Lecture 1 Flashcards
Substances which can affect the biological system.
Drugs
The study of drugs and their action on the body.
Pharmacology
The branch of pharmacology dealing with reactions between drugs and living systems.
Pharmacodynamics
The mathematical description of the processes through which a drug is handled once introduced into the body.
Pharmacokinetics
What a drug does to the body is ______.
Pharmacodynamics
What 3 characteristics of drugs are not capable of absorbing past a membrane?
Large molecules
Ionized drugs
Hydrophilic
What the body does to the drug is ______.
Pharmacokinetics
The study of how drug poison cells, critters, and/or ecosystems.
Toxicology
5 phases of pharmacokinetics:
Liberation Absorption Distribution Metabolism Elimination/Excretion
This is the process of the drug being freed from its carrier tablet, capsule, etc.
Liberation
Liberation is also known as ______.
Disintegration
The nature and characteristics of how a drug moves from its site of administration into usually the critter’s plasma is called ______.
Absorption
The dissemination of a drug throughout the “compartments” of a critter’s body, such as plasma, issues, or organs.
Distribution
Major vehicle for distribution is the _______.
Bloodstream
What 4 things affect absorption?
Drug solubility
Dosage form
Administration route
pH
What 3 characteristics of drugs are capable of absorbing past a membrane?
Small drug molecule
Nonionized drug
Lipophilic
What 3 things may affect distribution?
Blood flow
Fat or water solubility
Protein binding
_____ is affected by renal blood flow and kidney functions.
Elimination
The biotransformation of a drug into other (secondary) compounds.
Metabolism
Metabolism is frequently a tasked performed by which organ?
Liver
After the drug has been absorbed and distributed, the body works to break it down via metabolism into several components called ______.
Metabolites
The liver is the major organ for metabolism via drug oxidation by the _________ system.
Cytochrome P-450 enzyme
What does the Cytochrome P-450 enzyme system do?
Induce (increase) or inhibit (decrease) metabolic activity
What explains why people who frequently drink alcohol become more tolerant to it?
Enzyme induction by the P-450 Enzyme System
_____ is affected by liver function and enzymes.
Metabolism
The fetal liver contains _____ of the drug metabolism capacity of the adult liver therefore metabolism is _____ at birth.
1/3
Reduced
Aging alone accounts for a reduction of _____ of liver mass.
20-30%
______ is affected by protein binding, blood flow, and fat or water solubility.
Distribution
The processes that remove a drug from an organism.
Elimination/excretion
For each drug a certain percentage is converted from the original compound into some intermediate metabolite is called _______.
First pass effect
After the first past effect the drug then passes into the systemic circulation as either the ______ or as a ______.
Chemically intact drug
Metabolite
Why are oral doses higher than IV doses?
First pass effect
3 types of drug interactions:
Additive interactions
Synergistic interactions
Potentiation
The summation of the effects of two (or more) groups given together is equal to each of them given separately but at the same time are called ______ interactions
Additive
1+1=2
Two categories of drug administration
Enteral
Parenteral
If a drug isn’t excreted fast enough it _____ in the body.
Bio-accumulates
Acidic drugs get trapped as anions in _____ urine.
Alkaline
One drug (which has no direct effect) increases the response of the other drug, which normally has a lesser effect is called a ______ interaction.
Potentiation
1+0=3
Oral, sublingual, and buccal routes are called _____ administration.
Enteral
IV, intra-arterial, IM, SQ, inhalation, topical, IO, transdermal, and intrathecal/intraventricular routes are called ______ administration.
Parenteral
What 5 ways are drugs usually excreted?
Urine Feces Pulmonary Skin Hair
Basic drugs get trapped as cations in ____ urine.
Acidic
Rectal route is considered ______ administration.
can be both enteral and parenteral
A _____ (IV) dose gives a regulated, consistent dose over time, causing a steady state in drug concentration.
Continuous infusion
_____ diffusion is described by Fick’s Law.
Aqueous
An _______ (IV) has peaks and troughs in drug concentration.
