Acetazolamide 250mg, 100 Tablets
HYPP Medications for Horses
Product Description:
Used primarily to treat hyperkalemic periodic
paralysis (HYPP), a genetic disease of the neuromuscular system. Also used
to decrease intraocular pressure in the treatment of glaucoma in animals.
Drug Class:
Diuretic
Adverse Effects:
Acetazolamide can potentially produce
hypkalemia in some patients.
Contraindications, Precautions, and Drug
Interactions:
Do not use in patients with acidemia. Use with
caution in any animals sensitive to sulfonamides.
Small Animal Dosage Information:
Dogs and Cats: For glaucoma: 5-10 mg/kg, Every
8-12 hours, by mouth. For other dosage information see your veterinarian.
*When used to treat glaucoma, monitor
patient's ocular pressure.
What is HYPP?
Hyperkalemic Periodic
Paralysis Disease (HYPP) is a muscular disease that affects both horses and
humans. It is caused by a hereditary genetic defect that disrupts a protein
called a sodium ion channel, a tiny gateway in the membrane of muscle cells. The
genetic defect disrupts the channel's normal opening and closing, such that
uncontrolled sodium influxes occur. These influxes in turn change the voltage
current of muscle cells, causing uncontrolled muscle twitching or profound
muscle weakness. High levels of potassium in the blood usually are present when
the disruptions in the ion channel occur.
What Are Effects of HYPP?
Horses with HYPP can experience unpredictable
attacks of paralysis which, in severe cases, can lead to collapse and sudden
death. The cause of death usually is cardiac arrest and /or respiratory failure.
The disease is characterized by intermittent episodes of muscle tremors
manifested by generalized or localized shaking, trembling and weakness.
Occasionally, episodes are accompanied by respiratory noises resulting from
paralysis of the muscles of the upper airway (larynx and pharynx). In cases of
mild attacks, muscle tremors may be so subtle as to be detectable only by an
experienced clinician performing EMG testing.
Can Symptoms of HYPP Vary in Severity?
Clinical signs of HYPP do vary widely among
different horses. Homozygous horses are affected more severely than heterozygous
horses. Under ideal management practices, the defective gene does not appear to
have adverse effects, but stress and/or increased potassium in the serum can
trigger clinical signs of muscle dysfunction. Why some horses manifest severe
signs of the disease and other exhibit little or no signs is unknown but
currently under investigation. Unfortunately, a horse carrying the defective
gene but showing minimal signs has the same chance of passing the gene to future
generations as does the affected horse with severe signs.
What is the Origin of the Genetic Defect
Causing HYPP?
The original genetic defect causing HYPP was a
natural mutation that occurred as part of the evolutionary process. The majority
of such mutations, which are constantly occurring, are not compatible with
survival. However, the genetic mutation causing HYPP produced a functional, yet
altered, sodium ion channel. This gene mutation is not a product of
inbreeding. The gene mutation causing HYPP inadvertently became widespread when
breeders sought to produce horses with heavy musculature.
Is HYPP Limited To A Particular Bloodline of
Horses?
HYPP is associated with horses of heavy
musculature, but this does not mean that all horses with well developed
musculature are afflicted with the disease. The mutant gene causing HYPP
presently has been identified in the descendents of the horse "Impressive."
Research has not yet been performed on other bloodlines to ascertain whether the
same or similar genetic mutation existing in other bloodlines also may cause
HYPP. Since "Impressive" descendants are so numerous, the genetic mutation in
the bloodline is widespread. Theoretically, it is possible that other mutations
causing HYPP in different bloodlines may be more difficult to identify because
they are not so widespread.
HYPP is unique in that it is the first equine
disease in which breeding and molecular genetics have yielded a specific genetic
mutation identifiable with a named bloodline. It only is a matter of time before
other heritable conditions in various bloodlines likewise can be identified.
How is HYPP Inherited In Horses?
Based upon breeding trials conducted at the
Equine Research Laboratory at the University of California at Davis, it was
determined that HYPP is inherited as an autosomal dominant trait, which means it
can occur in both males and females. The trait is inherited from generation to
generation with equal frequency; it does not get "diluted" out. Breeding an
affected heterozygous horse (N/H) to a normal horse (N/N) will result in
approximately 50% normal offspring, while 50% will carry the defective gene
(N/H). Breeding an affected homozygote (H/H) will result in all offspring
carrying the gene mutation, regardless of the status of the other parent.
