Absorption describes how the medication moves from its site of administration into the systemic circulation (into the bloodstream). Some common routes of administration are shown in Table 13-1. Most medications must move from the site of administration into systemic circulation to be effective. Others, such as topical creams or inhalers, may provide therapeutic benefits through a localized effect. Although systemic absorption may not be necessary for effectiveness of topically applied medications, it can occur and result in side effects. For example, high dose, long-term use of inhaled corticosteroids to treat asthma has been shown to result in enough systemic absorption to increase the risk of developing osteoporosis.^12,15

Table 13-1

List of Common Routes of Administration

Route	Description	Example Medication(s)
Oral (PO)	Swallowed; uses the gastrointestinal tract	Most commonly used route of administration in U.S.; tablets, capsules, oral liquids
Sublingual (SL)	Under the tongue; medication rapidly absorbs into systemic circulation	Nitroglycerin tablets for chest pain
Rectal	Administered through the rectum; some absorb into systemic circulation, others provide a local laxative effect	Glycerin suppositories (laxatives) Promethazine (Phenergan) for nausea

Inhalation Into the lungs

Bronchodilators for asthma, such as albuterol inhalers

Corticosteroids for asthma such as flunisolide (AeroBid) inhalers

Intranasal Into the nose; some absorb into systemic circulation, others provide a local effect

Systemic absorption required for effectiveness: calcitonin (Miacalcin) nasal spray for osteoporosis

Localized effect: intranasal decongestants (Afrin)

Intravenous (IV) Directly into the veins; most rapid onset of action Common route of administration in hospitals; morphine, antibiotics Intramuscular (IM) Into the muscle Some vaccinations, penicillin G benzathine Subcutaneous (SQ, SC, SubCut) Into the subcutaneous layer of skin

Insulin

Teriparatide (Forteo) for osteoporosis

Intraarticular Into the joint space; causes a localized effect within the joint, some systemic absorption may occur Triamcinolone, methylprednisolone, hyaluronic acid (Orthovisc, Hyalgan) for osteoarthritis Epidural Into the epidural space (within the spinal column but outside the dura mater) Fentanyl, lidocaine, corticosteroids Transdermal (TD) Medication patches where the medication moves through the skin into systemic circulation Patches including: nicotine, nitroglycerin, clonidine, contraceptives, fentanyl, and lidocaine Topical Creams and ointments applied to the skin with an expected localized effect; systemic absorption may or may not occur Creams and ointments including BENGAY cream, capsaicin (Zostrix), hydrocortisone

The rate and extent of drug absorption through the skin can be dramatically increased by application of heat; therefore heat generating modalities (e.g., heating pads, ultrasound, infrared lamps, and warm hydrotherapy) should not be applied near transdermal medication patches. Electromagnetic (e.g., ultraviolet radiation, lasers, and diathermy) and electrical current modalities (e.g., transcutaneous electrical nerve stimulation [TENS]) should also not be used near medication patches because many patches have metallic backings that conduct electric currents, leading to significant heat generation and burns.³

Distribution describes movement of the medication from the bloodstream into various areas of the body such as the central nervous system (CNS), breast milk, and adipose (fat) tissue. This concept can be helpful in understanding medication actions and side effects. For example, opioid pain relievers act on the CNS to relieve pain; therefore an opioid will be most effective if it can easily distribute into the CNS. Only antibiotics with good distribution into bone tissue will be effective in treating osteomyelitis.

Medications are cleared from the body through metabolism, excretion, or both. Metabolism is the biotransformation or chemical alteration of the medication. The byproduct of drug metabolism is called a metabolite. Through metabolism, some medications are inactivated, whereas others remain active (active metabolite) but are more water soluble for easier elimination by the kidneys. Generally, metabolism takes place in the liver but it can occur through enzymatic processes in the kidneys, lungs, and bloodstream. Differences in drug response, side effects, and safe dose can be greatly affected by genetic differences in drug metabolism.²¹

Excretion describes elimination of the medication without prior metabolism (excreted unchanged) or, more commonly, elimination of the metabolites. Generally, excretion takes place through the kidneys (renal excretion, urine) but also occurs through the gastrointestinal tract (feces), lungs (breath), and skin (sweat).

