For 2nd year Medical Students

2022 Edition
 Drug Therapy of Anemia

Endogenous: intrinsic factor, erythropoietin & CSF

Normal erythropoiesis requires
Exogenous: iron, folic acid & vitamin B12

Drug therapy of iron deficiency Anemia

(Microcytic Hypochromic anemia)
IRON
Absorption: Ferrous>>>ferric from upper intestine ( Acidity → ↑solubility → ↑ absorption)

Factors affecting IRON absorption

Reticuloendothelial system
Ferrous

Ferrous
Ferric →
1. Antacids 1. Ascorbic acid
2. Tannic acid 2. Hydrochloric acid

 Ferrou
Ferritin
 Absorption

Duodenum
3. Desferrioxamine 3. ↑ Iron demand:

Ferrous
Transferrin

Absorption
4. Tetracyclines a. Anemia
5. Phosphates, Oxalate b. Infancy
6. Gastric resection c. Adolescence
7. Mal absorption syndrome
BLOOD

‫ ر‬available for absorption.

• Elemental iron: is the total amount of iron in the supplement ‫التكيبه الدوائيه‬
• 50-100 mg of iron (Fe) can be incorporated into hemoglobin daily.
• 25% of oral Fe given can be absorbed.
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Indications of iron therapy:
o Prophylactic: 30-60 mg
Dose elemental iron daily
o Treatment: 200-400 mg
o Duration: Continue till HB is normal. Then extra 2-3 months to fill iron stores
Iron-Deficiency Anemia due to:
• ↑ Demand: e.g. lactation, premature infants
• ↓ Absorption: e.g. gastrectomy, malabsorption syndrome
• Chronic blood loss: e.g. GIT bleeding, heavy menstrual bleeding, during hemodialysis ‫الغسيل الكلوي‬

Oral Iron Therapy (Route of choice)

Parentral iron Therapy (IV, IM , TDI)
Effective + cheap
1. Ferrous salts: Sulfate, Gluconate, Fumarate 1. Iron dextran ( hypersensitivity is common)
Adverse effects Preparations

2. New oral preparations (100% elemental iron)
• Polysaccharide-iron complex 150 mg
• Heme iron polypeptide: More expensive
• Carbonyl iron 150 mg
1. GIT disturbances: Nausea, epigastric pain &
constipation (given after meals - start with small
dose then gradually increase).
2. Black stool (mask diagnosis of GI bleeding).
3. Black staining of teeth (iron sulfide)
2. Iron Sodium gluconate complex
3. New Parentral preparations:
• Ferric carboxy maltose
• Ferumoxytol
1. IM: local pain – Staining at site of injection
2. IV: headache, fever, urticaria, lymphadenopathy & anaphylactic
shock (with iron dextran, start with a small test dose).

Calculation of Parentral Iron Indications of Parenteral iron therapy

(causes of failure of oral therapy)
Total iron deficit (mg) =
1. Non compliance to oral iron (due to GIT upset)
Body weight [kg] x (Target Hb – Actual Hb) [g/l] x 2.4
2. Mal absorption Syndrome
+ 500 [mg] (for iron stores) 3. Severe anemia e.g. Malignancy 2
Advantages of Total dose infusion (TDI)
1) Avoids non-compliance of the patient.
2) Avoids unpleasant effects of intramuscular injection (IMI) ‫الحقن العضلي‬
3) Allows delivery of the entire dose of iron necessary to correct iron deficiency at one time.
IRON TOXICITY
Acute Iron Toxicity (more in children) Chronic Iron Toxicity
Management (urgent and immediate) It occurs in:
1. Raw egg or milk  bind & precipitate iron as 1. Patients receiving repeated blood transfusions.
albuminate & caseinate as first aid 2. Patients with hemochromatosis; an inherited disorder
2. Desferrioxamine: characterized by  iron absorption  hemosiderosis
• 1-2 g IM or IV  chelates iron → ↑ renal excretion Management
• 5 g in 100 ml water swallowed or by stomach tube to 1. Venesection (if no anemia)  repeated weekly.
prevent further absorption (after gastric lavage with 2. Iron chelators:
bicarbonate solution). • Desferrioxamine: IM or SC.
3. IV infusion of saline, dextrose or bicarbonate to • Deferasirox: new oral iron chelator
correct water & electrolyte disturbances. 3. Large intake of tea  tannins in tea bind with iron → ↓ iron Abs.

