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1. Integrated
pharmacotherapy III
By Muktar Sano (B.Pharm, MSc in Clinical
Pharmacy,Assistant Professor)
1

2. Course
Objective
 Describe the pathophysiologic processes underlying
 hematological,
 psychiatric,
 neurologic,
 endocrine and metabolic,
 gynecology and obstetrics,
 urologic and
 dermatologic disorders.
 Analyze and interpret diagnostic findings relevant to above
diseases.
 Recommend appropriate treatment regimen for patients
suffering from above diseases.

3. Introduction Hematological disorders

4. Brain
storming
 Define hematology
 Explain components of
CBC
 Describe functions of
blood
4

5. Hematolo
gy
 Study of blood and blood forming tissues
 Key components of hematologic system are:
Blood
Blood forming tissues
Bone marrow
Spleen
Lymph system
5

6. What Does Blood
Do?
 Transportation
 Oxygen
 Nutrients
 Hormones
 Waste Products
 Regulation
 Fluid, electrolyte
 Acid-Base
balance
 Protection
 Coagulation
 Fight Infections
6

7. Components of
Blood
• Plasma - 55%
• Blood Cells-45%
– Three types
• Erythrocytes/RBCs
• Leukocytes/WBCs
• Thrombocytes/Platelets
7

8. Components of
Blood…

9. Erythrocytes/Red Blood Cells
 Composed of hemoglobin
 Erythropoiesis
 RBC production
 Stimulated by hypoxia( decrease in tissue oxygen)
 Controlled by erythropoietin
 Hormone synthesized in kidney
 Allows proliferation and maturation RBCs
 Induces Hb formation
 Hemolysis
 destruction of RBCs
 Releases bilirubin into blood stream
 Normal lifespan of RBC = 120 days
9

10. Leukocytes/White Blood Cells
 5 types
Basophils
Eosinophil
s
Neutrophils
Monocytes
Lymphocyt
es
10

11. Thrombocytes/Plate
lets
 Must be present for clotting to occur
 Involved in hemostasis
11

12. Structures of the Hematologic System
 Bone Marrow
 Liver
 Lymph System
12

13. Bone Marrow
 Soft substance in core of bones
 Blood cell production (Hematopoiesis):
 The production of all types of blood cells
generated by a remarkable self-regulated
system.
 RBC production may also
occur in liver and spleen

14. Live
r
 Receives 24% of the
cardiac output (1500 ml of
blood each minute)
 Liver has many functions
 Hematologic functions:
 Liver synthesis plasma
proteins including clotting
factors and albumin
 Liver clears damaged and
non-functioning
RBCs/erythrocytes from
circulation
14

15. Splee
n
 Located in upper Left
quadrant of abdomen
 Functions
 Hematopoietic function
Produces fetal RBCs
 Immune function
Lymphocytes, monocytes
 Storage function
30% platelets stored in
spleen
15

16. Assessment of the Hematologic System
Important Health Information
Past health history
Medications
Surgery or other treatments
―Physical Examination
 Skin
Lymph Nodes, etc.,
16

17. Diagnostic Studies :Complete Blood
Count
 WBCs
 Normal 4,000 -11,000 /µℓ - leukocytosis
 Associated with infection, inflammation, tissue
injury or death
 Leukopenia--  WBC
 Neutropenia --  neutrophil count
 RBC
 ♂ 4.5 – 5.5 x 106/uℓ
 ♀ 4.0 – 5.0 x 106/uℓ
 Hematocrit (Hct)
 The hematocrit is the percent of whole blood
that is composed of red blood cells.
 The hematocrit is a measure of both the number
of red blood cells and the size of red blood cells.
17

18. Diagnostic Studies : Complete Blood
Count …
 Platelet count
 Normal 150,000- 450,000
 Thrombocytopenia- platelet count
 Spontaneous hemorrhage likely when count is
below 20,000
 Pancytopenia
 Decrease in number of RBCs, WBCs, and platelets
18

19. Diagnostic Studies of the Hematologic
System
 Radiologic Studies
 CT/MRI of lymph tissues
 Biopsies
 Bone Marrow examination
 Lymph node biopsies
19

