Mark Troxel, DVM, DACVIM (Neurology), is a neurologist and neurosurgeon at Massachusetts Veterinary Referral Hospital in Woburn, Massachusetts. He earned his DVM from Iowa State University. He then completed a rotating internship at VCA South Shore Animal Hospital, a medicine specialty internship at Garden State Veterinary Specialists, and a neurology residency at University of Pennsylvania. Dr. Troxel has published numerous articles and book chapters. His clinical interests include feline brain tumors, vestibular dysfunction, and neurosurgery.
Which of the following drugs would be appropriate for this patient?
Based on the information provided, how would you grade the following drugs and why?
The following represents the best responses based on drug metabolism, pharmacokinetics, species, diagnostic differentials, clinical and laboratory data, and other pertinent findings.
Correct ResponseSafeAn immunosuppressive dosage of prednisone (4 mg/kg every 24 hours for 1-2 days in severe cases, then 2 mg/kg every 24 hours for 2 weeks) is the standard medication to treat SRMA, which is a presumably autoimmune condition. Repeat CSF analysis should ideally be performed to ensure CSF has normalized prior to initiating the taper; however, if clinical signs resolve within 2 weeks, the drug can be gradually tapered over many months. Although the exact duration for tapering has not been examined in peer-reviewed studies, the author tapers prednisone over at least 6 to 8 months (sometimes longer). Prednisone and other corticosteroids should not be administered concurrently with an NSAID.
The patient in this case was given carprofen prior to referral; therefore, a 48-hour washout period should be performed before prednisone administration.
Correct ResponseDo Not UseMeloxicam and other NSAIDs (eg, carprofen, deracoxib, grapiprant, piroxicam) should be avoided, except in cases of infectious meningitis or diskospondylitis, as these preclude the use of corticosteroids and other immunosuppressants. Due to a long elimination half-life and the withdrawal period required before administering corticosteroids, meloxicam and aspirin should especially be avoided in young patients with spinal hyperpathia or paresis/ataxia.
Correct ResponseProceed with CautionClindamycin is a lincosamide antibiotic with broad-spectrum coverage against many gram-positive aerobic cocci, anaerobes, and protozoal organisms (eg, Toxoplasma gondii, Neospora caninum), but its primary use in veterinary neurology is for treatment of protozoal infection. Bacterial meningitis is rare in dogs and cats, but if gram-negative bacterial meningitis is suspected, treatment with a cephalosporin may be preferable. Clindamycin crosses the blood–brain barrier, but CNS levels may only be 40% of that found in serum. GI adverse effects (eg, nausea, inappetence, vomiting, diarrhea) are most common. Clindamycin can be administered prior to infectious disease test results, but consideration should be given to antibiotic resistance.
Correct ResponseProceed with CautionDoxycycline is a bacteriostatic tetracycline antibiotic often used to treat a variety of organisms, including Borrelia spp, Rickettsia spp, Anaplasma spp, Ehrlichia spp, and Bartonella spp. Doxycycline is more lipid-soluble than other tetracyclines, allowing the drug to penetrate the CSF and eyes. Thus, doxycycline may be an appropriate antibiotic for several infectious diseases that mimic meningitis in dogs. The most commonly reported adverse effects of this drug are nausea, vomiting, and diarrhea. Dry pill administration may cause esophagitis or esophageal stricture, so medication should be administered with food (can also reduce GI adverse effects) or followed with water. Doxycycline can be administered prior to infectious disease test results, but consideration should be given to antibiotic resistance.
