Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
prevent the growth of existing clots but will not lyse
clots.
Formulations and dose rates
Heparin is available in ampoules in a range of concentrations (1000–
40,000 U/mL) as well as in prefi lled syringes (various concentrations
and amounts) and premixed with saline and half-normal saline in
250 mL, 500 mL or 1000 mL containers.
Thromboembolic disease
• 100–200 U/kg IV loading dose then 100–300 U/kg SC q.6–8 h
Low-dose prophylaxis
• 50–75 U/kg SC q.8–12 h
DIC
• 50–200 U/kg into plasma or whole blood to be transfused then
50–100 U/kg SC q.8 h once the antithrombin concentration is
greater than 60%
Pharmacokinetics
Heparin is not absorbed from the gut if given orally; it
therefore must be given parenterally to be effective. If
sufficient antithrombin is present, anticoagulant activity
begins immediately after intravenous injection and up
to 1 h after subcutaneous injection.
Heparin is extensively protein bound, primarily to
fibrinogen, low-density lipoproteins and globulins. It
does not cross the placenta or into milk in any appreciable
amounts. Heparin in humans appears to be
cleared and degraded primarily by the reticuloendothelial
system. A small amount of nondegraded heparin
also appears in the urine. In humans the serum half-life
averages 1–2 h and is dependent on the dose administered.
The half-life in humans may be shorter in patients
with pulmonary thromboembolism and prolonged in
patients with renal failure and hepatic cirrhosis.
Adverse effects
● The most common adverse effects associated with
heparin therapy are bleeding and thrombocytopenia.
In human medicine, major bleeding occurs in 1–33%
of patients receiving various forms of heparin
therapy. Mild thrombocytopenia occurs in a small
proportion of human patients 2–15 d after commencement
of therapy; in these patients therapy can
be continued if the platelet count does not fall below
100 × 10 6 /L. In rare cases, severe immune-mediated
thrombocytopenia can occur.
● Hypersensitivity reactions may occur if heparin is of
bovine or porcine origin.
● Uncommon adverse effects reported in humans
include:
– osteoporosis and spontaneous vertebral fractures
after long-term therapy
– hyperkalemia as a result of heparin inhibiting the
synthesis of aldosterone.
● In humans, mild increases in alanine aminotransferase
enzyme concentrations are common.
● Intramuscular injection can result in hematoma formation.
Hematomas, pain and irritation may also
occur after deep SC injection.
● Because heparin does not cross the placenta and has
not been associated with fetal abnormalities (in contrast
to warfarin), it is used for anticoagulation in
human pregnancies. However, its safety in pregnancy
has not been established. Indeed, it has been reported
that fetal mortality or prematurity occurs in onethird
of pregnancies where heparin has been used.
Known drug interactions
● Heparin sodium is incompatible with the following
solutions or drugs:
– sodium lactate 1/6 mmol/L
– aminoglycosides
– chlorpromazine HCl
– codeine phosphate
– cytarabine
– daunorubicin HCl
– diazepam
– doxorubicin HCl
– droperidol HCl ± fentanyl citrate
– erythromycin
– hyaluronidase
– levorphanol bitartrate
– pethidine HCl (meperidine HCl)
– methadone HCl
– morphine sulfate
– pentazocine lactate
– phenytoin sodium
– polymyxin B sulfate
– vancomycin sulfate.
● There is conflicting information on compatibility,
or compatibility is dependent on diluent or
concentration, for:
– dextrose-saline combinations
– dextrose in water
– lactated Ringer’s solution
– saline solutions
– ampicillin sodium
– cefalothin sodium
– dobutamine HCl
– hydrocortisone sodium succinate
– methicillin sodium
– oxytetracycline HCl
– penicillin G sodium/potassium
– tetracycline HCl.
● Heparin should be used with caution with other
drugs that change coagulation status of platelet
function, e.g.:
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