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Medication Considerations
You've been managing an 82-year-old female with respiratory distress for nearly half an hour. She has wheezes in all fields of her lungs and a long history of smoking, asthma and COPD. Even after the third 2.5 mg albuterol nebulizer treatment, she does not appear to have improved at all. The last time you gave albuterol, a single 2.5 mg dose completely relieved a 10-year-old child's asthma attack. Why did these patients respond so differently to the same drug? This article reviews anatomical and physiological differences specific to drug administration for geriatric and obstetric patients and explains drug safety for obstetrical patients.
Geriatric Patients
There are more than 35 million Americans over age 65.1 This population is responsible for more than half of all EMS requests for transport, during which time they may be given a variety of drugs, often forgetting that they are frequently already on several different drugs. The more drugs they are taking, the greater the risk for dangerous drug interactions. Furthermore, biological changes as we age change how drugs act in our bodies.
Cardiovascular System
As people age, they develop atherosclerosis (hardening of the vessels), and, at the same time, the myocardial or heart tissue begins to atrophy, or weaken. This can lead to a decreased left ventricular compliance, then blood pressure changes and increased risk of dysrhythmias.2 The end result is decreased blood circulation, which also means a decrease in the efficiency of drug circulation. Over time, the concentration of plasma proteins in the blood also decreases, leading to an increase in free drug availability. This means that the same amount of drug may be more effective in a geriatric patient than in a young adult.
Consider the following actual patient presentations. The first was a healthy 22-year-old, 200-lb. male who avulsed his thumb on a table saw. After bleeding was controlled and ice applied, he rated his pain at 8 on a 0-10 scale. Morphine was administered in 4 mg increments every 10 minutes. He required 16 mgs of morphine before his pain was rated at 2 out of 10.
A day later, an otherwise healthy 200-lb., 84-year-old male complained of 10 out of 10 hip pain after falling in his kitchen. The physical exam revealed outward rotation and 3-inch shortening of his right leg, and he was immobilized in a position of comfort. He was also given 4 mg morphine for pain management, which reduced his pain to 5 out of 10. Another 4 mg 15 minutes later completely relieved his pain and resulted in mild sedation. These two cases demonstrate how blood changes alter drug availability within the body, changing how elderly patients respond to like doses of drugs.
Respiratory System
A decrease in lung elasticity occurs, along with a loss of pulmonary muscle strength, resulting in a smaller tidal volume for each breath. When combined with alveolar dilation, which can increase the lung's surface area by up to 20%2 and a one-third decrease in pulmonary circulation,1 a slowing of carbon dioxide and oxygen occurs. This can lead to carbon dioxide retention, also known as hypercapnia, and hypoxia. 2 Essentially, this also increases dead air space within the lungs. This means when an inhaled drug like albuterol is given, the drug's effects are reduced, because more of the drug remains in the dead airspace. An increased dose may be needed to reach the same effect as a smaller dose in a younger patient.
Diseases like emphysema also destroy the alveolar walls, decreasing the surface area available for gas exchange and exacerbating hypoxemia and hypercapnia.
Neurologic System
A few neurologic changes occur with age that affect how drugs interact in the body. Neurons, nerves and nerve fibers all decrease in size and number, and there is slowing of conduction across synapses. This all can lead to a delayed onset of therapeutic action once drugs reach their target cells. Many drugs commonly taken by elderly patients can cause them to become depressed. Examples of these drugs include: analgesics/anti-inflammatory agents, anticonvulsants, antihypertensives, antimicrobials, anti-Parkinson agents, hormones, immunosuppressive agents and tranquilizers.
Some patients will refuse to take their prescriptions because of the depression. Missed medications, especially over an extended period of time, often result in EMS activation. If you see these drugs in a patient's home or observe them on your patient's medication list, determine if all of their medicines have been taken as directed. Do not reprimand patients who didn't take their medications, but try to determine why and share this information with receiving staff.
