Page 1224 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Prevention and Treatment of Poisoning Chapter | 82 1155

VetBooks.ir nary medicine to treat the following types of toxicoses: apparently has its highest affinity for the mu receptor,
Methocarbamol has been used successfully in veteri-
which makes it an ideal antagonist since most of the clini-
cally useful opioids work by binding to the mu receptor
permethrin in cats (Richardson, 2000a), metaldehyde
(Richardson et al., 2003), strychnine (Gwaltney-Brant and (Plumb, 2015; Volmer, 2006).
Rumbeiha, 2002; Plumb, 2015) and tremorgenic mycotox- Naloxone reverses most of the effects of opioids
ins (Schell, 2000). It is able to reduce the severity of including analgesia and respiratory and CNS depression
tremors without causing the severe CNS depression often (Plumb, 2015). It does not reverse the emetic actions of
encountered when using a barbiturate medication apomorphine in dogs (Volmer, 2006). At high doses, nal-
(Gwaltney-Brant and Rumbeiha, 2002). oxone increases dopamine levels and acts as a GABA
The dosage for dogs and cats is 55 220 mg/kg admin- antagonist (Plumb, 2015).
istered slowly IV at a rate of no more than 2 mL/min Because orally administered naloxone is only mini-
(Schell, 2000). Methocarbamol administration should be mally absorbed and the drug is destroyed rapidly in the
repeated if the signs recur; however, the total dose should digestive tract, an injectable formulation is preferred. The
not exceed 330 mg/kg in a 24-h period to avoid CNS and onset of action is normally within 1 2 min when given
respiratory depression (Gwaltney-Brant and Rumbeiha, IV and within 5 min when given IM. The duration of
2002; Richardson et al., 2003). The dosage for horses is action is usually 45 90 min but may be as long as 3 h.
4.4 55 mg/kg by slow infusion (Plumb, 2015). The drug Since the duration of action of naloxone may be shorter
should not be given SQ, and extravasation of methocarba- than the medication being reversed, additional doses may
mol should be avoided, as the solution can be irritating be required (Plumb, 2015).
(Plumb, 2015). The recommended dosage for dogs and cats is
In dogs and cats, adverse effects may include sedation, 0.01 0.04 mg/kg IV, IM or SC; and for horses,
salivation, emesis, lethargy, weakness, and ataxia. Slow 0.01 0.05 mg/kg IV (Plumb, 2015). In patients that have
administration of the drug can help to avoid salivation been intentionally given an opioid to treat a painful condi-
and emesis. Sedation and ataxia can be seen in horses fol- tion, abrupt reversal can lead to tachycardia, vasoconstric-
lowing methocarbamol administration. This medication is tion and hypertension. In these cases, the unwanted CNS
contraindicated in animals intended for food purposes and and respiratory depression can be reversed without revers-
in patients hypersensitive to it. The manufacturer ing the analgesia. To achieve this, dilute 0.04 0.1 mg of
lists known or suspected renal insufficiency as a contrain- naloxone in 5 10 mL of normal saline and give slowly to
dication to injectable methocarbamol therapy since the effect by dosing 0.5 1 mL per minute (Mathews, 2006).
injectable product contains polyethylene glycol 300, Naloxone is considered quite safe at therapeutic doses.
which has been found to increase acidosis and urea Very high doses have been associated with seizures in a
retention in renal-impaired humans (Plumb, 2015). few patients perhaps due to GABA inhibition. It is contra-
For this reason, veterinary patients treated with indicated in patients that are hypersensitive to it and
injectable methocarbamol should receive IV fluid support should be used with caution in animals with preexisting
and have kidney values monitored if renal impairment is cardiac abnormalities due to the potential cardiovascular
suspected or is a possible outcome of their clinical signs. adverse effects (Plumb, 2015).
For example, patients with prolonged tremors or seizures
can release muscular myoglobin. The myoglobin is N-Acetylcysteine
excreted by the kidneys and can lead to renal damage
(Volmer, 2004). N-Acetylcysteine (NAC) is used to prevent methemoglo-
binemia and hepatic necrosis in acetaminophen (APAP)
toxicosis. APAP is metabolized in the liver primarily via
Naloxone HCl
glucuronidation and sulfation to nontoxic metabolites.
Naloxone HCl (Narcan) is an injectable opiate antagonist However, other pathways of metabolism exist that yield
used to reverse the effects of opiate medications. It is able the toxic metabolites N-acetyl-para-benzoquinoneimine
to reverse opioid agonist/antagonists, such as butorphanol (NAPQI) and para-aminophenol (PAP) (Aronson and
as well. This drug is also being investigated for treatment Drobatz, 1996; McConkey et al., 2009). In a significant
of other conditions like septic, hypovolemic and cardio- APAP exposure, the glucuronidation and sulfation
genic shock (Plumb, 2015). pathways become saturated, leading to increased produc-
Naloxone is a pure opiate antagonist, and it has no tion of NAPQI and PAP. NAPQI is produced through
analgesic activity or other agonist effects. Although the the P450 mixed function oxidase system and is nor-
exact mechanism for its activity is not fully understood, it mally inactivated through conjugation with glutathione
is thought the drug acts as a competitive antagonist by (Richardson, 2000b). PAP is produced by deacetylation
binding to multiple opioid receptor sites. The drug and is removed both through conjugation with glutathione