Anemia of chronic disease

(Functional iron deficiency anemia).
Cause
• Infection and inflammation→ release of cytokines→ ↑ release
of hepcidin from the liver.
• Excess hepcidin prevent absorption & release of iron from its
storage sites (sequestrated anemia).
• Normal or high serum ferritin unlike iron deficiency anemia
Treatment: treat infection & inflammation. NOT TO GIVE IRON
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 Drug Therapy Of Megaloblastic Anemia
(Vitamin B12 and Folic Acid Deficiency)

Preparations of Vitamin B12

A. Cyanocobalamin
B. Hydroxocobalamin (preparation of choice):
1. More slowly absorbed.
2. More bound to plasma proteins.
3. Slowly excreted.
→ More sustained rise in serum cobalamin.

Therapeutic uses of Vitamin B12 Therapeutic uses of folic Acid

A. Megaloblatic Anemia 1. Nutritional megaloblastic anemia.
1. Pernicious anemia: vitamin B12 IM for life 2. Malabsorption syndrome.
• Initial: 1,000 g/day for 1-2 week to fill the stores. 3. chronic alcoholism ‫مدمني الخمره‬
• Then 1,000 g/week till normal blood count. 4. Pregnancy
• Maintenance therapy: 1,000 g/month for life. 5. Patients with liver disease & with hemolytic anemia.
2. Megaloblastic anemia due to diphylobothriasis. 6. Patients With long term therapy by anticonvulsant drugs.
Treatment: vitamin B12 and praziquantel. 7. Patients on dialysis (as folic acid is removed by dialysis).
3. Drug-induced megaloblastic anemia (CAN)
Colchicine, Antiepileptics & Neomycin→↓ absorption of DHF Reductase
Folic (FH2) Folinic (FH4): Active
vitamin B12.
Ө
B. Neurological Conditions PTM
Treated by Folinic acid Megaloblastic
Peripheral neuritis in diabetes mellites & retrobulbar
Anemia
neuritis in heavy smokers. P T M = Pyrimethamine, Trimethoprim, Methotrexate
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 Drug-induced blood disorders
A. Hemolytic Anemia (destruction of RBCs)
1. In G6PD-deficient subjects
1. Antimalarial drugs. 2. Aspirin.
3. Sulfonamides. 4. Quinine and quinidine.
2. As a Hypersensitivity Reaction : 1. Penicillin 2. Sulfonamides.
3. Autoimmune Hemolytic Anemia: α methyldopa. ‫دواء يستخدم يف عالج الضغط المرتفع‬
B. Thrombocytopenia
• Heparin - Indomethacin - Rifampin- quinine - quinidine.
• Treatment: stop the drug - platelet transfusion - corticosteroids.
C. Bone Marrow Depression (aplastic Anemia or agranulocytosis):
Cytotoxic drugs - Chloramphenicol - Chlorpromazine - Thiouracil.
Treatment of agranulocytosis or aplastic anemia
1. Eliminate the underlying causes.
2. Supportive therapy: Prevent & treat infection, hemorrhage & Anemia. Blood transfusion to replace lacking components.
3. Corticosteroids: reduce bleeding due to thrombocytopenia.
5. Bone marrow transplantation (treatment of choice) followed by immunosuppression with cyclosporin to prevent graft
rejection.
6. IV anti-thrombocyte immunoglobulin 7. Anabolic steroids
8. Erythropoietin.

