DRUGS ACTING ON BLOOD BY

Dr Ali Professor of pharmacology&Therapeutics

DRUGS USED IN ttt OF ANEMIAS

Def.

anemia is the reduction below normal range of RBCs number or Hb conc. r both.

: Classification Of anemias
I. deficiency anemia !due to " of factors essential for normal erythropoiesis#. 1- i !n deficiency anemia !hypochromic microcytic anemia# iron is re$uired for Hb prod% so absence of &e ' small red cells ( insufficient Hb. Ca"#e# ' ) inade$uate inta*e FGH2 E +, -./ 012 +34 567 89: +;-<=.<42 >?@A12 B>?CD ePcessiQe losses* IJ?3K42 L: M3, NO2 ! YZT +D# ..... +DR<42 >?G,12 S +DR<42 T2 U?V42 W;RX42 B>?CD ePcessiQe demands e.g. low birth* .weight% Pregnancy% lactation

hypochromic microcytic

[\ folic acid deficiency anemia !macrocytic anemia# e.g. in pregnancy ( some antiepileptic drugs !] malabsorption# in infants fed ( goat^s mil*% Qitamin C " in malabsorption syndrome.

II. a$%a#tic anemia !due to aplasia or hypoplasia of B._#. ) may be `ry or [ry due toB \ ePposure to P\ray or radioactiQe sub. \ drugs e.g. sulpha% chloramphenicol. \ chemicals% benaene b.. III. &aem!%ytic anemia# !due to ePcessiQe blood destruction# \ thalasemia. \ YEPD " !faQism# \ cong. Anomalies of RBCs !spherocytosis# \ sic*le cell anemia.

D "'# effecti(e in i !n deficiency anemia

pharmacokinetics
normally c\`d e. of &e in diet is absorbed !but in &e " anemia `d\[de (.absorbed *

*factors affecting absorb:

+++ .Qalency of &eB &eff better than &e( 1 [# acidity of stomach ++reduction of &efff ' &e .retard formation of insoluble ComplePes of &e ( food constituents antacids >?<.=,2 oD T2 :achlorhydria g4?h L: 2-i M.j -;-V42 k?l=D2 m4n4 :dietary factors( 3 reducing agents e.g. ascorbate% succinate %a.a containing\ pH gpB &efff ++ '& phosphate and phytate ' unabsorbable CompleP

) Site !f a*#! $ti!n +

any part of YZT but it^s greatest in duodenum and proPimal qequnum

) I !n di#t i*"ti!n# in n! ma% ad"%t+

rde ' Hb in RBCs `d\[de ' stored &e as ferritin and hemosiderin `de ' myoglobin in muscles less than `e ' cytochromes% enaymes.% transferrin !transport &e#

* iron absorption is regulated by:

\ leQel of serum &e \ saturation of transferrin !s` globulin# R}p vw?x<42 L: y?z<42 {/ LG=X; 5=h ?Dw|342 L: &e t<V; un42 \ leQel of &e stores.

* iron excretion:
there is no mechanism for iron ePcretion. nly small amounts are lost with epithelial cells which are des$uamated from s*in and YZT !stool# f traces are lost in urine% bile% sweat.

* iron requirements:
\ normal daily re$uirements for adult man c\`d mg. \ re$uirements Qary with growth% pregnancy% menstruation.

*iron preparations:
The only indication for the use of &e preparation is treatment or preQention of iron deficiency anemia

: I,. ! a% $ e$a ati!n)

\ should be giQen after meals to aQoid YZT irritation. \ for ~\E months to replenish &e stores. }PamplesB &errous sulphate ~dd mg t.d.s ![de elemental# &errous gluconate Edd mg t.d.s !`[e elemental# &errous fumarate [dd mg t.d.s !~de elemental# ?D; -;-h D `dd\cd 542 gi?h L: ;F<42 Bg7F42 FK: e[c g3 k?l=D12 uFlX7 -;-h D dd S [dd 542 gi?h L: ;F<42 \

ral iron correct deficiency rapidly and completely as parenteral &e in most cases if absorption is normal

}pigastric discomfort% colic*y pain% diarrhea or constipation )dose \ related. S time \ related ( ?34?

