Flashcards in Exam 1 - Pharmacokinectics Deck (61):
A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body
The study of how a drug enters the body, circulates within the body, is changed by the body, and leaves the body
What are the 4 major pharmacokinetic steps of drug movement in the body
The study of the biochemical and physiologic actions of drugs, and their mechanisms of drug action at the cell level and sub-cell level (what the drug does to the body)
What 4 characteristics of drug molecules influence whether a drug can cross a lipid membrane?
1. Lipid solubility
2. Degree of ionization (charge cannot cross)
3. Molecular Size
Weak acid in an acidic environment = ____
Weak acid in a basic environment =____
Weak base in acidic environment = ____
Weak base in a basic environment = ____
Water soluble (dissociates)
Water soluble (dissociates)
(lipid/water) soluble = non ionized (no charge)
(lipid/water) soluble = ionized (polar)
____ = drugs given by this route are placed directly into GI tract - ORAL/RECTAL
____= administration bypasses the GI tract and includes various injection routes, inhalation, and topical drug administration
9 parenteral drug routes
2. Intravenous *** MOST RAPID/PREDICTABLE
3. Intramuscular - slow
4. Topical - local or systemic
7. Transdermal - patch. more concentrated
8. Intrathecal - epidural
9. Intraperiotoneal - dialysis
T/F rectal (enteral) drug administration is poorly/irregularly absorbed from rectum
Describe rate of onset for:
1. Controlled rate/continuous/rapid/predictable
2. delivers large quantity, slow sustained due to high blood flow through skeletal muscles
3. continuous delivery, slow release
4. rapid delivery
5. slow onset
7. dose controlled
8. usually enteral, cheapest/easiest
4 ways molecules cross membranes
1. Diffusion - lipid soluble drugs/passive/high to low
2. Filtration - small molecules -> membrane pores
Specialized transport for large/ionized/water soluble molecules
3. Facilitated diffusion - carrier
4. Active transport - ATP
3 factors that influence rate of drug movement
1. Physiochemical factors
3. Route of administration
T/F the closer the site of administration is to a blood vessel, the faster a drug can be absorbed
Drugs that are administered orally pass from the stomach to the intestine to the portal veins to liver
"first pass effect" of drug metabolism after oral absorption (metabolize drugs to inactive forms before they have the change to enter the systemic circulation
What type of drugs bypass the first pass effect?
drugs given parenterally - direct to bloodstream
____= the fraction of the administered drug that becomes available in the plasma. FREQUENTLY influenced by the "vehicle" of the drug (difference between generic/brand name drugs)
Bioavailability - only IV administration gives 100%
FDA mandates that generics must have ___% of the availability of the parent compound
2 forms in which drugs are in the blood
1. Bound to plasma proteins - no effect
2. Free - can pass cell membranes and exert desired effect
____= most drugs cross easily; lipid-soluble drugs cross most easily
____= drugs that can cross this barrier are lipid-soluble, very small molecular weight/size, and exert effects on the CNS
Blood Brain Barrier
Drug Redistribution - movement of the drug from the site of ____ to nonspecific sites of ____. Duration of action can be affected by redistribution from one ____ to another. If redistribution occurs between specific sites and nonspecific sites, the drugs action will be ____. Example: An "____" agent is administered to induce sleep before anesthesia for surgery. After a few minutes, the action is terminated, bc the drug has been redistributed from the CNS via the plasma to skeletal muscle to finally ___ ___ in the body.
_____= converts lipid soluble drugs to water soluble metabolites (so kidneys can easily excrete and metabolites are less likely to bind to plasma proteins or store in fat)
Biotransformation aka drug metabolism
Where does biotransformation mostly occur?
Liver - also in kidneys, lungs, nerves, plasma, intestines
What 4 things can alter liver drug metabolism and often require a does modification?
1. Increased age
4. Damage from drugs
In the liver, where does most drug transformation take place?
Microsomes in hepatocytes
Active to inactive =_____
Inactive to active =_____
Active to active =______
Active to inactive = most common- formed from active parent drug
Inactive to active = converted to active after metabolism
Active to active = metabolite is active
What happens in the 2 phases of drug biotransformation?
Phase I - drug is modified through oxidation, reduction or hydrolysis
Phase II - drug molecule is modified by conjugation to a large polar endogenous molecule (adds bulky group) INACTIVE, prepares for excretion
When is microsomal oxidation enzyme system used?
Endoplasmic like intracellular organelles which possess the enzymes required for biotransformation of most drugs in liver hepatocytes
_____= known value describing excretion rates
clearance rates - all drugs in the blood are filtered by the kidneys
Salivary drug concentration mimics _____ concentration
Name 5 ways drugs are excreted from the body
6. breast milk
The amount of time needed for the plasma concentration of a drug to fall to 1/2 its blood level per unit of time is known as?
