Download Pharmacology Objectives 1

Pharmacology
Lecture 1 General Principles of Pharmacology
1) List the processes that define drug disposition. The processes that define drug
disposition include absorption, distribution, metabolism, and elimination (ADME).
Disposition rates influence tissue drug concentration.
2) List the routes of drug administration and for each state the major advantages
and disadvantages.
Route
Enteral
Oral
Advantages
Disadvantages
Convenient, practical, and cheap
Sublingual
Rectal
Parenternal
IV
Avoids first pass clearance by liver
Can use w/ nausea and vomiting
Cannot be used during nausea or vomiting. Some
drugs are not absorbed or too rapidly metabolized.
Not suitable for irritating or bitter drugs
Absorption is limited. Esthetics.
IM
Sub Q
Topical
Cutaneous
Inhalation
Ensures rapid delivery of
therapeutic plasma levels.
Ensures rapid delivery. Good for
oily solutions or suspensions.
Large amounts may be given
Administration skills required for all parenternal
routes. Painful. Possible infection.
Some drugs not absorbed from IM sites.
New formulations allow systemic
delivery.
Useful in management of some
diseases. Systemic effects lessened
Systemic dose is uncertain.
Skin injury from irritating drugs.
Administration skills required. Dose delivered is
uncertain.
3) List the physicochemical properties of drugs and the physiologic characteristics
of tissues that influence the passage of drugs across biologic membranes.
Drug
Lipid Solubility
Molecular Size and Weight
pKa
Tissue
pH
Membrane thickness
Local anatomy, i.e. surface area
Membrane permeability
Local blood flow
4) Define the terms acid and base as they relate to drugs. Drugs that are acidic are
more ionized in a basic solution and less ionized in an acidic solution. Drugs that are
basic are more ionized in an acidic solution and less ionized in a basic solution.
5) Write the Henderson-Hasselbalch equation.
pH = pKa + log [non-protonated species]/[protonated species]
For acids: pH = pKa + log [A-]/[HA]
For bases: pH = pKa + log [B]/[BH+]
6) Describe how pH influences the movement of drugs across membranes.
Chemicals that have acidic or basic groups may ionize in solution depeding on the
pH. This is important for drug movement because only the non-ionized lipid soluble
form of the drug can move across the membrane. For example a weak acid will be
less ionized in the stomach (pH ~ 1.0) and thus able to move across the gastric
mucosa to the blood (pH ~ 7.4) where it will become more ionized, and thus trapped
in the blood causing an overall movement towards absorption.
7) List the mechanisms by which drugs cross membranes and characterize each
process. Passive diffusion allows drugs to move down the concentration gradient in
an energy dependant and nonsaturable process. Carrier mediated diffusion is also
down the concentration gradient and energy independent but it is saturable. Active
transport, minor role for uptake major role for elimination, is energy dependant,
saturable and moves against a concentration gradient.
8) Define first-pass (presystemic) drug clearance and state how the physician may
avoid or deal with this process. First-pass (presystemic) drug clearance is when a
drug is absorbed through the stomach and must pass through the liver before being
delivered to other parts of the body. If the metabolism of the drug in the liver is too
great then this may cause less of the drug to be delivered to the rest of the body. A
physician may give the drug by another route to avoid the first-pass clearance, such as
IV, IM, Sub Q, or topical applications. In addition, drug metabolism may be inhibited
by other drugs or even dietary constituents (grapefruit juice).
9) List factors that may change or influence the rate or extent of drug absorption
from the gut. Stomach emptying time and passage of drug to the intestine may be
influenced by gastric contents, intestinal motility and blood flow. Stomach acid and
inactivating enzymes may destroy certain drugs. Interactions with food, other drugs,
and other constituents of the gastric milieu may influence absorption. Inert
ingredients or the special formulation of those preparations may alter absorption.
10) Define bioavailability. Bioavailability is the fraction of the drug (administered by
any route) that reaches the bloodstream unaltered. This is given as the area under the
curve for the route in question over the area under the curve of IV administration.
11) Describe situations wherein bioavailability problems may be of clinical
importance. Bioavailability differences are clinically important when: the drug is
used to treat clinically serious illness, there is a steep dose-response relationship, the
therapeutic index is small, and the indicators of clinical response are indistinct or
lacking. Bioavailability problems are most likely with highly complex formulations
and are nonexistent with IV administration.
12) List and characterize the renal mechanisms utilized for drug elimination. The
overall rate of elimination is influenced by rates of glomerular filtration and tubular
secretion and extent of tubular reabsorption. Glomerular filtration is affected by renal
blood flow, the number of nephrons available, the extent of protein binding, and the
pH effect. Tubular secretion involves separate paths for anions and cations, pH and
protein binding have no effect, but competition between similar ions may affect the
rate of secretion. Tubular reabsorption serves to concentrate excreted metabolites due
to water reuptake and may reduce excretion if metabolites are reabsorbed..
13) Describe how heredity, gender, age and disease influence drug disposition and
response to drugs. Variation in response to drugs is related to the plasma-drug
concentration caused by host factors including heredity, gender, age, diet,
environment, and disease. Hereditary factors primarily influence drug metabolism.
Age and disease have profound effects on kidney function and renal drug elimination.
Renal function is poorly developed at birth and deteriorates with increasing age even
in the absence of overt kidney disease. Creatinine clearance is an indicator of kidney
function and is generally higher for females than for males.
14) Describe the blood brain barrier and the characteristics of drugs that cross the
blood brain barrier. The blood brain barrier consists of bands of tight junctions
joining the epithelial cells of CNS capillaries. This limits the drug distribution into the
central nervous system to lipid soluble, non-ionized compounds. Water soluble and
ionized compounds do not enter the brain readily.