20. 20
Pharmacotherapy of
Anemias

21. Introductory
case
 A 27-year-old African American woman scheduled a prenatal visit
after a positive home pregnancy test. Previous pregnancies and
deliveries were uncomplicated; she has healthy children ages 1.5
and 3 years. No other significant past medical history. Earlier this
week she states feeling dizzy and short of breath after walking up
stairs.
a) What aspects of this patient’s history suggest she may be anemic?
b) What laboratory assessments are required to make an appropriate
diagnosis and therapeutic plan?
c) How would the requested laboratory parameter(s) aid your decision
making?
21

22. Learning
objectives
Upon completion of the chapter, each student will be able
to:
 Identify common causes of anemia.
 Describe common signs and symptoms of anemia.
 Describe diagnostic evaluation required to
determine the etiology of anemia.
 Recommend a treatment regimen considering the
underlying cause and patient-specific variables.
 Develop a plan to monitor the outcomes of
pharmacotherapy for the treatment of anemia
22

23. Outlin
e
 Definition
 Epidemiology and etiology
 Pathophysiology and
classification
 Clinical presentation and
diagnosis
 Treatment
 Outcome evaluation
23

24. Introducti
on
24
 Anemia is a group of diseases characterized by a
decrease in hemoglobin (Hgb) or RBCs, resulting in
decreased oxygen-carrying capacity of blood.
Normal values: RBCs
• Men: 4.2 – 5.4
million/mm3
• Women: 3.6 – 5.0
million/mm3
 WHO defines anemia as
 Hgb < 13 g/dL (<8.07 mmol/L) in men or
 Hgb < 12 g/dL (<7.45 mmol/L) in women.
 Normal Hgb values are
 Males= 14.0 to 17.5 g/dL (8.69–10.9 mmol/L) and

25. Epidemiology and
Etiology
 According to the WHO, almost 1.6 billion people (25% of
the
world’s population) are anemic.
 Patients with cancer and chronic kidney disease
(CKD) have significantly higher rates of anemia.
 The incidence of anemia in cancer patients=30%-90%.
 Due to the underlying malignancy and
myelosuppressive antineoplastic therapy.
 in CKD patients;
 15% to 20% in patients with CKD stages 1 -stage
3
 up to 70% in patients with stage 5.
25

26. Epidemiology and
Etiology…
 Anemia is a common diagnosis
 prevalence that varies widely based on age, gender, and
race/ethnicity.
 More common in blacks
26

27. Epidemiology and
Etiology…
 Age-related reductions in bone marrow reserve
can render elderly patients more susceptible
to anemia in addition to multiple factors like
nutritional deficiencies
 Pediatric anemias are often due to a
primary hematologic abnormality.
 The risk of IDA is increased by rapid growth
spurts and dietary deficiency
27

28. Etiology
…
 The causes of anemia can be divided into three
main categories:
1. decreased production
2. increased destruction, and
3. blood loss
28

29. 29

30. Classification of Anemia…
30

31. Pathophysiology of
Anemia
Erythropoiesis: begins with a pluripotent stem
cell in the bone marrow undergoing differentiation
and ends with the appearance of RBCs in
peripheral blood
 Reduction of oxygen-carrying capacity of blood=
stimulated by EPO…> RBCs
 EPO stimulates differentiation of RBC
precursors in the bone marrow to become
reticulocytes
 Reticulocytes become erythrocytes after 1 to 2
31

32. The process of
erythropoiesis
32

33. Destruction of
RBCs
33

34. Pathogenesis of
Anemia
1. Decreased-Production Anemias
 Nutritional Deficiencies
 Both folic acid and vitamin B12 are
required for the formation of DNA.
 Significant decreases in the amount of either
nutrient inhibits DNA synthesis and consequently
RBC production by hindering the process of
erythrocyte maturation.
 The deficiency of both can be caused by
inadequate dietary intake, decreased
absorption, and inadequate utilization.
34

