chapter 1 pharmacology Flashcards
Body of knowledge concerned with the action
of chemicals on biologic systems, especially by
binding to regulatory molecules (receptors) and
activating or inhibiting normal body processe
pharmacology
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 on
biologic systems
TOXICOLOGY
Identifies the exact mechanism of action
of one particular drug
Identifies the receptors
MOLECULAR BIOLOGY
Any substance that brings about a change
in biologic function through chemical actions
DRUG
Specific molecule in the biologic system that
plays a regulatory role
receptor
Drugs are given at a site ___________ from the
intended site of action
distant
general range of drug size
100 - 1000
MW For selective binding
100
MW For traversing to different barriers of the body
1000
MW
Cannot move within the body
Given directly at the site of action
> 1000
Chemical forces or bonds through which the drug interacts with the receptors Weaker bonds are more selective bonds
DRUG RECEPTOR BONDS
DRUG RECEPTOR BONDS
Strongest
Irreversible
COVALENT
DRUG RECEPTOR BONDS
More common
Weaker
Eg, between cation and an anion
ELECTROSTATIC BONDS
DRUG RECEPTOR BONDS
Weakest
Highly lipid soluble drug
HYDROPHOBIC BONDS
To reach its receptors and bring about biologic effect A drug molecule (eg, sedative) must travel from the site of \_\_\_\_\_\_\_\_\_\_ (eg, gastrointestinal tract) to the site of \_\_\_\_\_\_\_\_ (eg, brain)
administration- action
Movement of drug molecules into and within
the biologic environment
PERMEATION
Movement of molecules through the watery
extracellular and intracellular spaces
AQUEOUS DIFFUSION
aqueous diffusion is a passive or active process?
passive
AQUEOUS DIFFUSION is governed by
Governed by Fick’s law
where does aqueous diffusion take place? (membranes of ….)
Membranes of capillaries with small waterfilled pores
Movement of molecules through membranes
and other lipid structures
lipid diffusion
type of diffusion
Most important factor for drug permeation
lipid diffusion
LIPID DIFFUSION is governed by
Governed by Fick’s law
LIPID diffusion is a passive or active process?
PASSIVE
TYPE OF PERMEATION Drugs transported across barriers by mechanisms that carry similar endogenous substances Capacity limited
TRANSPORT BY SPECIAL CARRIERS
IS TRANSPORT BY SPECIAL CARRIERS GOVERNED BY FICK’S LAW
NO
TRANSPORT BY SPECIAL CARRIERS
TYPES OF TRANSPORT
ACTIVE TRANSPORT
FACILITATED DIFFUSION
No energy required
Downhill
FACILITATED DIFFUSION
Needs energy
Against a concentration gradient
ACTIVE TRANSPORT
type of permeation
Binding to specialized components
(receptors) on cell membranes
Internalization by infolding of the area of
the membrane and contents of the vesicle
are subsequently released into the cytoplasm
endocytosis
type of permeation
Permits very large or very lipid-insoluble
chemicals to enter the cell
Eg, B12 with intrinsic factor and iron with
transferrin
endocytosis
Reverse process
Expulsion 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
______ (eg, small intestine)
than from organs with ______________ (eg, stomach)
larger surface areas
smaller absorbing
areas
Drug absorption is faster from organs with
(eg, lungs) than
those with (eg, skin)
thin membrane barriers
thick barriers
fick’s law
measure of the mobility
of the drug in medium of the diffusion path
Permeability coefficient
fick’s law
length of the diffusion path
Thickness
a function of the electrostatic charge (degree of ionization,
polarity) of the molecule
Aqueous solubility
Water molecules are attracted to —— forming an aqueous shell
around them
charged
drug molecules
——- solubility of a molecule is inversely proportional to its charge
lipid
lipid solubility of a molecule is —— proportional to its charge
inversely
Many drugs are —- bases or —- acids
weak
determines the fraction of molecules charged (ionized) versus uncharged
(nonionized
pH of the medium
Fraction of molecules in the ionized state can
be predicted by means of the
H-H equation
Neutral molecule that can form a cation
(+ charged) by combining with a proton
(hydrogen ion)
WEAK BASE
Ionized, —– polar, —- water soluble
when they are protonated
more
Neutral molecule that can reversibly dissociate into an anion (- charged) and a proton ( hydrogen ion) Not ionized, less polar, less water soluble when they are protonated
WEAK ACID
base
charged,
more water-soluble
protonated weak base
base
uncharged,
more lipid soluble
unprotonated weak base
acid
uncharged,
more lipid soluble
protonated weak acid
acid
charged,
more water-soluble
unprotonated weak acid
Clinically important when it is necessary
to estimate or alter the partition of drugs
between compartments of different pH
Henderson-Hasselbach Equation
When a patient takes an overdose of a weak
acid drug, excretion maybe accelerated by
alkalinizing the urine
Weak acids dissociate to its
in alkaline urine and cannot readily diffuse back
from the renal tubule back to the blood
charged, polar form
amount absorbed into the systemic circulation /
amount of drug administered
BIOAVAILABILITY
ROUTES OF ADMINISTRATION
Maximum convenience
Absorption maybe slower, and less complete
- ORAL (swallowed)
Some drugs have low bioavailability when
given
orally
Subject to first-pass effect
oral administration
(significant amount
of the agent is metabolized in the gut wall,