Erythropoietin (IV or SC)

1. Regulator of erythropoiesis (acts on stem cells). Complications:
2. Used in anemia of chronic renal failure & severe anemia of cancer & AIDS. hypertension & thrombosis
3. It ↓the need for blood transfusion → ↓ risk of chronic iron toxicity

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 Drug therapy of Malaria
Blood schizonticides
1ry tissue phase • 4 Aminoquinolines: Chloroquine, Quinine & mefloquine
Pre erythrocytic cycle
• Antifolates: Pyrimethamine, Proguanil, Sulfadoxine
Schizonts • Artemisinin
• Atovaquone Prophylaxis & treatment
• Suppressive prophylaxis
• Radical cure in falciparum
Ѳ
• Clinical cure in ovale & vivax

Primaquine
Ѳ (8 aminoquinoline) Erythrocytic cycle

2ry tissue phase • Radical cure in ovale &

(Hypnozoites) vivax (prevent relapse)
• Terminal prophylaxis

Hemolysis → clinical attack

Gametocytes
Ѳ
Sporozoites Oocyte
Ѳ Primaquine
Antifolates Chloroquine
(Sporontocidal) (Gametocidal)
Eradication of disease ↓ Transmission of disease 6
 Drug Mechanism Indications Adverse effects
Blood schizonticide & 1. Prophylaxis & treatment of CERAG
gametocide chloroquine-sensitive malaria→ 1. CVS: quinidine like action (Hypotension,
Chloroquine

• Ө parasitic HB digestion→↓ Radical cure in falciparum & Arrhythmia)

nutrient amino acid supply to clinical cure in ovale & vivax. 2. CNS: headache, Dizziness, tinnitus
the parasites 2. Amoebic liver abscess. 3. Eye: Corneal opacity, Retinopathy
• Ө parasite heme polymerase 3. Rheumatoid arthritis 4. Rash & Resistance
→ accumulation of toxic heme 5. Anemia in G6PD deficiency
6. GIT upset: NVD
Blood schizonticide Treatment of chloroquine 1. CVS: Quinidine like action→ ---
resistant falciparum but not 2. CNS:

Treatment of Chloroquine resistant falciparum

4 aminoquinolines

in prophylaxis (too toxic). 3. Eye→ blurred vision up to blindness.

Quinine

4. Cinchonism: tinnitus, headache, blurring of

vision (CNS + eye)
5. Hemolysis - Black water fever
6. Oxytocic on uterus→ abortion
7. NM blocker → paralysis in skeletal muscles.
Same as quinine but Treatment & prophylaxis of 1. CVS: conduction defect
Mefloquine

• More effective chloroquine resistant 2. CNS: Headache up to convulsion

• longer acting falciparum 3. GIT: NVD
• less toxic.
Amodiaquine

1. Aplastic anemia
2. Agranulocytosis

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 Treatment of multidrug 1. GIT upset

Artemisinin
blood schizonticide
In presence of Hem → free resistance P. falciparum. 2. CVS: ↑ QT interval.
radicals → parasite death Halofantrine: as Artemisinin in uses
& adverse effects
Treatment & prophylaxis of 1. GIT upset.
Atovaquone

chloroquine resistant 2. CVS: Conduction defect

Blood & tissue Schizonticide falciparum 3. CNS: Headache, dizziness,…
Ѳ mitochondria →↓ ATP 4. Fever, rash.
5. Abnormal liver function test

Blood schizonticide & 1. Chloroquine resistant 1. Hypersensitivity reactions.

Sulfadoxine, Proguanil,

- Pyimethamine -

sporontocidal. falciparum: Pyrimethamine + 2. Megaloblastic anemia

Antifolate drugs

Pyrimethamine

Ѳ folate pathway at 2 sulfadoxine (fansidar). 3. Hemolytic anemia (in G6PDD).

sequential steps→ Ѳ DNA & 2. Toxoplasmosis: 4. GIT upset
RNA synthesis Pyrimethamine + sulfadiazine

1. Radical cure of relapsing malaria 1. Methemoglobinemia.

(after a blood schizonticide). 2. Teratogenic.
2. Terminal prophylaxis of 3. Hemolytic anemia (in G6PDD)
Primaquine

relapsing malaria 4. GIT

Tissue schizonticide &
(given after leaving the endemic
gametocide
area)
3. Prevents transmission of disease
(gametocide). May be in
falciparum