The rate at which a drug is cleared from the body is referred to as half-life. Technically speaking, half-life is the amount of time it takes to reduce the concentration of the drug in the body by half. Drug half-lives can range from seconds to days. Anything that slows a drug’s clearance will lengthen its half-life. Liver metabolism and renal clearance are slower in older adults (>70 years) as compared with younger adults, and likewise for persons with acute or chronic liver or kidney disease.⁷ The most common type of clinically significant drug-drug interaction occurs when the presence of one drug slows the metabolism of a second drug.²¹ When drug clearance is decreased for whatever reason and the patient’s daily dose is not also decreased, drug accumulation and toxicity can occur.

A medication’s duration of action (the length of time it is active in the body) is related to its half-life. Drugs with a long half-life will have a long duration of action. Medications with a short duration of action usually require multiple daily administrations, three or four times daily, as compared to those with longer durations of action, which may only require dosing once or twice daily. One way medications can overcome a short duration of action is if they are formulated as a sustained release product. A sustained release product is usually in tablet or capsule form and is specially designed to dissolve very slowly in the intestines. By dissolving gradually over 12 or 24 hours, its effects will last longer. In general, sustained release products should not be chewed, crushed or broken open. Doing so can destroy the product’s sustained release properties, causing the entire dosage to be released at once.

Pharmacodynamics

Simply put, pharmacodynamics is a term used to describe what the medication does to the body. It is a study of the relationship between the amount of drug in the body and the response observed.⁷ Pharmacodynamics include a wide variety of principles, such as the dose–response relationship, therapeutic window, adverse reactions, and toxicity.

The dose–response relationship describes the relationship between the amount of drug in the body and its expected effectiveness and likelihood and severity of side effects (e.g., the higher the dose, the more side effects seen). This is closely tied to the concept of therapeutic window. A drug’s therapeutic window may be described as wide or narrow. The window is defined as the minimum drug concentration needed for the drug to show effectiveness, without causing toxicity in the patient. Penicillins and most cephalosporin antibiotics have wide therapeutic windows. Drugs with narrow therapeutic windows include the anticoagulant, warfarin (commonly used after orthopedic surgeries), and antiseizure medications (commonly used to treat phantom pain after amputation or in diabetic neuropathic pain).

The term adverse drug reaction (ADR), also termed side effect, describes any unintended effect of the medication including an exaggerated medication response. An example of an exaggerated response is extreme hypotension after receiving a high blood pressure medication. Certain ADRs may be particularly problematic in the orthopedic population, including medications that may reduce safety or increase fall risk (e.g., orthostatic hypotension, dizziness, blurred vision, hypoglycemia, ataxia, gait abnormalities) or medications that affect cognitive function. There are also many medications that cause cardiovascular side effects that may complicate exertional activity by increasing heart rate (tachycardia) or blood pressure (hypertension), by blunting the expected exercise-induced increase in heart rate, or by reducing heart rate (bradycardia). The term toxicity is often used interchangeably with ADR or side effect, but it is most accurate to reserve the term for situations where the serum concentrations have exceeded normal levels.

Tolerance occurs when the reaction to a drug diminishes over time. Tolerance can occur to both the benefits of a medication (making it less effective over time) and the ADRs (making it better tolerated over time).⁴ Withdrawal symptoms indicate physical dependency and are expected to occur with certain medications when used over a prolonged period. Withdrawal symptoms are generally the opposite of the pharmacologic effects of the medication. For example, one withdrawal symptom of a medication used to lower blood pressure would be hypertension.

Psychological dependency, also called addiction, occurs with certain medications such as opioid analgesics, amphetamines, and benzodiazepine sleep aids, as well as other substances with abuse potential, including cocaine, heroin, alcohol, caffeine, and nicotine. Withdrawal symptoms do contribute to the development of addiction in that the patient continues to use the substance to avoid the unpleasantness of the withdrawal symptoms; but having withdrawal symptoms alone does not meet the definition of addiction. It is important to understand the difference between physical and psychological dependency.⁴ Psychological dependency and addiction involve strong cravings and desires for the drug that overwhelm daily life. There is a loss of control over its usage and use continues despite its negative impact on quality of life.^4,6 Drug addiction is most strongly associated with medications that rapidly distribute into the CNS causing high levels of euphoria and dysregulation of the neurotransmitters involved in the body’s natural reward and pleasure centers.

