Chapter 3 - Pharmacokinetics + Pharmacoynamics Flashcards
Pharmacokinetics
Study of how a drug moves into, through, and out of the body
Pharmacodynamics
Study of how the drug produces its effects on the body
Therapeutic Range/Window
A desirable range of drug concentrations
Maximum Effective Concentration
The top concentration of the normal therapeutic range - represents the border between concentrations that are beneficial vs. toxic
Minimum Effective Concentration
The bottom concentration of the normal therapeutic range below which the drugs will not work sufficiently
Subtherapeutic Concentrations
Drug concentrations below the minimum effective concentration
Metabolism
The rate at which the body removes the drug by elimination
Route of Administration
Route by which the drug dose is to be administered
Loading Dose
A larger initial dose that “loads” the body with sufficient drug to establish therapeutic concentrations
Maintenance Dose
Smaller than the loading dose, and given at an amount and rate that matches the amount eliminated by the body
Total Daily Dose
The combined amount of drug (mass) times the number of doses administered in a given day (dose interval)
Peak Concentration
Highest drug concentration
Trough Concentration
Lowest drug concentration
Narrow Therapeutic Range
Drugs in which the maximum effective dose and the minimum effective dose are very close to each other
Narrow Therapeutic Index
The dose that causes the beneficial effect is close to the dose that produces toxic side effects
Parenterally Administered Drugs
Drugs are given by injection in the space between the outside of the intestinal tract and the surface of the skin
Intravenously (IV)
Drugs are given directly into the vein
IV Bolus
Drugs are given as a single large volume one time
CRI (Constant Rate Infusion)
Drugs are injected slowly or “dripped” into the vein over a period of several seconds, minutes, or hours resulting in a steady accumulation of drug concentrations
Steady State/Plateau
Occurs when peak and trough concentrations don’t change with subsequent doses (bucket analogy)
Extravascular/Perivascular Injection
Accidental injection of an IV drug outside the vein
Intraarterial Injection (IA)
Injecting a drug into an artery (delivering the full dose to a specific tissue/organ causing very high and potentially toxic concentrations of the drug)
Intramuscular (IM)
Parenteral route of administration where the drug is placed into the skeletal muscle
Subcutaneous (SQ)
Injections administered under the skin, but above the muscle
Intradermal (ID)
Uses very small needles to place drugs into, but not below the narrow layers of the skin (dermis)
Intraperitoneal (IP)
Administered into the abdominal cavity
Per Os (PO)
By mouth
Per Rectum (rectally)
Drugs give via the rectum, typically suppositories
Topically
Applied onto the surface of the skin
Aerosol
Delivered to the lungs by “air or gas solution”
Passive Diffusion
The random movement of drug molecules down the concentration gradient (high–>low concentration) (requires no energy)
Concentration Gradient
Movement of drug molecules from an area of high concentration of drug to an area of lower concentration or vice versa.
Hydrophilic
Readily absorbing moisture – “water-loving”
Lipophilic
Having an affinity for fat – “fat loving”
Equilibrium
The number of drug molecules moving from point A to point B is the same number of molecules moving from point B to point A
Facilitated Diffusion
- Passive transport mechanism (no energy)
- Uses a special carrier molecule from the cellular membrane to move the drug molecule across the membrane.
- Revolving door*
Active Transport
- Involves a special carrier molecule
- Occurs only in one direction
- Cell expands energy
- Either move the drug molecule across the cell membrane or “resets” the carrier molecule after transportation is completed
- Electrical pump*
Pinocytosis
- Active transport (uses energy - less common)
- Cellular uptake of extracellular fluid and its contents by enclosing them in vesicles derived from the plasma membrane
- cell drinking*
Phagocytosis
- Active transport (uses energy - less common)
- Endocytosis of particulate material, such as microorganisms or cell fragments
- The material is taken into the cell in membrane-bound vesicles (aka phagosomes) that originate as pinched-off invaginations of the plasma membrane
“cell eating”
Saturated
Containing as much solute as may be dissolved under stated conditions
- All carrier molecules are continuously occupied in bringing drug molecules across the cell membrane
Transportation Maximum (T-Max)
- Transport system is saturated
- Transport system is then working at maximum speed
- crowded toll road*
Aqueous Medium
Water-based medium
Polarized
Drug molecule contains both positive (+) and negative (-) charges at the ends of the molecule
Ionized/Nonionized
Drug molecule contains a net positive (+) OR a net negative (-) charge but not both
Hydrophilic (water-loving) drug molecules are either ______ or _______
Polarized or ionized
Lipophilic (fat-loving) drug molecules tend to be ________ and _________ molecules
Nonpolarized and nonionized
What are the 4 basic steps of drug Pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion (or elimination)
Absorption
The movement of drug molecules from the site of administration to the systemic circulation (uptake of substances into or across tissues)
Distribution
Movement of a drug from the systemic circulation into tissues
Extracellular Fluid
Fluid/water outside of the cells
Basic/Alkaline
a pH of 10, 11, or 12
Less H+ ions present
Acidic
a pH of 1, 2, or 3
More H+ ions present
Acid Drugs
A drug whose chemical structure causes it to release a hydrogen ion into its liquid environment as the drug is placed into increasingly alkaline environments
As pH increases, H ion releases
Acidic pH
A liquid environment where there are many available hydrogen ions floating free in the liquid to react with drug molecules
Base Drugs
A drug that becomes more ionized when it acquires a hydrogen ion from an acidic pH environment and becomes more nonionized when it releases a hydrogen ion into the liquid of an alkaline pH environment
Drugs pKa
The negative logarithm of the ionization constant of an acid (Ka); The buffering power of a buffer system is greatest when its pKa equals the pH
Equal numbers of ionized and nonionized drug molecules - The pH level at which this occurs is the pKa
Ion Trapping
Accumulation of lipophilic/nonionized drug molecules trapped in this body compartment because of their significant shift to the ionized/hydrophilic form.