35. Pathogenesis of
Anemia…
 Deficiency of intrinsic factor causes decreased
absorption of vitamin B12(ie, pernicious anemia).
 Folic acid–deficiency anemia can be caused by
hyperutilization due to pregnancy, hemolytic
anemia, myelofibrosis, malignancy, chronic
inflammatory disorders, long-term dialysis, or
growth spurt.
 Drugs can cause anemia
 by reducing absorption of folate (eg, phenytoin) or
 through folate antagonism (eg, methotrexate)
35

36. Pathogenesis of
Anemia…
 Iron deficiency:
 Iron is also essential for RBC production.
 It is required forformation of Hgb.
 Lack of iron leads to a decrease in Hgb
synthesis and decreased RBC production.
 Approximately 1 - 2 mg of iron is absorbed
through the duodenum daily, and the same
amount is lost via
 blood loss, Menstruation
 desquamation of mucosal cells, or
 Utilized by muscles, BM
36

37. Pathogenesis of
Anemia…
 Iron-deficiency anemia (IDA) typically occurs
because of inadequate absorption of iron or
excessive blood loss.
 Common causes include
 inadequate dietary intake,
 inadequate GI absorption,
 increased iron demand (eg, pregnancy),
 blood loss(excessive menstruation, ulcers or
neoplastic lesions, surgery or trauma), and
 chronic diseases(CKD)
 Inadequate absorption occurs in intestinal conditions, like inflammatory
bowel
disease, celiac disease, or bowel resection.
37

38. Daily Iron
requirements
 Requirements for iron
are determined largely
by the rate of
erythrocyte production
- Infants and
children
- Adult females
- Pregnancy
38

39. Pathogenesis of
Anemia…
2.Dysregulation of Iron Homeostasis and
Impaired Marrow Production
 Chronic diseases associated with ACD include
 Infection,
 Autoimmune disease,
 CKD, and
 Cancer
 A major contributing factor for development of ACD
is disturbance of iron homeostasis related to
activation of the immune system.
39

40. Pathogenesis of
Anemia…
3. Anemia of inflammation (AI):
 is a newer term used to describe both anemia of
chronic disease and anemia of critical illness.
 AI is a hypoproliferative anemia that traditionally has
been associated with infectious or inflammatory
processes, tissue injury, and conditions associated
with release of proinflammatory cytokines
40

41. Diseases Causing Anemia of
Inflammation
41

42. Pathogenesis of
Anemia…
 In anemia of critical illness, the mechanism
for RBC replenishment and homeostasis is
altered by, for example, blood loss or
cytokines, which can blunt the erythropoietic
response and inhibit RBC production.
42

43. Clinical
Presentatio
ns
 Signs and symptoms depend on the rate of
development and the age and cardiovascular
status of the patient.
 Acute-onset anemia is characterized by
cardio- respiratory symptoms such as
tachycardia, lightheadedness, and
breathlessness.
 Chronic anemia is characterized by weakness,
fatigue, headache, vertigo, faintness, cold
sensitivity, pallor, and loss of skin tone.
43

44. ClinicalPresentations
…
 Iron-deficiency anemia is characterized
by
 glossal pain
 smooth tongue
 reduced salivary flow
 pica (compulsive eating of nonfood items)
and
 pagophagia (compulsive eating of ice).
 These symptoms are not usually seen until
44

45. ClinicalPresentations
…
 Vitamin B12- and folate-deficiency
anemias are characterized by
 Pallor
 icterus and
 gastric mucosal atrophy
 Vitamin B12 anemia is distinguished by
 neuropsychiatric abnormalities (e.g., numbness,
paresthesias, irritability) which are absent in
patients with folate-deficiency anemia.
45

46. Diagnos
is
 Rapid diagnosis is essential because anemia is
often a sign of underlying pathology.
 Initial evaluation of anemia involves
 a complete blood cell count
 reticulocyte index and
 examination of the stool for occult blood
46

47. Pertinent Laboratory Tests in the
Evaluation of Anemia
47

48. Laboratory
Tests…
48

49. Exerci
se Name: M.K Age:36
years
Sex:
male
Interpretation
:?
Causes:?
49
CBC: Results Normal
ranges
RBC (x1012/L) 4.2 4.2-5.4
Hgb (g/dL) 10.6 11.5-15.5
Hct 34.9% 38%-47%
MCV (fL/cell) 77.0 80-96
MCH(pg/RBC) 37.5 27-33
MCHC (g/dL) 30.4 32-36

