[Music] in this video we're going to cover pharmacokinetics we're going to break down what it is and the various components of adme let's get started pharmacokinetics is the study of how your body processes a drug it's what the body does to a drug or the movement of drugs into through and out of the body so first a drug requires a method of administration often known as a route of administration then it must be absorbed into the circulation and distributed to various tissues of the body where it's metabolized or broken down and finally eliminated from the body and we can break down this whole process into four main components absorption distribution metabolism and excretion the acronym is adme so now let's subtract complexity and go through absorption when a drug is absorbed it must enter the body by some route whether that be orally intravenously when it's injected directly into the bloodstream or intramuscularly when it's injected into a muscle other routes include inhalation which is rapidly absorbed transdermally this is on the skin like a patch containing the drug sublingually this means placing a drug under the tongue which is absorbed quite rapidly and there are also drugs that are administered via the eye ear and nerves and most of these drugs are delivered locally and are not absorbed systemically into the greater body now absorption varies greatly among different patient types so for example when we have food in the stomach the stomach acidity and blood flow to the gi tract can affect drug absorption and before a drug reaches the circulation you will need to cross one or more cell membranes this doesn't include intravenous administration because it's injected directly into the bloodstream now movement across the cell membrane can occur via passive transport which requires no energy or active transport which requires energy in the form of atp and there's also endocytosis let's go through these mechanisms there are two types of passive transport passive diffusion and facilitated diffusion in both types drugs move from an area of high concentration to low concentration passive diffusion helps small lipid soluble and non-polar molecules they will easily pass through a membrane down their concentration gradient without any help whereas water-soluble molecules will pass through a channel or pore now in facilitated diffusion larger water-soluble and polar molecules require the help of a channel or transporter okay moving on to active transport there are also some drugs that require active transport because the drug is transported against its concentration gradient so energy is required atp is required specific carrier proteins use atp to move the drug into the cell and sometimes there are molecules that are so large that the process of endocytosis is needed the drug is engulfed by the plasma membrane okay that's transport now earlier we mentioned how absorption varies among different patient types there are also drug related factors that influence the rate of absorption such as molecular weight solubility and formulation as well as the ph of the environment surface area and blood flow to the absorption site again small non-ionized and lipid soluble drugs can easily pass through the plasma membrane whereas water soluble and polar drugs can't easily pass through the membrane so the rate and extent of absorption or how quickly this process occurs and how much of the drug reaches the bloodstream are determined by a number of factors and this leads us to the concept of buyer availability buyer availability is the fraction of an administered dose of a drug that is unchanged when it enters the systemic circulation it's the percentage of a drug's dose that remains unchanged when it enters the systemic circulation let's break this down so for example let's say we ingested 100 milligrams of a drug and 100 milligrams of that was available to the body so 100 milligrams was absorbed into the circulation which means it would have a buyer availability of 100 percent okay if let's say only 70 milligrams of that drug were absorbed unchanged the buyer availability would be 70 intravenous drug administration always has 100 buyer availability because it goes directly into the bloodstream whereas oral medications have less this is because it gets metabolized in the gut and in the liver this process is known as the first pass effect which refers to the mechanism by which most drugs are converted into their inactive metabolites prior to entering the bloodstream okay so this reduces bioavailability because they undergo first pass metabolism reducing their concentration in the bloodstream that's why intravenous or intramuscular have high bioavailability because they bypass the first pass effect all right let's show this in a graph to show the relationship between time and the plasma concentration of the medication so a drug given intravenously will start at a concentration of 100 percent and with pure drugs it must be absorbed first and some of it will also get eliminated before it eventually reaches the systemic circulation okay now we can determine the area under these curves auc for short to help us estimate the bioavailability of a drug to estimate the bioavailability of an oral drug we can divide the auc of the oral form by the auc of the iv form and both aucs would need to be corrected by the dose of medication administered orally and intravenously okay now after a drug gets absorbed it gets distributed to various tissues around the body such as muscle and fat and there are several factors that influence drug distribution let's go through this a few factors include membrane permeability a drug must cross the membranes that separate the organ from the site of administration lipophilicity so lipophilic drugs will easily cross membranes and therefore these molecules are more likely to leave the bloodstream whereas hydrophilic molecules are less likely to cross membranes and more likely to remain in the bloodstream and then there's molecular size another factor is plasma protein binding plasma proteins such as albumin will slow down the distribution