Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Another way to describe the difference between the 2 disciplines is to say that pharmacokinetics is “what the body does to the drug," whereas pharmacodynamics is “what the drug does to the body.” When prescribing medications, physicians Physicians Individuals licensed to practice medicine. Clinician–Patient Relationship must take into account both the drug’s pharmacodynamics and its pharmacokinetics to determine the correct dosage Dosage Dosage Calculation and to ensure the appropriate effect.
Last updated: 21 Apr, 2022
Pharmacokinetics and pharmacodynamics are fields of study that focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast on the interplay between medications and the body.
Pharmacokinetics is the study of how the human body interacts with a drug:
Pharmacodynamics is the study of the effects of a drug and its organ-specific mechanism of action, including effects on the cellular level:
Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption is the transfer of a drug or substance from the site of administration to the bloodstream and is determined by:
Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption through the GI tract is affected by:
Drugs will cross membranes through:
D:
diffusion
Diffusion
The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport.
Peritoneal Dialysis and Hemodialysis constant for the drug
A: surface area of the membrane
T: thickness of the membrane
C: concentration gradient
Phenomenon of a drug undergoing 1st-pass metabolism, during which it is partially or completely metabolized in the intestinal wall or is absorbed in the intestine and enters the portal circulation Portal circulation A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. Systemic and Special Circulations and travels to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, where the drug is metabolized further.
Image by Lecturio.Distribution is the extent to which a drug is transported from the systemic circulation Systemic circulation Circulation is the movement of blood throughout the body through one continuous circuit of blood vessels. Different organs have unique functions and, therefore, have different requirements, circulatory patterns, and regulatory mechanisms. Systemic and Special Circulations to target tissues and organs.
The equation for the volume of distribution:
$$ V_{d}= \frac{Amount\ of\ drug\ in\ the\ body}{Concentration\ in\ the\ blood} $$Biotransformation is the process through which the human body chemically changes drugs into different molecules to either make the compound pharmacologically active or to facilitate elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy.
The assortment of cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-induced Liver Injury (CYP450) isoenzymes Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Basics of Enzymes
Image by Lecturio.Receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors are macromolecules involved in chemical signaling between and within cells.
Different categories of cell surface and intracellular receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
Image by Lecturio.G-protein–mediated signal
transduction
Transduction
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique.
Bacteriology and activation of a 2nd-messenger system:
(1) The 1st messenger or drug binds to the G-protein–coupled
receptor
Receptor
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors and (2) activates the G-protein, which (3) relays a signal to (4) activate the effector molecule.
The effector then (5) activates 2nd messengers to (6) elicit cellular responses.
The effect of a drug is the physical response it elicits. This may be a desired (therapeutic) effect or an undesired (toxic) effect. The effect can be modulated by the presence of antagonists and is also determined by its affinity to its target molecular receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. These effects are measured and can be visually represented through curves.
Dose–response curves in linear and log scale Scale Dermatologic Examination showing the drug dose or concentration that elicits a maximal effect (Emax) and the drug concentration that produces 50% maximal effect (EC50)
Image by Lecturio.Dose–response curve comparing agonist alone versus agonist with a competitive antagonist (left):
Note that the same effect occurs at a higher dose of agonist when the competitive antagonist is dissociated. The curve is simply shifted to the right.
Right curve: In comparison, this is a dose–response curve comparing agonist alone versus agonist with an irreversible antagonist. The 2 curves start at the same concentration but reach different maximal points given that the irreversible antagonist action is independent of the concentration of the agonist. The response is reduced to 50% of its maximum potential.
Binding curves in linear and log scale Scale Dermatologic Examination showing the maximal biologic response (Bmax) and dissociation Dissociation Defense Mechanisms constant (Kd) for a drug
Image by Lecturio.Binding curve illustrating the “spare
receptor
Receptor
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors” phenomenon:
There is a maximal biological response despite the presence of
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors that are not bound by the drug. Note that the drug concentration required to occupy 50% of
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors (Kd) is higher than the concentration needed to elicit a maximum response (ED50): Kd > ED50.
