final Flashcards
What are the assumptions made when using a 1 compartment model?
Body is a single uniform compartment
Instantaneous administration of entire dose
Rapid distribution throughout the body
Drug elimination starts immediately upon administration
Well stirred model
What is clearance?
Volume of plasma fluid cleared of drug per unit of time
What are the units for Clearance?
L/h
mL/min
What is k?
Elimination rate constant
Proportion of drug elimination and the amount of drug in the body
Hepatic or renal
What is t1/2?
Half life
Time it takes for a drug concentration to decrease by 50%
What is volume of distribution?
Volume of the single compartment that the dose was administered into but is not an actual volume just theorhetical
What are the units for AUC?
mg*h
How do you get Co?
Dose/Vd
How do you get k in one compartment model?
slope/2.3
How do you get clearance in one compartment model?
Vdk
How do you get t1/2 in one compartment model?
0.693/k
How do you get AUC in one compartment model?
A(n-1)-A(n)/2 *(tn-tn-1)
What are teh units of k?
1/h
What are the units of clearance?
L/h
How do you get concentration in one compartment model?
Coe^-kt
What is k independent of?
Concentration or amount of drug at any given time
What is Cl not dependent of?
The amount or concentration of the drug
What is delayed release?
A dosage form that releases a small amount of drug at a time other than immediate release after administration
An initial portion may be released after administration
What is delayed release?
A dosage form that releases a small amount of drug at a time other than immediate release after administration
An initial portion may be released after administration
What is the common form of pill for delayed release?
Enteric coated tablets
What is extended release?
Dosage form that allows at least twofold reduction in dosage frequency as compared to that drug presented as immediate release dosage form
What does extended release dosage form prevent?
Prevents very rapid absorption of drug
Where do extended release dosage forms release at?
At a predetermined rate at a specific site
What are microcrystalline cellulose spheres used for?
Increase durability of the slow release coverings
What is the multitablet system?
Many tiny tablets in a capsule
Each tablet can have different release characteristics
What are teh 5 advandages of ER formulation?
Less fluctuation in drug blood levels
Decrease in frequency of dosing
Enhance convenience and compliance
Reduction in adverse effects
Reduction in overall health care costs
What are the 3 disadvantages of ER formulations?
Dose dumping
Less flexible in dose adjustments
Less possiblity for high dose
How do ER formulations cause less fluctuations in drug plasma levels?
Eliminates the peaks and valleys in concentrations
How do ER formulations decrease the frequency in dosing?
Deliver more than a single dose
How do ER formulations enhance convenience and compliance?
Less frequency
Increased day and night time dosing
How do ER formulations decrease side effects?
Fewer peak blood levels so less toxicity
How do ER formulations decrease health care costs overall?
Enhanced therapeutic benefit
Fewer side effects
Decrease time to dispense and administor and monitor patient
What is dose dumping?
When the release of more than intended fraction of the drug may increase toxicity
The ER formulations cannot be crushed or chewed due to this
How would you get ER formulations out of the body?
Bowel evacuation and gastric lavage
very intrusive
Why cant you have high dosed ER formulations?
They would be too big to swallow
What is contained in gum type matrix systems?
Methylcellulose
Veegum
Alginic acid
Tragacanth
Are gum type matrices biodegradable?
Yes
What do gum type matrices do?
alter degredation based on hydration control, pH dependency, thickness, and viscosity
What kind of drugs can be in polymeric matrix?
biodegradable or non
Hydrophobic or philic
What is cautioned when using non biodegradable polymeric matrices?
GI decreased motility
What are polymeric matrices used for?
Implants
What does ionic exchange resin do?
Upon exposure in the GI tract, cations in the gut, such as K and Na, will displace drug from resin and release the drug
What does the osmotic pump do?
Push pull system
Water from GI tract enters the tablet to increase pressure in osmotic layer and pushes against the active drug layer and releases drug from laser filled orifice
How do you alter or affect release rate of drug in osmotic pumps?
Alter the size of the orifice
How is the drug delivery for osmotic pumps?