What is the time that most drugs are cleared by?
4-5 half lives (conversely, it takes approximately 4-5 half lives for a drug to build up to a steady state level)
What concept is described as the amount of drug eliminated is dependent upon the amount of drug in the plasma at any given time?
First order drug elimination - a constant fraction of the drug is eliminated per unit time = clearance rate
What is being described; following administration of multiple therapeutic dosages of a drug at regular time intervals, a plateau level of drug accumulates?
Plasma steady state concentration
What does the plateau level indicate during the plasma steady state concentration?
A rate of drug administration that is equal to the rate of drug elimination
How is the steady state concentration achieved?
At a regular dosing frequency, the drug does not accumulate and a steady state or equilibrium is eventually reached
What are the 2 most common ways drugs bind with receptors?
Hydrogen and iconic (other less common ways include covalent, ionic, or hydrophobic)
The affinity of a drug for a particular receptor and the type of binding is intimately related to the drug's what?
(Higher binding affinity to plasma proteins = remains in blood longer)
Drug binding occurs at _____ sites ( amino acid residues) on protein structure. Binding to one or more AA residue causes _____ ____ in the protein molecule (aka receptor) This results in a modification of the tertiary structure to bring other AA residues _____ to the drug, called "_____ ___". Drugs also bind to receptor proteins within the ____ structure. The receptor protein does not exist as an _____ substance external to the cell. Receptor protein may be a _____ or ____ component of the cell membrane (aka part of the cell membrane)
In drug-receptor interaction, the receptor proteins recognize selected molecules at the ____ surface and transmit information ____ the cell. These receptor proteins exist naturally as receptors for _____, _______, and ____ ____.
What type of protein receptor communicates with both sides of the cell membrane?
Molecule that binds to the receptor protein or receptor glycoprotein is called a?
Ligand - may be hormones, neurotransmitters, growth factors, or drug molecules
Name for when a ligand binds to a specific area of the receptor protein on the outer surface of the cell, or within the cell membrane, a CONFORMATIONAL CHANGE occurs in the receptor-protein molecule which is transmitted to the inner surface of the cell membrane.
Cell signaling - initiates the cells response to the binding for the ligand
What are 4 examples of cellular responses that occur following cell signaling.
1. Ion channel opening or closing
2. Formation of intracellular second messenger
3. Alteration in gene expression of the cell
4. Initiation or alterations in cell growth and differentiation
Ligand binding occurs directly to receptor at ____ site. Receptors are located on ___-___ channels and ___-___ channels. Bidning causes the channel to open, allowing for the ___ of ions. *Binding ____ cell membrane permeability to ___ and ___ which determines depolarization or _____ of nerve (aka the nerve firing)
What are the first messengers vs second messengers?
First messenger = ligand (receptors are located in cell membrane and transmit info from outside to inside cell.
Second messenger = pass the message from the inside of the cell to the effector organ (target site of action)
What are G-proteins and where are they located?
They are coupled with receptors which regulate the generation second messengers
Located at the internal portion of cell membranes
What are 3 results of effector activation?
1. Generate cAMP
2. Phospholipase C - phosphorylation of proteins
3. Change in membrane channel - change in ionic conductance
Term that is described as the amount of drug necessary to produce the effect
- Related to affinity of drug to its receptor
Term that is described as the degree of maximum intensity of the drug.
- max response produced by a drug
- related to receptor occupancy by drug molecules
- additional does produce no additional benefit "ceiling dose"
____ is dose, ____ is effect
____ drug produces SIMILAR EFFECTS as endogenous chemicals, it is able to bind to a receptor and produce an effect (think ligand)
____ drug produces NO EFFECT. It binds to receptor but is unable to active it therefore it reduces/inhibits an effect. "blocker" drug
Who binds first, an agonist or an antagonist?
ALWAYS THE ANTAGONIST
A competitive antagonist competes with agonist for the same ____ ____, and blocks the receptor. But it is ______. Administering additional agonist will ____ the antagonist from the receptor, allowing the ____ to produce its effect.
Noncompetitive antagonist binds _____ and cannot be displaced. Can bind to either the same receptor site as the agonist or a different site but both actions ___ the effect of the agonist. (think poisons)
____ ____: activates pathways that oppose the action of the agonist. Agonist and antagonist act independently on 2 different receptors. Less desirable in medicine than receptor-specific antagonists.
____ ____: Both agonist and antagonist compete for the same receptor site. Antagonist binds first. Prevents agonist from producing effect. Either competitive or non-competitive