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79 Cards in this Set

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Categor of matter characterized by submicroscopic size rather than by type of substance.
Colloid
Biodegradable polymer spheres as carriers for drug implants (SC or IM) small enough for injection by syringe.
Gradually degrades to gradually release incorporated drug.
Microspheres
What are some uses of Microspheres?
1. Injectable carrier to by-pass degradation by the oral route-proteins, peptides, nucleotide.
2. Extended duration of action (months)
3. Extends duration for cpds with short metabolic half-life.
4. Localizing targetting possibilities
System of finely divided solid particles or liquid droplets dispersed in a continuous gas medium.
Aerosol
What are some advantages of aerosols?
1. Rapid onset of action
2. Avoids degradation in the GI tract.
3. Dose titration for individual needs
4. Greater bioavailability
What are some disadvantages of aerosols?
1. Drug could be irritating to skin or pulmonary epithelium
2. Administration difficulties
What is a problem during administration of aerosols?
80% of aerosol gets deposited in the GI tract.
1. incorrect use
2. Upper airway bronci deposition removed through mucous
If London Dispersion and Van der Waals forces have random movement, how can there be a net movement among particles?
Diffusion still occurs and there is net movement from areas of high concentration to low concentration.
Submicroscopic vesicles composed of a phospholipid bilayer that are capable of encapsulating a drug.
Liposomes
What are some uses of liposomes?
1. Extend duration of drug.
2. Carriers for localizing drug to site of action
3. Delivery of protein: protect from degradation
4. Vector for transfer of DNA: gene therapy
What are some disadvantages of liposomes?
1. Protein interactions - decrease effectiveness, possible immune reactions
2. Somewhat "leaky"
3. Phagocytic cells clear these out of circulation within hours (RES)
Lipophilic core used to "solubilize" oil soluble drugs into water. Produce clear solution containing "dissolved" oil soluble drug.
Not subject to usual separation problems in disperse systems.
Can also be injected IV (not routine though)
Micelles
What are some common drugs used in micelles?
1. Vitamin K for life threathening anticoagulant overdose.
2. Oral children's vitamin drops.
What is a potential problem for micelle structure?
Structure is reversible and unwanted drug release can occur.
What are reverse micelles?
Micelle core from the polar groups with water. Lipophilic parts extend into external oil solution, for solubilizing water soluble cpds into oil.
What are some basic uses of biotechnology?
1. Produce exact molecules for biological response as drugs.
2. Identification of specific molecules or portions of molecules.
3. Genetic materials for research and therapeutics.
What are the 4 phases of clinical trials in drug development?
Phase I: Test small number of healthy volunteers for drug safety
Phase II: test larger population for effectiveness of drug.
Phase III: Test very large population for continued drug effectiveness and side effects
Phase IV: additional post marketing testing required by FDA. Possible recall
What are some problems with orrally administered Protein Drugs?
1. Chemical and enzyme degradation
2. Poor absorption of high MW cpds.
3. Protective polysaccarchide layer of epithelial cells minimizes close approach of large molecules.
4. First pass effect - metabolized in liver before entering systemic circulation
What is recombinant DNA?
DNA produced by joining pieces of DNA from different sources. It is inserted into a cell to induce cellular synthesis of a specific therapeutic protein.
Immune system derived proteins designed to recognize specific epitopes on an antigen. Produced from hybridoma cells which are fusions of a B lymphocyte and a cancer cell to continuously generate MAb.
Monoclonal Antibodies (MAb)
What are the steps in MAb production?
1. collect activated B cells
2. fuse with malignant myeloma cells
3. individual hybridoma cells cloned
4. Each clone expresses MAb with specificity for single epitope
How do MAb's work?
They bind to the antigen to block adverse biological processes and produce a therapeutic resonse.
What are radioisotopes used for?
A radioisotope is attached to a MAb that acts as a carrier. Then the radioisotopes are delivered to target tissue for imaging and detection, diagnosis and treatment evaluation, or treatment.
What are the major chemical degradation pathways in proteins?
1. Proteolysis
2. Deamination
3. Denaturation
4. adsorption
5. aggregation
6. precipitation
What are some conditions that influence proteolysis?
1. incr temp
2. pH extremes
3. adjacent residues
4. manufacture, transport, storage, admixtures
What are some conditions that increase deamination?
1. pH
2. temp
3. ionic strength increase
What are some causes and risks of denaturation?
1. temp about 40C
2. organic solvents
3. pH extremes
4. high ionic strength
5. manufacture, transport, storage, formulation, admixtures
Adsorption at surfaces causes proteins to denature somewhat...What are some causes of adsorption?
1. Foam bubbles - limit shaking, try to swirl
2. Type of material of container - protein adsorbs to plastic container sides and denatures
After partial denaturation, aqueous lipophilic residues have the tendency to associate to form aggregates. Why is this bad?
