dendy - chloroquine as anti inflammatory new

7/29/2019 Dendy - Chloroquine as Anti Inflammatory New

1/14

Referat

INTERNAL MEDICINE DEPARTMENT

MEDICAL FACULTY OF LAMBUNG MANGKURAT UNIVERSITY

ULIN HOSPITALBANJARMASIN

1


2/14

INTRODUCTION

Chloroquine [7-chloro-4-(4-diethylamino-1-methylbutylamino) quinoline, CHQ]malariatreatment in many Third World countries

cheap, widely available, relatively well tolerated,and having a rapid onset of action.

CHQanti-inflammatory drug rheumatoidarthritis, discoid lupus erythematosus and

amoebic hepatitis exact unclear. CHQ chronic inflammation, also bacteria-

induced inflammation

2


3/14

PHARMACOLOGY PROFILE

CHQ synthesis

First synthesised in

Germany by Bayer

Corporation in 1934

cheaper alternative

quinine

1946-1966 drug ofchoice for treatment and

prophylaxis of malaria

3


4/14

PHARMACOLOGY PROFILE

Orall almost completely absorbed from GIT,bioavailability of 75-80%

Routes: SC, IM and rectal.

Maximum plasma concentrations: 1-2 h and remain up

to 3.6 hours Half-life ranging 3-6 days

Elimination half-life of CHQ however varies greatlybetween plasma and tissue in humans, ranging from 2-

3 days in plasma to over 300 h in tissues >70% ingested dose of CHQ is excreted unchanged in

the urine, can still be detected > 120 days

4


5/14

MECHANISM OF ANTI INFLAMMATORY

EFFECT

Chloroquine Inhibits Proinflammatory Cytokine

Release

Mechanism of Endosomal TLR Inhibition

Effect of Chloroquine on Human Polymorphonuclear

Leukocytes

Chloroquine Stimulates Nitric Oxide

5


6/14

6

Chloroquine Inhibits Proinflammatory

Cytokine Release


7/14

Autoimmune desease immune response

activate with TLR TLR 3,7,8,9

TLR active with acid PHCHQ (weak base)

inhibit CpG DNA-driven cellular

activationTLR unactivated

Inhibition of endosomal TLRs great

therapeutic potential for the treatment of

autoimmune diseases.

7



8/14

8



9/14

Effect of Chloroquine on Human

Polymorphonuclear Leukocytes

CHQ: inhibits fosfolipid metilation, kinase protein, and

kalmodulin dependent

NO (nitrit oxide): stimulate NO synthesis NO exert cytotoxic effects it can block glycolysis, by

inhibiting glyceraldehyde 3-phosphate dehydrogenase, and

cell respiration, via nitrosylation of ironsulfur clusters of

enzymes (cis-aconitase) and electron transporters (complexes

I, II, and IV of respiratory chain.

Chloroquine is cytotoxic, but the mechanisms of its action are

controversial.

9


10/14

CHLOROQUIN EFFECTS AS ANTI

INFLAMMATORY AGENT

Ultraviolet light absorption

UV radiation local inflammation and cell injury to keratinocytes,leading to cell death and possibly TLR activation

Chloroquine negating this ultraviolet radiation-induced inflammation inhibition of antigen presentation and cytokine synthesis

MMP

TIMP modulation Matrix metalloproteinases (MMPs) are a group of enzymes involved in

extracellular matrix remodeling.

Tissue inhibitors of metalloproteinases (TIMPs) counter-regulatoryenzymes inhibit MMPs and maintain homeostasis of the extra cellularmatrix.

Imbalance between MMPs and TIMPs pathogenic role in auto immunediseases

Chloroquine inhibit MMPs in vitro and in vivo

10


11/14

CHLOROQUIN EFFECTS AS ANTI

INFLAMMATORY AGENT

Rheumatoid arthritis

Inflammation is effectively suppressed by chloroquine

(DMARD) reduce inflammatory process is at least the

major factor in joint destruction

SLE (Systemic Lupus Erythematosus)

Chloroquine Disease-modifying properties affect

inflammatory activity as well as favourably influence quality of

life, morbidity and prognosis

11


12/14

12


13/14

CONCLUSION

Chloroquinemalaria treatment and anti-inflammatory drug, though the exact mechanism ofhow chloroquine affects the immune system hasremained unclear.

Mechanisms of anti inflammatory effect ofchloroquine:

Inhibits proinflammatory cytokine release

Endosomal TLR inhibition

Effect on human polymorphonuclear leukocytes

Stimulates nitric oxide.

13


14/14

14

dendy - chloroquine as anti inflammatory new

Documents