Principles of Safe Medication Use

Although PTAs are not involved in the decision-making process regarding prescription and over-the-counter (OTC) medication use, having a general understanding of commonly used medications and knowing where to look for more information can help the PTA identify medication-related problems that should be brought to the attention of the prescriber or other health care team members. PTAs often spend more time with patients during therapy sessions than a prescriber spends with the patient during a typical office visit. This may provide opportunities to identify problems with compliance, lack of medication knowledge, ADRs, and lack of drug effectiveness. A variety of drug information resources exist that can be helpful in providing information, such as mechanism of action, dosing, therapeutic uses, and ADRs. See Table 13-2 for a list of helpful drug information resources. Although such resources exist, the PTA must be cautious about providing specific information to the patient that would be considered outside the PTA’s scope of practice.

Table 13-2

Helpful Drug Information Resources

Name of Reference	Description
Epocrates Skyscape Medscape

Free online websites and free downloads for mobile devices. Source of general drug and disease information; some have information on drug costs. Drugs.com Free online website. Source of general drug information, a drug-drug interaction checker, and pill identifier.

Drug Information Handbook

Publisher: Lexi-Comp, updated annually

For purchase in paperback and download for mobile devices. Source of comprehensive drug information.

Drug Facts and Comparisons

Publisher: Facts and Comparisons

For purchase in hardbound and download for mobile devices. Source of comprehensive and very detailed drug information.

The following general principles of safe medication use can be provided to any patient:

Keep a current list of all medications including prescription, OTC, and herbal

Keep medications in their original containers

Never take some else’s medication

Take medications exactly as directed

Do not start or stop medications without consulting the prescriber

Report any new symptoms to the prescriber

Don’t chew, crush, or break any capsules or tablets unless instructed

When measuring liquid medications, use only the measuring device provided

Be knowledgeable about the medications

Ask questions when things are unclear ¹⁰

MEDICATIONS TO TREAT AND PREVENT ORTHOPEDIC INFECTIONS

Antibiotic use in the treatment and prevention of orthopedic related infections is common. Antibiotics are medications with the ability to kill or inhibit growth of bacteria. Common examples of antibiotics used in the hospital and outpatient orthopedic settings are listed in Table 13-3. Orthopedic infections can result in slowed recovery, permanent joint damage, amputation, nonunion in cases of fracture, removal of implanted hardware, and death due to sepsis. Appropriate antibiotics are selected, taking into account the type of documented or suspected bacterial pathogens, the drug’s ability to distribute adequately to the site of infection, patient allergy history, side effects, and cost. Because the risk of infection following orthopedic surgeries is high, antibiotics are routinely administered before the procedure to reduce the risk of infection-related complications. The use of antibiotics to prevent an infection is referred to as prophylaxis.

Table 13-3

Common Antibiotics Used to Treat and Prevent Various Types of Orthopedic Infections ^∗

Drug Class	Specific Antibiotics
Penicillins	Amoxicillin (Amoxil) oral Dicloxacillin (Dynapen) oral Nafcillin (Nafcil, Unipen) injection Oxacillin (Prostaphlin) injection, oral Penicillin (various brands) injection, oral

Cephalosporins

Cefaclor (Ceclor) oral

Cefadroxil (Duricef) oral

Cefazolin (Ancef, Kefzol) injection

Cefixime (Suprax) oral

Cefpodoxime (Vantin) oral

Cetazidime (Fortaz) injection

Ceftriaxone (Rocephin) injection

Cephalexin (Keflex) oral

Tetracyclines

Doxycycline (Vibramycin) oral

Minocycline (Minocin) oral

Tetracycline (Sumycin) oral

Antifolate (sulfonamides) Sulfamethoxazole/trimethoprim (Bactrim, Septra) oral Quinolones

Ciprofloxacin (Cipro) injection, oral

Levofloxacin (Levaquin) injection, oral

Ofloxacin (Floxin) injection, oral

Miscellaneous

Clindamycin (Cleocin) injection, oral

Gentamicin (Garamycin) injection

Vancomycin (Vancocin) injection

^∗This is not an all-inclusive list of antibiotics.