If molecular aggregation becomes large enough, precipitation will occur. This can be lethal for IV formulations.
Genetic material that is administered to produce a therapeutic effect through the genetic processing of the cell.
Gene drugs
What is the goal of gene drugs?
Deliver DNA of a desired "drug" protein to target tissue, incorporate DNA into host cell genome in target tissue, then host cell expresses desired protein for therapeutic effect.
What is antisense oligonucleotides?
Block gene expression using an oligonucleotide strand that is complementary to a specific portion of genomic DNA or messenger RNA to prevent synthesis of a specific protein.
A test to ascertain the prescence, structure, purity, or concentration of a chemical. Results can be qualitative or quantitative.
Analysis
Typically both qualitative and quantitative in the sense that the analysis relies on the prescence of certain chemical features and the results provide the detectable amount or concentration of the desired species.
Assay
An experiment to estimate the potency of a substance by means of the reaction or response it elicits from biological material. It is frequently conducted to screen cmpds for biological activity.
Biological Assay
What is the general approach of a biological assay?
A Dilution Assay
What are 4 common uses of bioassays?
1. measurement of the pharmacological activity of new or chemically undefined substances.
2. Investigation of the function of endogenous mediators
3. Determination of the side-effect profile, including the degree of drug toxicity
4. Measurement of the concentration of known substances
What are some advantages of bioassays?
1. for macromolecules or other species that are initially difficult to define in terms of their chemical structure and three-dimensional conformations.
2. substances that do not have a chemical assay, such as insulin
3. effective for natural actives that are actually complex mixtures, such as digitalis, which is composed of several glycosides.
4. where purification is not possible or practical, such as vitamin D in irradiated oils
What are some disadvantages of bioassays?
1. Bioassays are typically less precise that chemical assays.
2. typically more time consuming than chemical assays
3. typically more expensive than chemical assays
4. results from bioassays do not translate well from species to species
What are the two types of Bioassays?
1. Radio-immunoAssay (RIA)
2. Enzyme-linked ImmunoSorbent Assay (ELISA)
What are the main drawbacks to RIA?
The expense and hazards in preparing and handling the radioactive antigen.
What are some advantages to ELISA assays?
1. The antigen does not need to be purified prior to use.
2. These assays are very specific for a certain antigen or antibody.
What is a qualification of MAb for use in ELISA?
MAb combinations must be qualified as "matched pairs", meaning that they can recognize separate epitopes on the antigen so they do not hinder each other's binding. There should be two separate antigenic determinants on the same antigen, each of which can bind its own antibody.
What are the 4 factors that ELISA is dependent on?
1. The number of molecules of the capture antibody that are bound to the solid phase.
2. The avidity (measure of binding strength) of the capture antibody for the antigen.
3. the avidity of the detection antibody for the antigen
4. The specific activity of the enzyme associated with the third antibody.
What are Physical assays best used for?
Physical assays are used to purify or isolate the analyte prior to detection and quantification.
What is a short description for how column chromatography separates materials?
A mobile phase and a stationary phase are used in a buret. Components with higher affinities for the column material than for the mobile phase will pass slowly through the column.
What are common materials used for as stationary phases in column chromatography?
Silica gel or magnesium silicate for hydrophilic effects.
Charcoal can be used because of its highly porous surface area.
What is the difference between normal phase and reverse phase chromatography?
When hydrophobic mobile phases pass through hydrophilic stationary phases, this is called normal phase chromatography. When hydrophilic mobile phases pass through hydrophobic stationary phases, it is reversed phase chromatography.
(most chromatography is reversed chromatography)
The more polar functional group allows the analyte to interact more strongly with the polar stationary phase and therefore, the mobile phase is less likely to carry it through the column quickly.
True or False?
True
What are the different kinds of chromatography?
1. Column Chromatography
2. Thin layer chromatography
3. Paper chromatography
4. HPLC
5. Gas Chromatography
6. Gel Chromatography
7. Size exclusion Chromatography
8. Ion exchange chromatography
Is thin layer chromatography qualitative or quntitative?
It is strictly qualitative.
What is the stationary phase made up of in size exclusion chromatography?
The stationary phase consists of polymers that have been crosslinked to produce, within each particle, a network with numerous pores or channels of a consistent diameter. Molecules that are too large to enter the pores are rapidly eluted. Molecules of smaller diamter go in and out of the pores.
What is the primary use of size exclusion chromatography?
Separation of small molecules from macromolecules.
What are two methods for detection of drug molecules?
1. UV/visible light absorption
2. Fluorescence spectroscopy
What qualifications should a drug have to be a controlled release dosage form?
1. Drug dissolves slowly
2. Drug is absorbed quickly but then is eliminated from the blood slowly
Can already achieve long action with these two
What might define why a drug is suitable for a controlled release product?
