Chloramphenicol

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Chloramphenicol is a broad-spectrum antimicrobial drug. In small animals, chloramphenicol is now

Table 1.2 Drugs that are therapeutically useful in cats but that may have different dosing/toxicity/activity profiles than in dogs

Drug

Toxicity that may be observed

Difference in dosing compared with dogs

Aspirin

Chloramphenicol Diazepam Doxorubicin Frusemide

Griseofulvin

Ketoconazole

Lignocaine Megestrol acetate

Metronidazole

Opioids

Morphine derivatives [excluding meperidine (pethidine), butorphanol and buprenorphine] Organophosphates

Tetracyclines

Thiacetarsamide

Hypernoea Hypersensitivity Hyperthermia Anaemia

Idiosyncratic hepatotoxicity® Renal failure Dehydration Hypokalaemia

Leucopenia and thrombocytopenia Non-reversible ataxia Dry hair coat Weight loss

Myocardial and CNS depression

Mammary hypertrophy and neoplasia

Cystic endometritis

Diabetes mellitus

Disorientation

Ataxia

Seizures

Blindness

Inconsistent sedation Increased risk of excitation

Acute toxicity: hypersalivation vomiting, diarrhoea, muscle tremors Chronic or delayed toxicity, paresis or paralysis which may or may not be reversible Hepatic lipidosis Increased ALT activity Ptyalism Anorexia Drug fever Respiratory distress Fulminant pulmonary oedema

Increased dosing interval Lower end of dose/kg range

Lower dose

Lower dose

Use lower end of dose range Check FIV status

Lower dose

Lower dose

Lower dose

Use with care, ensure product rinsed off coat a Center etat. (1996).

ALT: alanine transferase; FIV: feline immunodeficiency virus.

probably the drug of first choice only for bacterial infection of the chambers of the eye. There is mixed opinion as to whether chloramphenicol is the drug of choice for CNS infections (rare), but it does achieve high levels in the CNS and has a very broad spectrum. However, many other drugs also effectively cross the blood-brain barrier in the presence of meningitis and may be more effective and bactericidal. Chloramphenicol is a good alternative for anaerobic infections. It is eliminated primarily by hepatic glucuronide conjugation in the dog and only 5-10% is excreted unchanged in the urine.

Although the elimination half-life of chloramphenicol is similar in both species (4 h after intravenous administration, 7-8 h after oral administration), in contrast to the dog more than 25% of drug is excreted unchanged in the feline urine owing to the reduced ability of cats to glucuronidate drugs. This difference in metabolism results in a very different dosing schedule in cats (50mg/cat b.d.) compared with dogs (50 mg/ kgb.d.).

Reversible non-regenerative anaemia can occur in both dogs and cats. Cats may be more susceptible, but the increased incidence is probably related to relative overdosing of cats when using a dog dosing schedule, which is approximately five times higher per kilogram (Watson, 1991).

Digoxin

Digoxin is a positive ionotropic and negative chronotropic used in the management of cardiac failure in dogs and cats. It competitively binds to the site at which potassium normally attaches on the Na+/K+-ATPase pumps located on myocardial cell membranes. A therapeutic concentration of digitalis 'poisons' approximately 30% of the pumps. Inhibition of Na+/ K+-ATPase causes increased intracellular concentrations of sodium that is available for exchange with calcium (via the Na+/Ca2+ cation exchanger), resulting in increased intracellular calcium, increased storage of calcium in the sarcoplasmic reticulum and greater release of calcium with each action potential, cumulating in increased excitation-contraction coupling of actin-myosin.

Cats are more sensitive than dogs to digitalis-induced toxicosis (Boothe, 1990b). This is presumed to be because of the increased sensitivity of feline cardiac Na+/K+-ATPase to inhibition. The dosage should be reduced compared with dogs and further reduced if given concurrently with aspirin and furosemide (Atkins etal, 1988).

The half-life of digoxin is extremely variable in cats, ranging from 25 to 173 h in various reports. The elixir form results in serum concentrations approximately 50% higher than the tablet. However, cats generally dislike the taste of the alcohol-based elixir. When digoxin tablets are administered with food to cats, serum concentration is reduced by about 50% compared with the concentration without food (Kittelson, 2002). The recommended doses of digoxin in cats are:

Doxorubicin (see also Chapter 3)

Doxorubicin is an anthracycline antibiotic that penetrates cells, fixes to nuclear structures and intercalates with DNA, thus inhibiting DNA-dependent RNA synthesis as well as DNA duplication. It is used as a single agent or in combination protocols (particularly for treatment of lymphosarcoma). Doxorubicin is potent against a range of tumours and is the most common single agent used for solid tumours.

Doxorubicin when used at the 'dog dose' of 30 mg/m2 has been associated with induction of renal failure in cats (Cotter et al., 1985). The optimal dose has not been determined in the cat. Doses ranging from 20 to 30 mg/m2 and 1 mg/kg have been recommended. Because the cat is relatively resistant to developing doxorubicin-induced cardiomyopathy, no cumulative dose recommendation has been made.