Abdominal pain% Qomiting% hematemesis% bloody diarrhea% . acidosis% cardioQascular collapse% coma% death J?l42 >?@A12 L: -V; ?34? U?V42 N<=42 2nO .ho accidentally ingested iron tab , tab. nly can be lethal in children 10 .po ' urgent ttt is necessary

Treatment of acute iron poisoning:

`\ gastric aspiration followed by. [\ gastric laQage ( `e aHC ~ or phosphate !to form insoluble &e salts#. ~\ &e chelating agents e.g. desferroPamine !desferal# byB \ stomach tube !to bind gastric &e#. \ Z._ or Z. drip !to bind absorbed &e#. \ symptomatic treatment for !dehydration.% conQulsions b. #.

-II,. $a ente a% i !n $ e$a ati!n+

indicati!n#B \ in emergencies. \ when oral is impractical !e.g. malabsorption or post gastrectomy#.

* preparations: * Fe dextran (imferon) = complex of Fe(OH)3 + dextran

Z._ or Z. cd mgml !elemental# 5z. Ni [\` 542 gi?h L: ;F<42B \ [ ml eQery few days Z_. OR \ single Z infusion `\[ hours. * Fe sorbitol- citric acid complex 50 mg ml !"# |.42 -/ t3 g,?h J?3=2 gX9V N, `[ ?z72 5X 1T.

* parenteral iron toxicity:

- localB \ pain \ discoloration at site of inqection. - s$stemic% . &eQer % headache% malaise% arthralgia. gD?7 . tacchycardia% hypotension% bronchospasm. M6942 . encephalopathy f conQulsions. ?l712

C& !nic i !n T!.icity !haemochromatosis and haemosiderosis# \ when ePcess &e is deposited in heart% liQer% pancreas% other organs ' organ failure f death. \ occur in patientsB \ with congenital disorder characterised by ePcessiQe &e Absorption. \ who receiQe many blood transfusions.

/e nici!"# anemia and !t&e me'a%!*%a#tic anemia#

5X.D ?D \ pernicious anemia I failure of the stomach to secrete intrinsic factor ' B`[ " anemia. 5X.D ?D \ megaloblastic anemia I anemia with macrocytosis !B`[ " \ folic "# t< ?34?

- functions of !"# folic acid:

) they are essential for DA synthesis. ) their " ' " DA synthesis ' " mitosis f " maturation and function of cells !specially cells with rapid diQision as YZT and B_ #

- c%inica% $ict" e !f B101 f!%ic acid deficiency +

&- 'ematological% macrocytic hyperchromic anemia !why megaloblastic anemia]# " DA ' " diQision in the face of continued RA and Protein synthesis ' large RBCs. (- )!*% \ glossitis. \ diarrhea. \ achlorhydria. 3- ne+rological% \ peripheral neuritis. \ sub acute combined degeneration f spinal Cord !ataPia b.#. oD 89: B`[

(. B10 -cyan!c!*a%amin aetiology of anemia $ !"(:

intake of B122 RARE ( -

.0a&a, or"

intrin i! fa!tor2 .,"erni!io# a3.. $#%eni&eafter 'a tre!to()-

A,nor(a&itie in ter(ina& i&e#( .- inf&a(e. /e ion after re'iona&.re e!tion

*i"+)&o,ot+

) #!" ce# !f B10+ 456789:;< => ?<@AB< CD EF 4:56GH \ rich sourcesB meat% liQer% fish% egg yol*. \ in manB synthesiaed by intestinal bacteria in colon. \ in industryB side product in streptomycin industry !synth. by streptomyces micro b.# %eq.: [ ugday * kinetics: \ absorption Depends on intrinsic factor !glycoprotein formed in parietal cells of stomach# which bind to B`[ helping its absorption. !Zleum# \ after absorption ' it^s attached to B or ` globulin !transcoblamin# \ distribution ' the whole body but mainly stored in liQer% *idney S<6TK697> RPPP Q OPPP I JKLMN;< B`[ k?l=D2 W 22 ?<1?/ x42 ?l; v2 +K<D 42 +D N -./ B ?D?< &xc. : \ mainly Qia bile !enterohepatic# \ traces in urine% stool

