Pharmacology of Drugs for Anemia

7/30/2019 Pharmacology of Drugs for Anemia

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PHARMACOLOGY OF DRUGS FOR

ANEMIA

Dr.Datten Bangun MSc.SpFK

Dept.Farmakologi & TherapetikFak.Kedokteran UHN

M E D A N


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ANEMIA

Anemia can be defined as a reduction in the

hemoglobin,hematocrit or red cell number.

In physiologic terms an anemia is any disorder

in which the patient suffers from tissue

hypoxia due to decreased oxygen carryingcapacity of the blood


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Hematinics

These are drugs used to treat anemia

IronVitamin B12, Cyanocobalamin

Folic acid

Erythropoietin


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TYPES OF ANEMIA

Various classifications:Examples:

Iron deficiency anemia ----

microcytic , hypochromicMegaloblastic anemia ----

macrocytic , normochromic

due to Vit. B12 or Folic Acid deficiency

Anemia due to decreased Erythropoietin

as in chronic renal failure


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Causes of Anemia

1. Diminished production and or

replacement of red blood cells.

2. Excessive breakdown and loss of red

blood cells.

Hemodilution while not a cause of anemia, it

does cause an anemia-like effect.


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1. Diminished Production/Replacement of

RBCs Anemia's

Microcytic anemia deficiency of Fe RBCs appear pale and smaller, and we see more reticulocytes

in circulation.

Can be caused by the chronic use of aspirin, which irritatesthe stomach GI blood loss.

Normocytic anemia deficiency of Erythropoietin Caused by compromised renal function.

Macrocytic Anemia- deficiency of folic acid and B12 Diminished cell division and release of larger cells in

circulation.


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2. Breakdown of RBCs Anemia

Bleeding: can be due to an ulcer or in females bloodloss due to their menstrual cycle

Use of drugs that irritate the GI tract (aspirin)

Hemolysis (Hemolytic Anemia) can be caused by:

Autoimmune disease

Mechanical (heart valves, microvascular disease)

Toxins (e.g., snake venom)


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Anti anaemic Drugs

Haematopoiesis: it is the production of

erythrocytes, platelets, and leukocytes from

undifferentiated stem cells.

The haematopoietic machinary reside in the

bone marrow in adults.

It requires a constant supply of essential

nutrients iron, vit B12, folic acid and

presence of hematopoietic growth factors


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ANTI-ANEMIC DRUGS

Drugs effective in iron deficiency and otherhypochromic anemias:

Iron

Pyridoxine , Riboflavin , CopperDrugs effective in megaloblastic anemia:

Vitamin B12

Folic Acid

Hematopoietic growth factors:

Erythropoietin


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IRON FACTS

All body cells need iron. It is crucial for oxygen

transport, energy production, and cellular growth

and proliferation.

The human body contains an average of 3.5 g of

iron (males 4 g, females 3 g).

The typical daily normal diet contains 10

20 mg ofiron.

Only about 10% of dietary iron is absorbed (12 mg/day).


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Anti anaemic Drugs

Iron: Total quantity of iron in the body is 4-5G,

65-70% in the form of Hb in RBC, 4% in

myoglobin, 1% in various heme compound,

15-30% stored in the form of ferritin and

hemosiderin in RE system, liver, spleen,

intestinal mucosa and bone marrow


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IRON

Preparations:Oral:

Ferrous sulphate

Ferrous gluconateFerrous fumarate , etc.

Parenteral:

Iron dextran ---- i.m or i.v

Iron Sorbitol ----- i.m only.


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Pharmacokinetics

Absorption ---- depends on

requirements

iron stores

Ferrous (Fe++) / ferric (Fe+++) form

pH

Vitamin C Chelators or complexing agents

Malabsorption syndrome


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Iron transport

Most absorbed iron is transported in thebloodstream bound to the glycoprotein

transferrin.

Transferrin is a carrier protein that plays a

role in regulating the transport of iron from

the site of absorption to virtually all tissues.

