I.A. Introduction: The Nature of Drugs & Drug Development & Regulation Flashcards
can be defined as the study of substances that
interact with living systems through chemical processes
Pharmacology
defined as the science of substances used to prevent, diagnose, and
treat disease
medical pharmacology
the branch of pharmacology that deals with the undesirable effects of chemicals on living systems, from individual cells to humans to complex ecosystems
Toxicology
aimed at understanding the actions of drugs as chemicals on individualorganisms, especially humans and domestic animals
medical pharmacology and toxicology
deals with the absorption, distribution, and elimination of drugs
Pharmacokinetics
concerns the actions of the chemical on the organism
Pharmacodynamics
concerned with the effects of chemicals on all organisms and their survival in groups and as species
environmental toxicology
the science of drug preparation and the medical uses of drugs
materia medica
the relation of the individual’s genetic makeup to his or her response to specific drugs
Pharmacogenomics
T/F
the chemicals in botanicals (herbs and plant extracts,
“nutraceuticals”) are no different from chemicals in manufactured drugs except for the much greater proportion of impurities in botanicals
true
defined as any substance that brings about a change in biologic function through its chemical actions
drug
the drug molecule interacts as an ___ or ___ with a specific target molecule that plays a regulatory role in the biologic system.
agonist (activator) or antagonist (inhibitor)
target molecule is called a ___
receptor
are drugs that have almost exclusively harmful effects
Poisons
defined as poisons of biologic origin
Toxins
most drugs have molecular weights between ___
100 and 1000
Drugs interact with receptors by means of ___
chemical forces or bond
3 major types of bonds
covalent
electrostatic
hydrophobic
___ bonds are very strong and in many cases
not reversible under biologic conditions.
Covalent
___ is much more common than covalent
bonding in drug-receptor interactions
Electrostatic bonding
are usually quite weak and are probably important in the interactions of highly lipid-soluble drugs with
the lipids of cell membranes and perhaps in the interaction of drugs with the internal walls of receptor “pockets.”
Hydrophobic bonds
drugs that bind through weak bonds to their receptors are generally more ___ than drugs that bind by means of very strong bonds
selective
[because weak bonds require a very precise fit of the drug to its receptor
if an interaction is to occur]
a drug that interacts with adrenoceptors
carvedilol
Area of pharmacology concerned with the use of
chemicals in the prevention, diagnosis, and
treatment of disease, especially in humans
MEDICAL PHARMACOLOGY
Area of pharmacology concerned with the
undesirable effects of chemicals, whether it is a
drug or poison, on biologic systems
TOXICOLOGY
the relation of the individual’s genetic makeup to his or her response to specific drugs
PHARMACOGENOMICS
Any substance that brings about a change in
biologic function through chemical actions
DRUG
Hydrophobic bonds are usually quite ___
weak
___ MW For selective binding
100
___ MW For traversing to different barriers
of the body
1000
Cannot move within the body
because of impediments
____ MW
> 1000
Aspirin binds to the ___
platelets
The tendency of a drug that binds to a
receptor via a covalent bond is to have a
___ bond
permanent
a process to prevent and stop
bleeding in the body.
Hemostasis
Activates receptor-effector system
to the maximum extent (Ra-D
pool){activated form}
Full agonist
Binds to the same receptors and
activate them in the same way but
do not evoke as great a response
Partial agonist
Binds to a site on the receptor molecule
separate from the agonist binding site
Allosteric modulators
Enzymes are a class of ___
receptors
they could bind together with the agonist
allosteric modulators
Results in effects that are opposite of the
effects produced by conventional agonists
Inverse agonist
Binds to a receptor, compete with and
prevent binding by other molecules
Antagonist
They need to be activated by passing
through the liver
Prodrug
types of permeation
○ Aqueous diffusion
○ Lipid diffusion
○ Transport by special carriers
○ Endocytosis
○ Exocytosis
movement of molecules through the watery
extracellular and intracellular spaces
AQUEOUS DIFFUSION
AQUEOUS DIFFUSION occurs within…
LARGER aqueous compartments
of the body (eg: interstitial space, cytosol, etc.) and
across epithelial membrane tight junctions and
the endothelial lining of blood vessels
Movement of molecules through membranes and
