2016 SPRING: Antibiotics: Cidal and/or Static? | Purring Cats | Spider Bites | MDR1 Gene Mutation | Marijuana | Toxic World | Feline Anemia Clinical Trial | Waiting for Progress | Continuing Education
Antibiotics: Cidal and/or Static?
Is it wrong to simultaneously combine bactericidal and bacteriostatic antibiotics in my patient?
Bactericidal antibiotics, such as the cephalosporins and fluoroquinolones, bind to their bacterial cellular targets setting in motion a series of actions that actually kill bacteria and other susceptible microbes. By contrast, bacteriostatic antibiotics such as tetracycline, chloramphenicol, trimethoprim sulfa and azithromycin inhibit bacterial growth or replication by interfering with various bacterial cellular metabolic pathways. Disruption of these pathways inhibits bacterial protein production or bacterial DNA replication, allowing the immune system to overpower the infection.
Will these medications interfere with each other?
When the identity of a potential infectious agent is not known or multiple potential pathogens may be present in a patient, clinicians may need to consider administering both bacteriostatic and bactericidal antibiotics simultaneously. Many doctors are concerned that bacteriostatic antibiotics will either inhibit the metabolic pathways required by bactericidal antibiotics to produce lethal effect or induce metabolic pathways that block their cidal effects.
This concern, however, appears to be unfounded. Recent studies suggest that antibiotics in both classes are bacteriostatic or bactericidal depending on the concentration of the antibiotic achieved at the site of infection, as well as the susceptibility of the organism to be treated. Furthermore, studies and experience in both the human and veterinary fields have yet to confirm that combining static and cidal antibiotics reduces the efficacy of the individual medications. Administering both a cephalosporin and doxycycline to a patient who may be afflicted with bacterial and/or rickettsial infections appears to be effective, despite doxycycline being classified as a bacteriostatic. That being said, if the identity of the pathogen is known, the bactericidal medication is preferred.
Why Do Cats Purr?
With all we know about our pets, you would think that by now experts would have figured out how and why cats purr. However, it remains one of the mysteries of the animal kingdom.
Purring appears to be caused by the rapid repeated neurologic stimulation of the muscles of the larynx and the diaphragm. This stimulation causes vibrations in the air somewhere along the upper respiratory system resulting in the purring sound. The exact source of the sound, however, remains undetermined. Purring occurs both during inhalation and exhalation.
But why do cats purr? Cats most commonly purr when we are petting them or when they are nursing kittens. In these two instances, it would seem that purring serves to communicate some sort of message. But cats will also purr when they are stressed. We have all seen the terrified cats purring as we examine them. The purpose of this purr remains undetermined.
Interestingly, investigators have found that the frequency range of a cat’s purr stimulates bone and muscle metabolism and promotes healing. Some have theorized that purring may serve the purpose of maintaining muscle and bone health as a cat ages or during periods of illness or injury. In essence, purring serves as a form of physical therapy. This would be similar to the use of ultrasonic stimulation of muscles and bones by physical therapists.
Not Such an Itsy Bitsy Spider Bite
Almost all spiders are venomous. That’s how they kill their prey. Lucky for us and our pets, only a few of the spiders found in the United States produce venom that is potent enough to cause serious damage. Two such spiders are the black widow and the brown recluse.
Most spider bites are not exceedingly painful and go unnoticed. Some pets may react to the brief sting or demonstrate a local itching sensation. Without knowledge that a bite has occurred, associating a pet’s signs with a spider bite can be difficult. Occasionally, two tiny punctures can be found.
The Black Widow
Black widow spider
The venom produced by the black widow spider acts as a neurotoxin. It causes overstimulation of nerve synapses resulting in muscle pain, cramping and rigidity, paralysis and high blood pressure. The respiratory muscles may be affected resulting in respiratory compromise. Cats appear to be more sensitive to the venom than dogs. Recovery from a black widow bite can take many days. Treatment includes general support, pain medications, muscle relaxants, antihistamines and respiratory support. An antivenom is available but infrequently used due to its expense.
The Brown Recluse
The venom produced by the brown recluse spider contains a variety of cytotoxic and hemolytic enzymes which when released into the victim’s skin directly damage cell membranes in the surrounding tissue and blood vessels leading to necrosis. These enzymes also induce a severe immune response which further contributes to the cellular damage. The severity of the tissue damage appears to vary with the volume of venom injected and the particular pet’s sensitivity to the venom. Female spiders and larger, more mature spiders tend to inject higher volumes of venom.
