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Clinical pharmacology of
lithium
Domina Petric, MD
Bipolar affective disorder (BAD)
I.
Katzung, Masters, Trevor.
Basic and clinical
Bipolar affective disorder (BAD)
• Smaller percentage of bipolar patients
now recieve lithium because lithium has a
slow o...
Bipolar affective disorder (BAD)
• Maintenance treatment is about 60% effective
overall, but less in severely ill patients...
Bipolar affective disorder (BAD)
• The depressive phase of BAD often requires
concurrent use of an antidepressant drug.
• ...
Bipolar affective disorder (BAD)
• Bupropion may be efficacious, but it may
induce mania at higher doses.
• The anticonvul...
Bipolar affective disorder (BAD)
• Lithium ion at therapeutic
concentrations is devoid of autonomic
blocking effects and o...
Bipolar affective disorder (BAD)
Antipsychotics
Used in the manic phase:
aripiprazole, olanzapine,
quetiapine, risperidone...
Other applications
II.
Katzung, Masters, Trevor.
Basic and clinical
Other applications
Recurrent endogenous depression
Recurrent endogenous
depression with a cyclic
pattern is controlled by
...
Other applications
Schizoaffective disorder
• Schizoaffective disorder is characterized by a
mixture of schizophrenic symp...
Other applications
Schizophrenia
• Lithium alone is rarely successful in treating
schizophrenia.
• Adding the lithium to a...
Other applications
Unipolar depression
• Lithium may be added to tricyclic
antidepressants or SSRIs in patients with
unipo...
Monitoring treatment
III.
Katzung, Masters, Trevor.
Basic and clinical
Monitoring treatment
• An initial determination of serum lithium
concentration should be obtained about 5 days
after the s...
Monitoring treatment
• The serum concentration attained with
the adjusted dosage can be checked after
another 5 days.
• On...
Maintenance treatment
IV.
Katzung, Masters, Trevor.
Basic and clinical
Maintenance treatment
The decision to use lithium as prophylactic
treatment depends on:
• FREQUENCY and SEVERITY of previo...
Maintenance treatment
• If the present attack was the patient´s
first or if the patient is unreliable, one
might prefer to...
Maintenance treatment
Some patients can be maintained with
serum levels as low as 0,6 mEq/L.
The best results have been ob...
Drug interactions
V.
Katzung, Masters, Trevor.
Basic and clinical
Drug interactions
• Renal clearance of lithium is reduced about
25% by diuretics (eg, thiazides): doses may
need to be red...
Drug interactions
Many neuroleptics, except of
clozapine and the newer atypical
antipsychotics, may produce more
severe ex...
Adverse effects and complications
VI.
Katzung, Masters, Trevor.
Basic and clinical
Neurologic and psychiatric adverse
effects
Tremor is one of the most common adverse
effects of lithium treatment.
It occur...
Neurologic and psychiatric adverse
effects
Other neurologic abnormalities are:
• choreoathetosis
• motor hyperactivity
• a...
Neurologic and psychiatric adverse
effects
• Psychiatric disturbances at toxic
concentrations are generally marked by
ment...
Decreased thyroid function
• Lithium probably decreases thyroid function in
most patients exposed to the drug: reversible
...
Nephrogenic diabetes insipidus
• Polydipsia and polyuria are common, but
reversible concomitants of lithium
treatment, occ...
Other renal adverse effects
Chronic interstitial nephritis
Minimal-change glomerulopathy with
nephrotic syndrome
Decreased...
Warning!
Patients receiving lithium should avoid
dehydration and the associated increased
concentration of lithium in urin...
Edema
Edema is common adverse
effect of lithium treatment.
It may be related to some effect
of lithium on sodium retention...
Cardiac adverse effects
• The bradycardia-tachycardia (sick-
sinus) syndrome is a definite
contraindication to the use of ...
Katzung, Masters, Trevor.
Basic and clinical
Lifeinthefastlane.com
Use during pregnancy
• Renal clearance of lithium increases during
pregnancy and reverts to lower levels
immediately after...
Use during pregnancy
Lithium toxicity in newborns:
• LETHARGY
• CYANOSIS
• POOR SUCK REFLEX
• POOR MORO REFLEX
• HEPATOMEG...
Miscellaneous
• Transient acneiform eruptions: early in lithium
treatment, some of them subside with
temporary discontinua...
Overdose
VII.
Katzung, Masters, Trevor.
Basic and clinical
Overdose
• Therapeutic ovedoses are due to accumulation
of lithium resulting from changes in the
patient´s status: diminis...
Literature
• Katzung, Masters, Trevor.
Basic and clinical
pharmacology.
• Lifeinthefastlane.com
Katzung, Masters, Trevor.
...
