PHARM Chapter 5 - Adverse Effects, Interactions, and Contraindications

• To ensure safe medication administration and prevent errors, understand a medication's purpose, therapeutic effects, potential side/adverse effects, interactions, contraindications, and necessary precautions.

Adverse Medication Effects

• All medications can cause side and adverse effects.

Side Effects

• Side effects occur when a medication is given at a therapeutic dose.
• Discontinuation of the medication is usually not needed.

Adverse Effects

• Adverse effects are undesired, inadvertent, unexpected, and can be severe responses to a medication.
• Adverse effects can occur at both therapeutic and higher-than-therapeutic doses.
• Medications should be discontinued immediately if this occurs.
• Adverse effects are reported to the FDA using the MedWatch program.
• Responses to medications differ based on age, sex, disease process, and ethnic/genetic variations.

Central Nervous System (CNS) Effects

• Can result in CNS stimulation (excitement, seizures) or CNS depression (advise against driving or operating machinery).

Anticholinergic Effects

• Result from muscarinic receptor blockade, mainly affecting eyes, smooth muscle, exocrine glands, and the heart.
• Manage effects by sipping on liquids for dry mouth, using sunglasses for photophobia, and urinating before taking medication to reduce urinary retention.
• Avoid activities that could lead to overheating, because ability to produce sweat is decreased.

Cardiovascular Effects

• Can involve blood vessels and the heart.
• Antihypertensives can cause orthostatic hypotension.
• Monitor for lightheadedness or dizziness, and sit or lie down if these occur.
• Minimize postural hypotension by changing position slowly.

Gastrointestinal (GI) Effects

• Result from local irritation of the GI tract or stimulation of the vomiting center.
• NSAIDs can cause GI upset, so take them with food.
• Opioid analgesics slow peristalsis and can cause nausea and sedation.
• Methods to avoid constipation and GI irritation, and promote safety should be performed when taking.

Hematologic Effects

• Relatively common and potentially life-threatening with some medications.
• Bone marrow depression/suppression is generally associated with anticancer medications.
• Hemorrhagic disorders are generally associated with anticoagulants and thrombolytics.
• Monitor for bleeding (bruising, discolored urine/stool, petechiae, bleeding gums).
• Notify the provider if these effects occur.

Toxicity

• Toxicity is a severe, life-threatening adverse effect that can be caused by an excessive dose or occur at therapeutic dose levels.
• Liver damage occurs with an acetaminophen overdose, especially with chronic alcohol use.
• Acetylcysteine can be used to minimize liver damage with acetaminophen overdose.

Hepatotoxicity

• Can occur with many medications because the liver metabolizes most medications.
• Damage to liver cells impairs medication metabolism, which causes medication accumulation and adverse effects.
• Combining two or more hepatotoxic medications increases the risk for liver damage.
• Liver function tests are indicated when clients start a medication known to be hepatotoxic and periodically thereafter.
• Monitor for nausea, vomiting, jaundice, dark urine, abdominal discomfort, and anorexia.

Nephrotoxicity

• Can occur with certain antimicrobial agents and NSAIDs.
• Damage to the kidneys interferes with medication excretion, leading to medication accumulation and adverse effects.
• Aminoglycosides can injure cells in the renal tubules of the kidneys.
• Monitor blood creatinine and BUN, as well as peak and trough medication levels for clients taking medication that is nephrotoxic (acyclovir, aminoglycosides, cyclosporine, NSAIDs, amphotericin B).

Hypersensitivity/Allergies

• Hypersensitivity and allergy are interchangeable terms; the individual develops an immune response to a medication after previous exposure and antibody development.
• Hypersensitivity or allergies can result in a mild reaction (itching, rash, watery eyes, sneezing, rhinosinusitis) or a severe reaction resulting in anaphylaxis.
• Rapid or immediate hypersensitivity (atopic allergy) causes an overproduction of immunoglobulin E antibodies, resulting in acute inflammation, histamine release, and vasoactive amines release.
• Atopic allergies can result in hay fever, rhinosinusitis, and can become severe (angioedema, anaphylaxis, or allergic asthma) by inhaling, ingesting, injection, or direct contact with an allergen.
• Mild allergies (rash, hives, rhinosinusitis) is often treated with diphenhydramine.

Angioedema

• A severe allergic reaction that affects deep tissues (blood vessels, skin, subcutaneous tissue, mucous membranes).
• Generally, angioedema involves the lips, face, oropharyngeal cavity, and neck, but can also affect the intestinal system and other parts of the body.
• NSAIDs and angiotensin-converting enzyme inhibitors (ACE inhibitors) are the most common medications that can cause angioedema.
• Can occur within 24 hours or anytime thereafter.
• Administer oxygen and alleviate anxiety with reassurance, and if needed, maintain an open airway with intubation or tracheostomy if laryngeal edema, stridor, and inability to swallow develops.
• Treat with corticosteroids, diphenhydramine, and epinephrine depending on the severity of the client’s condition.
• Monitor for recurrence when medications wear off.