50. Treatment Of
Anemia
The goal of anemia therapy are
 To correct the underlying etiology (eg, restore substrates
needed for RBC production), replace body stores to improve
red cell oxygen- carrying capacity
 To alleviate signs and symptoms
 return of normal function and quality of life, and
 prevention or reversal of long-term complications such as
neurologic
complications of vitamin B12 deficiency
50

51. Treatment of
Anemia…
Goal values
a. To normalize Hgb and Hct
- 2g/dl increase in Hgb in 3 wks
- 6% increase in Hct in 3 wks
- Reticulocytosis will usually occurs within 1 wk
* If these indices do not improve within these time
frames, the diagnosis should be re-evaluated
b. Replete iron stores
- Although Hgb and Hct will return to normal within 1-2
months , iron therapy should continue for 3-6
months after Hgb is normalized to replace total body
iron stores
51

52. Treatment Of
Anemia…
General Approach to the Anemic Patient
 The underlying cause of anemia must be determined
and used to guide therapy
52

53. Nonpharmacologic
Therapy
1. Transfusion of RBCs.
 Safety concerns, cost, and the limited availability
of this therapy support efforts to establish the
“optimum” threshold for administering RBC
transfusions.
 Indication for transfusion “trigger for transfusion”
for patients without significant cardiovascular
disease is 7.0 g/dl
53

54. Nonpharmacologic
…
2. Diet
 ingesting a diet that is rich in iron, folic acid, or
vitamin B12 should be encouraged, but is
rarely the sole modality of treatment
54

55. Pharmacologic
Therapy
A) Iron-Deficiency Anemia(IDA)
1. Oral iron therapy: that provides 150 - 200 mg of
elemental iron daily.
 Reticulocytosis should occur in 7 to 10 days, and Hgb values
should rise by about 1.0 g/dl per week.
 with soluble ferrous iron salts, not enteric coated, not slow- or
sustained- release
 Administration on an empty stomach (1 hour before or 2 hours
after a meal) is preferred for maximal absorption.
55

56. Pharmacologic
Therapy…
 Ferrous sulfate=___ % of elemental
iron
 Ferrous gluconate=
 Ferrous fumarate=
56
Oral Iron Products

57. Exerci
se
 If patients develop intolerable GI side effects
(ie, heartburn, nausea, bloating) after taking
iron on an empty stomach, what to do ?
57

58. Pharmacologic
Therapy…
 Clinically significant drug interactions
involving iron products include
fluoroquinolones, tetracyclines, and
mycophenolate mofetil.
 The absorption of iron is influenced by gastric
acidity.
 drugs that decrease gastric acidity (antacids,
PPIs, and H2RAs) may impair the absorption of
iron.
58

59. Pharmacologic
Therapy…
2. Parenteral iron therapy
 indications
 Intolerant to oral formulations, or
 Noncompliant to oral therapy, or
 Failure to respond to oral iron because of
malabsorption syndromes
 Parenteral administration, however, does not hasten the
onset of hematologic response.
59

60. Pharmacologic
Therapy…
60

61. Pharmacologic
Therapy…
61 Equations for Calculating Doses of Parenteral
Iron

62. Pharmacologic
Therapy…
 adverse effects of parenteral iron therapy
 incidence of life-threatening adverse effects,
typically
anaphylactic-like reactions
 The newer products,sodium ferric gluconate and
iron sucrose, appear to be better tolerated than
iron dextran.
 Other adverse effects include arthralgias,
arrhythmias, hypotension, flushing, and pruritus
62

63. Pharmacologic
Therapy…
63
B) Vitamin B12 deficiency Anemia
 Oral vitamin B12 supplementation appears to be as effective
as
parenteral, even in patients with pernicious anemia,
 because the alternate vitamin B12 absorption
pathway is independent of intrinsic factor
 Initiate oral cobalamin at 1- 2 mg daily for 1-2 weeks,
followed by 1 mg daily.

