# Pharmacokinetics --- **Pharmacokinetics** is the portion of [[pharmacology]] that studies of the movement of a particular drug throughout the body, from where it is administered to where it is excreted. Pharmacokinetics deals with four major aspects: Absorption, Distribution, Metabolism, and Excretion (which you can remember as ADME). ## Absorption **Absorption** describes how the drug gets into the [[blood|bloodstream]]. There are many different ways of administering drugs (such as the GI tract, the integument, and the muscle), but they all move towards the bloodstream. Numerous factors affect the rate of absorption and the drug's **bioavailability**. >[!biology] Bioavailability >**Bioavailability** refers to the amount of drug in the system that is *available* to act on the body's cells. ## Distribution **Distribution** describes the mechanisms for how the drugs get to where it needs to go. Typically drugs enter and leave the bloodstream through the capillaries. The distribution of drugs depends heavily on how well blood is circulating through your system, and often by how much of the drug is bound to blood proteins such as [[albumin]] (which is the mostly plentiful and therefore affects drugs the most). Because albumin is so large, the drug molecule bound to it cannot leave the bloodstream. While it is bound to albumin it is considered "pharmacologically inactive", but as the serum concentration of the drug drops, more molecules are able to unbind. Essentially this sounds like it acts like a buffer system. ## Metabolism **Metabolism** or in this context sometimes called **biotransformation**, refers to the breakdown of the drug molecule into smaller, often inert molecules (called **metabolites**) that are then cleared from the body. The [[liver]] is the site of most drug metabolism, though I think some other organs do it too, to a lesser extent. Molecules need to be water soluble to be excreted later, so one important function is to break down lipid soluble drugs into less lipid soluble drugs. Sometimes the metabolites also have an effect on the body, and then they can also be broken down and/or excreted. There are other drugs still that are called **prodrugs** that are administered in an inactive form until they are broken down and those metabolites are the active form. >[!tip] Toxicity > Metabolism of a drug can either *increase* or *deacrease* that drug's toxicity, depending on the drug ### The First Pass Effect The **first pass effect** is what happens to drugs when they are acted upon by the liver before reaching it's active site. This happens for meds taken orally, but IV meds bypass the liver and enter the systemic circulation immediately. This means the drugs can go into effect very quickly and very strongly. The health of the liver will also effect the extent of the first pass effect. ### Bioavailability **Bioavailability** is the fraction of a drug that reaches systemic circulation after administration. Due to the first pass effect, the means that oral meds to not have a 100% bioavailability, but IV drugs do. ## Excretion **Excretion** refers to how the body ultimately gets rid of the drugs. The majority of this is done by the [[kidneys]], but sometimes it can happen in the bile (and therefore the feces), lungs, sweat, saliva and breastmilk. The time it takes varies on a number of factors, such as what the drug is, the dose and the administration route. The **half-life** of a drug is the amount of time required for the total amount of the drug in the body to reduce by half. Age plays a big role in how quickly a drug is excreted. The rate is reduced in newborns, children and the elderly. Newborns especially have a limited ability to excrete drugs for a few months. For the elderly, they is often a host of things that could have damaged the kidneys by now, and this slows or impairs drug excretion. Another aspect is that [[dialysis]] will filter out some drugs with prejudice, so it's essentially wasting a dose. ## Therapeutic Concentration The **therapeutic concentration** is the range of concentration in the blood where the drug is effective but not harmful. The concentration of the drug can be described in **peaks and troughs**. The **peak** is the highest concentration of the drug in the plasma that it reaches after administrations. Sometimes draws will be taken at a certain time to test for toxicity. The **trough** is the lowest drug plasma concentration. Ideally this occurs right before the administration of the next dose, and does not fall below the minimum effective concentration. Sometimes a draw will be done to check for satisfactory therapeutic levels. Basically we want to hit the sweet spot too keep plasma concentrations stay in the therapeutic range, without dropping low enough to be ineffective, but not getting high enough that it becomes toxic. It's different for every drug, and can change between populations as well. A **loading dose** is a really high dose that sometimes used as the first does to get the drug's concentration to a a therapeutic range really fast, and then **maintenance doses** are used to keep the concentration topped off. ## Considerations for the Child Age affects all our body systems, so there are some considerations to take into account for pharmacokinetics in [[stage of development#Child|infants and children]]. The [[liver]] function is not mature yet for young children: - 0-1 years old the liver is very slow to metabolize drugs - 1-2 years the rate is markedly elevated - 2-puberty there is a slow decline and eventually leading to the adult rate The [[kidneys|kidney function]] is also altered: - [[glomerular filtration|GFR]] starts slow and gradually increases adult levels by 12 months Additional factors are: - The [[blood-brain barrier]] is semi-permeable up to one year - gastric emptying time is longer in infants - subcutaneous/IM absorption can be more intense, rapid and also prolonged in infants - higher surface area to volume ratio and thinner skin are considerations for topical medications - some medicines (such as [[antibiotics]] or chlorohexidine rinses) can discolor teeth under 8 years old - [[acute liver failure|Reye's syndrome]] can follow some viral illnesses associated with aspirin therapy ## Considerations for the Older Adult Age affects all our body systems, so there are some considerations to take into account for pharmacokinetics in the [[older adult|older adults]]. **Absorption** Rate of absorption is *delayed* in older adults due to decreased gastric emptying, and decreased blood flow from the intestines. Gastric acidity is also reduced, which does affect some drugs' absorption. **Distribution** Rate of distribution is altered by reduced serum [[albumin]], as well as an increase in [[adipose tissue|body fat]] and a decrease in lean body mass. Also total body water is lower in older adults. **Metabolism** Older adults experience reduced hepatic blood flow, smaller liver size and decreased activity of some hepatic enzymes, which overall works to slow down drug metabolism. **Excretion** Older adults experience progressive decline in [[kidneys|kidney]] function, which slows down excretion and leads to an accumulation of drugs. This should be measured by creatinine clearance, not serum creatinine levels. ___