Flashcards in Exam 1: PharmacoKinetics Deck (84):
_________ is 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 steps of drug movement in the body?
1.Absorption 2.Distribution 3.Metabolism 4.Excretion
Determing a drugs ability to exert an effect: The ______ of drug that is able to pass through a cell membrane.... The ____ at which a drug moves through the body
________ = the more, the easier that the drug will cross
Degree of ionization (charge) = charged molecules cannot cross (must use _____/_____).
______ sized molecules cross more easily.
_____ of the drug molecule = molecules can “contort” to fit through the membrane
_______ = small molecules that are water- soluble pass through membrane pores by the bulk flow of water
_______ transport = large, ionized water-soluble drugs require a more complex mechanism than simple diffusion
________ = drug forms a complex with a component of cell membrane on one side; complex is carried through membrane; drug is released on inside
_______ are engulfed by cell membrane and are released unchanged in cytoplasm (endocytosis)
Movement of glucose across cell membranes is _______ by insulin
__________ = movement of drug molecules across biologic membranes against both a concentration and an electrochemical gradient...Requires _____
What are the 3 influences on the RATE a drug is moved across the membrane?
1.Physiochemical factors (size, charge, etc) 2.Solubility 3.Route of administration
_______ = drugs given by this route are placed directly into the gastrointestinal tract...THERE ARE ONLY 2 WAYS: ______ & ______
Enteral....Oral & Rectal
________= administration that bypasses the gastrointestinal tract and includes various injection routes, inhalation and topical drug administration.
Which route of drug administration is the cheapest, easiest, and most conveneient?
Liquid pills are absorbed more ______ then regular tablets.
A down side to recall route drugs are poorly or irregularly _______ from rectum. Poor patient _______, so its mainly used on ______.
Inhalation is a _____ way to access the circulation and it can be both ______ and systemic.
What is the MOST RAPID route for drug response, and it produces a _______ response.
IntraMuscular route allows for a _______ effect of the drug (absorbed more slowly)
Topical Route: can be either _____ or ______ in effect, depending on dose.
local or systemic
What is the newest route of drug administration in dentistry?
subgingival! (in pocket)
What is the official title for the route we use to give a IA block?
In a sublingual route the drug is _____ absorbed.
What is the most concentrated drug delivery vehicle?
The _______ route is an injection of solutions into the spinal sub-arachnoid space?
The _______ route places fluid into the peritoneal cavity for exchange of substances.
IntraPeritoneal Route (form of dialysis)
Drug _______ is the movement of the drug from its site of administration into the plasma.
Many drugs are weak ________ (either weak acids or weak bases)
As weak electrolytes, drugs can exist in either ionized or non-ionized state, depending on the ______ of the environment, the ________ form can diffuse across membranes.
A weak acid in an ______ environment = lipid soluble
A weak acid in a ______ environment = water soluble (dissociates)
A weak base in ______ environment = water soluble (dissociates)
Weak base in a _____ environment = lipid soluble
Aspirin is a weak _____; pKa for aspirin = 4.4....Therefore, In acid environment of stomach, aspirin dissociates to 1000 uncharged molecules (lipid soluble) to 1 charged molecule (polar, water soluble) = acid gets absorbed across wall of stomach (membrane) into plasma because most of drug is in lipid soluble form
Aspirin's story: However, once in the plasma (pH = 7.4), ratio of _______ aspirin molecules changes: 1000 charged (polar, water soluble) to 1 uncharged (lipid soluble) = aspirin cannot pass back through blood vessel wall membrane into stomach
_______ is the fraction of the administered drug that becomes available in the plasma...only _____ administration gives 100% of this.
FDA mandates that generics must have ___% of the bioavailability of the parent compound.
_________ = drug movement from the site of absorption to the site of action
What are the two ways drug distribution occurs in the blood?
1.bound to plasma proteins 2. free (unbound)
Of the 2 ways a drug can be distributed, only the ______ form can pass across cell membranes.
As free drug leaves the plasma, the bound drug becomes “unbound” therefore the “_____” of bound:unbound drug _________ in the blood.
"ratio" ....stays the same!!!
The bound form of a drug has _____ on the body.