) $ e$a ati!n#+ `. cyanocobalamin inqB `dd or `ddd ugml Z_ it^s the prep. f choice in ttt of pernicious anemia. B hydroPocobalamin is better than cyanocobalamin H] because it has high protein binding ' retained in body for longer periods. [. Qit B`[ ( intrinsic factor concentrateB orally 2?<4 not commonly used ~. liQer ePtract inqB -3K42 gj| \ Z_ S effectiQe by its content of B`[ uses: B`[ deficiency gj? .pernicious a * dosage: +73,2 -<4 ?D; 02FiTFKD `ddd F3 gX9h ttt F<.42 >A ?;FGH 02FiTFKD `dd Fj gX9h maintenance * toxicity: no toPic effects -3K42 gj| gX9h oD g,?h +K<D 89:# F3K42 ?7F42 oD 5=h#

F!%ic acid
water sol. it. f B compleP gp. :aetiology of folic a .(.dietary inta*e !nutrional megalobastic a. 1 re$uirement e.g. in pregnancy. 2 .megaloblastic. a. of pregnancy Recently ' foetal neural tube defect e.g. spina .bifida .absorption e.g. malabsorp. pyndrome. 3 drugs which interfere ( absorption of folic a. ' . anticonQulsant therapy e.g. hydantion .drugs interfere ( metabolism of folic a. 5 trimethoprim methotrePate pyrimethamine . inhibit dihydrofolate red. }na .'ources: east% liQer% green Qeg.% fruits

. 4

(etabolic functions:
\ folic a. is not actiQe as such. \ it^s reduced in duodenum and qequnum to tetrahydrofolic acid !folinic acid% TH&A# by tetrahydrofolate reductase ena. \ TH&A is conQerted in liQer to methyl deriQatiQe transported into bile ' undergo enterohepatic Circulation.

%eq.: cd ugday. Dosage: `d\[d mgday N@4?/ toxicity: o (2-i JU? 1?h L: g,?h#

. A$%a#tic a
- ttt i# #"$$! ti(e+ .( transplantation O L4?C<42 |.42 Bg V6D `. withdrawal of the causatiQe agent !if any# [. blood transfusion. antibiotics. 3 g4?h L: .Znf. f " granulocytic count . haemopoietic factors e.g. B`[% folic a.% liQer ePt.%. corticosteroids e.g. prednisone Ed .5 !N@4?/#o/?,2 ~ t12 567 mgday E. hormonal ttt e.g. testosterone% anabolic steroid]]]

. Uem!%ytic a
immediate withdrawal of causatiQe agent e.g. - 1 .drugs as aspirin b.. in YEPD .blood transf .2 +/6i<G42 =D Mh corticosteroids ' tend to abolish the production . 3 .of hemolysin splenectomyB in some cases e.g. spherocytosis%. 4 .thalasemia

A' an"%!cyt!#i#
.Def. condition ch.ch. by mar*ed leucopenia and neutropenia :)et. ccurs as a hypersensitiQity reaction to many drugs as . analgesicsB \ aminopyrine .phenyl butaaone antithyroid as thiouracil antibiotics >K@D2J6 T ?@642 gold .diagnosis: usually begins ( sore throat and feQer o;F, 0U -7 t<72T |.42 WT2 1?V42 nO tCD L: : ttt stop drug -1 {i?h NO2 (antibiotics !inf- 2 .Blood transf- 3 .adrenal steroids- 4 . B`[% folic a- 5