Correct ResponseSafeAzathioprine is a purine-antagonist immunosuppressant used in the treatment of a variety of autoimmune disorders (eg, immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, myasthenia gravis).1-4 Azathioprine (1-2 mg/kg PO every 24 hours for 1-4 weeks, then every 48 hours for 6-8 months) administered concurrently with prednisone has been reported in dogs with SRMA, especially in patients not completely responding to corticosteroids.5 Azathioprine is also used for faster dose reduction to reduce the adverse effects of corticosteroids. The most common adverse effects of azathioprine are myelosuppression, GI distress (eg, inappetence, vomiting, diarrhea), pancreatitis, and hepatotoxicity. CBC with platelet count and serum chemistry profile are recommended every 2 weeks for the first 2 months, then every 1 to 2 months during treatment, before azathioprine is administered.1
Correct ResponseSafeCyclosporine is FDA-approved for the treatment of atopic dermatitis in dogs and allergic dermatitis in dogs and cats and is often used extra-label for the treatment of autoimmune disorders, including several presumed immune-mediated CNS disorders (eg, GME). The mechanism of action is primarily directed toward cell-mediated immune responses by binding to T-cell cyclophilin, blocking calcineurin-mediated T-cell activation. This drug also inhibits cytokine production and release.6-8 There are anecdotal descriptions of cyclosporine use for treatment of SRMA, generally in combination with a corticosteroid, to improve remission rates and reduce adverse effects of corticosteroids by more quickly allowing a reduction in steroid dose. Adverse effects of cyclosporine include GI adverse effects (eg, inappetence, vomiting, diarrhea). Cyclosporine should ideally be administered on an empty stomach, but giving the medication with a small amount of food or freezing the capsules for 30 to 60 minutes before administration might reduce vomiting.9 A published dosage for SRMA does not exist, but the anecdotal recommendation is 5-10 mg/kg every 24 hours or divided and given every 12 hours. Therapeutic drug monitoring is ideal. A trough whole blood (not plasma) cyclosporine therapeutic range (300-500 ng/mL) has been suggested.10 However, cyclosporine levels do not appear to correlate to clinical effectiveness for atopic dermatitis or inflammatory bowel disease, so levels are not always pursued, and the dose can be changed based on clinical effects as compared with adverse effects.11,12
CYTOSINE ARABINOSIDE (ie, CYTARABINE)
Correct ResponseSafeCytarabine is an injectable immunosuppressant/antineoplastic agent used primarily for treatment of lymphoreticular neoplasms, leukemia, and presumed immune-mediated CNS inflammatory disorders (eg, GME, necrotizing meningoencephalitis). In one study, 10 out of 12 dogs responded to combined treatment with cytarabine and corticosteroids.13 Cytarabine inhibits DNA polymerase, thus inhibiting DNA synthesis, and is specific to the S phase of the cell cycle. Adverse effects of this drug are uncommon and more pronounced following IV administration than with SC administration. Reported adverse effects include GI signs, neutropenia, and thrombocytopenia.14,15 Minimal adverse effects have been reported with the lower dosages used to treat inflammatory CNS disease as compared with neoplasia.16 Although a study describing cytarabine for treatment of SRMA reported a high incidence of adverse effects,13 many of these occurred following IV infusion rather than SC injections. The author has seen minimal adverse effects with cytarabine; adverse effects have occurred more often in this author’s experience following IV infusion but are uncommon overall. Cytarabine (200 mg/m2 [NOT mg/kg] CRI over 8-24 hours; 50 mg/m2 [NOT mg/kg] SC every 12 hours for 48 hours [ie, 4 doses total]) is initially repeated every 3 weeks for 3 to 4 treatments, then slowly tapered by increasing the duration between treatments every 3 to 4 rounds of treatment. Some clinicians monitor CBC one week after treatment and before each treatment.
Correct ResponseProceed with CautionGabapentin (5-10 mg/kg PO every 8-12 hours) may be beneficial for the treatment of chronic pain, especially neuropathic pain, but the efficacy appears to be lower for treatment of acute pain. Gabapentin’s mechanism of action has not been fully elucidated, but it appears to bind to voltage-gated calcium channels, blocking the influx of calcium in the nerve terminal, thus inhibiting the release of excitatory neurotransmitters (eg, glutamate, substance P). The most common adverse effects of this drug are sedation and ataxia.
FENTANYL & OTHER OPIOIDS
Correct ResponseProceed with CautionFentanyl and other opioids (eg, methadone, hydromorphone), sometimes combined with other analgesics (eg, lidocaine, ketamine, dexmedetomidine), can be given parenterally as bolus doses or as CRIs and may be beneficial in treating acute pain in the hospital setting. Oral and transdermal opioids may also provide relief of acute pain in the home but should be used cautiously and only for short durations.