1. Drug Induced Kidney Disease

2. Introduction
Numerous diagnostic and therapeutic agents have been associated with the development of drug- induced kidney disease (DIKD) or nephrotoxicity.
It is a relatively common complication with variable presentations depending on the drug and clinical setting, inpatient or outpatient.

3. Introduction Manifestations of DIKD include acid–base abnormalities,
electrolyte imbalances
urine sediment abnormalities
proteinuria
pyuria and/or hematuria

4. Diagnosis
The initial diagnosis of DIKD typically involves detection of elevated serum creatinine and blood urea nitrogen, for which there is a temporal relationship between the toxicity and use of a potentially nephrotoxic drug.
Drug-induced kidney disease is best prevented by avoiding the use of potentially nephrotoxic agents for patients at increased risk for toxicity. However, when exposure to these drugs cannot be avoided, recognition of risk factors and specific techniques, such as hydration, may be used to reduce potential nephrotoxicity

5. Clinical Presentation
decline in GFR leading to a rise in Scr and BUN.
Alterations in renal tubular function without loss of glomerular filtration may be evident.

6. Symptoms
Patients may complain of malaise, anorexia, vomiting, shortness of breath, or edema, volume overload and HTN, particularly in the outpatient setting.
Signs
Decreased urine output may be an early sign of toxicity, particularly with radiographic contrast media, NSAIDs, and ACEIs, with progression to volume overload and hypertension.
Proximal tubular injury: Metabolic acidosis with bicarbonaturia; glycosuria in the absence of hyperglycemia; and reductions in serum phosphate, uric acid, potassium, and magnesium due to increased urinary losses.
Distal tubular injury: Polyuria from failure to maximally concentrate urine, metabolic acidosis from impaired urinary acidification, and hyperkalemia from impaired potassium excretion.

7. Laboratory Tests
An abrupt (within 48 hours) reduction in kidney function defined as an absolute increase in Scr of 0.3 mg/dL (27 mol/L),
Percentage increase in Scr of 50% (1.5-fold from baseline),
Reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than 6 hours)]

8. routine laboratory monitoring is essential for recognizing DIKD.
Scr or BUN concentrations and urine collection for creatinine clearance may subsequently be measured to quantify the degree of decline in GFR.

9. The primary principle for prevention of DIKD
Avoid the use of nephrotoxic agents for patients at increased risk for toxicity.
Awareness of potentially nephrotoxic drugs and knowledge of risk factors that increase renal vulnerability
Adjustment of medication dosage regimens based on accurate estimates of renal function, and careful and adequate hydration to establish high urine flow rates
Other preventative strategies are still theoretical and/or investigational and relate directly to the specific nephrotoxic mechanisms of a given drug.
Exposure to these drugs often cannot be avoided, so several interventions have been proposed to reduce the potential for the development of nephrotoxicity, for example,

10. Acute Tubular Necrosis (ATN)
Aminoglycoside Nephrotoxicity
Clinical presentation:
Gradual progressive rise in Scr and BUN and decrease in creatinine clearance.
Patients usually present with nonoliguria, i.e., they maintain urine volumes greater than 500 mL/day and sometimes have microscopic hematuria and proteinuria.
Hypomagnesemia

11. Aminoglycoside Nephrotoxicity
Full recovery of renal function is common if aminoglycoside therapy is discontinued immediately upon discovering signs of toxicity.
severe AKI may develop occasionally, and for these individuals renal replacement therapy may be required
The diagnosis of aminoglycoside-associated nephrotoxicity is often difficult, particularly in critically ill patients with multiple comorbidities and is confounded by other factors that are independently associated with the development of AKI
For instance, concurrent dehydration, sepsis, hypotension, ischemia, and use of other nephrotoxic drugs frequently contribute to AKI in patients who are receiving aminoglycosides.

12. Aminoglycoside Nephrotoxicity
Risk factors

13. Aminoglycoside Nephrotoxicity
Management
Aminoglycoside use should be discontinued or the dosage regimen revised if AKI is evident
[i.e., Scr increase of 0.5 mg/dL (44 mol/L) or more that is not attributable to another cause]
Other nephrotoxic drugs should be discontinued if possible
The patient should be maintained adequately hydrated and hemodynamically stable.
Short-term renal replacement therapy may be necessary, but ESRD has rarely been reported to be solely the result of aminoglycoside toxicity.