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Clinical pharmacology of lithium

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Lithium: indications, side effects, overdose, interactions

Publicado en: Salud y medicina
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Clinical pharmacology of lithium

  1. 1. Clinical pharmacology of lithium Domina Petric, MD
  2. 2. Bipolar affective disorder (BAD) I. Katzung, Masters, Trevor. Basic and clinical
  3. 3. Bipolar affective disorder (BAD) • Smaller percentage of bipolar patients now recieve lithium because lithium has a slow onset of action. • The overall success rate for achieving remission from the manic phase of BAD can be as high as 80%, but lower among patients who require hospitalization. Katzung, Masters, Trevor. Basic and clinical
  4. 4. Bipolar affective disorder (BAD) • Maintenance treatment is about 60% effective overall, but less in severely ill patients. • Increased use of combined treatment in severe cases! • After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. Katzung, Masters, Trevor. Basic and clinical
  5. 5. Bipolar affective disorder (BAD) • The depressive phase of BAD often requires concurrent use of an antidepressant drug. • Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings. • Selective serotonin reuptake inhibitors (SSRIs) are less likely to induce mania, but may have limited efficacy. Katzung, Masters, Trevor. Basic and clinical
  6. 6. Bipolar affective disorder (BAD) • Bupropion may be efficacious, but it may induce mania at higher doses. • The anticonvulsant lamotrigine is effective for many patients with bipolar depression. • Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. Katzung, Masters, Trevor. Basic and clinical
  7. 7. Bipolar affective disorder (BAD) • Lithium ion at therapeutic concentrations is devoid of autonomic blocking effects and of activating or sedating effects. • Lithium can produce nausea and tremor. • Prophylactic use of lithium can prevent both mania nad depression. Katzung, Masters, Trevor. Basic and clinical
  8. 8. Bipolar affective disorder (BAD) Antipsychotics Used in the manic phase: aripiprazole, olanzapine, quetiapine, risperidone… Lithium Treatment of BAD, especially in the manic phase. Bipolar depression Lamotrigine, bupropion, SSRIs Prophylactic use of Li Prevention of both mania and depression Combination Combined treatment in severe cases: lithium and antipsychotics Antipsychotics Li + Lamotrigine Li Katzung, Masters, Trevor. Basic and clinical
  9. 9. Other applications II. Katzung, Masters, Trevor. Basic and clinical
  10. 10. Other applications Recurrent endogenous depression Recurrent endogenous depression with a cyclic pattern is controlled by either lithium or imipramine. Katzung, Masters, Trevor. Basic and clinical
  11. 11. Other applications Schizoaffective disorder • Schizoaffective disorder is characterized by a mixture of schizophrenic symptoms and depression or excitement. • It is treated with antipsychotic drugs alone or combined with lithium. • Various antidepressants are added if depression is present. Katzung, Masters, Trevor. Basic and clinical
  12. 12. Other applications Schizophrenia • Lithium alone is rarely successful in treating schizophrenia. • Adding the lithium to an antipsychotic may salvage an otherwise treatment-resistant patient. • Carbamazepine may work equally well when added to an antipsychotic drug. Katzung, Masters, Trevor. Basic and clinical
  13. 13. Other applications Unipolar depression • Lithium may be added to tricyclic antidepressants or SSRIs in patients with unipolar depression who do not respond fully to monotherapy with the antidepressant. • For this indication, concentrations of lithium at the lower end of the recommended range for BAD are adequate. Katzung, Masters, Trevor. Basic and clinical
  14. 14. Monitoring treatment III. Katzung, Masters, Trevor. Basic and clinical
  15. 15. Monitoring treatment • An initial determination of serum lithium concentration should be obtained about 5 days after the start of treatment. If the clinical response suggests a change in dosage, simple arithmetic should produce the desired level: • New dose= 𝑷𝒓𝒆𝒔𝒆𝒏𝒕 𝒅𝒐𝒔𝒆 𝑿 𝑫𝒆𝒔𝒊𝒓𝒆𝒅 𝒃𝒍𝒐𝒐𝒅 𝒍𝒆𝒗𝒆𝒍 𝑷𝒓𝒆𝒔𝒆𝒏𝒕 𝒃𝒍𝒐𝒐𝒅 𝒍𝒆𝒗𝒆𝒍 Katzung, Masters, Trevor. Basic and clinical
  16. 16. Monitoring treatment • The serum concentration attained with the adjusted dosage can be checked after another 5 days. • Once the desired concentration has been achieved, levels can be measured at increasing intervals unless the schedule is influenced by intercurrent illness or the introduction of a new drug. Katzung, Masters, Trevor. Basic and clinical
  17. 17. Maintenance treatment IV. Katzung, Masters, Trevor. Basic and clinical
  18. 18. Maintenance treatment The decision to use lithium as prophylactic treatment depends on: • FREQUENCY and SEVERITY of previous episodes • CRESCENDO pattern of appearance • DEGREE to which the patient is willing to follow a program of indefinite maintenance therapy Katzung, Masters, Trevor. Basic and clinical
