142

This highlights the importance of obtaining a comprehensive medication history,

assessment of the patient’s renal function, and evaluation of the available druginformation resources for appropriate dosing recommendations for each patient.

SUMMARY

The kidneys play a vital role in maintaining homeostasis by regulating the excretion

of water, electrolytes, and metabolic by-products. In addition, the kidneys are the

primary route of elimination for many drugs. Pharmacokinetic changes, such as

altered bioavailability, protein binding, drug distribution, and elimination, can occur

with many drugs in patients with renal failure. Pharmacodynamic changes, such as

altered sensitivity or response to medications, can also occur in this patient

population. Renal replacement therapies, such as hemodialysis, CAPD, and CVVH,

will aid in the removal of fluid, electrolytes, and metabolic by-products in drugs as

well. Data from clinical trials provide valuable information about the disposition of

drugs in patients with renal failure. Pharmacokinetic principles should be applied

when appropriate to determine the optimal dose of drugs for patients with renal

failure.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Aronoff GR et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed.

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Guidance for industry. Pharmacokinetics in patients with impaired renal function-Study design, data analysis, and

impact on dosing and labeling. http://www.fda.gov/downloads/Drugs/Guidances/UCM204959.pdf.

Winter ME. Basic Clinical Pharmacokinetics. 5th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2010.

Key Websites

Cockroft-Gault Calculator. http://www.nephron.com/cgi-bin/CGSI.cgi.

MDRD calculator. http://touchcalc.com/e_gfr.

National Kidney Disease Education Program. http://nkdep.nih.gov/.

2014 Dialysis of Drugs. http://www.renalpharmacyconsultants.com/publications/.

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p. 678

Drug allergies are a subset of adverse drug reactions that are usually

mediated by the immune system. Although typically unpredictable, there

are several factors known to influence the frequency of allergic

reactions including age, sex, genetics, prior drug exposure, and drug

dose and route. A detailed drug history is key to assisting in the

diagnosis of a drug allergy.

Case 32-1 (Questions 1, 2)

Table 32-1

Skin testing for allergy to penicillin is an important diagnostic tool that

assists in determining whether or not a patient is truly allergic to this

class of drug. Patients presenting with a history of penicillin allergy but

who have a negative penicillin scratch test and a negative intradermal

test can be safely given β-lactam antibiotics.

Case 32-1 (Question 3)

Table 32-4

There are varying degrees of cross-reactivity between various β-lactam

antibiotics. Understanding the frequency of cross-reactivity is important

in making treatment decisions if skin testing is not available. The

frequency of cross-reaction between penicillins and cephalosporins has

been reported to be 5% to 15%, but it is likely much lower. The risk of a

cephalosporin reaction in a patient with a penicillin allergy decreases

with increasing cephalosporin generation, being lowest with the thirdand fourth-generation drugs. The frequency of cross-reaction between

penicillins and carbapenems or monobactams appears to be very low

(approximately 1%).

Case 32-1 (Question 4)

ANAPHYLAXIS

Anaphylaxis is a serious allergic reaction that has a rapid onset and

might cause death. It is caused by the rapid release of immune

mediators from tissue mast cells and peripheral blood basophils.

Symptoms such as pruritus of the hands, feet, and groin; flushing; lightheadedness; hypotension; tachycardia; and difficulty breathing can begin

within minutes of exposure to the precipitating agent, which is most

commonly foods, insect stings, and drugs. Prompt recognition and

treatment are critical to ensure a favorable outcome.

Case 32-2 (Questions 1, 2)

Table 32-2

Epinephrine is the drug of choice for treatment of anaphylaxis and should

be given immediately upon suspicion of an anaphylactic reaction.

Case 32-2 (Question 3)

Table 32-5

Epinephrine should be given intramuscularly into the lateral thigh as

often as every 5 minutes to treat symptoms. Intramuscular injection is

preferred over the subcutaneous and intravenous (IV) routes because

of rapid absorption and ease of administration. The patient should be

placed in the Trendelenburg position and second-line treatments

including oxygen, IV fluids, and a nebulized β-agonist initiated as

needed. Antihistamines and corticosteroids are also commonly used to

treat anaphylaxis although there are no data showing an impact on

outcome from these therapies.

p. 679

p. 680

GENERALIZED REACTIONS

Generalized hypersensitivity reactions can manifest in a number of ways

including drug fever, serum sickness, hemolytic anemia, vasculitis, and

autoimmune disorders. Specific organ systems such as the lungs, liver,

kidneys, and hematopoietic system can also be the target of allergic

drug reactions.

Case 32-3 (Question 1),

Case 32-4 (Questions 1, 2),

Case 32-5 (Questions 1, 2)

Tables 32-6, 32-7, 32-8

PSEUDOALLERGIC REACTIONS

Pseudoallergic reactions are drug reactions that exhibit clinicalsigns and

symptoms of an allergic response but are not immunologically mediated.

Pseudoallergic reactions can be relatively benign (such as red man

syndrome from vancomycin) or potentially life-threatening, clinically

resembling immune-mediated anaphylaxis as from radiocontrast media.

Several drugs are associated with pseudoallergic reactions including

aspirin and nonsteroidal anti-inflammatory drugs, opiates, angiotensinconverting enzyme inhibitors, and injectable iron products.

Case 32-6 (Questions 1, 2,

5),

Case 32-7 (Question 1)

Tables 32-9

The management of pseudoallergic reactions is the same as for true

allergic reactions.

Case 32-6 (Questions 3, 4),

Case 32-7 (Question 2)

PREVENTION AND MANAGEMENT OF ALLERGIC REACTIONS

The keys to preventing an allergic reaction in a patient with history of

allergy are a good description of the reaction and its causes,

distinguishing between drug allergy and drug intolerance, and good

documentation and communication of the reaction.

Case 32-1 (Questions 1, 2),

Case 32-8 (Question 1)

In some cases, it is necessary to treat a patient with a drug to which they

have a significant allergic reaction. To accomplish this, the process of

tolerance induction (or desensitization) may be used. Tolerance

induction starts with administration of a sub-allergenic dose of the drug

to which a patient is allergic and the progressive administration of larger

doses with the goal of modifying the patient’s response. Once tolerance

has been successfully induced, the patient must remain on the drug to

maintain the state of tolerance. Tolerance induction should not be used

in patients with a history of a severe non–IgE-mediated reaction such as

hepatitis, hemolytic anemia, Stevens–Johnson syndrome, or toxic

epidermal necrolysis.

Case 32-9 (Questions 1, 2, 4)

The oral route of tolerance induction is preferred over the IV route.

Patients may experience a mild reaction during desensitization, although

severe reactions are rare. Even after successful desensitization, patients

may experience an allergic reaction during full dose therapy.

Case 32-9 (Questions 2, 3)

A graded drug challenge (also called test dosing) is a process of giving

subtherapeutic doses of a drug to a patient to determine if they are

allergic. A graded drug challenge generally uses larger starting doses

than tolerance induction and involves fewer steps. Graded drug

challenge may be appropriate in patients with a distant or unclear history

of drug allergy, when the reaction seems minor or when diagnostic

testing is unavailable, or in cases where cross-reactivity is expected to

be low. Graded challenge should not be used in patients with a history of

a severe non-IgE–mediated reaction such as hepatitis, hemolytic

anemia, Stevens–Johnson syndrome, or toxic epidermal necrolysis.