      Document 0195
 DOCN  DRG0195
 UNIQUE IDENTIFIER        DRG-0052
 NAME OF SUBSTANCE        Quinine [USAN 1996]
 REGISTRY NUMBER          130-95-0
 RELATED REGISTRY NUMBER  6119-70-6 (sulfate salt)
 RELATED REGISTRY NUMBER  804-63-7 (anhydrous)
 RELATED REGISTRY NUMBER  60-93-5 (dihydrochloride)
 STANDARD CHEMICAL NAME   6'-Methoxycinchonan-9-ol [USAN 1996]
 SYNONYMS                 6'-Methoxychinchonan-9-ol sulfate (2:1)
                          (salt) [USP DI 1989]
 SYNONYMS                 Novoquinine [USP DI 1995]
 SYNONYMS                 Strema [USP DI 1989]
 SYNONYMS                 Quiphile [USP DI 1995]
 SYNONYMS                 Quindan [USP DI 1995]
 SYNONYMS                 Legatrin [USP DI 1995]
 SYNONYMS                 Quinamm [PDR 1995]
 SYNONYMS                 6-Methoxy-alpha-(5-vinyl-2-quinuclidinyl)-4-q-
                          uinolinemethanol [Merck Index 1989]
 SYNONYMS                 Alpha-(6-methoxy-4-quinolyl)-5-vinyl-2-quinuc-
                          lidinemethanol [Merck Index 1989]
 SYNONYMS                 Quin-260 [USP DI 1995]
 SYNONYMS                 Quin-amino [USP DI 1995]
 SYNONYMS                 Q-vel [USP DI 1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 027
 IND NUMBER               DRG-0052
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION:  Quinine acts on skeletal
                          muscle by 3 mechanisms: (1) it increases the
                          refractory period by direct action on the
                          muscle fiber, (2) it decreases the
                          excitability of the motor end-plate similarly
                          to curare, and (3) it affects the
                          distribution of calcium within the muscle
                          fiber; it is readily absorbed, when given
                          orally, in the small intestine, and is
                          metabolically degraded in the liver, with
                          less than 5 percent of an administered dose
                          excreted unaltered  in the urine; metabolic
                          degradation products (hydroxy derivatives)
                          are found in the urine, feces, gastric juice,
                          bile, and saliva; renal excretion is twice as
                          rapid when the urine is acidic as when it is
                          alkaline due to greater tubular reabsorption
                          of the alkaloidal base that occurs in an
                          alkaline medium; excretion is limited by
                          extensive binding (about 70 percent) to
                          plasma proteins, resulting in cerebrospinal
                          fluid levels that are only 2-5 percent of
                          those of plasma; peak plasma levels occur
                          within 1-3 hours after an oral dose, with a
                          half-life of 4-5 hours; its plasma level is
                          about 7 mcg/ml after chronic administration
                          of total daily doses of 1 g; its plasma level
                          becomes negligible within 24 hours after
                          termination of therapy; in pregnant women it
                          traverses the placental membrane and readily
                          reaches fetal tissues. [PDR 1995]
 DISEASES STUDIED/TREATED Possible use in reducing the amount of AZT
                          needed for treating patients with symptomatic
                          HIV infection (AIDS or symptomatic
                          AIDS-related complex, ARC), via impairment of
                          renal AZT elimination [Second International
                          Conference on AIDS 1986 Paris]
 DISEASES STUDIED/TREATED The combination of quinine sulfate and
                          clindamycin may be useful in the treatment of
                          cryptosporidiosis [AHFS Drug Information
                          1995]
 CLASSIFICATION CODE      Antimalarial [USAN 1996]
 CLASSIFICATION CODE      Neuromuscular [PDR 1995]
 OTHER MAJOR USES         Treatment of malaria, nocturnal recumbent leg
                          muscle cramps and Babesia microti infections
                          [AHFS Drug Information 1995]
 SUBSTANCE INTERACTIONS   Concomitant use with mefloquine may result in
                          cardiac arrhythmias. Cimetidine clearance can
                          be decreased and its half-life increased by
                          quinine administration. Increases plasma
                          levels of digoxin after concomitant quinine
                          administration. Concurrent use of
                          aluminum-containing antacids may
                          delay/decrease quinine absorption. Quinine
                          may depress the hepatic enzyme system that
                          synthesizes vitamin K-dependent factors,
                          resulting in hypoprothrombinemic conditions
                          which enhance the action of Warfarin and
                          other oral anticoagulants. It may potentiate
                          the effects of neuromuscular blocking agents
                          (pancuronium, succinylcholine, tubocurarine),
                          resulting in respiratory difficulties.