Integumentary System
With age come decreases in dermal and epidermal thickness as subcutaneous fat is lost. Transdermal drugs, such as lidocaine, morphine, fentanyl and nitroglycerin patches, will more easily be absorbed into the body; however, skin blood flow also decreases. This reduction can increase the absorption time of subcutaneous and intramuscular drug injections like epinephrine and glucagon.
GI System
Many age-related changes involving the GI tract greatly impact how drugs work in the body.
As the years pass, salivary glands decrease in size and numbers, creating a chronic dry-mouth feeling. The decrease in salivary secretions slows the absorption of sublingual medicines, and motility in the gastrointestinal tract slows, leading to decreased absorption of oral medicines. Drugs also spend more time in a patient's stomach, which takes longer to empty as GI-related muscles slow. Within the GI tract, pH changes also occur as less hydrochloric acid becomes available to aid digestion. Many drugs are designed to dissolve at a specific pH range. If the pH in the GI tract rises too much, drugs cannot dissolve or may be destroyed. Another very significant change occurs within the liver, which decreases in size and activity level. Slowed liver function delays drug metabolism and causes drugs to remain in circulation for a greater period of time.
Urinary System
Drugs eliminated through the kidneys remain in the body for a more extended period of time due to a decrease in kidney size. Throughout life, the glomeruli, which are the functional part of our kidneys, begin to break down and fewer are available for use. While each patient's kidneys decline at a different rate, in any given individual, up to 30%-40% of the glomeruli can stop functioning, greatly decreasing the number of working nephrons that work to remove waste and water from the body. A reduced response to the antidiuretic hormone (ADH) develops and dampens the kidneys' ability to concentrate urine and conserve water. The loss of water conservation can lead to excessive electrolyte loss, especially when patients are placed on diuretic drugs--sodium and potassium being the two electrolytes most frequently lost in the urine. Tied in with the circulatory system, there is a reduction in renal blood flow, which further slows the kidneys' rate of waste elimination. Decreased waste elimination is especially important when administering morphine and other drugs that are eliminated by the kidneys. When patients have decreased kidney function, these drugs last in the body longer and increase the chance the patient may experience an inadvertent overdose. When possible, consider using drugs that are not eliminated by the kidneys in these patients. For example, administer fentanyl instead of morphine.
Endocrine System
Roughly half of the population over age 70 has elevated blood sugar levels around 200 milligrams per deciliter. With age comes a decrease in basal metabolic rate and reduced insulin and aldosterone production. Fewer insulin-producing beta cells develop within the pancreas. Non-insulin diabetes can develop as the body builds up a resistance to insulin still produced. A slowed metabolism once again increases the length of time drugs remain in the body's systems. Further, insulin and blood sugar changes increase the likelihood of EMS intervention for diabetic-related problems.
Drug Administration
Give medications slowly and start in low doses, because almost all aspects of pharmacokinetics have been altered in geriatric patients. Absorption is slowed by decreased gastric acid content, which slows GI emptying and GI motility. Blood flow to the GI tract slows, increasing the time it takes to absorb nutrients and drugs from the intestines. Changes in pH may either destroy PO (by mouth) drugs before they can enter circulation, or protective coatings on PO drugs may be destroyed, allowing the drug to irritate the GI tract and causing ulcers. A thinning of adipose tissue speeds absorption of transdermal medicines, while a decrease in circulation to the periphery results in a slowed absorption of intramuscular injections. Changes in the respiratory tract result in increased dead air space, which decreases the surface area available for gas exchange. Inhaled drugs, such as albuterol, reach fewer alveoli as dead air space increases. More doses of inhaled drugs may be needed to gain the same effect. Monitor for delayed onset of the drug's therapeutic effects.
First-pass metabolism enzymes are depleted. Drugs usually metabolized in the liver thus have an increase in bioavailability and increase the effectiveness of lower drug dosages. Drugs that bind to muscle, such as digoxin, also have a greater bioavailability as body muscle decreases. Body fat tends to increase with age, giving fat-soluble drugs more substance to bind to. This keeps fat-soluble drugs such as morphine, lidocaine and Valium in the body longer, as they can be stored in fat for a greater period of time. Water-soluble drugs may have a higher concentration as a geriatric patient's body fluid levels are decreased.
