Antipyretic, analgesic

• Paracetamol
• Aspirin
• Ibuprofen

1. Acetaminophen (Paracetamol)

Other brands - Anacin-3, Liquiprin, Panadol,

Paracetamol, Tempra, Tylenol,
Acetaminophen is a widely used drug found in
many over-the-counter and prescription analgesics and
cold remedies.
When it is combined with another drug such as
diphenhydramine, codeine, or propoxyphene, the more
dramatic acute symptoms caused by the other drug
may mask the mild and nonspecific symptoms of early
acetaminophen toxicity, resulting in a missed diagnosis
or delayed antidotal treatment.

• Mechanism of toxicity
A) Hepatic injury
One of the products of normal metabolism of
acetaminophen by cytochrome P-450 mixed-function
oxidase enzymes is highly toxic; normally this reactive
metabolite (NAPQI) is detoxified rapidly by glutathione
in liver cells. However, in an overdose, production of
NAPQI exceeds glutathione capacity and the metabolite
reacts directly with hepatic macromolecules, causing
liver injury.
B) Renal damage
Renal damage may occur by the same mechanism,
owing to renal P-450 metabolism.
C) Pregnancy
Overdose during pregnancy has been associated
with fetal death and spontaneous abortion.
 • Pharmacokinetics
Absorption: Rapidly absorbed, with peak levels
usually reached within 30–120 minutes (Note:
Absorption may be delayed after ingestion of
sustained-release products or with co-ingestion of
opioids or anticholinergics).
Distribution: Volume of distribution (Vd) = 0.8–1
L/kg.
Elimination: is mainly by liver conjugation (90%)
to nontoxic glucuronides or sulfates; cytochrome P-450
mixed-function oxidase (CYP 2E1, 1A2) accounts for
only about 3–8% but produces a toxic intermediate.
The elimination half-life is 1–3 hours after a
therapeutic dose and may be greater than 12 hours
after an overdose.

• Toxic dose
A. Acute ingestion of more than 200 mg/kg in
children or 6–7 g in adults is potentially hepatotoxic.
1. Children younger than 10–12 years of age
appear to be less susceptible to hepatotoxicity because
of the smaller contribution of cytochrome P-450 to
acetaminophen metabolism.
2. In contrast, the margin of safety is lower in
patients with induced cytochrome P-450 microsomal
enzymes, because more of the toxic metabolite may be
produced. High-risk patients include alcoholics and
patients taking inducers of CYP 2E1 such as isoniazid.
Fasting and malnutrition also increase the risk of
hepatotoxicity, presumably by lowering cellular
glutathione stores.
B. Chronic toxicity has been reported after daily
consumption of supratherapeutic doses by alcoholic
patients and persons taking isoniazid. Children have
developed toxicity after receiving as little as 60–150
mg/kg/day for 2–8 days.
 • Clinical presentation
Clinical manifestations depend on the time after
ingestion.
A. Early after acute acetaminophen overdose,
there are usually no symptoms other than anorexia,
nausea, or vomiting.
Rarely, a massive overdose may cause altered
mental status and metabolic acidosis. Transient
prolongation of the prothrombin time (PT/INR) in the
absence of hepatitis has been noted in the first 24
hours; some, but not all, of these patients go on to
develop liver injury.
B. After 24–48 hours, when transaminase levels
[aspartate aminotransferase (AST) and alanine
aminotransferase (ALT)] begin to rise, hepatic necrosis
becomes evident. If acute fulminant hepatic failure
occurs, death may ensue.
Encephalopathy, metabolic acidosis, and a
continuing rise in PT/INR indicate a poor prognosis.
Acute renal failure occasionally occurs, with or
without concomitant liver failure.

• Diagnosis
Prompt diagnosis is possible only if the ingestion is
suspected and a serum acetaminophen level is
obtained.
However, patients may fail to provide the history
of acetaminophen ingestion, because they are unable
(eg, comatose from another ingestion), unwilling, or
unaware of its importance.
Therefore, many clinicians routinely order
acetaminophen levels in all overdose patients
regardless of the history of substances ingested.
A. Specific levels
1. After an acute overdose, obtain a 4-hour
postingestion acetaminophen level and use the
nomogram to predict the likelihood of toxicity. Do not
attempt to interpret a level drawn before 4 hours
unless it is "nondetectable." Obtain a second level at 8
hours if the 4-hour value is borderline or if delayed
absorption is anticipated.
2. The nomogram should not be used to assess
chronic or repeated ingestions.
3. Falsely elevated acetaminophen levels may
occur in the presence of high levels of salicylate and
other interferents by various methods. This problem is
rare with currently used analysis methods.
B. Other useful laboratory studies include
electrolytes, glucose, BUN, creatinine, liver
transaminases, and PT/INR.