14. 2. Radiographic Contrast Media Nephrotoxicity
CIN is usually transient in nature
presenting most commonly as non-oliguria with kidney injury apparent within the first 24 to 48 hours after the administration of contrast.
The Scr concentration usually peaks between 3 and 5 days after exposure, with recovery after 7 to 10 days.
The urine sodium concentration and fractional excretion of sodium are frequently low, with the latter typically <1% (<0.01).

15. Risk Factors Radiographic Contrast Media Nephrotoxicity
Decreased renal blood flow
Preexisting kidney disease, GFR <60 mL/min/1.73 m2
patients' specific risk factors
Congestive heart failure, dehydration/volume depletion, and hypotension.
Atherosclerosis and reduced effective circulating arterial blood volume
Diabetes (diabetic nephropathy).
Larger volumes or doses of contrast and use of low- and high-osmolar contrast agents
Intraarterial administration of contrast confers greater risk than intravenous administration.
concurrent use of nephrotoxins and drugs that alter renal hemodynamics such as NSAIDs and ACEIs also increases risk.
1/ exacerbates the ischemic and direct cytotoxic effects of contrast media on the renal tubules.
2/ is the most important risk factor present in up to 60% of patients who develop CIN.34,35

16. Management Currently there is no specific therapy Supportive care
Radiographic Contrast Media Nephrotoxicity
Management
Currently there is no specific therapy
Supportive care
Monitor Renal function (e.g., Scr, urine output), electrolytes (e.g., sodium, potassium), and volume status closely
renal replacement therapy should be used as indicated and needed

18. 3. Amphotericin B Nephrotoxicity
Dose-dependent nephrotoxicity is often evident after administration of cumulative doses of 2 to 3 g as nonoliguria, renal tubular potassium, sodium, and magnesium wasting, impaired urinary concentrating ability, and distal renal tubular acidosis.
Time to onset of kidney injury varies, ranging from a few days to weeks.
Tubular dysfunction usually manifests 1 to 2 weeks after treatment is begun
Potassium and magnesium replacement may be necessary
Renal function should be closely monitored
with Scr and BUN concentrations checked daily, and serum magnesium, potassium, and calcium concentrations monitored every other day and corrected as needed

19. Risk Factors preexisting kidney disease,
Amphotericin B Nephrotoxicity
Risk Factors
preexisting kidney disease,
large individual and cumulative doses
short infusion times
volume depletion
hypokalemia,
increased age,
concomitant administration of diuretics and other nephrotoxins (cyclosporine in particular)

20. Amphotericin B Nephrotoxicity
Management
discontinuation of therapy and substitution of alternative antifungal therapy, if possible.
Renal tubular dysfunction and glomerular filtration will improve gradually to some degree in most patients, but damage may be irreversible.
Renal function indices should be closely followed, with Scr and BUN concentrations checked daily, and serum magnesium, potassium, and calcium concentrations should be monitored daily and corrected as needed.

21. Hemodynamically Mediated Kidney Injury
ACEIs and ARBs
Therapy with ACEIs and ARBs will acutely reduce GFR; so a moderate rise in Scr after initiation of therapy should be anticipated.
An increase in Scr of up to 30% is commonly observed within 3 to 5 days of initiating therapy and is an indication that the drug has begun to exert its desired pharmacologic effect.
The increase in Scr typically stabilizes within 1 to 2 weeks and is usually reversible upon stopping the drug.

22. Pathogenesis ACEIs and ARBs
ACEI- or ARB-mediated kidney injury is the result of a decrease in glomerular capillary hydrostatic pressure sufficient to reduce glomerular ultrafiltration.
Normally, the kidney attempts to maintain GFR by dilating the afferent arteriole and constricting the efferent arteriole in response to a decrease in renal blood flow.
During states of reduced blood flow, the juxtaglomerular apparatus increases renin secretion. Plasma renin converts angiotensinogen to angiotensin I, and ultimately angiotensin II by angiotensin-converting enzyme. Angiotensin II constricts the afferent and efferent arterioles, but has a greater effect on the efferent arterioles, resulting in a net increase in intraglomerular pressure.
Additionally, renal prostaglandins, prostaglandin E2 in particular, are released and induce a net dilation of the afferent arteriole, thereby improving blood flow into the glomerulus.
Together these processes maintain GFR and urine output

23. ACEIs and ARBs

24. ACEIs and ARBs
When ACEI therapy (e.g., enalapril or ramipril) is initiated, the synthesis of angiotensin II is decreased, thereby preferentially dilating the efferent arteriole.
This reduces outflow resistance from the glomerulus and decreases hydrostatic pressure in the glomerular capillaries, which alters Starling forces across the glomerular capillaries to decrease intraglomerular pressure and GFR and then often leads to nephrotoxicity.

