ANTIFILARIAL DRUGS

Copyright, Purdue Research Foundation, 1996

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Thiacetarsamide sodium , arsenamide [Caparsolate sodiumR, FilaramideR]

Chemistry / Structure

TRIVALENT ARSENICAL

Sodium Salt

Therapeutic use

Historically, arsenicals were used for Rx of human syphilis and metazoan diseases

KILLS 98-100% of ADULT WORMS in 21 days.

dose of 0.1 ml/lb BID 2-3 days iv is from IVMA (of CAPARSOLATE SODIUM)

Pharmacokinetics

Elimination

Both renal and hepatic elimination are important

High doses -- Approx. 50% is excreted in 24 hours.

Therapeutic doses -- 10-15% excreted in urine within 24 hr

Toxicity Levels --

Normal dogs die after 4 mg/lb (8.8 mg/kg), i.v. Die within few days.

At recommended dose 4.4 mg/kg/day x 30 days, no problems observed.

Typical Dose and Schedule

0.1 ml/lb CAPARSOLATE SODIUM or 2.2 mg/kg I.V. BID for 2 days.

Dogs in poor condition -- 2.2 mg/kg SID q1d for 15 days.

Adverse effects

TISSUE SLOUGHING and PAIN if perivascular injection

VOMITION -- without other signs, may continue therapy

PERSISTENT VOMITING, ANOREXIA or ICTERUS -- STOP Rx

May see RESPIRATORY DISTURBANCES -- Cause: anaphylactoid response? Clumping of worms in pulmonary arteries? Tissue debris? Infarction?

Large doses, Same effect as inorganic ARSENIC on CAPILLARIES and ARTIERIOLES leading to VASODILATATION and CAPILLARY DAMAGE.

GASTROINTESTINAL TRACT signs -- VOMITING, DIARRHEA may occur 4-12 hours after injection and last for HOURS to DAYS.

KIDNEY -- Casts, mild albuminuria and slight increase in BUN which is temporary.

LIVER -- May cause HEPATIC DAMAGE as severe as acute yellow atrophy. Injury generally hepatic parenchyma, other times resembles bile duct occulusion.

Precautions

IMMATURE FEMALES MORE RESISTANT than males. May need to repeat treatment at intervals of a few months. Theodorides p207

LIVER and KIDNEYS must be functional. -- KEY TO SUCCESSFUL, NON-TOXIC THERAPY

Drug is EXTREMELY IRRITATING, TISSUE TOXIC, therefore, must have injection needle well seated.

IVMA RECOMMENDS ADMINISTRATION via CATHETER in jugular vein to minimize the possibility of sloughing.

Feed animal 30 minutes prior to each injection. [Merck91, p.74]

Use of adjuvant therapy to reduce toxicity.

Some practitioners use vitamin C, aspirin, and glucocorticoids in an attempt to lessen the toxicity of the thiacetarsamide therapy. BUT...

Vitamin C has not been shown to be helpful in reducing hepatotoxicity.

Aspirin (acetylsalicylic acid) at the time of administration may be useful

Glucocorticoids given with the thiacetarsamide actually decrease the effectiveness of the treatment. It may be useful to give glucocorticoids a day or so later, if the animal actually has signs of reacting to the treatment.

Treatment of Toxicity

Systemic toxicity

If SEVERE OVERDOSE, try using DIMERCAPROL (BAL, British AntiLewisite), which is useful for treating some heavy metal intoxications, e.g. Arsenic, Lead, Mercury, Cadmium.

Acts by CHELATION,

Hastens elimination

Relatively non-toxic.

g. If perivascular injection --

Perivascular injection

Topical DMSO

DMSO-dexamethasone tid for several days

Levamisole

Use

Used to remove microfilarial stage

Cleared for this use in dogs?? Have owner sign release.(IVMA)

Dose -- 5 mg/lb po/day until microfilariae are gone, BUT NOT LONGER THAN 15 DOSES.

Most dogs require only about 6 doses.

Adverse Effects

VOMITING, but can control with atropine pretreatment.

Causes for stopping therapy

RESTLESSNESS and NERVOUSNESS.

Dithiazanine iodide [DizanR]]

Used to remove microfilarial stage

Traditional drug now used very little if at all. Hepato- and nephrotoxic

Diethylcarbamazine citrate [CaracideR, HetrazanR, etc.]

Therapeutic use

Prevent development of infective larvae

No effect against adults

Actions against microfilariae, but are hazardous -- do not use in animals with microfilariae

PROPHYLACTIC -- MANY SCHEDULES

AVMA recommends -- 1.25 mg/lb (of base drug) per day during and 2 months following exposure to mosquitos.

If must alter dosage due to tablet size, adjust so that dose is on the high side.

Chemistry / Structure

Related to PIPERAZINE

Adverse effects

RELATIVELY NON-TOXIC.

GASTROINTESTINAL IRRITATION and VOMITION in few animals

Multiple generation studies -- no evidence of problems.

SEVERE REACTIONS in dogs that have circulating microfilariae

Ivermectin

Details elsewhere in VPH 445 notes

Therapeutic use for filarids / heartworms

Kill infective larvae of D. immitis

Not recommended for removing microfilariae

HEARTGARD 90 preparation specifically for this purpose

Pharmacokinetics

Used po

Administered 1 time per month

Precautions

Remember caution on use in COLLIES

Not as effective on tissue larvae older than 30 days! -- hence the schedule must be followed carefully.

REFERENCES


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Gordon L. Coppoc, DVM, PhD
Professor of Veterinary Pharmacology
Head, Department of Basic Medical Sciences
School of Veterinary Medicine
Purdue University
West Lafayette, IN 47907-1246
Tel: 317-494-8633Fax: 317-494-0781
Email: coppoc@vet.purdue.edu

Last modified 11:25 PM on 2/20/96 GLC