The BLOOD BRIAIN BARRIER: drugs that can cross this barrier are ______-soluble, very _____ molecular weight/size, and exert effects on the central nervous system (CNS).
Placenta = most drugs cross ______; ______- soluble drugs cross most easily
If a drug has a high binding affinity for plasma proteins: remain in the blood ______!
Hmmm...Cross reactions maybe?!?! When 2 or more drugs are competing for the same plasma protein binding sites for transport through the body, the drug with the highest ________ will become bound to plasma proteins..Other drug(s) will remain unbound or “free” to exert their effects by reacting with target tissue
Most of the drugs are cleared/removed from the body in __ to ___ half-lives.
4 to 5 half lives
It takes approximately __ to __ half-lives for a drug to build up to a steady state level (level amount) in the body.
4 to 5
_______ is the movement of the drug from the site of action to nonspecific sites of action...if it occurs the drug's action will be _______.
An "induction" agent that helps knock your ass out before surgery is an example of _______ because it's action is diminished after it moves from the CNS to muscle.
Drug metabolism is also known as _________.
Drug metabolism/biotransformation works by converting a drug from _____ soluble to ______ soluble metabolites that can be excreted by the kidneys.
Which organ is the most common drug metabolizer? What are its enzymes called?
the LIVER!...cytochrome P450 system)
Phase I of biotransformation: occurs in the _____ where the drug molecule is modified through _______, _______, or _______.
oxidation, reduction, or hydrolysis
In Phase II of biotransformation the drug molecule is modified by conjugation to a large _____ endogenous molecule. Phase II metabolites are pharmacologically _____.
Since metabolism breaks down or “inactivates” drugs, then increasing the rate of metabolism would ________ the action of the drug
If Drug A induces the metabolism of Drug B, then the action of Drug B would be _______.
If we “_____” cytochrome P450 liver enzymes, we decrease the rate of metabolism.
Since metabolism breaks down or “inactivates” drugs, then _________ the rate of metabolism would _______ the action of the drug.
If Drug A inhibits the metabolism of Drug B, then the action of Drug B would be ________.
The most common mechanism of biotransformation is ______ to inactive.
Mechanism of biotransformation: What is the nickname for drugs that go from inactive to active?
"prodrugs"-the inactive parent drug is converted to an active drug after metabolism
Mechanism of biotransformation: Active parent drug is converted to a second active drug (metabolite is active). this is called ______ to ______.
active to active
Liver function declines with age, so it often requires a _____ modification.
The first pass effect is only for drugs that are administered ______.
Drugs that are given ________ bypass the first pass effect.
What is the principle organ of drug excretion/elimination out of the body?
Did you know: Salivary drug concentration mimics ______ concentration!
If a drug is FAT SOLUBLE when it reaches the kidneys, it will be _______ by the kidneys and be placed back into the blood stream.
EVERYONE screws this up: _______ drug elimination: The amount of drug eliminated is dependent upon the amount of drug in the plasma at any given time.
First Order Drug Elimination
IN First Order Drug Elimination: A constant _______ of the drug is eliminated per unit time.
FRACTION (5%ofdrug/min) ((where as zero order is 5mg/min))
________ half-life = rapid decline in plasma drug concentration as 50% of drug distributed throughout the body
_______ half-life = time required to excrete 50% of drug from the system
_______ drug elimination: A given amount of drug is eliminated per unit time
ZERO order drug elimination
In Zero Order Drug elimination a _______ amount of drug is eliminated per unit time.
An example of Zero Order Drug Elimination is Alcohol, because it is eliminated at a rate of 1 gram per hour, the rate is ______.
_______ concentration: Following administration of MULTIPLE therapeutic dosages of a drug at REGULAR time intervals, a plateau level of drug accumulates.
A Steady-State concentration ______ represents a rate of drug administration that is EQUAL to the rate of drug elimination.
Stready State Accumulation: If the drug is taken too _____ (too ______) before the preceding dose is eliminated completely, the next dose will ADD to the residual amount of drug still remaining in the body. EVENTUALLY The rate of intake _______ the rate of elimination!!
At a ______ dosing frequency, the drug does not accumulate and a steady state or equilibrium is eventually reached.