25. ACEIs and ARBs

26. Risk Factors ACEIs and ARBs
Patients with bilateral renal artery stenosis or stenosis in a single kidney (i.e., renal transplant)
Patients with decreased effective arterial blood volume (i.e., prerenal states), especially those with congestive heart failure, volume depletion from excess diuresis or gastrointestinal fluid loss, hepatic cirrhosis with ascites, and nephrotic syndrome
Patients with preexisting kidney disease
Patients receiving concurrent nephrotoxic drugs

27. Prevention ACEIs and ARBs
Recognizing the presence of preexisting kidney disease and other diseases.
Initiate therapy with very low doses of a short-acting ACEI (e.g., captopril 6.25 mg to 12.5 mg), then gradually titrate the dose upward and convert to a longer-acting agent after patient tolerance has been demonstrated.
Outpatients may be started on low doses of long-acting ACEIs (e.g., enalapril 2.5 mg) with gradual dose titration every 2 to 4 weeks until the maximum dose or desired response is achieved.
Renal function indices and serum potassium concentrations must be monitored carefully, daily for hospitalized patients and every 2 to 3 days for outpatients.
Use of concurrent hypotensive agents and other drugs that affect renal hemodynamics (e.g., NSAIDs, diuretics) should be discouraged and dehydration avoided.

28. Management ACEIs and ARBs
Acute decreases in renal function and the development of hyperkalemia usually resolve over several days after ACEI or ARB therapy is discontinued.
Occasionally patients will require management of severe hyperkalemia.
ACEI or ARB therapy may frequently be reinitiated, particularly for patients with congestive heart failure, after intravascular volume depletion has been corrected or diuretic doses reduced.
Slight reductions in renal function [maintenance of a Scr concentration of 2 to 3 mg/dL (177 to 265 mol/L)] may be an acceptable trade-off for hemodynamic improvement in certain patients with severe congestive heart failure or renovascular disease not amenable to revascularization.77

29. 2. NSAIDs and Selective COX-2 Inhibitors
AKI can occur within days of initiating therapy, particularly with a short-acting agent such as ibuprofen, or within days of some other precipitating event (e.g., intravascular volume depletion).
Diminished urine output,
weight gain, and/or edema.
Urine sodium concentrations [<20 mEq/L (<20 mmol/L)]
fractional excretion of sodium [<1% (0.01)] are usually low
Elevated BUN, Scr, potassium, and blood pressure

30. Risk Factors age >60 years, preexisting kidney disease
NSAIDs and Selective COX-2 Inhibitors
Risk Factors
age >60 years,
preexisting kidney disease
hepatic disease with ascites
congestive heart failure
intravascular volume depletion/dehydration,
concurrent diuretic therapy
or systemic lupus erythematosus.
Combined use of NSAIDs or COX-2 inhibitors and concurrent nephrotoxic drugs, particularly other drugs that affect intraglomerular autoregulation should be avoided in high-risk patients.11
The elderly are at higher risk because of multiple comorbidities, multiple-drug therapies, and reduced renal hemodynamics.

31. Management Discontinuation of therapy Supportive care.
NSAIDs and Selective COX-2 Inhibitors
Management
Discontinuation of therapy
Supportive care.
Kidney injury is rarely severe, and recovery is usually rapid.
Occasionally, the hemodynamic insult is sufficiently severe to cause atn, which can prolong injury.24

32. Drug Induced Liver Disease

33. Introduction
The number of drugs associated with adverse reactions involving the liver is extensive
Alcohol-induced liver disease is the most common type of drug-induced liver disease.
All other drugs together account for less than 10% of patients hospitalized for elevated liver enzymes.
Drug-induced liver disease accounts for as much as 20% of acute liver failure in pediatric populations and at least that many of adults with acute liver failure.
In approximately 75% of these cases, liver transplantation is ultimately required for patient survival.
Of patients who required liver transplantation according to the United Network for Organ Sharing, acetaminophen, isoniazid, antiepileptics, and antibiotics collectively account for just over 60% of cases.