Usually constant drug delivery as long as the osmotic gradient stays constant
What are the clinical considerations for ER formulations?
Advise of frequency and dose
Not use interchably with IR
Advise that modified released drugs cannot be crushed or chewed
Empty shells can be in poop for osmotic devices
What are the 5 factors affecting percutaneous absorption?
Drug concentration per unit Surface area
Large the area and the longer the contact time the more drug absorbed
400kDa-100kDa is best for adequate liquid and aqueous solubiltiy
Patch applied to the skin
Hydration of skin
What are the 7 advantages of transdermal route?
- Bypass the GI absorption and 1st pass metabolism
- Substitute for oral when unsuitable
- Non invasive
- Extended therapy increases compliance
- Short half life drugs are extended through resovior
- Therapy is terminated when removed
- Easily identified during emergencies
What are the disadvantages of Transdermal route?
Only relatively potent drugs are suitable (limits of drug entry imposed by skin impermeability)
Difficult if they have skin conditions
What are the main patient counseling tips for Transdermal routes?
Percutaneous absorption may vary with site of location (use location in instructions)
Must rotate locations to allow for normal permeability
Transdermal patches should be applied to clean, hairless, dry skin (do not shave skin)
Patches should be worn for entire period of time and should always be removed
What is pharmaceutical biotechnology?
Technique that uses living organisms, using microorganisms in production or modification of products
What does recombinant DNA do?
Use rDNA in non human cells to manufacture proteins identical to those produced in human cells
What are teh 4 suffixes for monoclonal antibodies?
-omab
-ximab
-zumab
-umab/mumab
What does -omab indicate?
Murine - the earliest type of Mab derived from mice
What does -ximab indicate?
Indicates chimerics which has human constant region and murine variable region for MAB
What does -zumab indicate?
Humanized Mab 90% human and 10% murine in variable region
What does -umab/-mumab indicate?
Mabs created in mice murine genes are inactivated and replaced with human sequence
What is PCR?
Polymerase chain reaction
Biotech process where there is substantial amplification of a target gene (nucleic acid sequence)
What is gene therapy?
Process in which exogenous genetic material is transferred to the somatic cells to correct an inherited or acquired gene defect
what is ocusert?
A thin, flexible wafer placed under the eyelid to provide a week’s worth of pilocarpine in the treatment of glaucoma
What is Lacrisert?
Rod shaped water soluble form of hydroxypropyl cellulose
Placed in inferior cul de sac of eye either once or twice a day for dry eyes
What do implants do?
Provide long acting continuous release of drug for months to years
How are implants administered?
Parenterally for systemic
Sub q for local
Specific sites
What is antisense tech?
Reverse genetics
Study of function of specific proteins and Intracellular expression
What do antisense drugs do?
Recognize and bind to the nucleotide sequence of specific mRNA molecules preventing the synthesis of unwanted proteins and destroying the sense molecules
What does peptide tech serve as?
Either protein receptor agonists or antagonists
Which method of biotech utilizes b cells to produce drug?
Monoclonal antibodies
What do long acting parenterals use?
Crystal or amorphous drug forms having prolonged dissolution characteristics
Slowly dissolving chemical complexes of drug entity
What do stealth liposomes do to avoid detection by the immune system?
Developed with PEG on the outside of membranes to avoid detection by the body’s immune system
What is diffusion?
Molecular transfer across relatively non porous media
What is Kd?
Distribution coefficient
What happens to aqueous solubility as LogP increases?
Aqueous solubility decreases
Are weak acids ionized or unionized in the stomach and upper duodenom?
Unionized
What happens when you increase the surface area of the membrane?
The amount of drug increases diffusing per unit of time
What happens to the amount of drug diffusing through the membrane when h is increased?
H is the thickness so da/dt decreases
What kind of transporters are OATS?
Influx
What is permeation?
Drug moves through membrane
What is partitioning?
Drug going into the lipid bilayer
What is trancellular diffusion dependent on?
lipophilicity, polarity, and Molecular weight
What is paracellular transport dependent on?
Size of molecule and gap
How do you get concentration at a certain time for two compartment model?