Normal (N/N) offspring safely can be bred,
without fear of HYPP being inherited. Selective breeding to normal (N/N) horses
could entirely eliminate HYPP disease. As HYPP is inherited as a dominant
condition, it can and is being spread to other breeds. It is to everyone's
benefit to take the necessary steps to selectively breed HYPP out of existence
before it becomes so widespread that this is impossible.
Can Horses be Tested for HYPP?
A DNA test now has been developed and presently
is available at UC Davis to identify horses carrying the defective gene causing
HYPP. This blood test detects the presence or absence of the specific genetic
mutation which has been found in the extended pedigree of "Impressive"
descendants. From a whole blood sample a part of the gene coding for the horse
muscle sodium channel is amplified, cut (using enzymes which cut specific DNA
sequences), separated by electrophoresis, stained and read. Based on the number
of DNA fragments observed, it can be determined whether the horse does not carry
this specific mutation (a normal horse), or whether it carries one or two copies
of this abnormal gene mutation (heterozygous or homozygous for HYPP,
respectively).
How Accurate Is the DNA Blood Test for HYPP?
The test is accurate and reliable based upon
research studies. The presence of the genetic mutation has been found to be
associated with the disease. In a prior publication (Nature Genetics 1992,
Volume 2, p.144-147), we reported upon our testing of 51 related horses which
were diagnosed with HYPP based upon documented episodes of muscle fasciculations
or paralysis not induced by exercise. All 51 horses were positive (for the
sodium channel mutation) using this test. An equal number of related horses
which were determined to be normal (based upon potassium challenge and /or free
clinical signs of muscle disease) were negative for the gene mutation. We also
tested 130 horses from 5 different breeds to determine if the mutation could be
found with any frequency in the general horse population. The only horses to
date which have shown the mutation have been descendants of "Impressive" but,
theoretically, other mutations may exist for which we now have the tools to
start looking. The test has proven to be reliably repeatable, as we routinely
re-run samples and we have not encountered any discrepancies in results
following retesting.
Are False Negative or False Positive HYPP
Test Results Possible?
"False" Negatives: We have encountered a
rare few horses which show various clinical signs of muscle disease but are
negative for the specific gene mutation in the sodium channel. All are privately
owned horses which we have been unable to study thoroughly. None of these horses
has demonstrated increased blood potassium concentration in association with
abnormal clinical signs. Two horses had markedly high muscle enzyme
measurements, and one horse had marked muscle damage evident on muscle biopsy.
We feel at this time that these horses probably have another muscle disease and
not HYPP. We are sequencing the sodium channel for such horses to determine if a
second mutation actually exists.
"False" Positives: We have not
identified any horses which carry the gene mutation and do not have the disease.
Of 142 samples we have received accompanied by clinical information,
approximately 30% of the positive horses have not shown abnormal clinical signs
(according to their owners). All have been young horses (aged 4 or less). None
of these horses has tested negative by other means (such as response to
potassium challenge or electromyography).
No diagnostic test is 100% accurate. Errors
feasibly could occur by several means. If the test result conflicts with
clinical data, then it is possible that the tube of blood was mislabeled or
mishandled in the laboratory. Retesting should be performed. However, based on
the results to date, we can say with confidence that the presence of the
mutation is the cause of HYPP, and the test is accurate and reliable. The test
is extremely specific, and is accurate for the gene sequence substitution which
has been shown to cause HYPP in descendants of "Impressive". Theoretically, it
is feasible that a different horse bloodline could have a mutation in another
portion of the sodium channel which might produce a similar form of muscle
disease and not be detected by this test. If this occurs, careful documentation
of the clinical signs and corresponding laboratory results (including serum
potassium and muscle-derived enzyme concentrations) should be used to confirm
the diagnosis.
Which Horses Should Be Tested for HYPP?
As noted above, the DNA blood test for HYPP
identifies the specific genetic mutation which we now know exists in descendants
of "Impressive". We presently do not know whether different genetic mutations in
other bloodlines also cause HYPP, and the DNA blood test will not identify other
such mutations. Further scientific research is required as to other bloodlines.