34. Risk Factors of DILI
adults are at higher risk than children (with the notable exception of DILI from valproic acid, which is more common in children).
Women may be more susceptible than men, which may in part be due to their generally smaller size
Alcohol abuse
malnutrition in some cases, as is seen with acetaminophen toxicity

35. The National Institutes of Health (NIH) maintains a searchable database of drugs, herbal medications, and dietary supplements that have been associated with DILI

38. CLASSIFICATION
Drug-induced liver injury (DILI) can be classified in several ways, including:
Clinical presentation:
Hepatocellular (cytotoxic) injury
Cholestatic injury
Mixed injury
Mechanism of hepatotoxicity:
Predictable
Idiosyncratic
Histologic findings, such as:
Hepatitis
Cholestasis
Steatosis
Typically, DILI is initially categorized based on its clinical presentation. If a liver biopsy is required to make the diagnosis or assess the degree of damage, DILI can then be further categorized based on its histologic findings

39. Clinical presentation
DILI is often characterized by the type of hepatic injury. The type of injury is reflected by the pattern of liver test abnormalities
Hepatocellular injury (hepatitis):
Disproportionate elevation in the serum aminotransferases compared with the alkaline phosphatase
Serum bilirubin may be elevated
Tests of synthetic function may be abnormal
Cholestatic injury (cholestasis):
Disproportionate elevation in the alkaline phosphatase compared with the serum aminotransferases
DILI is considered acute if the liver tests have been abnormal for less than three months and chronic if they have been abnormal for more than three months

40. CLINICAL MANIFESTATIONS
Acute presentations of drug-induced liver injury (DILI) include
mild asymptomatic liver test abnormalities
cholestasis with pruritus
an acute illness with jaundice that resembles viral hepatitis
acute liver failure
Chronic liver injury can resemble other causes of chronic liver disease, such as
autoimmune hepatitis
primary biliary cirrhosis
sclerosing cholangitis
alcoholic liver disease.
In some patients, chronic injury secondary to DILI progresses to cirrhosis.

41. The presence of jaundice (serum bilirubin >2 times the ULN) in association with an elevation in serum aminotransferases (>3 times the ULN) is associated with a worse prognosis

42. Symptoms and examination findings
Many are asymptomatic and only detected because of laboratory testing.
Acute DILI may develop
Malaise, low-grade fever, anorexia, nausea, vomiting,
Right upper quadrant pain, jaundice, acholic stools, or dark urine.
Hepatomegaly may be present on physical examination.
In severe cases, coagulopathy and hepatic encephalopathy, indicating acute liver failure
Chronic DILI may develop
Significant fibrosis or cirrhosis
Signs and symptoms of decompensation (eg, jaundice, palmar erythema, and ascites
Hypersensitivity reactions
other organs toxicity (eg, bone marrow, kidney, lung, skin, and blood vessels)

43. Management The primary treatment is withdrawal of the offending drug.
Early recognition of drug toxicity and monitoring for acute liver failure.
Few specific therapies have been shown to be beneficial in clinical trials.
Two exceptions are
N- acetylcysteine  for  acetaminophen toxicity.
L-carnitine for cases of valproic acid overdose

44. Glucocorticoids are of unproven benefit for most forms of drug hepatotoxicity, although they may have a role for treating patients with hypersensitivity reactions
Give glucocorticoids to patients with
hypersensitivity reactions who have progressive cholestasis despite drug withdrawal or who have biopsy features that resemble those seen in autoimmune hepatitis.
Extrahepatic manifestations of a hypersensitivity reaction that warrant glucocorticoid treatment (eg, severe pulmonary involvement in patients with DRESS [drug reaction with eosinophilia and systemic symptoms])

45. PROGNOSIS Acute liver injury
 The majority of patients will experience complete recovery once the offending medication is stopped.
In the setting of cholestatic injury, jaundice can take weeks to months to resolve.
Factors associated with a poorer prognosis in patients with hepatocellular injury include:
The development of jaundice (bilirubin >2 times ULN) in the setting of ALT >3 times ULN)
Acute liver failure due to antiepileptics in children
Acute liver failure due to acetaminophen requiring hemodialysis
An elevated serum creatinine

46.  Chronic liver injury
generally resolves upon discontinuation of the offending drug, but this pattern of liver injury may progress to cirrhosis and liver failure.
Cholestasis can be prolonged, requiring several months (>3 months) to resolve
A progression to chronic disease is reported to occur in approximately 5 to 10 percent of adverse drug reactions and is more common among the cholestatic/mixed types of injury

47. Drug Induced Hematologic Disease

48. Introduction
Can be :
Predictable hematologic disease (e.g., antineoplastics), or
Idiosyncratic reactions which is not directly related to the drugs’ pharmacology.
Drug-induced hematologic disorders are generally rare adverse effects associated with drug therapy.
Reporting during postmarketing surveillance of a drug is usually the method by which the incidence of rare adverse drug reactions is established.
Because drug-induced blood disorders are potentially dangerous, rechallenging a patient with a suspected agent in an attempt to confirm a diagnosis may not be ethical.

