1) Morphine cannot be used in cats due to CNS excitement and slow metabolism AND Morphine causes histamine release in dogs
resulting in severe hypotension AND The most common adverse effects of opioids are cardiovascular and respiratory depression
Morphine is often used in cats without severe adverse effects or CNS excitement. "Morphine mania" was produced in cats by
administering 5-20 mg/kg SC – a dose 20-100 times the clinically recommended dose. High doses of opioids in any species can
produce CNS excitement and seizures. The plasma half-life of morphine in cats is ~1.3 hours compared to ~1 hour in dogs. Morphine
is rapidly eliminated in cats, but by a different metabolic pathway (sulfate conjugation) compared to dogs and other species
(glucuronide conjugation). The dose used in cats is lower (0.25 mg/kg IV, IM, SC q 2-4 hrs) because the volume of distribution
in cats is lower compared to dogs. The lower volume of distribution (Vd) means higher plasma concentrations (Cp) are achieved
with a given dose (Dose=Vd*Cp). The dosing interval is the same however since the half-lives are similar.
High doses of any opiate can produce bradycardia, vasodilation and subsequently hypotension. Clinically relevant doses of
morphine (0.5 mg/kg IV or less) produce large increases in histamine release (~500 fold increase) but have minimal effects
on blood pressure. The myth has been propagated due to high doses of morphine (3 mg/kg IV – 6 times the recommended IV dose)
which result in dramatic decreases in MAP (110 mm to 30 mm Hg). The same study administered 0.3 mg/kg morphine IV and saw
no significant changes in blood pressure or histamine in dogs. A separate study administered 0.5 mg/kg IV morphine to dogs
with no concurrent medication which also resulted in no significant changes in blood pressure. Hypotension can be encountered
and exacerbated when morphine is administered concurrently with other drugs which cause vasodilation (acepromazine, isoflurane,
sevoflurane, propofol, et al) or result in decreased cardiac output (isoflurane, sevoflurane, propofol, thiopental, pentobarbital,
et al).
The most common adverse effects of opioids are hypothermia, bradycardia, sedation, nausea, vomiting, panting, and defecation.
Despite the pronounced bradycardia, cardiac output remains stable, due to increased stroke volume in animals administered
clinically recommended dosages. A dose-dependent respiratory depression does occur with opioids, but clinically recommended
dosages produce clinically insignificant respiratory depressant effects. Mild respiratory depression is a concern in animals
with head trauma, some pre-existing pulmonary diseases, or when combined with other respiratory depressants.
2) Ciprofloxacin and enrofloxacin are identical antibiotics and are broad spectrum
Ciprofloxacin and enrofloxacin have significantly different pharmacokinetic properties. Fluoroquinolone efficacy is best related
to the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC:MIC) with optimal dosages achieving
a ratio of 125 or greater. Resistance to fluoroquinolones is minimized by achieving a maximum plasma concentration (CMAX)
to MIC ratio of 8 or greater.
Ciprofloxacin administered 15 mg/kg PO q 12 hours results in an AUC of ~ 24 hr*mcg/mL per day. Therefore this dose would be
optimal for bacteria with an MIC of 0.2 mcg/mL or less. The CMAX after 15 mg/kg of ciprofloxacin is ~ 2.0 mcg/mL which would
decrease the potential resistance in bacteria with an MIC of 0.25 mcg/mL or less.
Enrofloxacin administered 5 mg/kg PO results in an enrofloxacin AUC of 4.5 hr*mcg/mL and a ciprofloxacin AUC 2.7 hr*mcg/mL
for a total of 7.2 hr*mcg/mL sufficient for bacteria with an MIC of 0.06 mcg/mL or less. The CMAX of enrofloxacin is 1.2 mcg/mL
and ciprofloxacin is 0.4 mcg/mL for a total of ~1.6 mcg/mL sufficient to delay resistance in bacteria with an MIC of 0.2 mcg/mL
or less.
Fluoroquinolones typically are active against Staphylococcus spp. and gram negative aerobic bacteria (E coli, Klebsiella spp). Enrofloxacin, marbofloxacin, and ciprofloxacin have poor activity against anaerobic bacteria and Streptococcus spp. Therefore fluoroquinolones lack coverage in >1 quadrant in the typical 4 quadrant scheme of classifying bacteria. Enrofloxacin,
ciprofloxacin, marbofloxacin et al are poor choices for abscesses, oral infections, and dental prophylaxis among other uses.