• Treatment
A. Emergency and supportive measures
1. Spontaneous vomiting may delay the oral
administration of antidote or charcoal and should be
treated with metoclopramide or a 5-HT3 receptor
antagonist such as ondansetron (Ondansetron).
2. Provide general supportive care for hepatic or
renal failure if it occurs. Emergency liver transplant
may be necessary for fulminant hepatic failure.
Encephalopathy, metabolic acidosis, hypoglycemia,
and progressive rise in the prothrombin time are
indications of severe liver injury.
B. Specific drugs and antidotes
1. If the serum level falls between the two
nomogram lines, consider giving NAC if the patient is at
increased risk for toxicity; eg, the patient is alcoholic,
malnourished or fasting or is taking drugs that induce
P-450 2E1 activity [(eg, isoniazid (INH)]; after multiple
or subacute overdoses; or if the time of ingestion is
uncertain or unreliable.
2. If the serum level falls below the lower
nomogram line, treatment is not indicated unless the
time of ingestion is uncertain or the patient is
considered to be at particularly high risk.
3. Note: After ingestion of extended-release tablets
(eg, Tylenol Arthritis Pain™), which are designed for
prolonged absorption, there may be a delay before the
peak acetaminophen level is reached. This can also
occur after co-ingestion of drugs that delay gastric
emptying, such as opioids and anticholinergics. In such
circumstances, repeat the serum acetaminophen level
at 8 hours and possibly 12 hours. In such cases, it may
be prudent to initiate NAC therapy before 8 hours while
waiting for subsequent levels.
4. Duration of NAC treatment. The conventional US
protocol for treatment of acetaminophen poisoning
calls for 17 doses of oral NAC given over approximately
72 hours. However, for decades successful protocols in
Canada, the United Kingdom, and Europe have utilized
intravenous NAC for only 20 hours. In uncomplicated
cases, give NAC (orally or IV) for 20 hours and follow
hepatic transaminase levels and the PT/INR until 36
hours have passed since the time of ingestion. If
evidence of liver injury develops, NAC is continued until
liver function tests are improving.
5. Chronic acetaminophen ingestions: Patients may
give a history of several doses taken over 24 hours or
more, in which case the nomogram cannot accurately
estimate the risk of hepatotoxicity. In such cases, we
advise NAC treatment if the amount ingested was more
than 150–200 mg/kg or 6–7 g within a 24-hour period, if
liver enzymes are elevated, or if the patient falls within
a high-risk group. Treatment may be stopped 24–36
hours after the last dose of acetaminophen if liver
enzymes and PT/INR are normal.
C. Decontamination
Administer activated charcoal orally if conditions
are appropriate. Gastric lavage is not necessary after
small to moderate ingestions if activated charcoal can
be given promptly.
1. Although activated charcoal adsorbs some of
the orally administered antidote N-acetylcysteine, this
effect is not considered clinically important.
2. Do not administer charcoal if more than 3–4
hours has passed since ingestion unless delayed
absorption is suspected
D. Enhanced elimination
Hemodialysis effectively removes acetaminophen
from the blood but is not generally indicated because
antidotal therapy is so effective.
Dialysis should be considered for massive
ingestions with very high levels (eg, >1000 mg/L)
complicated by coma and/or hypotension.

2. Aspirin

The most widely used antiplatelet agent worldwide

is aspirin. As a cheap and effective antiplatelet drug,
aspirin serves as the foundation of most antiplatelet
strategies.