49. Drugs may produce hematologic toxicity by one of three general mechanisms:
Direct drug (or a metabolite) toxicity
Toxicity due to a drug effect on a genetic abnormality in the bone marrow
Toxicity involving immune mechanisms.

50. The most common drug-induced hematologic disorders include
Agranulocytosis or leukopenia (loss of the white blood cells)
Aplastic anemia (loss of all the formed elements of the blood)
Thrombocytopenia (loss of the platelets)
Hemolytic anemia (loss of the red blood cells).
The incidence of these adverse hematologic drug reactions, the relative importance of various etiologic chemicals, and their resultant morbidity and mortality vary.

51. Drugs Induced Agranulocytosis (Leukopenia)
Defined as a reduction in the number of granulocytes to ≤500 cells/mm3.
Drug-induced agranulocytosis is classified as Type 1 (due to an immune mechanism) and Type II (drug effect on bone marrow DNA synthesis).
In Type I reactions, blood immunoglobins are directed against drug-related antigens located on circulating leukocytes.

52. Table: Drugs Associated with Agranulocytosis

53. Occurs most commonly in females and the elderly (i. e
Occurs most commonly in females and the elderly (i.e. >60 years of age),
Has an estimated annual incidence of 1.1 to 12 cases per million population.
overall mortality rate of agranulocytosis is estimated to be 3.5% to 16%.
Mortality rate is highest among the elderly and patients with renal failure, bacteremia, or shock at the time of diagnosis.

54. Clinical Presentation
Sore throat, fever, malaise, weakness, chills, and other signs and symptoms of infection.
Onset: can appear rapidly, within days to weeks after the initiation of the offending drug.
But the time to onset is >1 month for most of these agents
Median duration of exposure prior to the development of agranulocytosis ranges from 19 to 60 days for most drugs.

55. Management Removal of the offending drug.
Most cases of neutropenia resolve over time.
Symptomatic treatment (e.g., antimicrobials for infections) and appropriate vigilant hygiene practices are necessary.
Sargramostim (GM-CSF 300 mcg/day sc) and filgrastim (G-CSF) can be used.

56. DRUG-INDUCED APLASTIC ANEMIA
First described by Ehrlich in 1888.
It is a rare, serious disease of unclear etiology.
An incidence of two to seven cases per million inhabitants reported.
This incidence is different in different regions.
The young and elderly are at increased risk.
It is characterized by pancytopenia.
It is considered the most serious drug-induced blood dyscrasia.
Pancytopenia:An abnormal deficiency in all blood cells (red blood cells and white blood cells and platelets); usually associated with bone marrow tumour or with aplastic anaemia

57. Drugs Suspected of Inducing Aplastic Anemia
Severe aplastic anemia is seen with a bone marrow of less than 25% of normal cellularity or a bone marrow of less than 50% of normal cellularity with less than 30% of the hematopoietic cells and at least two of the following peripheral blood values:
1) granulocytes fewer than 500/mm3
2) platelets fewer than 20,000/mm3
3) anemia with reticulocytes fewer than 1%.
About 65% of people with aplastic anemia die within 4 months of diagnosis; few die after this 4-month period

58. Drugs Associated with Aplastic Anemias

59. Management Remove the suspected offending agent.
Then provide adequate supportive care;
Appropriate antimicrobial therapy for the treatment of infection
Transfusion support with erythrocytes and platelets.
Do not include chemoprophylaxis, except in patients undergoing allogeneic hematopoietic stem cell
transplantation (HSCT).
Fever of unknown origin should be initially managed with broad-spectrum antibiotics.

60. If treatment is required;
The two major treatment options are
Allogeneic HSCT – Rx of choice for young pts.
Immunosuppressive therapy- Tends to be first-line therapy for older patients and those who are not candidates for HSCT.
Combination therapy with antithymocyte globulin (ATG) and cyclosporine.
Cyclosporine monotherapy
Corticosteroids are sometimes added to ATG-based immunosuppression.

61. Drug Induced Thrombocytopenia
Drug-induced immune thrombocytopenia is characterized by acute purpura, confluent petechiae or ecchy-moses- particularly after mild trauma-and gastrointestinal, central nervous system, or urinary tract bleeding,all associated with a mild or severe lack of blood platelets.
Drugs may induce marrow hypoplasia, destroy platelets directly, or be responsible for an immune reaction. Thrombocytopenia may be associated with several disease states (acute leukemia, Gaucher's disease, systemic lupus erythematosus, sarcoidosis); drug-induced thrombocytopenia usually remits 1 to 2 weeks after drug discontinuance. 

