Chapter 10 | Preclinical Studies Flashcards
An ideal drug is potent, efficacious, and specific
True
The data for pharmacodynamics, pharmacokinetics, and toxicity enable the dose and dosing regimen to be set for the clinical trials
True
The potency, efficacy, and safety of a drug depend on the chemical and structural specificity of drug-target interaction
True
Pharmacokinetics
pharma=medicine; kinetic movement/motion) the study of drug movements throughout the body
Pharmacodynamics:
(pharma=medicine; dynamics=change) refers to how a medicine changes the body
Pharmacokinetics are grouped into four categories:
absorption
distribution
metabolism
excretion
pharmacokinetic variables depend on the ability of a drug to cross plasma membranes
The Passage of Drugs Through Plasma Membranes
-Passive Diffusion
-Facilitated Diffusion
-Active Transport
-Pinocytosis
Passive Diffusion
the random movement of molecules in fluid
Facilitated Diffusion
from a region of high concentration to low concentration
Active Transport
requires energy to drive the transportation of drugs against the concentration gradient, from low to high
Pinocytosis
engulfing of fluids by a cell
Absorption
the process involving the movement of a substance from its site of administration, across body membranes, to circulating fluids
Factors that influence the absorption of medications:
- Drug formulation and dose
- Size of the drug molecule
- Surface area of the absorptive site
- Digestive motility or blood flow
- Lipid solubility
- Degree of ionization
- Acidity or alkalinity (pH)
- Interactions with food and other medications
Distribution
involves the transport of drugs throughout the body
Metabolism
also called biotransformation, is the process of chemically converting a drug to a form that is usually more easily removed from the body. It involves complex biochemical pathways and reactions that alter drugs, nutrients, vitamins, and minerals. The liver is the primary site of drug metabolism, although the kidneys and cells of the intestinal tract also have high metabolic rates.
Drug-drug interactions
- Addition: the action of drugs taken together as a total
- Synergism: the action of drugs resulting in a potentiated (more than total) effect
- Antagonism: drugs taken together with blocked or opposite effects
- Displacement: when drugs are taken together, one drug may shift another drug at a nonspecific protein binding site, thereby altering desired effect
Excretion of Medications
The rate at which medications are excreted determines the concentration of the drugs in the bloodstream and tissues. The concentration of drugs in the bloodstream determines their duration of action.
In an average-size person, approx 180L of blood is filtered by the kidneys each day.
Factors that affect drug excretion:
- Liver or kidney impairment
- Blood flow
- Degree of ionization
- Lipid solubility
- Drug-protein complexes
- Metabolic activity
- Acidity or alkalinity (pH)
- Respiratory, glandular, or biliary activity
Toxicology:
Toxicological studies show the functional and morphological effects of the drug. They are performed by determining the mode, site and degree of action, dose relationship, sex differences, latency, progression, and reversibility of these effects.
To determine toxicology: two studies: single dose and repeated dose.
The therapeutic response of most drugs is directly related to their level in the plasma.
True
The plasma drug concentration between the minimum effective concentration and the toxic concentration is called the therapeutic range of the drug.
single dose
purposes: the determination of repeated doses, identification of organs subjected to toxicity, and provision of data for starting doses in human clinical trials
repeated dose
to evaluate the longer-term effects of the drug in animals
carcinogenicity
carcinogenicity studies are carried out to identify the tumor-causing potential of the drug
genotoxicity
genotoxicity studies determine if the drug compound can induce mutations of genes
Onset of drug action represents the amount of time it takes to produce a therapeutic effect after drug administration.
True
Peak plasma level occurs when the medication has reached its highest concentration in the bloodstream.
True
Duration of drug action is the amount of time it takes for a drug to maintain its desired effect until termination of action.
True
Variables that can affect the duration of drug action:
- Drug concentration
- Dosage
- Route of drug administration
- Drug food interactions
- Drug supplement interactions
- Drug herbal interactions
- Drug drug interactions
The most common description of a drugs duration of action is its plasma half life, defined as the length of time required for the plasma concentration of a medication to decrease by one-half after administration.
The level of drug in the plasma is maintained continuously within the therapeutic range
plateau
The plateau may be reached faster by administration of loading doses followed by regular maintenance doses
True
Two fundamental ways to compare medications within therapeutic and pharmacologic classes:
- Potency
- Efficacy: magnitude of maximal response that can be produced from a particular drug
From a pharmacotherapeutic perspective, efficacy is almost always more important than potency
A useful way to visualize the concept of potency is by examining dose-response curves
True
Cellular Receptors and Drug Action:
Drugs act by modulating or changing existing physiological and biochemical processes. To exert such changes requires that drugs interact with specific molevules and chemicals normally found in the body. A cellular macromolecule to which a medication binds in order to initiate its effects is called a receptor.
The vast majority are proteins.
The aim of preclinical pharmacological studies is to obtain data on the safety and effectiveness of the lead compound.
True
Toxicity information in preclinical studies helps provide confidence about a drug’s safety.
True
Pharmacological studies using animals are regulated under Good Laboratory Practice.
True
Why do drugs administered to patients only contain APIs?
They don’t
A drug’s vesicles affect it’s ability to permeate membranes.
True
Through which barriers can lipid-soluble drugs usually pass?
cell membranes
How are weak acid drugs generally absorbed by the stomach?
More quickly than weak basic drugs.
Which route of administration does not completely bypass the liver?
rectal administration
Why are intravenous drug dosages easier to control than drugs administered transdermally?
The entire dose is available in the bloodstream to be distributed to the target site.
A drug’s lipid-solubility, polarity, and the __________ ___________ of the drug’s target tissue affect it’s distribution.
vascular nature
What medical term means “to apply the drug on the surface of the skin”?
transdermal