portal circulation, and liver before it reaches
the systemic circulation)
first pass effect
ROUTES OF ADMINISTRATION
Instantaneous and complete absorption
Bioavailability by definition is 100%
Potentially more dangerous, high blood
levels reached if administration is too rapid
- INTRAVENOUS (IV)/PARENTERAL
ROUTES OF ADMINISTRATION
Absorption is often faster and more complete
(higher bioavailability) than oral
Large volumes (>5 ml into each buttock) if the
drug is not irritating
- INTRAMUSCULAR (IM)
First-pass effect is avoided
Heparin cannot be given by this route,
causes bleeding in the —
INTRAMUSCULAR (IM)
ROUTES OF ADMINISTRATION
Slower absorption than IM route
First-pass effect is avoided
Heparin can be given by this route, does
not cause hematoma
- SUBCUTANEOUS
(in the pouch between gums
and cheeks or under the tongue)
Permits absorption direct into the systemic
circulation, bypassing hepatic portal circuit
and first-pass metabolism
BUCCAL AND SUBLINGUAL
ROUTES OF ADMINISTRATION
Slow or fast depending on formulation of
the product
BUCCAL AND SUBLINGUAL
ROUTES OF ADMINISTRATION
Partial avoidance of first-pass effect (not completely as the sublingual route) Suppositories tend to migrate upward in the rectum where absorption is partially into the portal circulation
- RECTAL (suppository)
ROUTES OF ADMINISTRATION
Larger amounts of unpleasant drugs
are better administered —–
May cause significant irritation
- RECTAL (suppository)
ROUTES OF ADMINISTRATION
For respiratory diseases
Delivery closest to the target tissue
Results into rapid absorption because of
the rapid and thin alveolar surface area
- INHALATION
Drugs that are gases at room temperature
(eg, nitrous oxide), or easily volatilized
(anesthetics)
Drugs that are gases at room temperature
(eg, nitrous oxide), or easily volatilized
(anesthetics)
- INHALATION
ROUTES OF ADMINISTRATION
Application to the skin or mucous membrane
of the eye, nose, throat, airway, or vagina
for local effect
- TOPICAL
ROUTES OF ADMINISTRATION
Rate of absorption varies with the area
of application and drug’s formulation
Absorption is slower compared to other
routes
- TOPICAL
ROUTES OF ADMINISTRATION
Application to the skin for systemic effect
Rate of absorption occurs very slowly
First-pass effect is avoided
- TRANSDERMAL
Influences absorption from IM, subcutaneous,
and in shock
BLOOD FLOW
High blood flow maintains a — drug depotto-blood concentration gradient
Maximizes absorption
high
Concentration gradient
Major determinant of the rate of absorption
(Fick’s law)
concentration
DETERMINANTS OF DISTRIBUTION
determines the concentration
gradient between blood and the organ
Eg, skeletal muscle and brain
- Size of the organ
DETERMINANTS OF DISTRIBUTION
Important determinant of the rate of uptake
- Blood flow
Well-perfused organs
Brain
Heart, kidneys
Splanchnic organs
If the drug is ____ in cells, the
concentration in the perivascular space
will be ______ and diffusion from the vessel
into the extravascular tissue will be facilitated
very soluble
lower
DETERMINANTS OF DISTRIBUTION
—- of drugs to macromolecules in
the blood or tissue compartment will tend
to increase the drug’s concentration in that
compartment
Binding
Binding
Amount of drug in the body to the
concentration in the plasma
APPARENT VOLUME OF DISTRIBUTION
METABOLISM OF DRUGS
Action of many drugs is terminated before they
are excreted
Metabolized to biologically inactive derivatives
Conversion to a metabolite is a form of
elimination
AS MECHANISM OF TERMINATION OF
DRUG ACTION
METABOLISM OF DRUGS
Inactive as administered and must be metabolized in the body to become active Eg, levodopa, minoxidil Many drugs are active as administered and have active metabolites as well Some benzodiazepines
AS MECHANISM OF DRUG ACTIVATION
PRODRUGS
METABOLISM OF DRUGS
Drugs not modified by the body
Continue to act until they are excreted
Eg, lithium
DRUG ELIMINATION WITHOUT
METABOLISM
Determinants of the duration of action for most
drugs
Dosage
Rate of elimination following the last dose
Disappearance of the active molecules
from the bloodstream
Are Drug elimination and drug excretion similar
NO.
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 ——
(except ——-)
kidneys
anesthetic gases-lungs
For drugs with active metabolites
(eg, diazepam), elimination of the parent
molecule by metabolism is not synonymous
with
termination of action
For drugs that are not metabolized,—-
is the mode of elimination
EXCRETION
Rate of elimination is proportionate to the
concentration (ie, the higher the concentration,
the greater the amount eliminated per unit
time)
Drug’s concentration in plasma decreases
exponentially with time
A. FIRST ORDER ELIMINATION
Half-life of elimination is constant regardless
of amount of drug in the body
Concentration of such drug in the blood will
decrease by 50% for every half-life
Most common process
Followed by most drugs
FIRST ORDER ELIMINATION
Rate of elimination is constant regardless
of concentration
Occurs with drugs that saturate their
elimination of mechanism at concentrations
of clinical interest
ZERO ORDER ELIMINATION
Concentration of such drugs in plasma
decrease in linear fashion over time
With higher doses, there will be bigger
chances of toxic effect because the patient
may not be able to eliminate it
Eg, alcohol, phenytoin, aspirin
ZERO ORDER ELIMINATION
