Pharmacokinetics & Metabolism (PDF)

PHARMACOKINETICS (metabolism) Pharmacokinetics refers to the movement and modification of a drug or medication inside the body. So once the medication is administered, it first has to be: 1. absorbed into the circulation 2. then distributed to various tissues throughout the body 3....

PHARMACOKINETICS (metabolism) Pharmacokinetics refers to the movement and modification of a drug or medication inside the body. So once the medication is administered, it first has to be: 1. absorbed into the circulation 2. then distributed to various tissues throughout the body 3. metabolized or broken down 4. and finally, eliminated or excreted in the urine or feces. This process can be broken down into four components with the acronym “ADME”, which stands for absorption, distribution, metabolism, and excretion. Let’s focus on metabolism, which refers to the conversion, or biotransformation, of a medication. ✔ In most cases, metabolic reactions act by turning an active medication into a less active metabolite ✔ as well as turning lipid soluble medications into a more water soluble metabolite, which can be eliminated more easily from the body, mainly via the urine or feces. ✔ Some other medications, though, are administered in an inactive form, also known as a prodrug, that needs to be metabolized into its active form before it can be effective. All right, now most metabolic reactions take place in the liver; although certain medications can be metabolized by other tissues and organs, including: - the lungs - kidneys - skin - and walls of the small intestine. After a medication is taken orally: o it is absorbed from the walls of the small intestine o and transported into the liver via the portal vein. ✔ Once in the liver, hepatic enzymes work on the medication to metabolize it; this process is known as first-pass metabolism or first-pass  effect, and is responsible for breaking down most medications, as well as converting certain prodrugs into their active metabolites. ✔ For example, enalapril, an ACE inhibitor used to treat hypertension, gets converted into its active metabolite, enalaprilat, in the liver. ✔ Similarly, codeine, a weak opioid, is converted by hepatic enzymes into morphine, which is more effective for pain management. o As a result of first-pass metabolism ✔ certain medications that are highly metabolized by the liver can lose their effectiveness when taken orally ✔ so alternative routes of administration must be used to achieve the desired therapeutic effect. Alternative routes include: intravenous intramuscular transdermal sublingual or inhaled medications which go straight into the systemic circulation and exert their effect before reaching the liver, so they are often more effective than the oral route. This is especially true for medications that undergo extensive first-pass metabolism, including: morphine diazepam lidocaine and nitroglycerin. *** All right, now the liver’s main mechanism to metabolize medications is via a family of enzymes called cytochrome P450, or CYP450 for short. These enzymes are often abbreviated as CYP followed by a series of numbers and letters indicating the exact enzyme subtype. Each enzyme is involved in either: ✔ activating  ✔ or inactivating multiple medications so if two medications are metabolized by the same enzyme, they can interfere with each other’s normal rate of metabolism. In other cases, certain medications, foods, or supplements can: - induce - or inhibit metabolic enzyme activity. When a substance increases the ability of an enzyme to break down a medication ✔ the effects of that medication are decreased whereas if a substance decreases enzyme activity ✔ the effects and the risk of toxicity of that medication are increased. Examples of metabolic inducers include: carbamazepine rifampin and St. John’s wort while metabolic inhibitors include: the antifungal fluconazole and grapefruit juice. Additionally, because metabolic enzyme systems are only partially developed at birth ✔ newborns may have some difficulty metabolizing certain medications. As people age ✔ enzymatic activity also decreases, so elderly individuals may not be able to metabolize medications as well as children and younger clients. Also, since most metabolic reactions take place in the liver ✔ chronic liver disease may lead to a decrease in enzyme activity. Finally, there’s a huge variability in the rate of metabolic reactions as a result of genetic variability. ✔ Some clients, known as poor metabolizers, have fewer enzymes, or enzymes that work slower and less effectively against certain medications. In such cases, medications can build up in the body, resulting in dangerous side effects or toxicity. ✔ On the other hand, there are rapid and ultra-rapid metabolizers, who inactivate medications so fast that it’s difficult to achieve therapeutic levels for certain medications. In such cases, clients may require larger doses than usual, or the use of an alternative medication. Okay, before administering any medication to a client, keep in mind some of the general pharmacokinetic principles that relate to how the medication is metabolized in your client’s body. Begin by: 1. reviewing their medical history, taking note of conditions that could impact medication metabolism, such as cardiovascular, hepatic, or renal disease. 2. Also ask your client about lifestyle choices that could impact medication metabolism, including tobacco and alcohol use. 3. Ask about their dietary habits as well, and emphasize the importance of eating a well-balanced diet in order to ensure the vitamins that act as cofactors in hepatic metabolism are readily available. 4. Lastly, review your client’s recent laboratory test results for evidence of impaired renal or hepatic function. Now, you’ll also want to keep in mind client characteristics that affect medication metabolism. For example - medication metabolism can be incomplete or delayed by an infant’s immature liver. - On the flip side, older adults experience changes to their liver that can make the liver less efficient in metabolizing medications and extend the half-life of some medications, including: decreased liver size  decreased hepatic blood flow and less metabolically active hepatocytes. Next, review your client’s current medications and supplements ✔ and be sure to closely monitor your client for interactions that could affect their treatment. ✔ Be alert for potential interactions between medications that are metabolized by the same CYP450 enzyme ✔ or when one medication either induces or inhibits other medications prescribed for the client. ✔ Also, be especially alert for polypharmacy, where a client is prescribed multiple medications, as this increases the risk for medication interactions consult with the pharmacist and primary healthcare provider to ensure your client is receiving the therapy they need while reducing the risk of medication toxicity. ✔ Lastly, remind your client to consult their healthcare provider before starting new supplements or over-the-counter medications, in order to prevent potentially harmful medication interactions. ✔ Finally, after your client has started their medication, keep an eye out for any adverse effects that could be related to altered medication metabolism. Continue to assess factors that can influence medication metabolism, monitor relevant laboratory test results as well as serum medication levels as indicated and use this information to evaluate the therapeutic response. Quick review… Pharmacokinetics refers to the movement and modification of a medication inside the body, and includes: o absorption o distribution o metabolism o and elimination. Metabolism is the: o biotransformation of medication into either a less active or more active metabolite o as well as the conversion into a more water soluble metabolite to facilitate its elimination. Most metabolic reactions occur in the liver, but they can also take place in: o the lungs o kidneys o skin o and small intestine. Factors that affect medication metabolism include: o the extent of first-pass metabolism a medication undergoes o CYP450 hepatic enzyme activity o in addition to client-specific factors such as age, genetic variability, and the presence of liver disease. Nursing considerations related to metabolism focus on: o client assessment and monitoring to help the client achieve a therapeutic response. o Client education centers around how to optimize medication metabolism by teaching lifestyle considerations, possible dietary changes needed, and awareness of medication and supplement interactions.