Prelim Biopharmaceutics Flashcards
Exam
effect of rate & extent of drug
absorption
Bioavailability
“what the body does to the drug”
-involves experimental and theoretical studies
-uses statistical methods
Pharmacokinetics
involves multidisciplinary approach to
individually optimize dosing strategies based on
patient disease state & patient specific
consideration
Clinical Pharmacokinetics or Therapeutic Drug
Monitoring (TDM
What are the Factors considered in TDM
Disease
Age
Gender
Genetic
Ethnic difference
pharmacokinetic differences of drugs in
various population groups
Population Pharmacokinetics
What are the monitoring parameters
Plasma drug concentration
pharmacodynamic endpoint
Common drugs monitored
Aminoglycosides
Anticonvulsants
Vancomycin
Digoxin
cancer chemotherapy
drugs with NTI
concentration of drug at the site of action
-biochemical effect of the drug
-physiologic effect of the drug
-“what the drug does to the body
Pharmacodynamic
refers to drug dose in body fluids
Drug exposure
direct measure of the pharmacological
effect of the drug
Drug response
application of pharmacokinetic principles
to the design, conduct and interpretation of
drug safety evaluation studies & in validating
dose-related exposure in animals
Toxicokinetic
study of adverse effects of drugs and toxic
substances in the body
Clinical Toxicology
Usually involved in toxicity cases:
Acetaminophen
Salicylates
Morphine
TCAs
most direct approach to assessing
pharmacokinetics of the drug in the body.
Blood plasma
devoid proteins
from filtered plasma
Unbound drug concentration
with proteins
from unfiltered plasma
Total plasma drug concentration
time required for a drug to reach
MEC
Onset time
difference between
the onset time & time for the drug to decline
back to MEC.
Duration of drug action
concentration between MEC and MTC; ratio
between toxic and therapeutic dose.
Therapeutic window/Therapeutic index
maximum drug
concentration
Peak plasma level
time of maximum
drug level.
Time for peak plasma level-
amount of drug
absorbed systematically; measure of the amount
of drug in the body
Area under the curve (AUC)
to ascertain if the drug
reached the tissues & reach the
proper concentration within the
tissue
Drug concentration in
tissues
drugs that are bound to
plasma protein are inactive drugs
Plasma protein binding
(PPB)
indirect method to ascertain
bioavailability of a drug
Drug concentration in urine and feces
reflect drug that has not been absorbed or expelled by biliary secretion
after systemic absorption.
Feces
approximates free drug level; secondary
indicator
Drug concentration in saliva
application of science to personal injury,
murder and other legal proceedings
-used in investigation
-concerned with medico-legal aspects of harmful effects of
chemicals on humans and animals
Forensic drug measurements
Best indicator:
plasma, urine, feces
-alter normal physiologic function or process
-interaction of drug molecules and cellular components (receptor) alter the functions
of the latter.
Functional Modifiers
Supplements existing endogenous substances that are deficient or lacking
Replenishers
Agents used to determine the presence or absence of a condition or disease.
Diagnostic Agents
Used to kill or inhibit growth of cells considered as foreign to the body
Chemotherapeutic agents
a molecule that binds to the receptor
LIGAND
a drug that binds to (affinity) and activates receptor
(intrinsic activity)
Agonist
a drug that produces 100% of the maximum
possible biologic response.
Full agonist
-binds to or block receptors (affinity only)
-prevents binding of agonist
-opposite effect of agonist
Antagonist
binds
reversibly to the same
active site of an enzyme
as an agonist; can be
overcome by increasing
the concentration of the
agonist. Ex: Enzyme
agonist
Competitive
antagonist
binds
irreversibly to the
different active site
of an enzyme as an
agonist; cannot be
overcome by
increasing the
concentration of the
agonist.
Non-competitive
antagonist
a drug that binds to a different receptor, producing an effect
opposite to that produced by the drug it is antagonizing
Physiologic Antagonist
a drug that interacts directly with the drug being
antagonized to remove it or to prevent it from reaching its
target (direct effect)
Chemical Antagonist
macromolecule typically made of proteins that interacts
with endogenous ligand or drug to mediate an effect.
RECEPTOR
is caused by continuous prolonged exposure of receptors to drugs that discrupt the homeostatic
equilibrium; due to altered levels of receptors.
Down Regulation
-result of down regulation; effect of subsequent exposure of the receptor to the same concentration
of the drug is reduced.