Intermittent dose
____ drugs (like warfarin) have a lower pK.
Acidic
_____ drugs get trapped as anions in alkaline urine.
Acidic
The use of pharmaceuticals or medical devices for an (FDA) unapproved age group, unapproved dosages, unapproved form of administration, or unapproved indication is called ______ n
Off label
______ are immune-mediated and induce a hypersensitivity reaction.
Drug allergies
_____ diffusion allows the drug to move from an area of high concentration to low concentration.
Passive
______ diffusion is used for “large” molecules and can be “saturated”.
Facilitated
Basic drugs (like neo) have a ____ pK.
Higher (>7.00)
Type of movement of drugs across barriers that doesn’t require energy.
Diffusion (passive and facilitated)
______ is the engulfment of large drugs by a cell in a membrane-lined vesicle.
Endocytosis/exocytosis
_____ is affected by drug solubility, dosage form, administration route, and pH.
Absorption
_______ type of movement that can move drugs against a concentration gradient, can be saturated, and requires energy (ATP).
Active transport
Endocytosis/exocytosis requires _____ and _____.
Energy and cells
Acidic drugs (like warfarin) have a ____ pK.
Lower (<7.0)
The Fick Equation
Thickness of diffusion interface surface
2 types of passive diffusion
Aqueous diffusion
Lipid diffusion
Basic drugs get trapped as _____ in acidic urine.
Cations
Aqueous diffusion is described by ______.
Fick’s Law
Heparin/protamine is an example of ____ antagonism.
Chemical
_____ bind to a receptor and prevent binding of other molecules/drugs. They often have little or no inherent response.
Antagonists
All drug allergies are considered ______.
Adverse drug reactions (ADR’s)
An _____ drug has an intrinsic activity of 0.
Antagonistic
Are all ADR’s considered drug allergies?
No
The summation of each individual drug’s activity exceeds the dum of the two individuals are called ______ interactions.
Synergistic
1+1=3
Acidic drugs get trapped as ____ in alkaline urine.
Anions
____ drugs (like neo) have a higher pK.
Basic
_____ drugs tend to be protonated and non-polar at a low pH and non-protonated and polar at high pH.
Acidic
_____ drugs tend to be non-protonated and non-polar at a high pH and protonated and polar at low pH.
Alkaline
_____ = the extent to which a drug acts at one specific receptor site.
Drug selectivity
______ is a macromolecule or the component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to the drugs observed effects.
Receptor
When a drug binds to a receptor, three things may happen:
An ion channel can be opened or closed
Biochemical messengers activated
Normal cellular functions turned off or on
Many drugs are available in _____ mixtures, which contain two different isomers.
Racemic
An ____ has the exact same elemental components but the molecular arrangement is different. Each one can have different pharmacologic activity.
Isomer
_____ are compared by the EC50.
Potencies
Low of mass action applies to drug-receptor interactions in what 4 ways?
1) Pharmacological effects are reversible because the drug-receptors complex is reversible.
2) Pharmacological effects are proportional to the number of receptors occupied.
3) Pharmacological effects plateau because they are limited by the total number of receptors.
4) Drug effects are proportional to the doses.
_____ bind to and activate a receptor which directly or indirectly brings about an effect.
Agonists
Agonists _____ the receptor.
Activates
_____ = measure of a drug’s effectiveness of causing a response (efficacy).
Intrinsic activity
“Spare Receptor” Concept
1) ____ response can be achieved by an agonist even if only a fraction of the receptors are occupied.
2) ____ of the cell to an agonist concentration depends on affinity of receptors for the drug and total receptor concentration.
Maximal
Sensitivity
Effect-Concentration Curves are the _____ curved.
Dose-response
Dexamethasone/insulin and lisinopril/epinephrine are examples of ______ antagonism.
Physiologic
Potencies are compared by the ____.
EC50
Example of chemical antagonism
Heparin/protramine
4 types of receptors:
Regulatory proteins
Enzymes
Transport proteins
Structural proteins
Three aspects of drug-receptor function:
1) Receptors determine the nature and characteristics of the “Drug Concentration-Effect Curve”
2) Receptors function as regulatory proteins and part of chemical signaling mechanisms that provide target for drugs.
3) Receptors determine the therapeutic and toxic effects of drugs.
4 transmembrane signaling mechanisms:
Ligand-gated ion channels
G protein-coupled receptors
Enzyme-linked receptors
Intracellular receptors
The higher the pK, the more ____ it is.
