 with severe nausea secondary to NAC may be

pretreated with IV metoclopramide (Reglan) 10

mg every 6 hrs
 Metoclopramide acts as an antiemetic while
increasing the rate of NAC absorption.

Medical Toxicology MPH@24

SALICYLATES AND ACETYLSALICYLIC
ACID (ASPIRIN, ASA)

Medical Toxicology MPH@24

 Available dosage forms: __________________
OTC: oral, rectal, and topical

 Half-life __________
6 to 12 hrs at lower doses
 Overdose Half-life may be prolonged to more than
______hrs
20

 Clinical presentation:
 Mild Toxicity: nausea, vomiting, tinnitus, and malaise
 Severe Overdose: Lethargy, convulsions, coma, and
metabolic acidosis
Medical Toxicology MPH@24
a. 40 to 60 mg/dL: tinnitus
b. 60 to 95 mg/dL: moderate toxicity
c. More than 95 mg/dL: severe toxicity
d. With the presence of acidemia and aciduria, evaluate
ABGs

Medical Toxicology MPH@24

Medical Toxicology MPH@24
high serum concentrations of salicylic acid

HCO3 -/H2CO3
interference with acid-base balance

↑ H+

metabolic acidosis
Medical Toxicology MPH@24
 Decontamination: Repetitive doses of activated charcoal
> 150mg/kg
every 6 hrs if ingested ___________
 Alkaline diuresis is given as noted in decontamination section
to enhance salicylate excretion. This is indicated for
> 40 mg/dL
levels_________.
 Hemodialysis is used for severe intoxications when serum
>100 mg/dL
levels are_____________. Method of decontamination is
much better than repetitive doses of activated charcoal.

Medical Toxicology MPH@24

 Fluid and electrolyte replacement is administered as
needed.
 Vitamin K (Aquamephyton) and fresh frozen plasma
are used to correct any coagulopathy

Medical Toxicology MPH@24

1. Heparin/Low-Molecular-Weight
Heparin (LMWH)
2. Warfarin (Coumadin)
3. Pradaxa (dabigatran)

Medical Toxicology MPH@24

 Available dosage forms include parenteral dosage
forms for IV and subcutaneous administration
 Toxicokinetics. Heparin has a half-life of ________hrs
1 to 1.5

liver
and is primarily metabolized in the_______. The newer
LMWHs—enoxaparin (Lovenox), dalteparin (Fragmin),
longer half-life
tinzaparin (Innohep)— have a____________, especially
in patients with renal failure.
Medical Toxicology MPH@24
 Clinical presentation. Look for any signs or symptoms
bleeding
of ________ or bruising.
 Laboratory data.
 ________________
PTT

 ________________
Bleeding time

 ________________
platelet counts

Medical Toxicology MPH@24

site of action:
antithrombin III

Medical Toxicology MPH@24

1. Stopping heparin administration 1 to 2 hrs and restarting therapy at a reduced dose

Protamine
2. Severe overdoses __________________
• Protamine + Heparin (_____mg 1 protamine
neutralizes ____
100 U heparin)
• Protamine should be administered slowly,
intravenously over _____mins.
10 The maximum dose
of protamine is _____mg
5o in any 10-min period
Medical Toxicology MPH@24
 Available dosage forms include oral tablets and a
solution for parenteral administration
 Toxicokinetics. Warfarin is well absorbed after oral
administration. Its mean half-life is ___
35 hrs; protein

binding is ___%,
99 with 5-day duration of activity.
Vitamin K-dependent clotting factors begin to decline
___hrs
6 after administration, but therapeutic
anticoagulation may require several days.
Medical Toxicology MPH@24
 Clinical presentation includes minor bleeding, bruising,
hematuria, epistaxis, and conjunctival hemorrhage.
More serious bleeding includes GI, intracranial,
retroperitoneal, and wound site.
 Laboratory data include
PT
 ____________________
 ____________________
international normalized ratio (INR)

 ____________________
Bleeding time

Medical Toxicology MPH@24

Medical Toxicology MPH@24
 If PT or INR is slightly elevated, withhold warfarin for
24 to 48 hrs, → __________________________
Reinstitute therapy with s reduced dosage

 If PT or INR is elevated and bleeding →

administer 10mg of phytonadione (vitamine k) over 30 mins
___________________________________________
Patients who are bleeding may require the
administration of blood products that contain clotting
factors.