We presently recommend that all descendants of "Impressive" be tested for
diagnostic, treatment and breeding purposes.
Are HYPP Test Results Confidential?
Test results are treated as confidential at our
facility. We notify the individual who requested the test by mail or fax of the
results.
Do Horses Outgrow HYPP?
No. An affected horse is affected for life, but
symptomatology does seem to decrease with age. The disease also appears to be
associated with periods of stress, transport, concurrent diseases, initiation of
training or intensive training, and dietary changes. It is possible that older
horses do not experience the same degree of stress as young horses (i.e., they
are not subject to the rigorous show schedules of younger horses and their
owners have discovered the best diet and management routines for these older
horses).
Can Effective Treatment Be Rendered to
HYPP-Afflicted Horses?
HYPP in horses can be managed, and incidents of
mortality significantly reduced, by proper diet and the administration of
medication. While further studies on the mortality rate of HYPP are required, it
is important to put HYPP into perspective relative to the many other conditions
afflicting horses. Horses afflicted with HYPP, if properly managed, can lead
productive, useful lives, and bring their owners many hours of pleasure.
The first step towards effectively managing
HYPP is to have the disease properly diagnosed. It can be confused with other
conditions, such as "tying up". It is essential that you consult with your
veterinarian if you wish to ascertain whether your horse has HYPP. We recommend
the DNA blood test as the most effective and reliable means of diagnosing HYPP.
What Emergency Treatment is Recommend For
Acute Attacks of HYPP?
For a mild attack (when the horse is not
down but has muscle tremors), one or more of the following emergency treatments
are recommended.
Exercise the horse, either by walking or
longing. Exercise stimulates adrenalin which helps replace potassium inside
cells. However, use caution, as the horse could stumble and fall while
sustaining muscle tremors.
Feed grain (oats, dry corn-oats-barley or light
Karo syrup for glucose supplement). Feeding carbohydrates supplies glucose which
stimulates the release of insulin and promotes potassium uptake by cells.
Administer acetazolamide orally (3 mg/kg). This
is usually 6 to 8 tablets if the tablets are 250 mg each. Acetazolamide
increases potassium excretion from the kidney and also affects glucose
metabolism.
For severe attacks, immediate veterinary
attention is necessary. If the horse is down and unable to stand, have your
veterinarian:
Place intravenous (IV) catheter and administer
23% calcium gluconate (150 cc in 1-2 liters of 5% glucose/500 kg horse). The
majority of horses respond immediately to this and stand up.
If no response, follow with 1 L 5% sodium
bicarbonate IV (dose is 1 meq/kg).
Still no response, give 3 L 5% dextrose IV, and
monitor potassium levels in blood.
All of these treatments help stabilize the
muscle membranes and lower blood potassium. Your veterinarian should draw a
blood sample prior to initiation of treatment in order to analyze the blood
potassium and muscle enzyme concentrations. This is required to confirm that the
horse was suffering an attack of HYPP and not something else (i.e., colic).
What Management Practices Will Help control
HYPP?
The following management practices will greatly
assist in the control of HYPP:
Establish regular feeding and exercise
schedule. Avoid fasting and water deprivation. Horses do better if allowed
access to a paddock or pasture rather than strict stall confinement. Daily or
nightly turnout is helpful.
Adult horses do very well on grass or oat hay
alone or pasture. If it is necessary to use alfalfa to balance the ration for
growing horses, then mix alfalfa with grass hay or oat hay and grain (oats are
best) to decrease potassium content of diet. Feed equal amounts of hay and grain
two or three times daily. Avoid rapid changes in diet. Provide access to a white
salt block or feed loose salt. Administer acetazolamide (Diamox), a diuretic, (2
mg/kg orally twice a day). Many halter-horse owners continue to feed alfalfa hay
as the only roughage but maintain their horses on this drug for all or most of
their lives. Please note that this drug is a forbidden substance under AQHA and
AHSA regulations.
Inform your veterinarian of HYPP condition
prior to any general anesthesia, which may precipitate an episode of paralysis.
Maintain acetazolamide therapy before and after surgery or anesthesia.
Use common sense while hauling. Be sure to stop
and water horse frequently (every 2 hours). Acetazolamide treatment is helpful
to prevent problems.