process because it will reduce the amount of drugs that are not protein bound in the blood so the amount of drugs that can enter various tissues decreases and this leads us to volume of distribution which relates the amount of drug in the body to the concentration of drug in the blood or plasma this is the theoretical amount of the drug compared to its plasma concentration in other words where in the body is the drug accumulating is it in the blood or in the tissue okay so drugs with high volumes of distribution are highly distributed into tissues molecules that are smaller and lipophilic will also be highly distributed into tissues and will achieve a larger volume of distribution and drugs with low volumes of distribution are highly bound to plasma proteins so there's less distribution to other tissues this is useful in estimating the dose required alright now let's move on to metabolism this is the phase where a drug is converted into a less or more active form known as metabolites once it has been converted to an inactive metabolite it can then be excreted metabolic reactions can convert an active drug into less active or inactive forms or an inactive or less active drug known as a pro drug into a more active form okay and we can divide drug metabolism into two main phases phase one and phase two take note though that there are some medications where phase two may occur before phase one or only phase one may occur or only phase two may occur alright but drug metabolism occurs primarily in the liver let's go through phase one in phase one drugs are oxidized or reduced to a more polar form this is where the enzymes called cytochrome p450 come in what these enzymes do is convert non-polar lipid-soluble drugs into more polar and water-soluble metabolites through oxidation hydrolysis or reduction now i want to mention that cytochrome p450 can be induced or inhibited that is its activity can be increased or decreased by several drugs or chemicals moving on to phase two drugs or metabolites are conjugated or joined with another compound by the addition of a polar group so this includes methylation acetylation sulfation and glucuronidation the aim here is to produce polar and water-soluble metabolites so they are easily eliminated by the kidneys and this leads us to the last phase which is elimination which is the removal of a medication from the body elimination involves both the metabolism and excretion of the drug most drugs are excreted in the urine other processes occur in the liver the lungs and other organs so excretion can also take place through the bile and feces this brings in clearance which is the rate at which a drug is eliminated from the blood or we can calculate clearance values for different systems total body clearance is the sum of individual clearance processes such as kidney liver and other other include the lungs or muscle okay now let's move on to half-life which is the time it takes for the plasma concentration of a drug in the body to be reduced by one-half half-life and volume of distribution help with figuring out how long a drug's effects last and how frequently it needs to be administered and also how much time to reach steady state let's break this down there are two different types of elimination there's zero order kinetics and first order kinetics in zero order kinetics the rate of elimination is constant the drugs that are eliminated by zero-order kinetics are independent of drug concentration in the body if we were to graph this it would produce a straight line okay an example of a drug that is eliminated by zero order kinetics is aspirin now in first order kinetics the amount of drug eliminated over time is directly proportional to the drug concentration in the body the amount eliminated for each time period would be different but the fraction would be constant most drugs are eliminated by first order kinetics and if we were to graph this the curve would look like this exponential let's expand on this each dot on the curve represents a half-life okay at time 0 we have a concentration of 100 of the drug then after one half-life we have a concentration of 50 because it's reduced by 50 percent and after two half-lives we have a concentration of 25 by this point we've already reduced the original amount by a total of 75 percent and then after three half-lives we have a concentration of 12.5 so once we get to about five half-lives 97 of the drug has been eliminated from the body so a half-life is how long it takes for half of the drug to be eliminated from the body and we can produce this information to predict steady-state concentration which will be focusing on first order kinetics here so it takes about four to five half-lives to reach steady-state concentration which is where the concentration doesn't change or the rate of administration equals the rate of elimination so the amount we dos will be eliminated after each nursing interval if we continue to doze at the same frequency as a result medication levels in the body remain steady now why is this important why is reaching a steady state important that's because we want a drug concentration that is high enough to be effective but not harmful therefore if a drug has a short half-life the more rapidly the steady state is reached but what happens then if you have a drug with a long half-life and someone who needs to achieve therapeutic effect fast how can you get that effect without having to wait because it still takes the same amount of time to achieve a steady state which is four to five half-lives so alerting those a higher amount of medication is administered on treatment initiation to reach the desired concentration more quickly it will still take four to five half-lives to reach steady state but the initial concentration will be closer to the eventual steady-state concentration thank you for watching this video make sure you subscribe to ekg science so you don't miss a single lecture and remember subtract complexity and slow down to study the next lecture simply click the next video or you can view the entire playlist hey stop procrastinating