• Mechanism of Action
Aspirin produces its antithrombotic effect by
irreversibly acetylating and inhibiting platelet
cyclooxygenase (COX)-1 a critical enzyme in the
biosynthesis of thromboxane A2.
At high doses (~1 g/d), aspirin also inhibits COX-2,
an inducible COX isoform found in endothelial cells and
inflammatory cells.
In endothelial cells, COX-2 initiates the synthesis of
prostacyclin, a potent vasodilator and inhibitor of
platelet aggregation.
 Site of action of
antiplatelet drugs.
Aspirin inhibits
thromboxane A2 (TXA2)
synthesis by irreversibly
acetylating
cyclooxygenase-1 (COX-
1). Reduced TXA2 release
attenuates platelet
activation and recruitment
to the site of vascular
injury. Ticlopidine and clopidogrel irreversibly block
P2Y12, a key ADP receptor on the platelet surface.
Therefore, these agents also attenuate platelet
recruitment. Abciximab, eptifibatide, and tirofiban
inhibit the final common pathway of platelet
aggregation by blocking fibrinogen binding to activated
glycoprotein (GP) IIb/IIIa.
COX-2 inhibitors were developed to block the
production of inflammatory prostaglandins without
affecting platelet function. The various COX-2 inhibitors
differ in their selectivity for COX-2 relative to COX-1.
By blocking prostacyclin synthesis without
concomitant inhibition of thromboxane A2 production,
highly selective inhibitors of COX-2 increase the risk of
cardiovascular events.
Thus, long-term rofecoxib therapy increases the
risk of myocardial infarction (MI) three- to fivefold, a
finding that led to the withdrawal of this drug from the
market.

• Indications
Aspirin is widely used for secondary prevention of
cardiovascular events in patients with coronary artery,
cerebrovascular, or peripheral vascular disease.
 Compared with placebo, aspirin produces a 25%
reduction in the risk of cardiovascular death, MI, or
stroke. Aspirin is also used for primary prevention in
patients whose estimated annual risk of MI is >1%, a
point where its benefits are likely to outweigh harms.
This includes patients over the age of 40 with two
or more major risk factors for cardiovascular disease or
those over the age of 50 with one or more such risk
factor.
Aspirin is equally effective in men and women. In
men, aspirin mainly reduces the risk of MI, while in
women aspirin lowers the risk of stroke.

• Dosages
Aspirin is usually administered at doses of 75–325
mg once daily. Higher dose aspirin is not more effective
than lower aspirin doses, and some analyses suggest
reduced efficacy with higher doses.
Because the side effects of aspirin are dose-
related, daily aspirin doses of 75–100 mg are
recommended for most indications.
When rapid platelet inhibition is required, an initial
aspirin dose of at least 160 mg should be given.

• Side Effects
Most common side effects are gastrointestinal and
range from dyspepsia to erosive gastritis or peptic
ulcers with bleeding and perforation.
These side effects are dose-related. Use of enteric-
coated or buffered aspirin in place of plain aspirin does
not eliminate the risk of gastrointestinal side effects.
The overall risk of major bleeding with aspirin is 1–3%
per year.
The risk of bleeding is increased when aspirin is
given in conjunction with anticoagulants, such as
warfarin. When dual therapy is used, low-dose aspirin
should be given (75–100 mg daily).
 Eradication of Helicobacter pylori infection and
administration of proton pump inhibitors may reduce
the risk of aspirin-induced gastrointestinal bleeding in
patients with peptic ulcer disease.
Aspirin should not be administered to patients with
a history of aspirin allergy characterized by
bronchospasm. This problem occurs in ~0.3% of the
general population but is more common in those with
chronic urticaria or asthma, particularly in individuals
with nasal polyps or chronic rhinitis. Hepatic and renal
toxicity are observed with aspirin overdose.

• Aspirin Resistance
Clinical aspirin resistance is defined as the failure
of aspirin to protect patients from ischemic vascular
events. This is not a helpful definition because it is
made after the event occurs.
Furthermore, it is not realistic to expect aspirin,
which only blocks thromboxane A2–induced platelet
activation, to prevent all vascular events.
Aspirin resistance has also been described
biochemically as failure of the drug to produce its
expected inhibitory effects on tests of platelet function,
such as thromboxane A2 synthesis or arachidonic acid–
induced platelet aggregation.
However, the tests of platelet function used for
diagnosis of biochemical aspirin resistance have not
been well standardized. Furthermore, these tests are
not proven to identify patients at risk of recurrent
vascular events.

3. Ibuprofen

• GENERIC NAME: ibuprofen

• BRAND NAME
 Advil, Children's Advil/Motrin, Medipren, Motrin,
Nuprin, PediaCare Fever etc.