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 Mechanism of action of Antimalarial Drugs

HB
Chloroquine
HEME Globin Ө parasitic HB digestion→↓
↓ nutrient amino acids supply to the
HEME polymerase a.a parasites
Non toxic Ө parasite heme polymerase →
accumulation of toxic heme Artemisinin
In presence of Hem →
formation of free radicals →
Atovaquone parasite death
ATP Ѳ microtubules → ↓ ATP

Sulfonamides Pyrimethamine & proguanil

Folate synthetase
PABA Folic Acid Dihydrofolate Folinic acid (FH4)
Reductase

Fansidar: Sulfadoxine + pyrimethamine

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 Concepts of treatment of Leukemia
Modalities (methods) of treatment of cancer
1. Surgery 2. Chemotherapy 3. Hormonal 4. Targeted 5. Radiation 6. Bone Marrow transplantation

1. Antimetabolites ..mab
2. Alkylating agents GF
3. Antimitotic agents
• Combination TK
↓ resistance to chemotherapy
--nib
↓ adverse effects of chemotherapy
• More selective on cancer cell → less adverse effects
• Taken in Cycles
• Affect normal & cancer cells

Acute leukemia
Phases of treatment of acute leukemia
Phase Aim
1. Remission induction therapy Kill leukemic cells in blood & bone marrow
2. Remission continuation therapy Kill any remaining cells (inactive) that may cause relapse
(Post remission )
CNS prophylaxis therapy: Is usually given during each phase. To ↓recurrence. Radiation or chemotherapy

Standard treatment of acute leukemia

❶ Chemotherapy ❷ Radiation

• To stop or to kill cancer cells • To stop or to kill cancer cells

• Given systemically or intrathecal • To prevent or treat CNS affection
(CNS) • Not used in children younger than 4 years 10
❸ Chemotherapy with stem cell transplant ❹ targeted therapy

• Autologous ‫ من المريض نفسه‬or homologous‫من متبرع‬ • Attack cancer cells without affecting normal cells.
• Give small chemotherapy → remove stem cells → • Monoclonal antibodies. ---mab
give large dose of chemotherapy • Tyrosine kinase inhibitors …. nib
• Homologous: immunosuppressive should be added

❺ Supportive care

To control complications of the therapy & Cancer

A. For neutropenia
• Empiric antibiotics
• CSF (G-CSF or GM-CSF) . Given in ALL but cautiously in AML
Advantages:
- ↓ duration of neutropenia
- ↓ Infection rate & mortality
- Given courses of chemotherapy on time

B. For thrombocytopenia
C. For Anemia
• Platelet transfusion
• Stop menstruation (OCP) • Blood transfusion
• Gastric ulcer prophylaxis • Erythropoietin (used cautiously in AML)
• Management of bleeding attacks

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 Chronic leukemia
Chronic Myeloid leukemia
Chronic Phase Accelerated Phase
Aim: Aim (Goal):
• Maintain chronic phase & ↓ progression to accelerated or blast phases • Retain to second chronic phase
Treatment: Treatment:
• TK inhibitors (Imatinib) • TK inhibitors (Imatinib)
• Chemotherapy • Chemotherapy (high doses)
• Chemotherapy with donor stem cell transplant • Stem cell transplant
• Splenectomy • Splenectomy
• Transfusion of deficient blood elements

Blastic Phase (crisis)

Aim: Chronic lymphocytic leukemia
• Retain to chronic phase
• Waiting when there are few or no signs
Treatment:
• Monoclonal antibody or tyrosine kinase inhibitor
• TK inhibitors (Imatinib)
• Chemotherapy
• Chemotherapy
• Radiation on area such as spleen or lymph nodes
• Stem cell transplant

Tumor Lysis Syndrome ?

• Hyperuricemia: Add Allopurinol
• Electrolyte disturbance: ↑ Phosphates , ↓ calcium,….

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