Compliance with the prescribed antibiotic regimen is essential to reduce the risk of bacterial resistance and to improve outcomes. Patients taking oral antibiotics should take the medication exactly as instructed for the full course of therapy. It is common for patients to stop taking their antibiotic when they start to feel better (e.g., fever resolves, pain at the site of infection is reduced). Stopping the antibiotic too early can allow the infection to return and/or increase the risk of developing bacterial resistance to that antibiotic. To assure optimal oral absorption, dosing instructions should be followed carefully. For example, some antibiotics should be taken on an empty stomach, defined as at least 1 hour before or 2 hours after a meal; others should be taken with meals to avoid stomach upset; others should not be taken within 2 hours of calcium-containing antacids or milk.

Another important concept regarding antibiotic compliance is around-the-clock dosing. To achieve steady blood levels of the antibiotic at the site of infection, antibiotics should be dosed at regularly spaced intervals throughout the day. For example, an antibiotic ordered to be taken three times daily should not be taken at breakfast, lunch, and supper but rather, divided evenly throughout the day every 8 hours. When the concentration of antibiotic falls below the minimum level needed to kill or inhibit bacterial growth, the weaker pathogen strains will be affected, leaving the strong pathogens to replicate and grow in numbers. This can quickly lead to bacterial resistance. Skipping doses creates a similar problem.

The PTA can improve outcomes by discussing the importance of following antibiotic instructions carefully, completing the full course of therapy as prescribed, and referring noncompliance issues to the appropriate health care provider. Antibiotic compliance is important for all orthopedic patients, but is especially important in those with reduced peripheral circulation, such as those with peripheral vascular disease (PVD) and diabetes. Delivery of antibiotics to the site of infection may be particularly reduced in these populations. The PTA can also help prevent the spread of infection through thorough hand washing and adequately cleaning rehabilitation equipment between patients.

MEDICATIONS TO TREAT PAIN AND INFLAMMATION

Effective treatment of pain and inflammation not only reduces suffering, but speeds healing following injury. Patients experiencing inadequately treated pain often have compromised mobility, restricted activities of daily living, disturbed sleep, and reduced quality of life. As a result, they may not be able to participate in beneficial physical therapy to the fullest potential.

Pain is often undertreated. Pain management is heavily associated with biases related to socioeconomic status, race, culture, age, and gender. Some prescribers do not understand treatment of different types of pain; pain is not always considered to be a treatment priority; and there are misperceptions regarding the risk of opioid addiction and side effects.

The Joint Commission has emphasized pain treatment as a responsibility of health care providers and a patient’s right by requiring routine pain assessment as the “fifth vital sign.” It is recommended that regular assessment and documentation of pain severity, functional ability, progress towards achieving therapeutic goals, and presence of ADRs occur in both children and adults.1,6

An analgesic is any medication that reduces pain. There are three broad categories of oral and IV analgesics: (1) opioids, (2) acetaminophen, and (3) antiinflammatory agents. Appropriate analgesics are chosen based upon the type of pain (acute/chronic, nociceptive/neuropathic, inflammatory/noninflammatory), level of pain, side effects, and cost.

Types of Pain

Nociceptive pain results from actual tissue damage. Nociceptive pain may be inflammatory or noninflammatory or both. Examples include osteoarthritis, bone pain, muscle sprains, and postsurgical pain. This type of pain responds well to opioid analgesics, acetaminophen, and antiinflammatory agents. Nociceptive pain specifically caused by inflammation is referred to as inflammatory pain. As expected, inflammatory pain responds best to the antiinflammatory agents, including corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Examples of inflammatory pain include rheumatoid arthritis, muscle aches and sprains, and bursitis.