Basic
_____ = the amount of drug necessary to produce an effect of a given magnitude.
Potency
An antagonistic drug has an intrinsic activity of ____.
0
_____ = (1) one drug molecule interacts with many receptors and (2) the activated receptors can persist for longer than the original drug ligand/receptor complex existed
Signal amplification
____ = increased amount of drug is needed to produce the same effect.
Tolerance
______ = long-term exposure of a drug to cells or tissues makes those tissues less responsive over time.
Desensitization
Differences in potency can be overcome ____.
Giving more drug
Why is absorption in the intestine more efficient in the stomach?
The intestines receive more bloodflow and have a higher surface area due to microvilli.
____ = the ability of a drug to elicit a response when it interacts with are receptor.
Efficacy
Which is generally more important…potency or efficacy?
Efficacy
Think of fentanyl being more potent than morphine and both are more efficacious for pain than aspirin.
Just an example
Formula for therapeutic index
ED50
_____ = occurs over a longer period than desensitization (hours to days to weeks) and the receptors are internalized and eliminated.
Down-regulation
Amount of drug required to produce 50% of the maximal effect.
EC50
The effects of down-regulation are _____-lasting.
Longer
_____ drugs get trapped as cations in acidic urine.
Basic
We can “trap” acidic or basic drugs in the renal tubules for increased excretion by making them ______.
More polar
_____ = the ratio of the drug doses that produces a specified toxic effect in 50% of the population vs. the dose that produces a specified therapeutic effect in 50% of the population.
Therapeutic Index
For drugs administered IV, absorption is not a factor, and the initial phase (from immediately after a administration through the rapid fall in concentration) represents the ____ phase.
Distribution
______ is the transfer of a drug from the site of administration to the bloodstream.
Absorption
____ is a measure of the strength of the interaction of a compound with a proton.
pK
______ is achieved when the permeable form of a drug achieves equal concentration in all body water spaces
Distribution equilibrium
_____ drugs do not Leslie penetrate cell membrane and must pass through slit junctions.
Hydrophilic
The _____receives much more bloodflow in the stomach, so absorption is favored here.
Intestines
What administration route has minimized absorption during shock?
SQ because blood flow to cutaneous tissues is reduced.
What upset does food have a drug absorption in the stomach?
The presence of food in the stomach both dilutes the drug in slows gastric emptying, therefore absorption is slower.
_____ “pumps” drugs out of the cells and is also associated with multi drug resistance.
P-glycoprotein
What happens in areas of high expression of P-glycoprotein?
Drug absorption is reduced
Determining bioavailability is important for calculating drug Jessicas for _____ routes of administration.
Non-IV
By availability is determined by comparing plasma levels of a drug after particular route of administration with levels achieved by ____ route of an administration
IV
Vd is a useful for pharmacokinetic parameter for calculating the ______ dose of a drug.
Loading
When a drug is a door from the G.I. tract, it enters the ____ before entering systemic circulation.
Portal circulation
If a drug is rapidly metabolized in the ____ or ____ during this initial passage, the amount of unchanged drug entering the system and is decreased.
Liver
Gut wall
The lower the pK, the more ____ it is.
Acidic
First pass metabolism by the intestine or liver limits of the _____ of many oral medications
Efficacy
Why is nitroglycerin primarily administered via the sublingual and transdermal route?
More than 90% is cleared during first-pass metabolism.
What must be necessary (regarding solubility) for a drug to be readily absorbed?
It must be largely lipophilic, yet have some solubility in aqueous solutions.
What makes drug formulations bioequivalent?
If they have comparable bioavailability and similar times to achieve peak blood concentrations.
To drug formulation are therapeutically equivalent if they are _____ with similar clinical and safety profiles.
Pharmaceutically equivalent
Meaning same distance form, same after the gradient, same route of administration
Metabolism leads to production of products with increased polarity, which allows the drug to be ______.
Eliminated
Are all drugs that are bioequivalent considered therapeutically equivalent?