Transferrin binds only two iron atoms.

Normally, 2045% of transferrin binding sites

are filled (measured as percent transferrin

saturation [TS]).


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Iron transport


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Ferritin molecules storethousands of iron atoms

within their mineral core.

When excess dietary iron is

absorbed, the body

responds by producing

more ferritin to facilitate

iron storage.


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Importance of Iron

Iron forms the nucleus of the iron-porphyrin heme ring,

This with globin chains forms hemoglobin.

Function of Haemoglobin:

Reversibly binds oxygen and provides the critical

Mechanism for oxygen delivery from the lungs to other

tissues.

In the absence of adequate iron, small erythrocytes

with insufficient hemoglobin are formed, giving rise to

Microcytic hypochromic anemia


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Acute Oral toxicity (overdose ; poisoning)

Necrotizing gastroenteritis with ----

vomiting, abdominal pain, bloody diarrhea

Shock , lethargy & dyspnea

Severe metabolic acidosis

Coma

Death

A O l i i ( d i i )


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Acute Oral toxicity (overdose ; poisoning):

(Contd.)

Treatment:Whole bowel irrigation

Desferrioxamine (Deferoxamine)

orally --- for Unabsorbed iron Parenteral ( i.m. , i.v. ) --- for iron absorbed

Desferrioxamine + ferric iron

Ferrioxamine --- excreted in urine and bile.


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Chronic iron toxicity (iron overload): (Contd.)

Hemosiderosis:

a focal or general increase in tissue iron stores

without associated tissue damage

Hemochromatosis:

associated with tissue damage

h i i i i (i l d)


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Chronic iron toxicity (iron overload)

(Contd.)

Treatment:

IntermittentVenesection(Phlebotomy)----

when there is no anemia

Chelation (Desferrioxamine) ----

for transfusional overload


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Adverse effects of Parenteral iron therapy

Local pain & tissue staining

(browndiscoloration of tissue overlying the injection

site).

Headache , light-headedness , fever , arthralgias,

nausea , vomiting , back pain , flushing ,

urticaria, bronchospasm , & ,

Rarely anaphylaxis & death


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VITAMIN B12

Chemistry

Porphyrin-like ring with a central cobalt atom

& nucleotide.

Cobalamins = various organic groups covalentlybound to cobalt atom

Cyanocobalamine hydroxycobalamin & other

cobalamins (found in food sources) are convertedto active forms Deoxyadenosylcobalamin

&methylcobalamin


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Active forms of vitamin B12 in human:

Deoxyadenosylcobalamin

Methylcobalamin

Vitamin B12 available for therapeutic uses:

Cyanocobalamin

Hydroxycobalamin

Hydroxycobalamin --- is preferred becauseit is highly protein-bound & therefore

remains longer in the circulation.

Ph ki ti


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Pharmacokinetics

Absorption:

Intrinsic factor (IF) --- a glycoprotein ,secreted by parietal cells of gastric mucosa

IF-Vit.B12 Complex --- absorbed by

active transport in the distal ileum

Transported in plasma bound to the

glycoprotein transcobalamin II &

is taken up by tissues where required &

stored in hepatocytes

Pharmacokinetics (Contd )


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Pharmacokinetics (Contd.)

Route of administration

Mostly ------ Parenteral ---- i.m.

Oral

Aerosol

Pharmacokinetics (Contd )


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Pharmacokinetics (Contd.)

Elimination:

not significantly metabolized

pass into bile

Enterohepatic circulation

Excreted via kidney

Features of Vitamin B12 deficiency


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Features of Vitamin B12 deficiency

Impairment of DNA synthesis

affects all cells but most apparently RBCs.

Megaloblastic Anemia

GI symptoms

neurologic abnormalities


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Features Vitamin B12 deficiency (Contd.)

Neurological abnormalities :

Degeneration of brain and spinal cord (Subacute

combined degeneration ) and peripheral nerves.