other lipid structures
LIPID DIFFUSION
LIPID DIFFUSION is governed by ___
Fick’s law
TRANSPORT BY SPECIAL CARRIERS 2 TYPES
- Active transport
- Facilitated diffusion
NET (norepinephrine transporter)
- Physiologic Function
- Pharmacologic Significance
- Norepinephrine reuptake from synapse
- Target of cocaine and some tricyclic antidepressants
SERT (serotonin reuptake transporter)
- Physiologic Function
- Pharmacologic Significance
- Serotonin reuptake from synapse
- Target of selective serotonin reuptake inhibitors and some tricyclic antidepressants
VMAT (vesicular monoamine transporter)
- Physiologic Function
- Pharmacologic Significance
- Transport of dopamine and norepinephrine into adrenergic vesicles in nerve endings
- Target of reserpine and tetrabenazine
MDR1 (multidrug resistance protein - 1)
- Physiologic Function
- Pharmacologic Significance
- Transport of many xenobiotics out of cells
- Increased expression confers resistance to
certain anticancer drugs; inhibition increases blood levels of digoxin
MRP1 (multidrug resistance-associated protein -1)
- Physiologic Function
- Pharmacologic Significance
- Leukotriene secretion
- Confers resistance to certain anticancer
and antifungal drugs
the process by which the substance is bound at a cell-surface receptor, engulfed by the cell
membrane, and carried into the cell by pinching off of the newly formed vesicle inside the membrane
ENDOCYTOSIS
Expulsion (or secretion) of
membrane-encapsulated material from the cell
EXOCYTOSIS
Predicts the movement of molecules across a
barrier
FICK’S LAW OF DIFFUSION
Drug absorption is faster in organs with larger
___
surface areas
Drug absorption is faster from organs with ___ membrane barriers
thin
The passive flux of molecules down a concentration gradient is governed by ___
Fick’s law
Water soluble drugs are (polar/nonpolar)
polar
(they follow the water diffusion)
Lipid soluble drugs are (polar/nonpolar)
nonpolar
Aqueous solubility of a drug is a function of the ___ (degree of ionization, polarity) of the molecule
electrostatic charge
Lipid solubility of a molecule is ___
proportional to its charge
inversely
Clinically important when it is necessary to
estimate or alter the partition of drugs between
compartments of different pH
THE HENDERSON-HASSELBACH EQUATION
amount absorbed into the systemic circulation
BIOAVAILABILITY
When the drug passes through the ___, it is
metabolized and when the drug goes to the blood circulation, it will be less than 100% of what you administered
liver
Instantaneous and complete absorption
INTRAVENOUS (IV) / PARENTERAL ABSORPTION
Absorption maybe slower, and less complete
ORAL (swallowed)
Absorption is often faster and more complete
(higher bioavailability) than oral
INTRAMUSCULAR (IM) ABSORPTION
___ cannot be given by IM, causes
bleeding in the muscle
heparin
Most vaccines are administered through
___
intramuscular injection
___ are injected subcutaneously to avoid being
recycled by the liver
Insulin
Slower absorption than IM route
SUBCUTANEOUS ABSORPTION
____ drugs are pressed under
the tongue and the buccal
Nitroglycerin antianginal
Application to the skin or mucous membrane of the
eye, nose, throat, airway, or vagina for local effect
TOPICAL
Application to the skin for systemic effect
TRANSDERMAL
ABSORPTION OF DRUGS
ROUTES OF ADMINISTRATION (9)
- ORAL (swallowed)
- INTRAVENOUS (IV) / PARENTERAL
- INTRAMUSCULAR (IM)
4.. SUBCUTANEOUS - BUCCAL AND SUBLINGUAL
- RECTAL (suppository)
- INHALATION
- TOPICAL
- TRANSDERMAL
(high/low) blood flow maintains a high drug
depot-to-blood concentration gradient
high
Major determinant of the rate of absorption (Fick’s
law)
CONCENTRATION
DETERMINANTS OF DISTRIBUTION
SIZE OF THE ORGAN
BLOOD FLOW
SOLUBILITY
BINDING
determines the concentration
gradient between blood and the organ
Size of the organ
Important determinant of the rate of uptake
BLOOD FLOW
If the drug is very soluble in cells, the concentration in the perivascular space will be ___ and diffusion from the vessel into the extravascular tissue will be ___
lower
facilitated
Binding of drugs to macromolecules in the blood or tissue compartment will tend to ___ the drug’s concentration in that compartment
increase
Amount of drug in the body to the concentration in
the plasma
Vd
Drug elimination is the same as drug excretion
(T/F)
FALSE
*A drug maybe eliminated by metabolism long before the modified molecules are excreted from the body
For most drugs, excretion is by way of the ___
kidneys
Rate of elimination is proportionate to the
concentration
FIRST ORDER ELIMINATION
Drug’s concentration in plasma ___
exponentially with time
decreases