Medical Toxicology MPH@24

 oral direct-acting thrombin inhibitor
 Available dosage forms include oral capsules.
 Toxicokinetics. Dabigatran is poorly absorbed
following oral administration, but it has a half-life of
12 to 17
_____________ hrs in healthy subjects with normal
renal function.

Medical Toxicology MPH@24

 Clinical presentation includes minor bleeding, bruising,
hematuria, and epistaxis. More serious bleeding
includes GI, intracranial, retroperitoneal, and wound
site.
 Laboratory data specialized hematologic monitoring
may be required such as ________________
thrombin clotting time
and
ecarin clottig time
_________________.
Medical Toxicology MPH@24
  Mild bleeding. Local treatment and withholding one
dose
 Moderate bleeding. Consider blood product
transfusion and/or hemodialysis
 Severe bleeding.
charcoal filtration along with other recombinant factor VII or prothrombin complex concentrates
____________________________________________________

Medical Toxicology MPH@24

 Mild bleeding. Local treatment and withholding one
dose
 Moderate bleeding. Consider blood product
transfusion and/or hemodialysis
 Severe bleeding.
____________________________________________________

Medical Toxicology MPH@24

1. Tricyclic antidepressants (TCAs)
2. Selective serotonin reuptake
inhibitors (SSRIs)

Medical Toxicology MPH@24

 Available forms include amitriptyline (Elavil),
nortriptyline (Aventyl), imipramine (Tofranil),
desipramine (Norpramin), doxepin (Sinequan),
protriptyline (Vivactil), and clomipramine (Anafranil)
 Toxicokinetics.The compounds are hepatically
metabolized, undergo ____________________,
enterohepatic recirculation are
highly bound to plasma proteins, and have an
elimination half-life of approximately ______ 24 hrs.
Medical Toxicology MPH@24
Effect Manifestation
Anticholinergic effects mydriasis, ileus, urinary retention, and
hyperpyrexia.
Cardiopulmonary
tachycardias, conduction blocks, hypotension, and pulmonary edema
toxicity
CNS manifestations
agitation and confusion to hallucinations, seizure and coma

Medical Toxicology MPH@24

 Blood level monitoring does not correlate well with
clinical signs and symptoms of toxicity.
 Some authors suggest that electrocardiographic
monitoring is a better guide to assessing the severity of
ingestion.

Medical Toxicology MPH@24

1. GI decontamination.
 _______________
syrup of ipecac
is not recommended because
patients may quickly become comatose, increasing
the risk of ______________.
aspiration

 _________________
activated charcoal
is given every 6 hrs.

Medical Toxicology MPH@24

2. Alkalinization.
sodium bicarbonate
 ____________________1 to 2 mEq/kg to maintain an
arterial pH of _____________
7.45 to 7.55 decreases the free
fraction of the absorbed toxins, while reversing some
of the cardiac abnormalities

Medical Toxicology MPH@24

3. Phenytoin (Dilantin) and/or benzodiazepines
 may be required to ______________.
control seizures

 administered at a rate not exceeding 25 mg/min

because of ____________________.
hypotensive side effects

▪ Fosphenytoin (Cerebyx) may be used because it

has a lower incidence of _____________
hypotension than
phenytoin
Medical Toxicology MPH@24
4. Physostigmine
 ____mg
2 IV over 1 min may be used to reverse
__________________________.
severe anticholinergic activity

 Because this antidote may cause asystole, the use

of this antidote for TCA overdoses is declining.

