Physiology of neonatal (0-2 weeks), infant (2-6 weeks), and pediatric (6-12 weeks) dogs and cats differs from that of adults in several important ways that can impact drug metabolism and disposition. Proportion of total body water is substantially higher in puppies and kittens, leading to a higher volume of distribution and lower than expected plasma concentrations of water-soluble drugs; the reverse is true for fat-soluble drugs. Renal and hepatic function are also immature until at least 3-6 weeks of age. In addition, young animals have slower gastrointestinal transit time and a more permeable blood-brain barrier than adults. Because of the latter and because certain systems are still developing (e.g. physes, tooth buds) younger dogs and cats may be more susceptible than adults to certain adverse drug reactions.
For some drugs, specific information exists to support safe use in puppies and kittens as young as 4 weeks old. Other drugs (e.g. oclacitinib) have been demonstrated to have increased risk of toxicity in young compared with mature animals. However, for most drugs, neither of the above is true, and label restrictions may simply reflect lack of safety assessment in a pediatric age group. Consequently, recommendations for use of specific drugs in puppies and kittens are often based on a combination of information from other species, theoretical support or concerns, and clinical experience. In general, beta-lactam antibiotics, benzodiazepines, and opioids have a wide margin of safety in pediatric animals, and short-term opioid use is likely to be safe in pregnant, nursing, and neonatal dogs and cats. Macrolides are not overtly toxic, but undergo hepatic recirculation and may disrupt GI flora. Chloramphenicol has caused blood dyscrasias in 8-12 week old puppies at 50 mg/kg twice a day, and causes cardiac depression in neonates of other species (e.g. humans). Aminoglycosides have a narrow therapeutic index and young age has been listed as a risk factor for nephrotoxicity; however, these agents may still be used if adequate hydration is ensured. If metronidazole is used, very young puppies and kittens should be closely monitored for neurotoxicity. Tetracycline-induced tooth staining (which appears less common with doxycycline but has still been reported to occur) and cartilage damage with fluoroquinolones in large-breed puppies up to 18 weeks of age are often cited as reasons not to use these drugs in young animals. However, if life-threatening infection is present, fluoroquinolones may be appropriate as a means of Gram-negative coverage. NSAID use is to be avoided in pregnant animals based on numerous studies in other species documenting fetal nephrotoxicity (as COX-2 is important for the developing kidney) and teratogenesis. NSAIDs are also not recommended for animals less than 6 weeks of age because of ongoing hepatic and renal maturation. Acepromazine may cause CNS depression in young animals and dose reductions to 0.005-0.025 mg/kg have been recommended. Pyrantel has a
wide safety margin and has frequently been used in animals as young as 2 weeks of age. Many other antiparasitics and flea/tick control products have been marketed by veterinary pharmaceutical companies, and age recommendations can be found on the product label. Both phenobarbital and potassium bromide have been used to manage seizures in young puppies. This lecture will include several case examples of clinical decision-making in pediatric patients.
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