Page 1057 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 58 Management of the Poisoned Patient 1043

The first sign of salicylate toxicity is often hyperventilation is mainly seen with nifedipine and related dihydropyridines, but
and respiratory alkalosis due to medullary stimulation. Metabolic in severe overdose all of the listed cardiovascular effects can occur
acidosis follows, and an increased anion gap results from accumu- with any of the calcium channel blockers.
lation of lactate as well as excretion of bicarbonate by the kidney Treatment requires general supportive care. Since most
to compensate for respiratory alkalosis. Arterial blood gas testing ingested calcium antagonists are in sustained-release form,
often reveals a mixed respiratory alkalosis and metabolic acidosis. it may be possible to expel them before they are completely
Body temperature may be elevated owing to uncoupling of oxida- absorbed; initiate whole bowel irrigation and oral activated char-
tive phosphorylation. Severe hyperthermia may occur in serious coal as soon as possible, before calcium antagonist-induced ileus
cases. Vomiting and hyperpnea as well as hyperthermia contrib- intervenes. Calcium, given intravenously in doses of 2–10 g,
ute to fluid loss and dehydration. With very severe poisoning, is a useful antidote for depressed cardiac contractility but less
profound metabolic acidosis, seizures, coma, pulmonary edema, effective for nodal block or peripheral vascular collapse. Other
and cardiovascular collapse may occur. Absorption of salicylate treatments reported to be helpful in managing hypotension
and signs of toxicity may be delayed after very large overdoses or associated with calcium channel blocker poisoning include high-
ingestion of enteric coated tablets. dose insulin (0.5–1 unit/kg/h) plus glucose supplementation
General supportive care is essential. After massive aspirin inges- to maintain euglycemia; glucagon; veno-arterial extracorporeal
tions (eg, more than 100 tablets), aggressive gut decontamination membrane oxygenation (ECMO-VA); and methylene blue. A
is advisable, including gastric lavage, repeated doses of activated few case reports have suggested benefit from administration
charcoal, and consideration of whole bowel irrigation. Intrave- of lipid emulsion (normally used as an intravenous dietary fat
nous fluids are used to replace fluid losses caused by tachypnea, supplement) for severe verapamil overdose.
vomiting, and fever. For moderate intoxications, intravenous
sodium bicarbonate is given to alkalinize the urine and promote
salicylate excretion by trapping the salicylate in its ionized, polar CARBON MONOXIDE & OTHER TOXIC
form. For severe poisoning (eg, patients with severe acidosis, GASES
coma, and serum salicylate level >90–100 mg/dL), emergency
hemodialysis is performed to remove the salicylate more quickly Carbon monoxide (CO) is a colorless, odorless gas that is ubiq-
and restore acid-base balance and fluid status. uitous because it is created whenever carbon-containing materials
are burned. Carbon monoxide poisoning is the leading cause of
BETA BLOCKERS death due to poisoning in the USA. Most cases occur in victims
of fires, but accidental and suicidal exposures are also common.
In overdose, β blockers inhibit both β and β adrenoceptors; The diagnosis and treatment of carbon monoxide poisoning are
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selectivity, if any, is lost at high dosage. The most toxic β blocker described in Chapter 56. Many other toxic gases are produced in
is propranolol. As little as two to three times the therapeutic dose fires or released in industrial accidents (Table 58–4).
can cause serious toxicity. This may be because propranolol in
high doses may cause sodium channel-blocking effects similar to CHOLINESTERASE INHIBITORS
those seen with tricyclic antidepressants, and it is lipophilic, allow-
ing it to enter the CNS (see Chapter 10). Organophosphate and carbamate cholinesterase inhibitors (see
Bradycardia and hypotension are the most common manifesta-
tions of toxicity. Agents with partial agonist activity (eg, pindolol) Chapter 7) are widely used to kill insects and other pests. Most
cases of serious organophosphate or carbamate poisoning result
can cause tachycardia and hypertension. Seizures and cardiac con- from intentional ingestion by a suicidal person, but poisoning
duction block (wide QRS complex) may be seen with propranolol has also occurred at work (pesticide application or packaging) or,
overdose. rarely, as a result of food contamination or terrorist attack (eg,
General supportive care should be provided as outlined earlier.
The usual measures used to raise the blood pressure and heart release of the chemical warfare nerve agent sarin in the Tokyo
subway system in 1995).
rate, such as intravenous fluids, β-agonist drugs, and atropine, are Stimulation of muscarinic receptors causes abdominal cramps,
generally ineffective. Glucagon is a useful antidote that—like β diarrhea, excessive salivation, sweating, urinary frequency, and
agonists—acts on cardiac cells to raise intracellular cAMP but does increased bronchial secretions (see Chapters 6 and 7). Stimulation
so independent of β adrenoceptors. It can improve heart rate and of nicotinic receptors causes generalized ganglionic activation,
blood pressure when given in high doses (5–20 mg intravenously).
which can lead to hypertension and either tachycardia or bradycar-
dia. Muscle twitching and fasciculations may progress to weakness
CALCIUM CHANNEL BLOCKERS and respiratory muscle paralysis. CNS effects include agitation,
confusion, and seizures. The mnemonic DUMBELS (diarrhea,
Calcium antagonists can cause serious toxicity or death with rela- urination, miosis and muscle weakness, bronchospasm, excitation,
tively small overdoses. These channel blockers depress sinus node lacrimation, and seizures, sweating, and salivation) helps recall
automaticity and slow AV node conduction (see Chapter 12). They the common findings. Blood testing may be used to document
also reduce cardiac output and blood pressure. Serious hypotension depressed activity of red blood cell (acetylcholinesterase) and