No
The distribution of a drug from the plasma to the interstitium depends on: (5)
CO and local blood flow Capillary permeability Tissue volume Degree of binding of the drug to plasma and tissue proteins Solubility of drug
_____ is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and the tissues.
Drug distribution
____-soluble drugs rarely penetrate the CNS because they dissolve in the endothelial cell membrane.
Lipid
Ionized or polar
______ drugs generally fail to enter the CNS because they cannot pass through the endothelial cells that have no split junctions
____ drugs readily move across most biological membranes because they dissolve in the lipid membrane and penetrate the entire cell surface.
Lipophilic
Value of distribution is calculated by dividing _____ by _____.
Dose that gets to systemic circulation
—————————————————
Plasma concentration at time zero
What are the three functional a distinct compartment of body water?
Plasma
Extracellular
Total body water
Once a drug enters the body, it has the potential to do distribute into ____ or become _____.
Any of the 3 compartments of water
Sequestered in a cellular site
If a drug has a high molecular weight or is extensively protein-bound, it is too large to pass through the slit junction of the capillaries and, thus, is effectively trapped within the _____ compartment.
As a result it has a ____ Vd.
Plasma (vascular)
Low
Is a drug has a low molecular weight but is hydrophilic, it can pass through the endothelial slit junctions of the capillaries into the interstitial fluid, but cannot move across the lipid membranes to enter the intracellular fluid, therefore is in the ______ compartment.
Extracellular fluid
If I drive has a low molecular weight and is lipophilic, we can move into the interstitium through the slick junctions and also pass through the cell membrane into the intracellular fluid, therefore is in the ______ compartment.
Total body water
T/F
A drug rarely associates exclusively with only one of the water compartments of the body
True
______ means that a constant fraction of the drug is eliminated per unit of time.
First-order
When is time zero?
Time of IV bolus
The fact that drug clearance is usually a ____ process allows calculation of Vd.
First-order
If a drug has a barge Vd, most of the drug is in the _____ space and is unavailable to the _____.
Extraplasmic
Excretory organs
Any factor that increases _____ can increase the half-life and extend the duration of action of the drug.
Vd
What should you consider if a drug has an explicitly large Vd?
Sequestration of the drug in some tissues or compartments.
What’s a drug inches the body, the process of _____ begins.
Elimination
Three major routes of elimination:
Hepatic metabolism
Biliary elimination
Urinary elimination
Zero-order kinetics are also known as ______ kinetics.
Non-linear
Give an example of three drugs that use zero order kinetics.
ASA
Ethanol
Phenytoin
The inside is saturated by a high free drug concentration, and the rate of metabolism remains the same overtime, this is called _____ kinetics.
Zero-order
Describe metabolism and elimination of a drug with zero-order kinetics.
Constant amount of the drug is metabolized per unit of time.
The rate of elimination is constant and does not depend on the drug concentration.
The kidneys cannot efficiently eliminate ____ drugs, which are reabsorbed into the distal convoluted tubules. Due to this, these drugs are first metabolized into more _____ substances in the _____
Lipophilic
Polar
Liver
Cytochrome P450 complexes system is also called ______.
Microsomal mixed-function oxidases
Cytochrome P450, is the superfamily of heme-containing isozymes that are located in most cells, but primarily in the ____ and ____.
Liver
GI tract
Drugs must be sufficiently ____ to be eliminated from the body.
Polar
Drugs that are not absorbed after oral administration or drugs that are secreted directly into the intestines or into the bile are eliminated in the ______.
Feces
The sole determinant of the rate that a drug achieves steady-state is the _____ of the drug.
Half-life
I dread reaches steady-state in about blank half lives.
4-5
Using smaller doses at shorter intervals reduces the amplitude of fluctuation and drug concentration, however does not affect ______.
Steady-state concentration
What is the goal of drug therapy?
To achieve and maintain concentration within a therapeutic response window while minimizing toxicity and/or side effects
What 2 rates are important to achieve a given concentration?
Rate of administration
Rate of elimination
What are two disadvantages of loading doses?
Increased risk of toxicity
A longer time for plasma concentrations of fall if excess levels occur.
_____ leads to production of products with increased polarity, which allows the drug to be eliminated.
Metabolism
_______ is a useful for pharmacokinetic parameter for calculating the loading dose of a drug.
Vd
The major factor influencing the distribution of lipophilic drugs is _____.
Blood flow to the area