• DRUG CLASS AND MECHANISM

Ibuprofen belongs to a class of drugs called non-
steroidal anti-inflammatory drugs (NSAIDs). Other
members of this class include aspirin, naproxen
(Aleve), indomethacin (Indocin), nabumetone (Relafen)
and several others.
These drugs are used for the management of mild
to moderate pain, fever, and inflammation. Pain, fever,
and inflammation are promoted by the release in the
body of chemicals called prostaglandins.
Ibuprofen blocks the enzyme that makes
prostaglandins (cyclooxygenase), resulting in lower
levels of prostaglandins. As a consequence,
inflammation, pain and fever are reduced.

• PREPARATIONS
Tablets of 200, 400, 600, and 800 mg;
Chewable tablets of 50 and 100 mg;
Capsules of 200 mg;
Suspension of 100 mg/2.5 ml and 100 mg/5 ml
Oral drops of 40 mg/ml.

• STORAGE
Ibuprofen should be stored at room temperature,
between 15-30°C (59-86°F).

• PRESCRIBED FOR
Ibuprofen is used for the treatment of mild to
moderate pain, inflammation and fever caused by
many and diverse diseases.

• DOSING
 For minor aches, mild to moderate pain, menstrual
cramps, and fever, the usual adult dose is 200 or 400
mg every 4 to 6 hours.
Arthritis is treated with 300 to 800 mg 3 or 4 times
daily.
When under the care of a physician, the maximum
dose of ibuprofen is 3.2 g daily. Otherwise, the
maximum dose is 1.2 g daily.
Individuals should not use ibuprofen for more than
10 days for the treatment of pain or more than 3 days
for the treatment of a fever unless directed by a
physician.
Children 6 months to 12 years of age usually are
given 5-10 mg/kg of ibuprofen every 6-8 hours for the
treatment of fever and pain. The maximum dose is 40
mg/kg daily.
Juvenile arthritis is treated with 20 to 40
mg/kg/day in 3-4 divided doses.
Ibuprofen should be taken with meals to prevent
stomach upset.

• DRUG INTERACTIONS
Ibuprofen is associated with several suspected or
probable interactions that can affect the action of other
drugs. Ibuprofen may increase the blood levels of
lithium (Eskalith) by reducing the excretion of lithium
by the kidneys.
Increased levels of lithium may lead to lithium
toxicity. Ibuprofen may reduce the blood pressure-
lowering effects of drugs that are given to reduce blood
pressure.
This may occur because prostaglandins play a role
in the regulation of blood pressure.
When ibuprofen is used in combination with
aminoglycosides [for example, gentamicin
(Garamycin)] the blood levels of the aminoglycoside
may increase, presumably because the elimination of
aminoglycosides from the body is reduced.

• PREGNANCY
There are no adequate studies of ibuprofen in
pregnant women. Therefore, ibuprofen is not
recommended during pregnancy.
Ibuprofen should be avoided in late pregnancy due
to the risk of premature closure of the ductus
arteriosus in the fetal heart..

• NURSING MOTHERS
Ibuprofen is not excreted in breast milk. Use of
ibuprofen while breastfeeding, poses little risk to the
infant.

• SIDE EFFECTS
The most common side effects from ibuprofen are
rash, ringing in the ears, headaches, dizziness,
drowsiness, abdominal pain, nausea, diarrhea,
constipation and heartburn.
NSAIDs reduce the ability of blood to clot and
therefore increase bleeding after an injury.
Ibuprofen may cause ulceration of the stomach or
intestine, and the ulcers may bleed.
Sometimes, ulceration can occur without
abdominal pain, and black, tarry stools, weakness, and
dizziness upon standing (orthostatic hypotension) due
to bleeding may be the only signs of an ulcer.
NSAIDs reduce the flow of blood to the kidneys and
impair function of the kidneys. The impairment is most
likely to occur in patients who already have impaired
function of the kidney or congestive heart failure, and
use of NSAIDs in these patients should be cautious.
People who are allergic to other NSAIDs, including
aspirin, should not use ibuprofen. Individuals with
asthma are more likely to experience allergic reactions
to ibuprofen and other NSAIDs.
Fluid retention (edema), blood clots, heart attacks,
hypertension and heart failure have also been
associated with the use of NSAIDs.

