affective (manic-depressive) disorder. Carbamazepine has also been recognized as effective in some groups of manic-depressive patients despite not being formally approved for such use. Valproate has recently been approved for the treatment of mania and is being evaluated as a mood stabilizer.

Lithium:

  • Adverse Effects & Complications
    Many adverse effects associated with lithium treatment occur at varying times after treatment is started. Some are harmless, but it is important to be alert to adverse effects that may signify impending serious toxic reactions.
    A. NEUROLOGIC AND PSYCHIATRIC ADVERSE EFFECTS
  • Tremor is one of the most common adverse effects of lithium treatment, and it occurs with therapeutic doses.
  • Propranolol and atenolol, which have been reported to be effective in essential tremor, also alleviate lithium-induced tremor.
  • Other reported neurologic abnormalities include choreoathetosis, motor hyperactivity, ataxia, dysarthria, and aphasia.
  • Psychiatric disturbances at toxic concentrations are generally marked by mental confusion and withdrawal.
  • Appearance of any new neurologic or psychiatric symptoms or signs is a clear indication for temporarily stopping treatment with lithium and close monitoring of serum levels.


B. DECREASED THYROID FUNCTION
  • Lithium probably decreases thyroid function in most patients exposed to the drug, but the effect is reversible or nonprogressive.
  •  Obtaining a serum TSH concentration every 6-12 months, however, is prudent.


C. NEPHROGENIC DIABETES INSIPIDUS AND OTHER RENAL ADVERSE EFFECTS
  • Polydipsia and polyuria are common but reversible concomitants of lithium treatment, occurring at therapeutic serum concentrations. The principal physiologic lesion involved is loss of responsiveness to antidiuretic hormone (nephrogenic diabetes insipidus).
  • Lithium-induced diabetes insipidus is resistant to vasopressin but responds to amiloride.
  • Patients receiving lithium should avoid dehydration and the associated increased concentration of lithium in urine. Periodic tests of renal concentrating ability should be performed to detect changes.


D. EDEMA
Edema is a common adverse effect of lithium treatment and may be related to some effect of lithium on sodium retention. Although weight gain may be expected in patients who become edematous, water retention does not account for the weight gain observed in up to 30% of patients taking lithium.


E. CARDIAC ADVERSE EFFECTS
The bradycardia-tachycardia ("sick sinus") syndrome is a definite contraindication to the use of lithium because the ion further depresses the sinus node.

F. USE DURING PREGNANCY

  • Renal clearance of lithium increases during pregnancy and reverts to lower levels immediately after delivery.
  • A patient whose serum lithium concentration is in a good therapeutic range during pregnancy may develop toxic levels following delivery.
  • Special care in monitoring lithium levels is needed at these times. Lithium is transferred to nursing infants through breast milk, in which it has a concentration about one-third to one-half that of serum.
  • Lithium toxicity in newborns is manifested by lethargy, cyanosis, poor suck and Moro reflexes, and perhaps hepatomegaly.
  • An earlier report suggested an increase in the frequency of cardiac anomalies, especially Ebstein's anomaly,

G. MISCELLANEOUS ADVERSE EFFECTS

  • Transient acneiform eruptions have been noted early in lithium treatment. Some of them subside with temporary discontinuance of treatment and do not recur with its resumption.
  • Leukocytosis is always present during lithium treatment, probably reflecting a direct effect on leukopoiesis rather than mobilization from the marginal pool. This adverse effect has now become a therapeutic effect in patients with low leukocyte counts.

Carbamazepine:

  • The most common dose-related adverse effects of carbamazepine are diplopia and ataxia.
  • The diplopia often occurs first and may last less than an hour during a particular time of day.
  • Considerable concern exists regarding the occurrence of idiosyncratic blood dyscrasias with carbamazepine, including fatal cases of aplastic anemia and agranulocytosis. Most of these have been in elderly patients with trigeminal neuralgia, and most have occurred within the first 4 months of treatment. The mild and persistent leukopenia seen in some patients is not necessarily an indication to stop treatment but requires careful monitoring.
  • The most common idiosyncratic reaction is an erythematous skin rash

 

Valproic acid:

  • The most common dose-related adverse effects of valproate are nausea, vomiting, and other gastrointestinal complaints such as abdominal pain and heartburn.
  • The drug should be started gradually to avoid these symptoms.
  • The idiosyncratic toxicity of valproate is largely limited to hepatotoxicity,
  • Some clinicians recommend treatment with oral or intravenous L-carnitine as soon as severe hepatotoxicity is suspected.
  • Careful monitoring of liver function is recommended when starting the drug; the hepatotoxicity is reversible in some cases if the drug is withdrawn.
  • The other observed idiosyncratic response with valproate is thrombocytopenia, although documented cases of abnormal bleeding are lacking. It should be noted that valproate is an effective and popular antiseizure drug and that only a very small number of patients have had severe toxic effects from its use.

Haloperidol:

  • The drug is noted for its strong early and late extrapyramidal side-effects.
  • The risk of the facial disfiguring tardive dyskinesia is around 4% per year in younger patients, higher than with most other antipsychotic drugs.
  • Akathisia manifests itself with anxiety, dysphoria, and an inability to remain motionless.
  • Other side effects include dry mouth,lethargy, restlessness of akathisia, muscle-stiffness, muscle-cramping, restlessness, tremors, and weight-gain; side effects like these are more likely to occur when the drug is given in high doses and/or during long-term treatment
  • Depression, severe enough to result in suicide, is quite often seen during long-term treatment.
  • The potentially fatal neuroleptic malignant syndrome (NMS) is a significant possible side effect. Haloperidol and fluphenazine are the two drugs which cause NMS most often.
  • Children and adolescents are particularly sensitive to the early and late extrapyramidal side-effects of haloperidol.
  • QT prolongation with sudden death is rarely seen.

 

Sertraline: it is a tricyclic antidepressant

Tricyclics side-effects  
Sedation Sleepiness, additive effects with other sedative drugs
Sympathomimetic Tremor, insomnia
Antimuscarinic Blurred vision, constipation, urinary hesitancy, confusion
Cardiovascular

Orthostatic hypotension, conduction defects, arrhythmias

Psychiatric

Aggravation of psychosis, withdrawal syndrome

Neurologic

Seizures

Metabolic-endocrine Weight gain, sexual disturbances

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