Reabsorption
The act of process of absorbing again
P-glycoprotein (P-gp)
An active transport pump - found in the cells making up the barrier lining the intestinal tract (enterocytes). Actively transports selected molecules out of the cell and back into the lumen of the intestine, preventing their absorption
Dissolution
Process of breaking down dosage forms to the individual molecules
Gastric Motility
Stomach contractions that mix stomach contents and move the contents from the stomach into the small intestine
Intestinal Motility
The mixing and peristaltic contractions of the intestine
Hepatic Portal System
System of blood vessels that conducts the blood from the capillaries of the GI tract to the capillaries of the l River and allows the liver to remove poisons, toxins, and other potentially dangerous substances absorbed from the GI tract before they reach systemic circulation
Xenobiotics
A chemical foreign to a given biological system (aka foreign substances or “poisons”)
First-Pass Effect
The Phenomenon by which the liver removes so much of the drug that little reaches the systemic circulation
Perfusion
The extent to which tissue is supplied with blood
Vasoconstriction
Reduced blood flow to an area - decreases perfusion
Vasodilation
Dilation of blood vessels - enhances perfusion
Fenestrations
Small holes or “windows” in the capillary walls that allow water and small drug molecules to move readily back and forth between the blood and the surrounding tissue, while keeping larger molecules, proteins and RBCs within the capillary
Blood-Brain Barrier
Provides an excellent defense against many poisons, but also prevents distribution of beneficial drugs to the brain or CNS.
(Made up of continuous capillary cell wall, membranes of the supporting cells surrounding the capillaries, and the P-glycoprotein active transport molecules)
Redistribution
Relocating the drug to an area of the body that is less likely to produce adverse reactions
Apnea
Cessation of breathing
Protein Bound Drug
Drug molecules attached to the blood protein
Free Form
Drug molecules not attached to the blood protein
Depot-like Effect
A drug molecule intentionally formulated to bind to blood protein so that the drug is slowly distributed into the tissue over a more extended period of time
Volume of Distribution (Vd)
A pharmacokinetic value that provides an approximation of the extent to which a drug is distributed throughout the body
Assessed by looking at the drug concentration in the blood shortly after an IV bolus is given
Receptor
A specifically shaped protein located on the cells surface or within the cell
Affinity
The drugs ability to bind or fit with the receptor
Intrinsic Activity
The ability of a drug molecule to produce a cellular effect when it combines with the receptor
Agonist
A drug with both a good affinity for the receptor and the ability to produce intrinsic activity
Antagonist
A drug with good affinity, but little or no intrinsic activity
occupies the receptor site and blocks the effect of any other agonist drug trying to stimulate that receptor
Reversal Agents/Inhibitors
Drugs that are capable of combing with with a receptor and blocking the receptor site from exogenous (from outside the body) agonist drugs and “reversing” or nullifying the effect of the agonist drug
Blockers
Antagonist drugs that occupy a receptor and prevent endogenous (from within the body) agonist compounds (i.e hormones/neurotransmitters) from combining with the receptor and stimulating the cell
Competitive Antagonist Drug
A CAD that nearly equally competes for the receptor site with the agonist drug (the drug that succeeds in occupying the receptor is usually determine by which drug is present in greater amounts)
Surmountable/Reversible Antagonism
This is a form of competitive antagonism where the effect of the antagonist can be reversed by giving more of the agonist
Noncompetitive Antagonist
A drug combines with a receptor very tightly,preventing other molecules from accessing the receptor site OR the noncompetitive antagonist drug modifies receptor so the agonist drug can no longer dock with the receptor
Irreversible/Insurmountable Antagonism
Because NcAs have some advantage over the competing drugs, simply adding more of the competing drugs will not reverse the effect of the NcA. Usually the antagonism caused by the NcA drug is not truly irreversible, but it occurs very slowly.