Medical Toxicology MPH@24

Available forms (nontricyclic agents) include:
 fluoxetine (Prozac)
 sertraline (Zolof )
 paroxetine (Paxil)

Medical Toxicology MPH@24

Toxicokinetics.
 SSRIs are well absorbed after oral administration.
 Peak levels occur within ___________
2 to 6 hrs
hepatically
 SSRIs are _______________ metabolized with a half-
life between ______________.
8 and 30 hrs

Medical Toxicology MPH@24

Clinical presentation
 mild symptomatology.
 Patients may become ___________,
agitation

 _______________________.
drowsiness or confusion

 Seizures and cardiovascular toxicity are rare.

Medical Toxicology MPH@24

Laboratory data.
 ______________is
ECG monitoring recommended.
 Blood level monitoring is not recommended.

Medical Toxicology MPH@24

Treatment:
 ___________and
gastric lavage supportive treatment.
 may recommend the use of cyproheptadine (Periactin)
to manage the serotonin syndrome, which may
manifest as a result of these ingestions
 Cyproheptadine compete with __________________.
serotonin receptor

Medical Toxicology MPH@24

Treatment:
 ___________and supportive treatment.
 may recommend the use of cyproheptadine (Periactin)
to manage the serotonin syndrome, which may
manifest as a result of these ingestions

Medical Toxicology MPH@24

Medical Toxicology MPH@24
Available forms include:
 chlordiazepoxide (Librium)
 diazepam (Valium)
 flurazepam (Dalmane)
 midazolam (Versed)
 lorazepam (Ativan)
 alprazolam (Xanax)
 triazolam (Halcion)
Medical Toxicology MPH@24
Toxicokinetics. These drugs are hepatically metabolized.
Clinical presentation includes:
 _____________
DROWSINESS

 _____________
ATAXIA

 _____________
CONFUSION

 Fatalities are rare

Medical Toxicology MPH@24

a. Supportive treatment includes
 _________________
GASTRIC EMPTYING

 _________________
ACTIVATED CHARCOAL

 _________________
CATHARTIC

Medical Toxicology MPH@24

b. Flumazenil (Romazicon) is given _______
0.2 mg IV over
______secs;
30 repeat doses of _______
0.5 mg over 30
secs at 1-min intervals for a maximum cumulative
dose of ____mg.
5

Medical Toxicology MPH@24

 Compete with BDZ
receptor and reverse
its effect

Flumazenil is an
imidazolebenzodiazepine

Medical Toxicology MPH@24

Flumazenil
 has a short elimination half-life.
 Careful observation for resedation is necessary,
especially for ingestions of long-acting
benzodiazepines.
 Flumazenil is contraindicated in mixed overdose
patients (particularly involving tricyclic
antidepressants) in whom seizures are likely.
Medical Toxicology MPH@24
Medical Toxicology MPH@24
 ꞵ-adrenergic
antagonists
Available dosage forms.
Oral and parenteral
dosage forms are
available.
Class examples include:
 propranolol (Inderal),
 metoprolol
(Lopressor),
 atenolol (Tenormin).
Medical Toxicology MPH@24
Toxicokinetics.
 All of the members within this class differ in regard to
_______________, _______________,
RENAL VERSUS HEPATIC ELIMINATION LIPID SOLUBILITY

____________________.
PROTEIN BINDING

 Patients may become toxic owing to changes in organ

function.

Medical Toxicology MPH@24

Clinical presentation includes:
 ___________________
HYPOTENSION

 ___________________
BRADYCHARDIA

 ___________________
ATRIOVENTRICULAR BLOCK

 Bronchospasm may occur, particularly with

noncardioselective agents.

Medical Toxicology MPH@24

Laboratory data include
 serum electrolytes and
 blood glucose (patients may become _____________).
HYPOGLYCEMIC

Medical Toxicology MPH@24

a. GI decontamination includes
▪ __________________
gastric lavage

▪ __________________
ACTIVATED CHARCOAL

b. Glucagon is given ___________mcg/kg as a loading

50-100

dose over 1 min, followed by a continuous infusion of

_________mg/hr.
1-5

Medical Toxicology MPH@24

 Site of
catecholamine adenyl cyclase
receptor

 Glucagon acts by directly

increasing cardiac inotropy by
activating adenyl cyclase by a
secondary mechanism
separate from that of
catecholamines, bypassing
beta blockade.