Brown recluse lesion on 3 1/2 year-old Labrador retriever. The dead spider was found under the dog’s favorite chair.
Brown recluse spider
Evidence of tissue injury usually appears within hours of the spider bite. Ischemic and necrotic changes develop over days to weeks leaving a large ulcerated lesion. Healing is slow due to vascular compromise, and severe scarring typically develops. Infrequently, systemic signs such as fever, GI upset and even shock may develop. Secondary renal failure and DIC have been described.
There is no antidote for a brown recluse spider bite. Dapsone, a leukocyte inhibitor, has been used in animal models to limit the skin necrosis. It acts by reducing the secondary immune reaction which contributes to the injury. Dapsone can have serious side effects including liver damage, neurotoxicity and cytopenia.
Debridement of the wound and healing by second intention is typically recommended, but wounds heal very slowly. Early surgical closure of the wound has not consistently proven to be effective, and skin grafts may be necessary to complete the healing. Hyperbaric oxygen therapy has also been advocated to improve tissue oxygenation and promote healing. Most pets require antibiotic therapy and pain medications. For patients demonstrating systemic signs, aggressive treatment with intravenous fluids, pain medications and corticosteroids are indicated.
Brown recluse spiders can be recognized by the violin shaped marking on their backs. They are usually brown to gray in color and vary from 8 to 15 mm in size. Generally nocturnal, brown recluse spiders prefer to hide under objects where they can’t be disturbed in dark, warm regions of the house. They survive by feeding on other insects and tend to be nonaggressive, biting only when threatened. Brown recluse spiders can be found in the south, south-central and mid-western states from Georgia to Texas and up to Wisconsin.
Potential Toxicity? MDR1 Gene Mutation?
When it comes to being suspicious for the presence of a toxic reaction, you shouldn’t just look at the potential chemical exposure. You also have to consider the health status of the patient. The presence of an underlying problem in a pet can change what would typically be a safe chemical exposure into a life threatening exposure. What would be a good example of this? How about the presence of a MDR1 gene mutation in some herder breeds.
What is the MDR1 gene mutation?
The development of ivermectin to prevent heartworm disease and treat other parasites was a tremendous step forward for the veterinary profession. It did not take long, however, to realize that in collies recommended doses of ivermectin, found to be safe in other breeds, caused severe neurologic signs. Subsequent research determined that many collies carried an inherited defect in their multi-drug resistance (MDR1) gene. This gene encodes for P-glycoprotein. P-glycoprotein is located in the cell membranes of the liver, pancreas, intestines, kidney and brain capillary endothelium. It functions to bind and actively transport certain chemicals that have leaked into the cell cytoplasm out of the cell. Collies who possessed the MDR1 gene mutation did not produce adequate P-glycoprotein concentrations needed to remove the ivermectin that leaked into their brain cells. The excessively high concentration of intracellular ivermectin was responsible for the abnormal neurologic signs.
P-glycoproteins are responsible for clearing a number of other chemicals and drugs from within susceptible cells. A list of drugs to be concerned about can be found on the Washington State University college of veterinary medicine’s website. The administration of these drugs to dogs with the MDR1 gene mutation has been reported to cause variable and potentially severe side effects including neurologic signs, gastrointestinal signs and myelosuppression (decreased blood cell counts):
A number of breeds have been shown to potentially carry the MDR1 gene mutation, namely collies, Australian shepherds, Shetland sheepdogs (shelties), old English sheepdogs, and long-haired whippets. Infrequently, the defect has been found in other breeds. The disorder is inherited as an autosomal recessive gene. There is a screening test to confirm the presence of the mutated MDR1 gene available at Washington State University’s college of veterinary medicine. Test results indicate if the dog carries two, one or no copies of the mutated gene. Even heterozygous dogs may show some susceptibility to toxicity.
What should you do if you have a breed that carries the MDR1 gene mutation?
It is safest to avoid the drugs to which the dog may be sensitive. If you must use a potentially toxic drug, the dose should be decreased by 50% in homozygous dogs and 25% in heterozygous pets. Pet owners should be informed of the associated risks of treating the patient.
Did you know?
The presence of P-glycoprotein in some cancer cells is likely responsible for rendering them multidrug resistant. Researchers are looking for ways to inhibit the action of P-glycoproteins in cancer cells to improve the efficacy of anticancer medications.