Neuropathic pain results from damage to or dysfunction of nerves. Examples include nerve compression, fibromyalgias, diabetic neuropathy, postherpetic neuralgia, spinal cord injuries, and phantom pain following amputation. Neuropathic pain is relatively resistant to opioids, acetaminophen, and antiinflammatory agents, although they may be helpful in certain cases. The most effective medication to treat neuropathic pain will vary by patient. The medications that tend to be most effective in treating neuropathic pain are medications that slow or block nerve conduction. Antidepressants such as duloxetine (Cymbalta), amitriptyline (Elavil), desipramine (Norpramin), venlafaxine (Effexor), and others are commonly used, as are anticonvulsants such as pregabalin (Lyrica), gabapentin (Neurontin), carbamazepine (Tegretol), and others. Effective topical products include lidocaine (Lidoderm) patch and capsaicin (Zostrix) cream.13,19,20 The opioid analgesic, tramadol (Ultram), is also often used to treat neuropathic pain because it is an opioid analgesic with additional antidepressant-like properties on nerve conduction.

Acute pain occurs following injury to the body and generally disappears when the injury heals. Chronic pain continues past the normal time of expected healing, which is assumed to be about 3 months.6,11 Persistent pain, whether acute or chronic, generally responds better to around-the-clock dosing rather than on demand dosing (also called prn dosing or as needed dosing). Many types of inflammatory pain as well as neuropathic pain are chronic rather than acute. Opioids, acetaminophen, and NSAIDs have quick onsets of action, within minutes to hours, whereas drugs for neuropathic pain, such as antidepressants and anticonvulsants, generally are not effective for several weeks. Ideally, when treating persistent chronic pain, patients are prescribed medications with a long duration of action and/or sustained release products to prevent the need for frequent daily administration. Patients may then take a shorter-acting analgesic or immediate release product for breakthrough pain. Breakthrough pain is pain that occurs despite the use of regularly scheduled pain medications.⁶

Opioid Analgesics

Opioid analgesics are all chemically related to opium. Commonly used prescription opioid medications include morphine, oxycodone, hydrocodone, and codeine. See Appendix A for others. Opioid analgesics work within the CNS to block the transmission of pain and create a feeling of euphoria. It is important to note that although pain is relieved, the underlying disease process or cause of the pain is not altered. Opioids are the most powerful medications available for treatment of nociceptive pain; they are also effective for some patients with neuropathic pain. IV opioids are more commonly used for inpatient settings for moderate to severe acute pain. Oral agents can be used for mild, moderate, or severe acute or chronic pain in any setting. Opioids are sometimes administered epidurally to provide highly effective pain control directly upon the spinal cord. Fentanyl (Duragesic) is available as a transdermal patch that provides control of severe, chronic pain.

Side effects of the opioid analgesics include nausea and vomiting (take with food to minimize risk), allergic reactions, sedation, drowsiness, dizziness, constipation, hypotension and orthostatic hypotension, slowed heart rate, slowed respiration, impaired judgment, physical dependence, and addiction.¹⁴ Several of these side effects reduce the patient’s safety and may increase risk of falls and injury. Constipation caused by chronic opioid use is extremely common but can be treated and prevented with over-the-counter stool softeners and mild laxatives including senna, docusate (Colace), and bisacodyl (Dulcolax) tablets.

Health care providers and patients alike may overestimate the risk of developing addiction when managing pain with opioids. This misperception can lead to inadequate pain control through underprescribing or underdosing, and patients skipping doses or “taking as little as possible.” The actual risk of developing opioid addiction following chronic use for medical management of pain is difficult to assess, but has been estimated at approximately 0.2% (2 in 1000) for persons with no prior history of substance abuse, and 3.3% (33 in 1000) for the general population.⁸

Tolerance and physical dependency are likely to occur with chronic use and are not equivalent to addiction. Although certain behaviors may seem like warning signs of addiction, the PTA should not make assumptions. Behaviors such as aggressively complaining about pain, occasionally taking more than prescribed, drug hoarding during periods of reduced pain, openly acquiring similar drugs from other medical resources, reporting unintended psychiatric effects, and resistance to changes in therapy are not necessarily signs of addiction. These behaviors are equally likely to occur in nonaddicted patients experiencing tolerance, an increase in pain level, poorly controlled pain, and anxiety related to a return of pain.¹⁸ Prescribers must balance the legitimate medical need for opioids in patients with chronic pain with the possibility of addiction and abuse.⁶