Enrofloxacin

Enrofloxacin is a fluoroquinolone antimicrobial agent that has broad-spectrum antimicrobial activity, especially against Gram-negative bacteria as well as Brucella, Mycoplasma, Chlamydia and Mycobacterium infections. Adverse effects are uncommon in dogs and cats. An apparent species-specific toxicity is acute retinal degeneration, recently reported in cats. Blindness often results, but some cats may regain vision. In a recent study of affected cats (Gelatt et al., 2001), the daily and total doses of enrofloxacin administered and the duration of treatment were highly variable.

Frusemide

Frusemide is a loop diuretic that is secreted into the proximal tubule by the organic acid secretory mechanism. Loop diuretics inhibit sodium chloride (NaCl) reabsorption at the lumenal face of the cells in the thick ascending loop of Henle by actively blocking sodium-potassium-chloride cotransport. Because of the large NaCl absorptive capacity of this segment, diuretics that act at this site produce a diuretic effect much greater than other classes of diuretics.

Cats are more sensitive than dogs to frusemide (Boothe, 1990b; Kittleson, 2002). The increase in urine volume is comparable between normal cats and normal dogs in doses from 0.625 to 10 mg/kg i.m. However, in cats sodium excretion is between 1.3 and 2.2 times (average 1.7 times) that seen in dogs at each dosage.

The recommended dose in cats is 1-2 mg/kg b.d.

Griseofulvin

Griseofulvin is a fungistatic drug used primarily for the treatment of dermatophycosis in cats and dogs caused by Trichophyton and Microsporum spp. It has no effect on other fungi. Although griseofulvin has traditionally been considered the drug of choice for systemic therapy of dermatophytosis in dogs and cats, it has been replaced to some degree by itraconazole, which is often better tolerated (especially in cats) and may be more efficacious for the treatment of M. canis.

Bone-marrow suppression (usually manifested as neutropenia) may occur as an idiosyncratic reaction, especially in kittens (Shelton etal, 1990). For this reason, griseofulvin should not be used in kittens under 8 weeks of age, and many authors recommend a minimum age of 12 weeks. In addition, neutropenic reactions are more common in cats infected with feline immunodeficiency virus (FIV). Consequently, FIV testing should be performed before the initiation of griseofulvin therapy, and cats that are FIV positive should receive an alternative therapy (such as itraconazole or terbinafine).

In general, adverse reactions to griseofulvin therapy occur more often in Himalayan, Abyssinian, Persian and Siamese cats than in other breeds (Taboada & Grooters, 2002). Non-reversible ataxia has been reported in a kitten treated with the drug.

The recommended dose in cats is 20-50 mg/kg per day p.o. (It may be given in divided doses and should be administered with a fatty meal to enhance absorption.)

Ketoconazole

Ketoconazole is an azole antifungal drug that blocks biosynthesis of fungal lipids, especially the ergosterol in cell membranes. It inhibits fungal ergosterol biosynthesis 30-70 times more readily than mammalian cholesterol metabolism; thus, fungal membrane permeability is affected.

In contrast to the effect in dogs, ketoconazole does not alter production of steroid hormones such as Cortisol, testosterone and progesterone in cats. However, dose-related gastrointestinal side-effects (anorexia and vomiting) are relatively common in this species.

The recommended dose is 5-10 mg/kg p.o. every 8-12 h.

Lignocaine

Lignocaine is used clinically to treat acute life-threatening ventricular arrhythmias in many different clinical settings. Cats develop seizures with lignocaine more commonly than dogs and it must be used cautiously in this species.

In cats the initial dose is 0.25-0.75 mg/kg i.v., followed by an infusion administered at 10-40 (xg/kg per minute.

Megestrol acetate

Megestrol acetate is a synthetic progestagen that has been used for reproductive, behavioural and dermatological disorders in cats. However, it is not recommended for the treatment of behavioural or dermatological disorders owing to the risk of serious side-effects.

The most serious side-effects associated with megestrol acetate treatment in cats include mammary hypertrophy and neoplasia, cystic endometritis and diabetes mellitus. The mechanism for diabetes mellitus appears to be different to that in the dog (where it relates to increased growth hormone production). Megestrol-induced diabetes in the cat may be transient or permanent. Megestrol acetate also causes adrenal suppression in the cat (Boothe, 1990c).

The recommended dose for control of oestrus can be achieved by using 5mg/cat for 3 days then 2.5-5 mg once a week for 10 weeks.

Morphine

Cats appear to be more sensitive to the effects of several opioid analgesics, particularly morphine. Adverse effects observed include inconsistent sedation and increased risk of excitation. This may be due to differences in the type or concentration of opioid receptors in cats as well as decreased rate of metabolism (Page & Maddison, 2002).

Organophosphates

Organophosphates are used widely in the control of ectoparasites, especially fleas in cats, although their use is declining as a result of newer flea treatments that more specifically target the flea.

Cats are more sensitive than dogs to the effects of organophosphates, although the mechanism for this is unknown (Boothe, 1990c). It is not related to different hepatic metabolising capacity as organophosphates are metabolised by cholinesterases located at nerve endings.

Toxicity may be acute (similar signs to dogs), or chronic or delayed. Chronic or delayed toxicity manifests as paresis or paralysis, which may or may not be reversible. Toxic epidermal necrolysis has been reported in cats treated topically with organophosphate-based flea rinses. A survey of the effects of flea collars in cats revealed a high number of adverse reactions, ranging from dermatitis to death (Wilkins, 1980).

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