Marijuana: A Growing Toxicity
Marijuana is believed to be the most commonly used illicit drug in the United States. With its legalization for medical use in humans and its recent decriminalization in Colorado and Washington, the frequency with which pets are being exposed to marijuana or one of its derivatives is increasing.
The toxic chemical in marijuana is delta 9-tetrahydrocannabinol or THC. Dried leaves and flowers of the hemp plant Cannabis sativa contain 1-8% THC. Hashish, compressed resin produced from the flowering tops of the plants, contains 10% THC. Hash oil or butter, a concentrated form of hashish or marijuana in which the cannabinoids are extracted into the fat of oil or butter, can have a THC concentration exceeding 50%.
The most common means by which dogs and, uncommonly, cats are exposed to marijuana is by ingestion of home cooked or commercial products containing THC. THC is stored in the tissues of the brain, liver and kidneys. Being highly lipid soluble the chemical is also stored in fat deposits where it can remain for days. The majority of the THC is excreted via the biliary system and eliminated via the feces.
Signs of marijuana intoxication typically occur within 60 minutes of exposure and can last several days. The THC binds to cannabinoid receptors in the brain where it interacts with the neurotransmitters norepinephrine, dopamine, serotonin and gamma-aminobutyric acid inducing varying stimulatory and inhibitory signs involving the GI, cardiovascular and neurologic systems.
Signs of marijuana intoxication:
- Depression or dysphoria
- Hyperstartle response
- Urine dribbling
Is it marijuana?
The challenge in diagnosing marijuana toxicity is getting the pet owner to confirm the pet’s potential exposure. Routine blood testing and imaging typically fail to demonstrate significant abnormalities. Furthermore, over-the-counter drug tests as well as laboratory tests for THC have not yet been proven effective in pets. Luckily the signs of THC toxicity, i.e. dysphoria, drowsiness, a hyperstartle response and especially urine dribbling are pretty recognizable.
What’s the best treatment?
Treatment after immediate exposure to marijuana could include induction of emesis and the administration of activated charcoal. Both would be contraindicated if the clinician feels the patient’s mental state predisposes the pet to the possibility of aspiration pneumonia. Interestingly, induction of emesis may not be effective as one of the marijuana’s medical uses is to inhibit nausea and vomiting in human cancer patients. The repeat administration of activated charcoal 6-8 hours after an initial administration should be considered to reduce GI absorption of the THC as it goes through eneterohepatic circulation.
Symptomatic supportive care should be individualized to the patient and would typically include IV fluids to ensure hydration and perfusion, external heating or cooling as indicated, and anti-anxiety therapy. More severely affected patients may require cardiovascular medications, oxygen supplementation or even ventilation. Intralipid therapy should be considered in more severely affected patients and those with prolonged duration of signs. Because THC is lipid soluble, it can be leached from the body with intralipid therapy. Close monitoring of these patients is important. Luckily THC has a high safety margin. To be lethal most dogs must be exposed to greater than 3 g/kg.
Could marijuana be beneficial for treating ill pets?
In humans, marijuana and its derivatives have been shown or suggested to have many potential medical uses including:
- Stimulating appetite and reducing nausea in cancer patients
- Treatment of glaucoma
- Increasing lung capacity
- Controlling epilepsy
- Reducing cancer spread
- Slowing the progression of Alzheimer’s disease
- Reducing the pain of multiple sclerosis
- Relieving arthritis discomfort
- Treating inflammatory bowel disease
Reports of marijuana’s effectiveness for treating ill pets are very limited and at best anecdotal. Marijuana is a Schedule I narcotic. Even if you live in a state where medical marijuana is sanctioned, as a veterinarian it remains illegal for you to prescribe or recommend it to treat a patient.
If you feel you may be dealing with a pet who has a potential toxicity or desire closer 24 hours or after-hours monitoring of your patient, please don’t hesitate to give us a call. Our emergency and critical care services have loads of experience dealing with all types of toxicities.
It’s a Toxic World
It’s a toxic world if you think about it. And it is our job as veterinarians to look at the world that way. Not everything is toxic, you insist. How about the air that we breathe or the tap water we drink? Well I hate to break it to you, but have you ever heard of oxygen toxicity or water toxicity. Even the most common mundane chemicals in our environment, if taken in concentrations or quantities our bodies or those of our patients can’t handle, can be toxic.