Symptoms may be psychiatric & physical.Paresthesia & weakness in peripheral nerves

spasticity, ataxia, & other CNS dysfunction


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Uses

Pernicious (addisonian) anemia

After partial or total gastrectomy

Malabsorption syndromes

Insufficient dietary intake

Hydroxycobalamin (Not cyanocobalamin)

Tobacco Amblyopia

Cyanide toxicity

d ff


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Adverse effects

Allergic hypersensitivity reactionsAntibodies to hydroxycobalamin-transcobalamin

II complex

Arrhythmias secondary to hypokalemia


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FOLIC ACID (PTEROYLGLUTAMIC ACID; VITAMIN B9)

Is inactive Active form is ---- tetrahydrofolic acid


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Pharmacokinetics

Route of administration ----- usually oral

In diet ---- Polyglutamate form

For absorption ---- must be converted to ---Mono-glutamyl form

Absorbed mostly --- in proximal jejunum


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Functions

Is required for synthesis of Amino acids ,

purines, pyrimidines, & DNA ; &

therefore in the cell division


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Features of folic acid deficiency

Mitotically active tissues such as

erythroid tissues are markedly affected.

Anemia

Congenital malformations ---

neural tube defects ( e.g., spina bifida)

Vascular disease


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Vitamin C

Vitamin C deficiency can cause megaloblastic anemia


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Uses

Prevention & treatment of folic acid deficiency

Dietary insufficiency (e.g. in elderly)

Pregnancy & lactation

to prevent --- Congenital malformations ---neural tube defects ( e.g., spina bifida)

High red cell turn over --- e.g. in

hemolytic anemias ---

Premature infants

Malabsorption syndromes

Uses (contd )


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Uses (contd.)

Drugs

Antiepileptics ---- enzyme inducers

Phenytoin

Primidone

Phenobarbitone

Antimalarials

pyrimethamine

Methotrexate

FOLINIC ACID (not folic acid)


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Uses (contd.)

Myelofibrosis

Exfoliative dermatitis

Rheumatoid arthritis

Malignant disease , e.g., lymphoma Chronic hemodialysis


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Adverse effects

Generally well tolerated

Rarely ---

G.I. Disturbances

hypersensitivity reactions Status epilepticus may be precipitated


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ERYTHROPOIETIN (EPOTEIN)

a glycoprotein hormone

produced :

90% --- by peritubular cells in kidney

remainder --- by liver and other tissues is essential for normal reticulocyte production

synthesis is stimulated by hypoxia

synthesized for clinical use ---- by ---

recombinant DNA technology


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Pharmacokinetics

Route of administration --- S.C. or I.V.

Plasma t1/2 ---- 4 - 13 hrs in patients with

chronic renal failure.

Not cleared by dialysis


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Mechanism of action

increases rate of stem cell differentiation

increases rate ofmitosis in red cell precursors,

blast-forming units, colony forming cells.

increases release ofreticulocyte from marrowincreases Hb synthesis

its action requires adequate stores ofiron

Uses


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Uses

Anemia associated with chronic renal failure

premature infantsAnemia during chemotherapy ofcancer

Anemia ofAIDS (which is exacerbated by

zidovudine treatment)

to increase the yield ofautologous blood before

donation

Anemia of chronic inflammatory conditions

such as rheumatoid arthritis

MISUSED --- by sports people


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Adverse effects

Usually due to excessive increase in hematocrit

increase blood pressure

thrombosis

seizures

headache

hypertensive crises with encephalopathy-like

symptoms

clotting in dialyser


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Adverse effects

Transient influenza-like symptoms ------

chills & myalgias

iron deficiency

transient increases in platelet count

hyperkalemia

skin rashes

pure red cell aplasia --- discontinue the drug

antibodies to epoetins

/ d


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Precautions / contraindications

hypertension should be well controlled

seizures

thrombocytosis

ischemic vascular disease

iron , folic acid , vit. B12 supplements may be

needed

heparin during dialysis

i


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Monitor

hematocrit

blood pressure

platelet count

serum potassium


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Pharmacology of Drugs for Anemia

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