  19. 19. Maintenance treatment • If the present attack was the patient´s first or if the patient is unreliable, one might prefer to terminate treatment after the episode has subsided. • Patients who have one or more episodes of illness per year are candidates for maintenance treatment. Katzung, Masters, Trevor. Basic and clinical
  20. 20. Maintenance treatment Some patients can be maintained with serum levels as low as 0,6 mEq/L. The best results have been obtained with higher levels, such as 0,9 mEq/L. Katzung, Masters, Trevor. Basic and clinical
  21. 21. Drug interactions V. Katzung, Masters, Trevor. Basic and clinical
  22. 22. Drug interactions • Renal clearance of lithium is reduced about 25% by diuretics (eg, thiazides): doses may need to be reduced by a smiliar amount. • A similar reduction in lithium clearance has been noted with several of the newer NSAIDs that block synthesis of prostaglandis, but not with aspirin and acetaminophen. Katzung, Masters, Trevor. Basic and clinical
  23. 23. Drug interactions Many neuroleptics, except of clozapine and the newer atypical antipsychotics, may produce more severe extrapyramidal syndromes when combined with lithium. Katzung, Masters, Trevor. Basic and clinical
  24. 24. Adverse effects and complications VI. Katzung, Masters, Trevor. Basic and clinical
  25. 25. Neurologic and psychiatric adverse effects Tremor is one of the most common adverse effects of lithium treatment. It occurs with therapeutic doses. Propranolol and atenolol alleviate lithium- induced tremor. Katzung, Masters, Trevor. Basic and clinical
  26. 26. Neurologic and psychiatric adverse effects Other neurologic abnormalities are: • choreoathetosis • motor hyperactivity • ataxia • dysarthria • aphasia Katzung, Masters, Trevor. Basic and clinical
  27. 27. Neurologic and psychiatric adverse effects • 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 for close monitoring of serum levels. Katzung, Masters, Trevor. Basic and clinical
  28. 28. Decreased thyroid function • Lithium probably decreases thyroid function in most patients exposed to the drug: reversible and nonprogressive effect. • Few patients develop frank thyroid enlargement. • Fewer show symptoms of hypothyroidism. • Obtaining a serum TSH concentration every 6-12 months is recommended. Katzung, Masters, Trevor. Basic and clinical
  29. 29. Nephrogenic diabetes insipidus • Polydipsia and polyuria are common, but reversible concomitants of lithium treatment, occuring at therapeutic serum concentrations. • The principal physiologic lesion involved is loss of responsiveness to antidiuretic hormone (nDI). • Lithium-induced nDI is resistant to vasopressin, but responds to amiloride. Katzung, Masters, Trevor. Basic and clinical
  30. 30. Other renal adverse effects Chronic interstitial nephritis Minimal-change glomerulopathy with nephrotic syndrome Decreased glomerular filtration rate Katzung, Masters, Trevor. Basic and clinical
  31. 31. Warning! 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. Katzung, Masters, Trevor. Basic and clinical
  32. 32. Edema Edema is common adverse effect of lithium treatment. It may be related to some effect of lithium on sodium retention. Katzung, Masters, Trevor. Basic and clinical
  33. 33. Cardiac adverse effects • The bradycardia-tachycardia (sick- sinus) syndrome is a definite contraindication to the use of lithium because this ion further depresses the sinus node. • T-wave flattening is often observed on the ECG. Katzung, Masters, Trevor. Basic and clinical
  34. 34. Katzung, Masters, Trevor. Basic and clinical Lifeinthefastlane.com
  35. 35. 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 after delivery. • Lithium is transferred to nursing infants through breast milk, in which it has a concentration about one third to one half that of serum. Katzung, Masters, Trevor. Basic and clinical
  36. 36. Use during pregnancy Lithium toxicity in newborns: • LETHARGY • CYANOSIS • POOR SUCK REFLEX • POOR MORO REFLEX • HEPATOMEGALY Katzung, Masters, Trevor. Basic and clinical
  37. 37. Miscellaneous • Transient acneiform eruptions: early in lithium treatment, some of them subside with temporary discontinuance of treatment and do not recur with its resumption. • Folliculitis: less dramatic, more frequently. • Leukocytosis: always present during lithium treatment, therapeutic effect in patients with low leukocyte counts. Katzung, Masters, Trevor. Basic and clinical
  38. 38. Overdose VII. Katzung, Masters, Trevor. Basic and clinical
  39. 39. Overdose • Therapeutic ovedoses are due to accumulation of lithium resulting from changes in the patient´s status: diminished serum sodium, use of diuretics, fluctuating renal function. • Any value over 2 mEq/L must be considered as indicating likely toxicity. • Lithium is a small ion and it is dialyzed readily: peritoneal dialysis, hemodialysis. Katzung, Masters, Trevor. Basic and clinical
  40. 40. Literature • Katzung, Masters, Trevor. Basic and clinical pharmacology. • Lifeinthefastlane.com Katzung, Masters, Trevor. Basic and clinical

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