Mucolytic
• Carbocysteine
• Bromhexine
• Acetylcysteine

1. Karbotsistein (carbocysteine)

• Synonyms
Bronkatar, Bronhobos, Bronhokod, Drill
otharkivayuschy, Mukodin, Mukopront, Mukosol,
Fluifort, Flyuvik, Flyuditek, Actithiol, Anatac, Broncatar,
Bronchipect, Bronchocod, Caltusine, Carsitil, Drill
expectorant, Ectofus, Flemex, Fluditec, Fluifort, Fluvic,
Karbocistein, Lagan, Lisomucil, Mucifan, Mucodyne,
Mucolase, Mucolisil, Mucolit, Mucopront, Mucosol,
Pectox, Pneumoclar and others.
Applied lung disease involving accumulation
viscous sputum (acute and chronic bronchitis,
traheobronhity, asthma and bronchitis etc.), with
middle ear inflammatory diseases and sinusal nose, as
well as in preparation for tomography and bronhografii.
Assign into adults and 1 canteen spoon syrup 5%
(0.75 g) 3 times a day for 1-2 or 2-3 capsules twice a
day (depending on the current process and
performance).
Children under 2 year teaspoon 2.5% syrup 2
times a day, from 2 year to 5 years and 1 teaspoonful
of 2.5% syrup 2 times a day, 5 years and over-1
teaspoonful of 5% syrup, or 2 tea spoons 2.5% syrup 3
times a day.
The drug is usually well. In some cases, possible
nausea, vomiting, diarrhea, gastrointestinal bleeding,
allergic reactions (skin rashes, swelling Kvinke etc.).

• Contraindications
Karbotsistein contraindications to gastric ulcers
and duodenal ulcer in the process of being increased,
disrupting kidney function, in the first trimester of
pregnancy.
Enhance of glucocorticosteroids and teofillina;
Protivokashlevye and atropinopodobnye drugs weaken
karbotsisteina effect.

• Method of production
2.5% syrup for children in bottles of 100, 125 and
200 ml, 5% in syrup bottles of 100, 110, 125, 150, 200
and 300 ml, or 9%, to 100 ml;
Capsules of 0, 375 g (N. 8, 10, 20);
Chewing pill to 0.75 g (N. 20);
Granules bags to 5 g (2.7 g).

2. Bromhexine

Bromhexine is a mucolytic agent used in the

treatment of respiratory disorders associated with
viscid or excessive mucus. In addition, bromhexine has
antioxidant properties.

• Brand names
 Bisolvon Forte - link International website
Bisolvon.com
Hoesttabletten Bromhexine HCl
Paxirasol
Barkacin
Vasican
Bisolex

• Function
Bromhexine supports the body's own natural
mechanisms for clearing mucus from the respiratory
tract.
It is secretolytic: that is, it increases the production
of serous mucus in the respiratory tract and makes the
phlegm thinner and less sticky.
This contributes to a secretomotoric effect: it helps
the cilia - tiny hairs that line the respiratory tract - to
transport the phlegm out of the lungs. For this reason it
is often added to some antitussive (cough) syrups.
Bromhexine is a synthetic derivative of the herbal
active ingredient vasicine. It has been shown to
increase the proportion of serous bronchial secretion,
making it more easily to be expectorated.
Bromhexine also enhances mucus transport by
reducing mucus viscosity and by activating the ciliated
epithelium.
In clinical studies, Bromhexine showed secretolytic
and secretomotoric effects in the bronchial tract area
which facilitates expectoration and eases cough.
It is indicated as “secretolytic therapy in
bronchopulmonary diseases associated with abnormal
mucus secretion and impaired mucus transport”.
Bromhexine is contained in various formulations,
high and low strength syrups 8mg/5ml, 4 mg/5ml,
tablets and soluble tablets (both with 8 mg
bromhexine) and solution for oral use 10 mg/ 5 ml),
adapted to the need of the patients.
 The posology varies with the age, but there are
products for all age groups from infant on.
Bromhexine is a well established and well tolerated
product in its indication.