1. Half-life - drugs with short biological half-lives make good candidates
2. Drugs with narrow therapeutic windows are good candidates since exceeding the maximum safe concentration is undesireable
3. Drugs with good solubility
4. Stability over wide range of pH and enzymes in GI tract.
What might define why a drug is NOT suitable for a controlled release product?
1. If the dose is too large, the reservoir would need to be large.
2. A drug with a narrow absorption window in the GI tract.
3. Drugs metabolized by the liver during the process of absorption from the GI tract are not good candidates
What is this controlled release form?
One dose is released, and then a second dose is released later. Each dose is released rapidly.
Repeat Action
What controlled release form is this?
Immediate release of a portion of the dose, and, later more drug is released slowly. A longer than usual pharmacological effect of the drug occurs.
Prolonged/Extended Action
Sustained Release
This type of formulation releases the drug at a slow, approximately constant rate which is intended to maintain constant or almost constant blood levels.
What are the advantages of controlled released products?
1. fewer doses - more convenient
2. patient compliance increases
3. blood level fluctuations are managed
4. In some cases, it might be possible to reduce the total amount of drug administered.
5. Incidence of side effects might be reduced by the MSC not being reached.
What are the disadvantages of controlled release products?
1. They don't permit abrupt termination of therapy.
2. Limited dose choices available
3. Controlled release drugs are made for the AVERAGE patient. Should a patient with different pharmacokinetic makeup use these drugs, they might not be served adequately.
4. More expensive than immediate release
5. Dose dumping can occur
6. Possible lower bioavailability
What are the two classifications of controlled release medications?
1. Coated pellets in hard gelatin capsules
2. "Complex" tablets for controlled release
What are some different coating agents used in coated pellets?
1. a wax
2. a fatty alcohol (stearyl alcohol)
3. an ester
4. enteric coating i.e. cellulose acetate phthalate
What are the 3 ways a drug can release from the coated pellet?
1. Slow diffusion out of the coat.
2. The coat erodes
3. In-flux causes pressure build up to rupture segment of pellet
What are the 3 types of matrix systems?
1. fatty or waxy hydrophobic matrix
2. hyrdophillic matrix
3. plastic matrix
What is a major problem with Hydrophobic matrixes?
Incomplete drug release occurs as the drug is completely surrounded by matrix. PVP is an example of a hydrophilic agent that assists in the entry of fluid to promote drug release.
How are tablets with a plastic matrix formed?
The powdered drug and plastic are compressed and the plastic particles fuse to form the matrix.
How do hydrophillic matrix forms work?
The hydrophillic matrix is made out of a cellulose polymer which hydrate and swell to form a gel. The gell is a barrier which slows the entry of fluid into the tablet and slows the release of the drug from the tablet.
What are the advantages of hydrophillic matrix forms over the other matrixes?
1. They essentially release 100% of drug.
2. The tablet is not apparent in the stool
3. Hydrophobic and plastic matrixes require an excess drug since a portion of the drug will never by completely released.
Which types of drug delivery systems avoid first-pass metabolism?
1. Transdermal
2. Transmucosal
3. Intranasal/Respiratory
What are the factors that can influence gastric emptying?
1. type of meal and its caloric content
2. hydrogen ion concentration
3. physical state of meal contents
4. volume of meal
5. viscosity of meal
6. osmolarity of contents
7. coadministered drugs
8. body posture
9. exercise history
10. emotional state
11. disease state
What are the factors that can influence the performance of an Oral Controlled release product?
1. GI motility and transit time
2. pH in the different regions of the GI tract
3. GI secretions
4. blood flow at the GI wall
5. luminal contents
6. luminal metabolism
7. membrane permeability
8. site specific absorption
Describe the membrane diffusion controlled system.
This is available in two fashions.
The entire insoluble membrane covering the dosage form can be the barrier through which the drug must diffuse after fluid has permeated the membrane, entered the dosage form and dissolved the drug.
Also, the membrane can be made up of a mixture of soluble and insoluble materials. When the soluble components dissolve, pores allow dissolved drug to exit the dosage form.
What are potential advantages of transderman drug delivery?
1. Since high concentrations are not found in plasam, side effects are reduced
2. Drug concentrations at or above the MEC can be maintained
3. Drug is not lost by first-pass metabolism or by metabolic processes, so less drug is needed to deliver a dose comparable to oral delivery.
Qualifications of a potential transdermal candidate???
1. Fairly potent drug
2. high first pass effect
3. short plasma half-life
4. MW less than 1000
5. low melting point
6. Oil/water partition less than 1
7. no skin irritation
How does penetration enhancement such as iontophoresis assist in drug delivery?
Iontophoresis employs an electrical current to assist drug transport across the skin. Penetration enhancement is believed to be due to the electrical current causing water to move through the skin more easily and the water, carries the drug with it. This technique is useful in transporting larger drug molecules such as insulin.
What are the two means of control drug release employed in patches.
Membrane permeation and Matrix diffusion
What is the easiest way to control the dosing of a patch?
Adjust the patch square area.