Quantal dose–response curve (looks at population, not single receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors) noting the dose of a drug that produces a predetermined effect in 50% of subjects (E50)
Image by Lecturio.Graph of a
toxicity
Toxicity
Dosage Calculation curve:
The blue dose–response curve represents a drug’s desired effect in a population, and the red dose–
toxicity
Toxicity
Dosage Calculation curve represents the drug’s undesirable effect. The therapeutic ratio, or index (TI), lies between the 2 curves and equals dose for a toxic effect in 50% of population/drug concentration that produces 50% maximal effect (TD50/EC50), starting at the 50% maximal effective dose and ending at the 50% toxic dose. The inset shows the relation between therapeutic ratio and adverse effects seen. The greater the therapeutic ratio, the fewer occurrences of adverse effects, and vice versa.
Illustration of dose–response curves of different drugs for comparison of their concentration needed to produce a 50% maximal effect (EC50):
Emax is the maximal effect. Lower EC50 = greater potency. The drug farthest to the left on the graph (represented by the dotted gray line) has the highest potency of the 4 drugs plotted because it has the lowest concentration (indicated on x-
axis
Axis
The second cervical vertebra.
Vertebral Column: Anatomy) needed to produce a 50% maximal effect. Shifting from the curves left to right, the potency of the drugs decreases, with the solid gray line to the far right being the least potent drug.
Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy is the process of conversion of a drug to inactive metabolites, which are ultimately excreted from the body.
Rate of elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of drug ( mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast/time) = clearance x concentration.
General:
Calculating renal clearance:
Creatinine is the primary renal filtration marker used clinically to approximate the
glomerular filtration
Glomerular filtration
The kidneys are primarily in charge of the maintenance of water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. Glomerular filtration is the process of converting the systemic blood supply into a filtrate, which will ultimately become the urine.
Glomerular Filtration rate (
GFR
GFR
The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance.
Kidney Function Tests):
Creatinine is freely filtered and is not reabsorbed. However, creatinine is also secreted from the peritubular
capillaries
Capillaries
Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time.
Capillaries: Histology, causing around a 10% overestimation of
GFR
GFR
The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance.
Kidney Function Tests.
Hours | Amount of drug (mg/L) remaining in the body | % of drug eliminated | Amount of drug (mg/L) eliminated |
---|---|---|---|
0 | 1 | — | — |
1 | 0.85 | 15 | 0.15 |
2 | 0.70 | 18 | 0.15 |
3 | 0.55 | 21 | 0.15 |
4 | 0.40 | 27 | 0.15 |
5 | 0.25 | 38 | 0.15 |
Graphical representation of a drug’s half-life:
In this example, the half-life is 10 hours. Cmax = maximal concentration of drug in the bloodstream, Tmax = time at which the concentration of drug in the blood is at it’s maximum. T1/2= half life, the time it takes for the drug level to go from Cmax to ½ of Cmax.
Graphical representation of the drug in the table above that undergoes zero-order
elimination
Elimination
The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth.
Cancer Immunotherapy kinetics:
The x-
axis
Axis
The second cervical vertebra.
Vertebral Column: Anatomy is the unit time in hours, and the y-
axis
Axis
The second cervical vertebra.
Vertebral Column: Anatomy is the amount of drug, in milligrams, remaining in the body (or
plasma
Plasma
The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.
Transfusion Products concentration of the drug). At time zero, there is 1.0 mg of drug present, and an equal amount of drug is eliminated every hour—in this example, 0.15 mg.
Graphical representation example of a drug that undergoes 1st-order
elimination
Elimination
The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth.
Cancer Immunotherapy kinetics:
The x-
axis
Axis
The second cervical vertebra.
Vertebral Column: Anatomy is the unit time in hours, and the y-
axis
Axis
The second cervical vertebra.
Vertebral Column: Anatomy is the amount of drug, in milligrams, remaining in the body (or
plasma
Plasma
The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.
Transfusion Products concentration of the drug). At time zero, there is 1.0 mg of drug present, and then an equal percent/proportion of the drug (in this example, 50%) is eliminated every hour.