Partial Agonist
Causes effects with a lower potency than that of the natural ligand
Ligand
Substance or drug that binds or inserts into the receptor
Receptor Antagonist
A drug ligand blocks the normal action of the receptor (using a key that fits but doesn’t open the door)
Receptor Agonist
Mimics an endogenous substance that normally interacts with the receptor
Endogenous agonist
Natural bodily molecule that binds to and activates its receptor
Full Agonist
Binds and activates the receptor with a potency equal to that of the natural ligand
Superagonist
Binds to the receptor but produces a more potent action than that of the endogenous ligand
Inverse Agonist
Both inhibits the function of the natural ligand and causes an effect opposite to that produces by the natural ligand
Non receptor-Mediated Drug Reaction
Drug molecule does not attach to any cellular receptor to produce the desired effect
Chelators
Type of chemical that combines with ions or other specific compounds and produces a biological effect by non receptor- mediated reactions
Biotransformation/Drug Metabolism
Drug structures being chemically altered by enzymes as they pass through the liver
Metabolite
Altered drug molecule from biotransformation
Hepatocytes
Liver cells, where most drug metabolism occurs
Cytochrome P-450 (CYP)
Family of enzymes involved in enzymatic breakdown of drug molecules in the GI tract and Liver
Mixed Function Oxidase Enzymes
Hepatic biotransformation enzymes
Prodrugs
Drugs that are biotransformed into a more active form
Conjugation (come together)
Metabolite is chemically combined to another molecule such as glucuronic acid, sulfate or gylcine
Inducible Enzymes
When the Livers CYP enzymes are repeatedly exposed to and metabolize certain drug molecules, the cell is stimulated to produce additional CYP enzymes to increase the rate the drug molecules are metabolized
Induced
When the metabolism of a drug is sped up by the inducible enzyme process it is said to be induced
Metabolic Induction
When drug molecules have induced metabolism, they are inactivated at a faster rate than usual. So to produce the same degree of drug effect on the body the drug dose must increased
Tolerance
Diminution of response to a stimulus after prolonged exposure (Ex someone ‘addicted’ to coffee)
Elimination/Excretion
The movement of drug molecules out of the body, most typically into the feces or urine
Renal Excretion/Elimination
Excretion by the kidney through the urine
Hepatic/Biliary Excretion/Elimination
Excretion of drugs by the liver, through the livers bile duct and subsequently through the feces
Renal Elimination Process
Circulating drugs eliminated through the kidney via filtration, active secretion, and reabsorption in different parts of the nephron
Filtration
Passive diffusion that occurs as the blood flows from the afferent renal arteriole into the glomerulus
Glomerulus
Specialized tuft of capillaries in the kidney
Afferent Renal Arteriole
Incoming renal arteriole that carries blood to the glomerulus
Efferent Renal Arteriole
Outgoing renal arteriole that carries blood away from the glomerulus (slightly smaller than afferent arteriole)
Bowman’s Capsule
First part of the nephron - Cup-shaped end of a renal tubule or nephron enclosing a glomerulus (with the glomerulus, it is the site of filtration in the kidney)
Proximal Convoluted Tubule
Segment of the nephron, twisted tubular segment that contains many active transport mechanisms for moving electrolytes, glucose, selected drug + other essential molecules back and forth between the urine and the renal tubular cell, and the renal tubular cell and the peritubular capillaries
Peritubular capillaries
A continuation of the efferent renal arteriole by which blood exits the glomerulus, they surround the renal tubule
Active Secretion
In the proximal convoluted tubule some drug molecules are actively transported from the peritubular capillaries into the urine (energy-requiring transport carrier mechanism - not reliant on concentration gradient*)
Loop of Henle
Filtrate flows from the proximal convoluted tubule, along the nephron into the LOH where some of the drug molecules may reabsorb back into the body
Reabsorption
A drug previously ‘eliminated’ into the urine by glomerular filtration or active secretion is now being reabsorbed back into the body via passive diffusion
Sinusoids
A specialized liver blood cavity that drugs from the GI system enter the liver through
Enterohepatic Circulation
Movement of drug from liver excreted into intestinal tract, reabsorbed back into systemic circulation, and eliminated again by the liver
Cirrhosis
Replacement of functional liver cells by nonfunctional fibrous tissue
Clearance
The rate at which drugs leave the body
Half-Life of Elimination
A time value that describes how long it takes for the drug concentration, usually measured in the blood or plasma, to decrease by 50%
Withdrawal Times
Amount of time that must pass from the last drug administration until the animal can be sent to market for slaughter or the eggs/milk can be safely used for human consumption (usually expressed in days)