Lucky for us, our pets, living in secure homes, are not exposed to as many toxins, or not in the concentrations required to cause illness. But toxicity is a relative thing. It’s not just about how much of the particular chemical that the pet was exposed to. It’s also about the means of exposure, the rate of exposure, and the ability of the patient to metabolize and excrete the chemical. Toxicology is really pharmacology. Even the medications we prescribe to our patients have the potential to be toxic if the pet can’t metabolize the chemical adequately. See what happens when you give a normal dose of ivermectin to an Australian shepherd with a MDR1 gene mutation or a NSAID to a dog with kidney failure. Lucky for us, the toxic potential and properties of a tremendous number of environmental and household chemicals have been studied and documented. Our own drug formularies are filled with listings of the toxic effects of the medications we use. We don’t need to figure out if a chemical is toxic. The challenge for us is recognizing when an ill patient is demonstrating a toxicity.
Trupanion’s list of top poison and toxicity claims in 2015
- Rat poison
- Common household drugs
- Grapes and raisins
- Onions and garlic
WANTED: Cats for a Fully-Funded Feline Anemia Trial
BluePearl Veterinary Partners in Overland Park is currently recruiting patients for a fully-funded trial to evaluate the safety and efficacy of an oral medication to manage anemia associated with chronic kidney disease in cats. The study consists of two phases: the efficacy phase (28 days) and the maintenance phase (8 weeks).
- Cats, > 1 year old, male or female, > 2.0 kg
- Not pregnant, lactating or intended for breeding
- Diagnosis of chronic kidney disease
- Non-regenerative anemia with PCV < 27% at study days -7 and 0
- Stable concurrent medical conditions
- Cats may be receiving SQ fluids
- Fractious cats • Positive urine culture on study day -7
- Systolic blood pressure > 165 mmHg on study days -7 or 0
- Previous treatment with erythrocyte stimulating agents (ESA), including erythropoietin (EPO)
- Previous blood transfusion since being diagnosed with CKD
- Severe clinical signs of inflammation not attributed to CKD
- Other significant uncontrolled medical issues
- FeLV+ or FIV+ (if not vaccinated, sponsor will cover the cost to test)
- Obvious signs of GI bleeding
The study medication, diagnostic lab work and examinations will be provided at no cost to owners. Owners will be expected to administer the study medication at home, keep an owner diary and comply with study protocols.
*Note that this study is not funded for diagnostic or treatment costs associated with the underlying renal disease. Those costs must still be assumed by the owner.
For more information, or if you have a patient who may meet the above requirements, please contact Beth Rogers at our Overland Park hospital, 913.642.9563.
FROM THE MEDICAL DIRECTOR
Medical Director’s Column: Waiting on Progress
I am still waiting.
Progress is a wondrous thing. At first glance there would seem to be a lot of new technologies to help us diagnose and treat our patients. But has the means of collecting data really changed? Blood samples are still being drawn from patients to check chemical levels to determine if a particular organ is irritated. Stethoscopes are still being placed on the chest cavity, and thermometers are still being poked up the butts of dogs and cats. Blood pressure cuffs are still being wrapped around legs and arms. Even the CT unit is nothing more than a radiograph machine that spins around the patient. The real progress would seem to be the computer systems attached to these age-old technologies that are correlating and presenting the data. This may just be an old DVM talking, but I want to know, when am I going to get my Star Trek Tricorder? Now that would be progress.
Jeff Dennis, DVM, DACVIM
BluePearl is strongly committed to the veterinary community. One of the ways we demonstrate this commitment is through our continuing education program, which is subsidized in part by our Partners in Education.
All BluePearl CE lectures are free and open to all area veterinary professionals. All events will have a meal served at 6:30PM with the lectures starting at 7PM. Lectures are FREE; however, a $5 donation to Frankie’s Friends charitable pet foundation is appreciated.
Registration is required. To register, please contact Meagan Hake at 913.642.9563 or firstname.lastname@example.org. For the most current information about BluePearl CE, please check our online calendar regularly.
The following CEs are for technicians.
|Date||Topic and Speaker||Description of Course||Location|
|May 19||Dental Prophylaxis and Blocks
Gary Modrcin, DVM, DAVDC
||Stoney Creek Hotel and Convention Center|
|June 23||Rehabilitation and Your Patients
Connie Schulte, DPT, CCRP
||Maple Woods Vet Tech Building|
|Aug 18||Blood Chemistry Panels and Complete Blood Counts
Shannon Quinn, RVT
||BluePearl Overland Park|
|Nov 17||Cardiopulmonary Cerebral Resuscitation – Staying Alive!
Ryan Bragg, DVM, DACVECC
||Maple Woods Vet Tech Building|