                          Urinary alkalizers (acetazolamide, sodium
                          bicarbonate) may increase quinine blood
                          levels with potential for toxicity. [PDR
                          1995]
 ADVERSE EFFECTS          May cause acute hemolysis, thrombocytopenic
                          purpura, agranulocytosis,
                          hypoprothrombinemia, visual disturbances,
                          headache, nausea, vomiting, fever,
                          apprehension, restlessness, confusion,
                          syncope, cutaneous rashes, pruritus, flushing
                          of the skin, sweating, edema of the face,
                          asthmatic symptoms, anginal symptoms,
                          epigastric pain, hepatitis. [PDR 1995]
 CONTRAINDICATIONS        May cause fetal harm and congenital
                          malformations when administered to pregnant
                          women, and is contraindicated in women who
                          are or may become pregnant. It is also
                          contraindicated in patients with known
                          quinine hypersensitivity, glucose-6-phosphate
                          dehydrogenase deficiency, history of
                          thrombocytopenic purpura, tinnitus or optic
                          neuritis, or history of blackwater fever.
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Alkaloid obtained form the
                          bark of the cinchona tree. [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C20H24N2O2;
                          (C20H24N2O2)2.H2S04.2H20 (Quinine Sulfate)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 324.41; 782.95 (Quinine
                          Sulfate Dihydrate) [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C74.04%; H7.46%;
                          N8.64%; O9.86% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 177 C (some decomposition);
                          sublimes in high vacuum at 170-180 C; the
                          trihydrate microcrystalline powder melts at
                          57 C and is efflorescent; the tartrate melts
                          at 211 to 212.5 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: 1 g dissolves in 1900 ml water,
                          760 ml boiling water, 0.9 ml alcohol, 80 ml
                          benzene, 1.2 ml chloroform, 250 ml dry ether,
                          20 ml glycerol, and 1900 ml of 10 percent
                          ammonia water; almost insoluble in petroleum
                          ether [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Exhibits especially strong
                          blue fluorescence in dilute sulfuric acid
                          [Merck Index 1983]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Quinine sulfate occurs
                          as a white crystalline powder, which darkens
                          on exposure to light. It is odorless and has
                          a persistent, very bitter taste. [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (260 mg). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral (sulfate).
                          Intravenously (dihydrochloride). [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at room temperature, below 86
                          F (30 C). [PDR 1995]
 MANUFACTURERS            Merrell Dow Pharmaceuticals
 REFERENCES               Niyongabo T, Deloron P, Aubry P, Ndarugirire
                          F, Manirakiza F, Muhirwa G, Ndayiragije A,
                          Brelivet JC. Prognostic indicators in adult
                          cerebral malaria: a study in Burundi, an area
                          of high prevalence of HIV infection. Acta
                          Trop. 1994 Apr;56(4):299-305.
 REFERENCES               Dayachi F, Kabongo L, Ngoie K. Decreased
                          mortality from malaria in children with
                          symptomatic HIV infection. Int Conf AIDS.
                          1991 Jun 16-21;7(2):164 (abstract no.
                          W.A.1291).
 REFERENCES               Colebunders R, Bahwe Y, Nekwei W, Ryder R,
                          Perriens J, Nsimba K, Turner A, Francis H,
                          Lebughe I, Van der Stuyft P, et al. Incidence
                          of malaria and efficacy of oral quinine in
                          patients recently infected with human
                          immunodeficiency virus in Kinshasa, Zaire. J
                          Infect. 1990 Sep;21(2):167-73.
 REFERENCES               Kornhauser DM, Petty BG, Hendrix CW, Woods
                          AS, Nerhood LJ, Bartlett JG, Lietman PS.
                          Probenecid and zidovudine metabolism [see
                          comments]. Lancet. 1989 Aug 26;2(8661):473-5.
 ENTRY MONTH              8906
 LAST REVISION DATE       960209
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