In response to these changes, increase time intervals between dose administrations. Decreased cardiac output and liver perfusion greatly slow drug metabolism, leading to a prolongation of drug action duration. To illustrate, benzodiazepines have a half-life increase from 20 to 90 hours.2 Drugs can also accumulate and reach toxic levels more quickly than in a younger person, further emphasizing the importance of increasing dose intervals. The kidneys, which are responsible for most drug excretion, experience decreased function as people age. Some drugs are excreted unchanged, and dosages should be reduced to prevent toxic drug levels developing in the bloodstream.
Ob Patients
You arrive on scene for a call for a woman actively seizing. Her husband advises you she is 26 years old and 20 weeks pregnant with their first child. She had seizures as a young child, but has been seizure-free for 20 years.
He tells you she had a sudden headache and, within three minutes, collapsed and began to seize, which she has been doing for eight minutes now. The pregnancy has been uneventful, and, on a quick physical exam, you observe no pedal edema, no obvious signs of injury. While starting an IV, your partner asks if you want to administer diazepam.
Do you? Is it safe to give to a pregnant patient? Is something else safer? This doesn't appear to be eclampsia, which doesn't onset until the third trimester in most cases. When we are caring for a pregnant woman, any drugs we administer are given both to her and her fetus. During the course of her pregnancy, a woman experiences many physiologic changes to adapt to the needs of her growing fetus that require an ever-increasing supply of nutrients and oxygen. These physiologic changes also alter the pharmacokinetics of drugs we give. This section reviews drug administration to the obstetrical patient.
Cardiovascular
Dynamic cardiovascular changes that occur to support the fetus's life affect the mother's heart rate, blood pressure, cardiac output and blood volume. A blood volume increase of 40%-50%, which is mostly in plasma volume, is necessary to accommodate increases in blood needs to uterus, fetus, maternal tissue and for birth blood loss. At the same time, red blood cell volume increases by only 20%, leading to a mild maternity-induced anemia for the mother.2 To support the metabolic needs of the growing uterus and fetus, the mother's cardiac output increases between 30%-50%. EMS providers will see this with an increase in the patient's resting heart rate of about 10 beats per minute. Afterload decreases as the uterus and placenta develop, creating more space for the increased blood flow. Hormonal changes, particularly progesterone changes, lead to vasodilation and decreased systemic vascular resistance, which can lower blood pressure by 10-15 millimeters of mercury (mmHg). Progesterone will also cause a pregnant patient's skin to remain pink and warm despite the presence of hypovolemia. Do not rely on skin appearance for pregnant patients who may have hypovolemia.
Respiratory System
Oxygen consumption increases during pregnancy by 20%, causing the mother's tidal volume and respiratory rate to increase. Essentially, her breaths become deeper and more rapid. Due to all of the fetus's oxygen needs, the mother's PaO2--the partial pressure of dissolved oxygen in the blood (normally 80-100)--increases to 104-108 mmHg. This increased oxygen saturation helps force oxygen through the placenta and to the fetus. Additionally, the mother needs to be able to accept carbon dioxide from the fetus to facilitate waste removal. Her increased tidal volume and respiratory rate help decrease her PaCO2 from a normal 35-45mmHg to 27-32mmHg. Keeping the blood saturation level of carbon dioxide lower than normal allows the mother to easily accept the fetus's carbon dioxide, but creates a respiratory alkalosis for the mother,2 which changes how well some drugs can be used and metabolized in her body. Be prepared for some drugs to not work as well as you otherwise might expect.
Renal System
Renal blood flow increases by up to 50% during pregnancy, increasing waste removal and urine production. Drugs administered will be removed by the kidneys more quickly, so it may be necessary to administer drugs more frequently or administer continuous IV infusions.
