Clinical toxicology

Salicylates

Salicylate
is used as an analgesic agent for the
treatment of mild to moderate pain.
Aspirin is used as an anti-inflammatory
agent for the treatment of soft tissue and
joint inflammation and vasculitides such
as acute rheumatic fever .
antipyretic drug.
Low-dose aspirin helps to prevent
thrombosis

SALICYLATES
Salicylate poisoning is a potentially lifethreatening conditions
! Availability in many OTC oral preparations,
various
cold
preparations;
topical
keratolytic preparations (methyl salicylate)

syndrome caused by a
dangerous level of toxins in the body)

Toxidromes

(a

confusion,
dehydration,
and
acidosis are often attributed
pneumonia, or gastroenteritis

metabolic
to sepsis,

SALICYLATES
Aspirin poisoning may affect people of all
ages
Children are most susceptible:
fatal
outcome enhanced with dehydration and/or
febrile
Elderly: chronic toxicity due to alterations
in
the
elimination
process
and
simultaneous ingestion of other drugs

Side effects
1.Gastrointestinal ulceration and intolerance

(GI)

2.Blockage of platelet aggregation

3.Inhibition of prostaglandin-mediated renal

function
4.Inhibition of uterine motility
5.Hypersensitivity reactions
6.Reyes syndrome in children with viral
infections (is a syndrome has effect tomany
organs unknown cause associated aspirin
and viral infection in children==rash ,
vomiting and liver damage

SALICYLATES.PK
ACETYLATED SALICYLIC ACID (aspirin) &
NONACETYLATED
SALICYLIC
ACID
(sodium salicylate, choline salicylate,
magnesium salicylate)

are readily absorbed from the stomach

Absorption depends on formulation:
enteric coated tablets..absorbed slowly

. The volume of distribution of salicylate is

about 0.10.3 L/kg, but this can be
increased by acidemia, which enhances
movement of the drug into cells.

SALICYLATES.PK
Effervescent tablets rapidly absorbed
Other factors: rate of gastric emptying,
concurrent ingestion of food and drugs, GI
diseases
ELIMINATION: mostly by hepatic metabolism at
therapeutic doses, but renal excretion becomes
important with overdose
..saturation of hepatic enzyme.zero-order
elimination kinetics
Furosemide.inhibit
salicylate
excretion;
Acetazolamide: enhance the ability of nonionized
form to penetrate CNS (metabolic acidosis).

Aspirin - Pharmacokinetics
Rapidly absorbed from GI tract
through passive diffusion
80-90% is bound to plasma proteins,
mainly albumin
Can displace several other drugs from
plasma protein resulting in higher
effective plasma concentrations
Rapidly hydrolyzed in blood and liver
to salicyclic acid

Aspirin Toxicity: changes

in acid-base balance
Phase 1 of the toxicity is characterized
by hyperventilation resulting from
direct respiratory center stimulation,
leading to respiratory alkalosis
In phase 2
aciduria in the
presence of continued respiratory
alkalosis occurs when sufficient
potassium has been lost from the
kidneys

CNS effects of salicylate intoxication

Salicylate level increases in the brain

Stimulate respiratory center

hyperventilation
PCO2

Respiratory
alkalosis periph
Uncouple

Inh
Inhibition
krebs
a.a
oxidative
Renal
glu
cycle enz
metabolismcompensati
phosphorylatio
demand
n ATP
Inc
Aminoacidu on
organic
ria
glycolysis
acids, aStim lipid met
ketoglute
rate
ketone bodies
Inc lactic and pyruvic acid
Metaboli

SALICYLATES
The major early toxic manifestations of salicylate
poisoning result from stimulation of the CNS
These
include
nausea,
vomiting,
tinnitus,
headache,
hyperapnea,
and
neurological
abnormalities
(confusion,
slurred
speech,
convulsions)
Another
serious
effect
of
salicylates
is
dehydration??
1.uncouple oxidative phosphorylation in the
mitochondria; this generates heat and may
increase body temperature
2.Renal compensated respiratory alkalosis
results in loss of carbonate, followed by Na
and K and water

SALICYLATES
This dehydration is more common in
children and usually associated with
moderate
to
severe
levels
of
salicylate toxicity
A useful means of evaluating the degree
of potential following an acute oral
ingestion of salicylate is to correlate the
blood concentration with the clinical
status of the patient

NB: daily therapeutic dose is 4060 mg/kg/d

Range of
toxicity

S &S

Asymptoma
tic

Blood
level
range
(mg/d
l)

Single
oral
dose
ingeste
d
(mg/kg
)