Anaphylaxis and Allergic Asthma

• Anaphylaxis is a life-threatening, immediate systemic reaction caused from an allergic response to a medication, dye, food, or insect bit or sting.
• Allergic asthma also has a rapid onset with similar causes.
• Manifestations of anaphylaxis can start with anxiety, weakness, generalized itching and hives that progress to erythema and angioedema of the head and neck.
• Crackles, wheezing, decreased breath sounds, a feeling of a lump in the throat, hoarseness, and stridor can develop into a life-threatening condition that results in respiratory failure, hypoxemia, hypotension, tachycardia, and death.
• Allergic asthma has similar manifestations that involve the pulmonary system that can become life-threatening.
• If the allergy is known, the client should wear a medical alert bracelet and have injectable epinephrine available.
• Immediately stop suspect medication and notify the Rapid Response team.
• Establish an airway to maintain ventilation and administer bronchodilators if needed.
• Treat with epinephrine IM or IV every 5 to 15 minutes as needed to constrict blood vessels, improve cardiac contraction, and promote bronchodilation of the pulmonary system.
• Administer diphenhydramine, an antihistamine, to decrease manifestations of the angioedema and urticaria.
• Continue to administer oxygen, obtain arterial blood gases, and plan for the client to receive inhaled beta-adrenergic agonist or bronchodilators (albuterol, metaproterenol) every 2 to 4 hr.
• Administer corticosteroids for late recurrence of manifestations.
• Monitor hemodynamics and pulmonary status, and watch for fluid overload from too rapid of IV fluid infusions.

Extrapyramidal Symptoms (EPSs)

• Abnormal body movements that can include involuntary fine-motor tremors, rigidity, uncontrollable restlessness, and acute dystonia.
• Can occur within a few hours or take months to develop.
• Are associated with medications affecting the CNS (those used to treat mental health disorders).
• Most EPSs can be treated with anticholinergic medications.

Immunosuppression

• Decreased or absent immune response.
• Immunosuppressant medications (glucocorticoids) can mask the usual manifestations of infection (fever).
• Monitor clients taking an immunosuppressant (a glucocorticoid) for delayed wound healing and subtle manifestations of infection (sore throat).
• Avoid contact with anyone who has a communicable disease.

Drug-Drug Interactions

• Medications given together can potentiate their action to increase therapeutic effects.

Increased Therapeutic Effects

• If with asthma, use albuterol (a beta2-adrenergic agonist inhaler) 5 min before triamcinolone acetonide (a glucocorticoid inhaler) to increase triamcinolone acetonide absorption.

Increased Adverse Effects

• Clients can take two medications that have the same adverse effect, which increases the risk of potentiating these findings.
• Diazepam and hydrocodone bitartrate/acetaminophen have CNS depressant effects; using them together increases the risk for CNS depression.

Decreased Therapeutic Effects

• One medication can increase the metabolism or block the effects of a second medication, decreasing the blood level and effectiveness of the second medication.
• Phenytoin increases hepatic medication-metabolizing enzymes that affect warfarin, decreasing warfarin's blood level and effect.

Decreased Side/Adverse Effects

• One medication can be given to counteract the side/adverse effects of another medication.
• Ondansetron hydrochloride (an antiemetic) can be administered to counteract the side effects of nausea and vomiting for clients receiving chemotherapy.

Increased Blood Levels, Leading to Toxicity

• One medication can decrease the metabolism of a second medication, increasing the blood level of the second medication, and leading to toxicity.
• Fluconazole inhibits hepatic medication-metabolizing enzymes that affect aripiprazole, increasing blood levels of this medication.

Over-the-Counter (OTC) Medication Interactions

• Ingredients in OTC medications or herbal supplements can interact with other OTC or prescription medications.
• Inactive ingredients (dyes, alcohol, or preservatives) can cause adverse reactions.
• A potential exists for overdose because of the use of several preparations (including prescription medications and herbal supplements) with similar ingredients.
• Obtain a complete medication history to include any prescription medications, OTC medications, illicit drug use, as well as herbal and other dietary supplements.
• Instruct clients to follow the manufacturer’s recommendation for dosage.
• Interactions of certain prescription and OTC medications can interfere with therapeutic effects.
• Advise clients to use caution and to check with the provider before using any OTC preparations (antacids, laxatives, decongestants, herbal supplements, or cough syrups).
• Antacids can interfere with the absorption of cimetidine and other medications.

Medication-Food Interactions

• Food can alter medication absorption and/or can contain substances that react with certain medications.
• Consuming foods with tyramine while taking monoamine oxidase inhibitors (MAOIs) can lead to hypertensive crisis,.
• Clients taking MAOIs should be aware of foods containing tyramine (cheese and processed meats) and avoid them.
• Vitamin K can decrease the therapeutic effects of warfarin and place clients at risk for developing blood clots.
• Clients taking warfarin should include a consistent amount of vitamin K in their diet.
• Tetracycline can interact with a chelating agent (milk) and form an insoluble, unabsorbable compound.
• Instruct clients not to take tetracycline within 2 hours of consuming dairy products.
• Grapefruit juice inhibits medication metabolism in the small bowel, increasing the amount of medication available for absorption of certain oral medications.
• This increases therapeutic or adverse effects.
• Do not drink grapefruit juice if taking such a medication.
• Food often decreases the rate of medication absorption.
• Some foods increase the rate of absorption of certain medications.

Contraindications and Precautions

• A specific medication can be contraindicated for a client based on the client’s condition.
• Penicillin derivatives are contraindicated for a client who has an allergy to penicillin.
• Precautions should be taken for a client who is more likely to have an adverse reaction than another client.
• Morphine depresses respiratory function, so it should be used with caution for clients who have asthma or impaired respiratory function.

Pregnancy Labeling

• The Pregnancy and Lactation Labeling Rule (PLLR) mandates three sections for labeling: pregnancy, lactation, and females and males of reproductive potential.
• Before administering any medication to a client who is pregnant or could be pregnant, determine whether it is safe for use during pregnancy.