GI System
Increased gastrointestinal motility (one of the causes of morning sickness) helps remove nutrient drugs from the intestines more quickly to support fetal nutritional needs. However, there is also a slowing of gastric emptying, meaning food stays inside the stomach for greater periods of time and allowing stomach acids to potentially destroy oral drugs before they can be absorbed.
Other Changes
On the whole, drugs administered to pregnant women are absorbed and processed more quickly. An increased metabolism speeds biotransformation of drugs, and increased blood volume makes the same quantity of drug more dilute in the body. So, drugs are introduced more quickly, are more dilute and removed more quickly. What does this mean? Simply that the same quantity of drug used on a non-pregnant patient may be less effective during pregnancy. This does not mean simply give more, however, because doing so may not be safe.
The Placenta
The placenta is very dependent on a consistently high blood flow. Unfortunately, when a pregnant patient becomes injured or ill, the placenta is the first organ to have blood shunted away. This is important to keep in mind when a patient is positioned in a way that changes blood flow, or a paramedic is considering administering vasoactive drugs like dopamine and magnesium sulfate.
A pregnant patient's blood and her fetus's blood never mix. They are kept separate by the blood-placenta barrier, which allows nutrients and waste to be exchanged, but not blood cells. However, many drugs can cross the blood-placenta barrier.2 Once they cross the barrier, whatever effect they have on the mother also affects the fetus.
FDA Drug categories
To help prevent drugs from harming a fetus, the Food and Drug Administration (FDA) has developed a list of categories to define how safe a drug's administration is during pregnancy (see Table 1). Every drug approved for human administration is assigned to a category. The safest are Category A drugs, while Category X drugs are never safe to administer to pregnant women. When preparing to administer any drug to a pregnant patient, check to make sure it is safe. You may be surprised by how some drugs are categorized. Many drugs used by EMS providers are Category C, meaning there is no research recommending for or against their use.
| Category | Description | Examples |
|---|---|---|
| Category A | Multiple studies on pregnant patients suggest there is no risk to the fetus during the first or later trimesters of pregnancy | magnesium sulfate, folic acid, vitamin B6 |
| Category B | Animal studies haven’t demonstrated a fetal risk, but there are no human studies, OR animal studies suggest a risk but human studies have not demonstrated a risk during any trimester | glucagon, acetaminophen, terbutaline, ondansetron, dobutamine, ibuprofen |
| Category C | Animal studies have shown adverse effect on fetus, but no human studies exist, OR neither animal nor human studies have been performed | albuterol, nitroglycerin, epinephrine, morphine, fentanyl, hydrazaline, mannitol |
| Category D | Some evidence of human fetal risk; in some cases, potential benefit to mother outweighs potential risk | nicotine, benzodiazepines, Dilantin, furosemide, lithium, amiodarone |
| Category X | Animal and human studies demonstrate significant fetal risk. Risk of use outweighs benefit | quinine sulfate, thalidomide, many topical drugs |
Summary
Because geriatric patients have a slowed metabolism and delayed ability to eliminate drugs from their body, they become more sensitive to drug doses and may benefit from decreased drug quantities at increased intervals. When administering drugs to pregnant women, remember that every drug you give them will also be given to their fetus. Refer to FDA drug categorization prior to administering any drug to pregnant women. If you are unsure, contact a physician prior to administration.
References
1. Bledsoe BE, Benner RW. Critical Care Paramedic, 1st Edition. Upper Saddle River, NJ: Pearson Education Inc., 2006.
2. Morton PG, Fontaine DK, Hudak CM, Gallo BM. Critical Care Nursing: A Holistic Approach, 8th Edition. Philadelphia, PA: Lippincott, Williams & Wilkins, 2005.
Kevin T. Collopy, BA, CCEMT-P, NREMT-P, WEMT, is an educator and e-learning content developer. He is also a flight paramedic for Spirit Ministry Medical Transportation in central Wisconsin and a lead instructor for Wilderness Medical Associates. Contact him at kcollopy@colgatealumni.org.