3. Acetylcysteine (N-Acetylcysteine [NAC])

• Pharmacology
Acetylcysteine (N-acetylcysteine [NAC]) is a
mucolytic agent that acts as a sulfhydryl group donor,
substituting for the liver's usual sulfhydryl donor,
glutathione.
It rapidly binds (detoxifies) the highly reactive
electrophilic intermediates of metabolism or it may
enhance the reduction of the toxic intermediate,
NAPQI, to the parent, acetaminophen.
It is most effective in preventing acetaminophen-
induced liver injury when given early in the course of
intoxication (within 8 to 10 hours), but may also be of
benefit in reducing the severity of liver injury by
several proposed mechanisms (improved blood flow
and oxygen delivery, modified cytokine production,
free radical or oxygen scavenging) even when given
after 24 hours.
This proposed role of NAC as a glutathione
precursor, direct sulfhydryl binding agent, and
antioxidant has also been the basis for its
investigational use for poisonings from agents
associated with a free radical or oxidative stress
mechanism of toxicity or that bind to sulfhydryl groups.
It may be used empirically when the severity of
ingestion is unknown or serum concentrations of the
ingested drug are not immediately available.

• Indications
A. Acetaminophen overdose.
 B. Case reports of or investigational use in carbon
tetrachloride, chloroform, acrylonitrile, doxorubicin,
arsenic, gold, amanitin mushroom, carbon monoxide,
chromium, cyanide, paraquat, and methyl mercury
poisoning.
C. Pennyroyal oil and clove oil poisoning (case
reports). The mechanism of hepatic injury by
pennyroyal oil and clove oil are similar to that of
acetaminophen, and empiric use of NAC seems justified
for any significant pennyroyal oil or clove oil ingestion.
D. Cisplatin nephrotoxicity and prevention of
radiocontrast-induced nephropathy.

• Contraindications
Known acute hypersensitivity or IgE-mediated
anaphylaxis (rare). Anaphylactoid reactions, while
similar in clinical effects, may be prevented or
ameliorated.

• Adverse effects
A. Acetylcysteine typically causes nausea and
vomiting when given orally. If the dose is vomited, it
should be repeated. The dose calculation and proper
dilution (to 5%) should be verified (this effect may be
dose and concentration dependent). Use of a gastric
tube, slower rate of administration, and a strong
antiemetic agent
B. Rapid intravenous administration can cause
flushing, rash, angioedema, hypotension, and
bronchospasm (anaphylactoid reaction).
Death (status epilepticus, intracranial
hypertension) was reported in a 30-month-old child
accidentally receiving a massive dose intravenously
(2,450 mg/kg over 6 hours, 45 minutes), and fatal
bronchospasm occurred in an adult with severe
asthma.
 Reactions might be reduced by giving each dose
slowly (over at least 60 minutes) in a dilute (3–4%)
solution (this effect is dose and concentration
dependent) and exercising extreme caution in
asthmatics (avoid IV use or carefully titrate with more
dilute solutions and slower infusion rates).
If an anaphylactoid reaction occurs, stop the
infusion immediately and treat with diphenhydramine if
urticaria and or angioedema is present, and
epinephrine for more serious reactions (shock,
bronchoconstriction).
Once symptoms have resolved, the infusion may
be recommenced at a slower infusion rate (by further
dilution and given over at least 1 hour
C. Use in pregnancy.
There is no evidence for teratogenicity. Use of this
drug to treat acetaminophen overdose is considered
beneficial to both mother and developing fetus.
However, maternal hypotension or hypoxia due to a
serious anaphylactoid reaction from IV administration
may harm the fetus.

• Drug or laboratory interactions

A. Activated charcoal adsorbs acetylcysteine and
may interfere with its systemic absorption. When both
are given orally together, data suggest that peak
acetylcysteine levels are decreased by about 30% and
that the time to reach peak level may be delayed.
However, these effects are not considered clinically
important.
B. NAC can produce a false-positive test for
ketones in the urine.