Medical Toxicology MPH@24

 Glucagon raises blood
sugar through glucagon
activation of hepatic receptors glycogenolysis
glucagon receptors,
stimulating
glycogenolysis and the
release of glucose.
glucose

Medical Toxicology MPH@24

c. Epinephrine should be used cautiously in ꞵ-blocker
overdoses. Unopposed α-receptor stimulation in the
face of complete ꞵ-receptor block may lead to
profound hypertension.
d. Calcium salts may provide benefits for hypotensive

Medical Toxicology MPH@24

Medical Toxicology MPH@24
 Available
forms

Dihydropyridine Non-Dihydropyridine

Verapamil
Nifedipine
Diltiazem
Amlodipine
others
Nicardipine
others MPH@24
Medical Toxicology
Onset of action is approximately ______
30 mins, whereas
6-8
the duration is _______hrs.
Several compounds are available as sustained-release
dosage forms, which may contribute to prolonged
toxicity.

Medical Toxicology MPH@24

 Hypotension is common to all classes.
 Bradycardia and atrioventricular block are more
Verapmil
commonly seen with ingestions of ____________ or
Diltiazem
______________.
 _______________
Pulmonary edema and _______________
Seizure (verapamil)
have been reported.

Medical Toxicology MPH@24

 ECG
 serum electrolytes

Medical Toxicology MPH@24

a. GI decontamination
 ________________
Gastric lavage

 _________________
Activated charcoal

 _________________________(especially
Whole bowel irrigation for
ingestions with sustained-release products).

Medical Toxicology MPH@24

 Increase Ca+
influx to the cell
b. Calcium.
Calcium chloride
__________________
10% (10 to 20mL)
IV push is given for
the management of
hypotension, Increase contractility
bradycardia, or heart
block
Medical Toxicology MPH@24
c. Glucagon dosage
is the same as for
ꞵ-blocker Augment
overdose intracellular Ca+
Short-term therapy
Side effect: Improve inotropy
Tachyphylaxis and chronotropy
N&V, hyperglycemia
Medical Toxicology MPH@24
d. High-dose insulin
↑ utilization of glucose

Inhibit insulin
release

↑ carbohydrate + inotropic effect

demand

Ca+ channel blocker toxicity Medical Toxicology MPH@24

d. Combined insulin and dextrose administration has been
used in selected cases.
 Regular insulin 1 U/kg and a loading dose along
0.5
with IV dextrose _______ g/kg.
 Followed with a continuous infusion of insulin at a
rate of _____
0.5 to 2 U/kg/hr along with continuous
dextrose infusions of ___ g/kg/hr to maintain serum
glucose levels within a 100 to 250 mg/dL range.
Medical Toxicology MPH@24
Medical Toxicology MPH@24
USE:
• Congestive heart failure
• Atrial fibrillation

Medical Toxicology MPH@24

Available dosage forms include oral and parenteral.
Toxicokinetics.
 Digoxin is well absorbed,
 is primarily renally eliminated, and
36 to 48
 has a half-life of ____________ hrs.
 Its volume of distribution is _________L/kg.
7 to 10

 Equilibration between serum level and myocardial

binding requires _________ hrs
Medical Toxicology MPH@24
 confusion, anorexia, nausea, and vomiting in mild
cases.
 In more severe cases, cardiac dysrhythmias are seen.

Medical Toxicology MPH@24

 serum digoxin levels,
 electrolytes,
 particularly serum potassium levels,
 ECG

Medical Toxicology MPH@24

a. Decontamination with activated charcoal is
recommended.
b. Supportive therapy includes managing hyperkalemia
or hypokalemia and inotropic support as needed.

Medical Toxicology MPH@24

c. Digoxin-
specific Fab
antibodies
(Digibind)

Medical Toxicology MPH@24