64. Pharmacologic
Therapy…
Vitamin B12 deficiency Anemia…
 Parenteral therapy acts more rapidly than oral therapy
and is recommended if neurologic symptoms are
present.
 cyanocobalamin 1000mcg IM daily for 1 week,
then weekly for 1 month, and then monthly.
 Initiate daily oral administration after symptoms
resolve
 Adverse events are rare with vitamin B12 therapy
64

65. Pharmacologic
Therapy…
C) Folate-deficiency Anemia
 Oral folate, 1 mg daily for 4 months, is usually sufficient for
treatment of folic acid–deficiency anemia, unless the etiology
cannot be corrected.
 If malabsorption is present, a dose of 1-5 mg daily may be
necessary.
65

66. Pharmacologic
Therapy…
D) Anemia Of Inflammation (AI)
 Treatment of AI is less specific than that of other
anemias and should focus on correcting reversible
causes.
 Reserve iron therapy for an established IDA; iron
is not effective when inflammation is present.
 RBC transfusions are effective but should be
limited to episodes of inadequate oxygen transport
and Hgb of 8 – 10 g/dl.
66

67. Pharmacologic
Therapy…
 Erythropoiesis-stimulating agents (ESAs) can
be considered, but response can be impaired in
patients with AI (off-label use).
 The initial dosage for
 Epoetin alfa is 50 -100 units/kg three times weekly
and
 Darbepoetin alfa 0.45 mcg/kg once weekly
 ESA use may result in iron deficiency. Many
practitioners routinely supplement ESA therapy
67

68. Early treatment of anemia in patients with CKD has been associated with
slower disease progression and a lower risk of death once patients
receive dialysis

69. Pharmacologic
Therapy…
 In patients with anemia of critical illness,
parenteral iron is often used but is
associated with a theoretical risk of
infection.
 Routine use of ESAs or RBC
transfusions is not supported by clinical
studies.
69

70. Pharmacologic
Therapy…
E)Anemia In Pediatric Populations
 Anemia of prematurity is usually treated with RBC
transfusions.
 ESA use is controversial because it has not been shown
to clearly reduce transfusion requirements.
 the daily dose of elemental iron, administered as iron
sulfate, is 3 mg/kg for infants and 6 mg/kg for older
children for 4 weeks.
 Continue for 2 additional months in responders to replace
70

71. Pharmacologic
Therapy….
E)Anemia In Pediatric
Populations…
 The dose and schedule of vitamin B12
should be titrated according to the clinical
and laboratory response.
 The daily dose of folate is 1 – 3 mg
 Anemia of prematurity is usually treated with
RBC transfusions.
 The use of epoetin alfa is controversial.
71

72. Evaluation Of Therapeutic
Outcomes
 IDA:
 Positive response to oral iron therapy
characterized by modest reticulocytosis in a
few days with an increase in Hgb seen at 2
weeks.
 Reevaluate the patient if reticulocytosis does not
occur.
 Hgb should return to normal after 2 months;
continue iron therapy until iron stores are
72

73. Evaluation Of Therapeutic
Outcomes
 Megaloblastic anemia:
 Signs and symptoms usually improve within a few
days
after starting vitamin B12 or folate therapy.
 Neurologic symptoms can take longer to improve or
can be irreversible, but should not progress during
therapy.
 Reticulocytosis should occur within 3 – 5 days.
 Hgb begins to rise a week after starting vitamin
B12 therapy and should normalize in 1 – 2
months.
73

74. Evaluation Of Therapeutic
Outcomes
 ESAs:
 Reticulocytosis should occur within a few days.
 Monitor iron, TIBC, transferrin saturation, and
ferritin levels at baseline and periodically
during therapy.
 The optimal form and schedule of iron
supplementation are unknown.
 Discontinue ESAs if a clinical response does
not occur after 8 weeks.
 Pediatrics:
 Monitor Hgb, Hct, and RBC indices 6 to 8
weeks after initiation of iron therapy.
 Monitor Hgb or Hct weekly in premature infants.
74