• Dosage and method of administration

A. Oral loading dose.
Give 140 mg/kg of the 10% (1.4 ml/kg) or 20% (0.7
ml/kg) solution diluted to approximately 5% in juice or
soda to enhance palatability: dilute the loading dose of
10% NAC with 1.4 mL/kg of juice or soda (for 20% NAC
dilute with 2 mL/kg of juice/soda).
B. Maintenance oral dose. Give 70 mg/kg (as a 5%
solution) every 4 hours. To make an approximately 5%
solution, dilute the maintenance dose of 10% NAC (0.7
mL/kg) with 0.7 mL/kg of juice or soda (for 20% NAC
dilute 0.35 mL/kg with 1 mL/kg of juice/soda).
The conventional protocol for treatment of
acetaminophen poisoning in the United States calls for
17 doses of oral NAC given over approximately 72
hours. However, successful shorter protocols in Canada
and Europe utilize intravenous NAC for only 20 hours
for uncomplicated poisonings without evidence of liver
injury treated within 8 hours of ingestion.
C. An intravenous preparation (Acetadote,
Cumberland Pharmaceuticals) was approved in 2004 by
the U.S. FDA and is indicated if the patient is unable to
tolerate the oral formulation because of vomiting, ileus,
intestinal obstruction, or other GI problems.
D. Dosage during dialysis. Although acetylcysteine
is removed during dialysis, no change in dosage is
necessary.
E. Dosage for prevention of radiocontrast-induced
nephropathy. Give 600 mg of PO NAC twice on the day
before and the day of the procedure (4 doses total).
This is coupled with IV hydration using 1/2 NS at 1
mL/kg/h for 12 hours before and after the
administration of the contrast agent.

• Formulations

A. Oral The usual formulation is as a 10% (100-

mg/mL) or 20% (200-mg/mL) solution, supplied as an
inhaled mucolytic agent (Mucomyst, or generic).
 This form is available through most hospital
pharmacies or respiratory therapy departments. This
preparation is not FDA approved for parenteral use.
B. The new intravenous formulation (Acetadote) is
available as a 20% solution in 30 mL (200 mg/mL) vials
in a carton of 4 vials. Note: special precautions are
needed to avoid accidental overdose or over-dilution
with D5W in pediatric patients (see Table III–3 for IV
Acetadote administration guidelines and precautions).
C. Suggested minimum stocking level for
treatment of a 70-kg adult for the first 24 hours: 20%
(oral) solution, 7 vials (30 mL each) and or 20% (IV)
solution, 1 carton of 4 vials (30 ml each).

Actifed

• USES
Antihistamines provide relief of symptoms of
allergies such as rash, hives, watery eyes, runny nose,
itching eyes and sneezing. Decongestants relieve
congestion, promote sinus draining and improve
breathing.
 • How To Use
May be taken with food or milk to prevent stomach
upset.
It is recommended to drink plenty of fluids while
taking this medication, unless doctor instructs
otherwise.
If symptoms do not improve after 7 days or are
accompanied by a high fever, notify doctor.
Do not increase the dose or take this more frequently
than recommended.

• Pharmacokinetics
Because there is some evidence that chronic,
excessive consumption of alcohol may increase the risk
of acetaminophen-induced hepatotoxicity, chronic
alcoholics should be cautioned to avoid regular or
excessive use of acetaminophen, or alternatively, to
avoid chronic ingestion of alcohol.
The manufacturers currently caution that patients
who generally consume 3 or more alcohol-containing
drinks per day should ask their clinician whether to use
acetaminophen or an alternative analgesic for self-
medication because acetaminophen may increase the
risk of hepatotoxicity.
However, the US Food and Drug Administration
(FDA) has proposed eliminating this statement from the
labeling of OTC acetaminophen-containing preparations
and adding a new warning that would highlight the
potential for severe liver damage to occur under
certain circumstances, including in individuals who
consume 3 or more alcohol-containing drinks per day
while taking acetaminophen.

• Absorption
Pseudoephedrine is readily and almost completely
absorbed from the GI tract and there is no evidence of
first-pass metabolism.
 Following oral administration of a 60- or 120-mg
dose of pseudoephedrine hydrochloride as an oral
solution, peak plasma concentrations of about 180–300
or 397–422 ng/mL, respectively, were achieved in
approximately 1.39–2 or 1.84–1.97 hours, respectively.
Absorption from extended-release preparations is
slower and peak plasma concentrations of the drug are
achieved in about 3.8–6.1 hours.
Following oral administration of single 30- or 60-
mg doses of pseudoephedrine hydrochloride as a
solution in pediatric patients (6–12 years of age), mean
peak serum concentrations of 244 or 492 ng/mL,
respectively, were achieved after 2.1 or 2.4 hours,
respectively.
Food delays absorption of the drug when
administered as a solution, but appears not to have an
effect on absorption when the drug is administered as
extended-release preparations.
Plasma pseudoephedrine concentrations of 274
ng/mL have been associated with a mean nasal
decongestant response of 57.2%. After oral
administration of 60 mg of pseudoephedrine
hydrochloride as tablets or oral solution, nasal
decongestion occurs within 30 minutes and persists for
4–6 hours.
Nasal decongestion may persist for 8 hours
following oral administration of 60 mg and up to 12
hours following 120 mg of the drug in extended-release
capsules.