-Increased concentration of the drug is required to produce the same effect as the initial
concentration.
Desensitization
-occurs when target cells are subject to long term exposure to receptor antagonists followed by
abrupt cessation of administration of the drug.
-Up-regulation through new synthesis of new receptors
Hyperactivity/supersensitivity
-graph of response versus the logarithm of the dose yields
the efficacy (Emax) and potency (ED50).
GRADED-DOSE-RESPONSIVE CURVE
measured by its maximum effect.
Efficacy
related to the amount of drug necessary to cause
an effect
-related in the ED50 or the dose at 50% of the Emax
-The smaller the ED50, the greater the potency, the greater
the potency of the drug.
Potency
-graph of the number of patients that responds by a
specified dose.
-median effective (ED50), median toxic (TD50), median
lethal dose (LD50) can be obtained.
QUANTAL DOSE-RESPONSIVE CURVE
-The pharmacological effects depends on the percentage o f the receptors occupied
drug must have affinity to receptor.
-If all receptors occupied = maximum effect
.Hypothesis of Clark
-The drug molecule must “fit into a receptor” like a “key fits into a lock”
Lock and key theory
Postulates a complementary relationship between the drug molecule and its active site.
-Provides for mutual conformational changes between the drug and its receptor.
Induced-fit theory
-Occupational theory of response.
-Postulates that for a structurally specific drug, the intensity of the
pharmacological effect is directly proportional to the number of
receptors occupied by the drug.
-affinity + intrinsic activity or efficacy
-effectiveness lasts as long as the receptors are occupied
Hypothesis of Ariens and Stephenson
-Effectiveness = occupation + proper stimulus
Hypothesis of Paton (Rate theory)
When two drugs with the same effect are given together,
resulting in a drug effect that is equal in magnitude to the
sum of the individual effects of the 2 drugs.
Addition (1+1=2)
- Alcohol + Barbiturates: ↑ seddation
- Alcohol + Antihistamines: ↑ sedation
- Alcohol + CNS depressants: ↑ sedation
- Alcohol + Chloral hydrate: ↑ sedation
- Alcohol + Chlorpropramide: ↑ hypoglycemic effects
- Flecainide + Verapamil: ↑ negative inotropic and
chronotropic effects
Examples of Addition
When 2 drugs with the same effect are given together,
producing a drug effect that is greater in magnitude than
the sum of the individual effects of the 2 drugs.
Synergism (1+1=3)
Sulfamethoxazole + Trimethoprim (↑ bactericidal effect)
Example of Synergism
-Occurs when one drug, lacking an effect of its own,
increases the effect of another drug that is active.
Potentiation (1+0=2)
Amoxicillin + Clavulanic acid: ↑ Amoxicillin’s antibiotic
effect
* Ampicillin + Sulbactam: ↑ Ampicillin’s antibiotic effect
* Piperacillin + Tazobactam: ↑ Piperacillin’s antibiotic effect
* Levodopa + Carbidopa: ↑ Levodopa’s effect
Examples of Potentiation
Drug inhibits the effect of the other
Antagonism (1+1=0)
- Phenoxybenzamine + Catecholamines: management of
pheocromocytoma - Warfarin + Vitamin K: antidote for Warfarin toxicity
- Opioids + Naloxone: antidote for Opioid toxicity
- Benzodiazepine + Flumazenil: antidote for
Benzodiazepine toxicity - Atropine + Physostigmine: antidote for Atropine toxicity
- Procaine + Sulfonamides: antagonism of Sulfonamide’s
antibacterial activity - Heparin + Protamine SO4: antidote for Heparin toxicity
Examples of Antagonism
mathematical terms used to describe quantitative
relationship relationship concisely
Model
practical, but not very useful in explaining the mechanism
of the actual process by which the drug is absorbed,
distributed & eliminated in the body
Empirical Model
Physiologically-based model (Flow model)
where there is blood, there is drug
a very simple and useful tool in pharmacokinetics.
Compartmentally-based model
-overly simplistic view of drug disposition in the human body,
a drug’s pharmacokinetic properties can frequently be
described using a fluid-filled tank model
specific, involves drug carriers
Multicompartment model
-most common compartment model
-the total amount of drug in the body is simply the sum of
drug present in the central (plasma) compartment plus
the drug present in the tissue compartment.
Mamillary model
consists of one or more compartments around a central
compartment like satellites
Catenary model