62. is usually defined as a platelet count below 100,000 cells/mm3 or >50% reduction from baseline values.
The annual incidence of drug-induced thrombocytopenia is approximately 10 cases per 1,000,000 population.

63. Drugs Associated with Thrombocytopenia

64. Mechanisms Direct toxicity reactions,
Result in suppressed thrombopoiesis and produce a decrease in the number of megakaryocytes in the bone marrow.
Mostly by cancer chemotherapy agents,
often by organic solvents, pesticides, drugs that influence folic acid metabolism, and inamrinone.
Hapten type immune reactions – eg. heparin induced reaction.

65. Mechanisms cont…. Platelet-reactive auto antibodies
Gold compounds and procainamide
The causative drug does not have to be present for the reaction to occur.
Drug dependent antibodies
Requires the presence of the drug to allow antibody binding.

66. DRUG-INDUCED HEMOLYTIC ANEMIA
Causes: defective RBCs or abnormal changes in the intravascular environment.
Mechanisms: immune or metabolic.
The onset of drug-induced hemolytic anemia is variable and depends on the drug and mechanism of the hemolysis.

67. Drugs Associated with Hemolytic Anemia

68. DRUG-INDUCEDIMMUNE HEMOLYTIC ANEMIA
Best diagnosed by Coombs test:
Direct (or direct antiglobulin test [DAT])- involves combining the patient’s RBCs with the antiglobulin serum.
Indirect - combining the patient’s serum with normal RBCs, then subjecting them to the direct Coombs test.
Mechanisms: hapten mediated, innocent bystanders, autoimmune.
Eg. Streptomycin, sulfonamides, semi synthetic penicillines.
Rx: withdrawal, supportive, steroids, rituximab, immunoglobulin.

69. DRUG-INDUCED OXIDATIVE HEMOLYTIC ANEMIA
Most often accompanies a glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency.
NADPH in RBCs keeps glutathione in a reduced state.
Reduced glutathione is a substrate for glutathione peroxidase
An enzyme that removes peroxide from RBCs, thus protecting them from oxidative stress.
Without reduced glutathione, oxidative drugs can oxidize the sulfhydryl groups of hemoglobin, removing them prematurely from the circulation (i.e., causing hemolysis).
Rx: removal and avoidance of offending agents.

70. DRUG-INDUCED MEGALOBLASTIC ANEMIA
In this case the development of RBC precursors called megaloblasts in the bone marrow is abnormal.
May be due to the direct or indirect effects of the drug on DNA synthesis.
Antimetabolite class of chemotherapeutic agents is most frequently associated with it.
Other drugs are cotrimoxazole, phenytoin, or the barbiturates.

71. Management
The anemia becomes an accepted side effect of therapy if it is due to chemotherapy
Folinic acid 5 to 10mg qid if it is due to SMX-TMP.
Folic acid supplementation of 1 mg every day if it is due to antiepileptic agents (phenytoin, phenobarb).

72. Drugs Associated with Oxidative Hemolytic Anemia

73. Drugs Associated with Megaloblastic Anemia

74. Heparin –induced thrombocytopenia
At least two types:
HIT Type I- most common, occurs in approximately 10% to 20% of patients treated with heparin.
It is a mild, reversible, nonimmunemediated reaction that usually occurs within the first 2 days of therapy.
Is usually an asymptomatic condition and is thought to be related to platelet aggregation.

75. HIT cont….
HIT type II- is less common but more severe and can be associated with more complications.
Approximately 1 to 5% of patients receiving unfractionated heparin and up to 0.8% of patients receiving lowmolecular- weight heparin (LMWH) can develop HIT.
The platelet count generally begins to decline 5 to 10 days after the start of heparin therapy.
patients who have had recent, major surgery are one of the highest risk groups

76. Causes of HIT
HIT is caused by the development of antibodies against platelet factor-4 (PF-4) and heparin complexes.
LMWHs bind less well to PF-4 than unfractionated heparin, and therefore antibody formation is less common.
Thrombosis is one of the major complications of HIT…..anticoagulants needed.
Less common complications are heparin-induced skin necrosis and venous gangrene of the limbs.
RX: Remove heparin, symptomatic rx, steroids???

77. Thank You!