• Distribution
Following oral administration of single 30- or 60-
mg doses of pseudoephedrine hydrochloride as a
solution in children (6–12 years of age), the mean
apparent volume of distribution at steady-state was 2.6
or 2.4 L/kg, respectively.
 Although specific information is lacking,
pseudoephedrine is presumed to cross the placenta
and to enter CSF. Pseudoephedrine distributes into
breast milk; about 0.5% of an oral dose is distributed
into breast milk over 24 hours.

• Elimination
Pseudoephedrine is incompletely metabolized (less
than 1%) in the liver by N-demethylation to an inactive
metabolite. The drug and its metabolite are excreted in
urine; 55–96% of a dose is excreted unchanged.
Urinary pH can affect the elimination half-life of
pseudoephedrine, prolonging it when alkaline (pH 8)
and reducing it when acidic (pH 5).
The elimination half-life of pseudoephedrine
ranges from 3–6 or 9–16 hours when urinary pH is 5 or
8, respectively, while when urinary pH is 5.8, the
elimination half-life of the drug ranges from 5–8 hours.
In one study in children 6–12 years of age, the
elimination half-life of pseudoephedrine averaged
about 3 hours when urinary pH was 6.5. The rate of
urinary excretion of pseudoephedrine is accelerated
when urine is acidified to a pH of about 5 by prior
administration of ammonium chloride. When the urine
is alkalinized to a pH of about 8 by prior administration
of sodium bicarbonate, some of the drug is reabsorbed
in the kidney tubule and the rate of urinary excretion is
slowed.
Renal clearance of pseudoephedrine is about 7.3–
7.6 mL/minute per kg in adults.
Following oral administration of a single 30- or 60-
mg dose of pseudoephedrine hydrochloride given as an
oral solution in children 6–12 years of age, total body
clearance was faster than that reported in adults,
averaging about 10.3 or 9.2 mL/minute per kg,
respectively.
 • Side Effects
May cause drowsiness, dizziness, headache, loss of
appetite, stomach upset, blurred vision, restlessness,
irritability and dry mouth and nose.
These effects should subside as your body adjusts
to the medication. If they persist or become
bothersome, inform your doctor.
Notify doctor if develop breathing difficulties, heart
pounding, irregular heartbeat, chest pain, ringing in the
ears, or difficulty urinating while taking this medication.
May cause dizziness especially when rising quickly
from a seated or lying position.
Change positions slowly and be careful on stairs.
Use caution engaging in activities requiring
alertness.

• Precautions
If have asthma, glaucoma, an ulcer, difficulty
urinating due to an enlarged prostate gland, heart
disease, high blood pressure, seizures, or an overactive
thyroid gland, do not use this drug unless your doctor is
aware of medical condition.
Check other medicines take for duplications.
Do not drink alcoholic beverages.
This drug should be used only if clearly needed
during pregnancy.
Consult doctor before breast-feeding.
Do not give this medication to a child younger than
six years of age unless directed to do so by a doctor.

• Missed Dose
If you miss a dose, take as soon as remembered; do
not take if it is almost time for the next dose, instead,
skip the missed dose and resume usual dosing
schedule.
Do not "double-up" the dose to catch up.
 • Drug Interactions
Tell doctor what medications that take, especially
medication for high blood pressure, seizures, or
depression; sleeping pills, sedatives, tranquilizers,
muscle relaxants, narcotic pain medication, other cold
or allergy medication and of any other drugs may use,
both prescription and nonprescription.
Do not take this drug if have taken an MAO inhibitor
(e.g., furazolidone, phenelzine, selegiline,
tranylcypromine) within the last two weeks.
Do not start or stop any medicine without doctor or
pharmacist approval.