Approximate
n. of tab
Baby
aspirin

Adult
aspiri
n

<45

mild

N,V,mild
45-65
hyperpnea, tinnitus

150200

Up to
37

Up to
9

Moderate

Hyperpnea,
hyperthermia,
sweating,
dehydration

65-90

200300

37-74

9-18

Sever

Sever Hyperpnea,

90-

300-

74-

18-30

ASPIRIN
Complications
E lyctrolyte Disturbance
Hypokalemia and deranged Na+ levels
Glucose (hypo)
Cerebral and pulmonary edema may
occur due to unknown reason
Salicylates alter platelet function and
may also prolong the prothrombin time
Significant GI bleeds secondary to
gastritis or PUD (peptic ulcer disease).

Management
Treatment of salicylate toxicity should
involve:
GI decontamination
Correct Dehydration
Correction of metabolic acidosis
Hyperthermia control
Hypokalemia control
Hypoglycemia control

Hypocalcemia control
Hypoprothrombinemia control
Seizure control
Hemodialysis

Management
Treatment of salicylate toxicity should
involve:
GI decontamination
Correct Dehydration
Correction of metabolic acidosis
Hyperthermia
Hypokalemia
Hypoglycemia

G.I decontamination
Not necessary for patients with chronic
intoxication
If acute.within 1-2 hr post ingestion (no if >
12hrs):
Administration of oral activated charcoal and if
necessary gastric lavage
Whole-bowel irrigation is recommended to help
move the pills and charcoal through the intestinal
tract
Enhanced elimination by sodium bicarbonate
(PH 7.5) or hemodialysis are very effective
methods

Extracorporeal methods
Hemodialysis is required for any
of the following:
Seum levels >100mg/dl in acute
intoxication,
Serum levels > 60mg/dl in chronic
intoxication
Persistent/progressive acidosis
Deteriorating
level
of
consciousness
Renal insufficiency

Correct Dehydration
Dehydration is common with salicylate
poisoning
Due to hyperthermia, electrolyte imbalance
and kidney shutdown and vomiting

Usually treatment with parenteral fluids

Important to keep the patient hydrated
to maintain kidney function (renal
excretion)
Not overhydrated as it may contribute
to pulmonary edema

Correct Dehydration
Note: if patient has pulmonary
edema will not tolerate fluids load
and must be considered for
dialysis

Management
Treatment of salicylate toxicity should involve:
G.I decontamination
Correct Dehydration
Correction of metabolic acidosis
Hyperthermia
Hypokalemia
Hypoglycemia

Correction of metabolic
acidosis

Sodium bicarbonate is added to the i.v.

fluids
to
correct
metabolic
acidosis
associated with moderate to sever toxicity
This will also rise the PH of the urine, so
enhance salicylate elimination
Do not use acetazolamide for urine
alkalinization (acidify the serum)
(Caution is advised for patients receiving
concomitant high-dose aspirin and Diamox, as
anorexia, tachypnea, lethargy, metabolic
acidosis, coma, and death have been
reported.

Management
Treatment of salicylate toxicity should involve:
G.I decontamination
Correct Dehydration
Correction of metabolic acidosis
Hyperthermia
Hypokalemia
Hypoglycemia

Hyperthermia
Rectal temp must be obtain coz oral
route may be falsely low (tachypnea)
Hyperthermia is a problem
moderate-severe poisoning

with

Begin external cooling with tepid

(lukewarm) sponging and fanning.
This evaporative method is the most
efficient method of cooling

Management
Treatment of salicylate toxicity should involve:
G.I decontamination
Correct Dehydration
Correction of metabolic acidosis
Hyperthermia
Hypokalemia
Hypoglycemia

Hypokalemia
Potassium chloride is added to
the IV fluids to correct hypokalemia
Serum K levels should be closely
monitoredarrhythmias

Management
Treatment of salicylate toxicity should involve:
G.I decontamination
Correct Dehydration
Correction of metabolic acidosis
Hyperthermia
Hypokalemia
Hypoglycemia

Hypoglycemia
Glucose is added to i.v. fluids to
correct the hypoglycemia and ketosis
Note:Salicylate-poisoned patients may
have low brain glucose levels despite
normal measured serum glucose.
(hypoglycemia may ensue from impaired
gluconeogenesis and increased utilization
In addition, salicylate intoxication may
decrease CNS glucose levels despite a
normal peripheral glucose level if CNS
glucose utilization exceeds blood supply)

Other procedures
Diazepam for seizures
Calcium
supplement
for
hypocalcemic tetany
Vitamin K1 for coagulation defects