Ae^(-alphat) + Be^(-Betat)
How do you find AUC for Two compartment model?
A/alpha +B/beta
How do you find CLt?
V1*k10
How do you find CLd?
K12V1=k21V2
How do you find Co?
A+B or
Dose/V1
What are the three objectives of PK?
Describe the rate of movement/transfer of drug between compartments
Explain relationship of concentration of drug with time after drug dose
Predict the time course of drug in the body to keep it in therapeutic range
What are PK models used to describe?
Differential equations used to describe the rate of change in the drug concentration in the body
Wht is a paste?
Semisolid preparation with highly potent finely powdered solids in ointments
Occlusive
What are gels?
Thickened lotion (water based) with hydrophobic and hydrophilic bases
Good on hair
What are creams?
Emulsion of oil in water
Cooling agent
Emoliet
Not good on hair
What are ointments?
Greasy insoluble in water emulsifying agent
Avoid hair
Occlusive
What are lip balms?
Applied to lips without fingers
Prevent drying and preotect from environmental factors
What are suppositories?
Dosage form of various weights, sizes, and shapes for insertion into a body cavity
Local and systemic effects
How do you make ointments by incorporation methods?
Reduce particle size of drug and levigate it with mineral oil and put it into ointment base
Or you can put into a solvent then into the base
What ingredients are in lip balms?
Waxes for structure
Butters and oil for emolient and lube
Preservatives and antioxidants
What are in suppositories?
Diluents
Adsorbants
Lube
Preservatives
Coloring agents
What is Cocoa butter used for?
Suppository bases
Fatty base for supps
What are absorbents?
Absorb moisture from skin and local wounds and thereby maintain dry conditions to discourage bacterial growth.
What are astringents?
Arrest blood hemorrhage by coagulating blood. These agents help wounds and cuts heal quickly.
What are caustics?
Destroy skin at the applied site (corrosive). They are useful in the treatment of warts, keratoses, and hyperplastic tissues.
What are counter irratants?
Used to promote a secondary irritation that helps to counter an initial irritation.
What are demulcents?
Can alleviate irritation of mucous membranes or abraded tissues.
What are humectants?
Promotes retention of water on the surface of the skin.
What do keratolytics do?
Cause desquamation (peeling) of skin. These agents are useful in the treatment of
eczema, acne, etc.
What is levigation?
Is the incorporation of a small quantity of powder medication into a small amount of
liquid or ointment base to get a concentrated mixture for easy further dilution with more
ointment base.
What are moisturizers?
increase the water content of the outer layer of the skin,
What do emollients do?
help maintain a soft and smooth skin feel by preventing water loss by
evaporation.
What are occlusions?
Refers to skin covered directly or indirectly by impermeable films or substances such as diapers, tape, chambers, gloves, textiles garments, wound dressings, transdermal devices, etc.
What do protectives do?
Shield exposed skin surface and other membranes from harmful stimuli.
What do rubefacients do?
Increase the skin temperature by increasing the circulation at the surface.
What do stablizers do?
Include preservatives in liquid or aqueous-containing products to prevent microbial
growth; buffers to provide conducive environment to impart good stability where degradation occurs due to pH-related; and chelating agents are also used as stabilizers to prevent heavy metals from catalyzing degradation.
What is stability?
extent to which a product retains, within specified limits, and throughout its period of storage and use (i.e., its shelf-life) the same properties and characteristics that it possessed at the time of its manufacture or compounding
What happens during physical instability?
Changes in original physical properties of the product
What happens during microbiological instability?
Drug product grows signs of microbial growth such as mold
What happens during chemical instability?
When the integrity of chemical structure of the active ingredient is degraded?
What is therapeutic instability?
Chemical instability that causes a loss of efficacy or toxicity
are the sources of drug instability?
Water
Temperature
Light
Excipients
pH of environment
Oxygen
What kind of reactions does water cause for instability?
Hydrolysis
Isomerization
Polymerization
What kind of reactions are caused by temperature?
Hydrolysis
Oxidation
What reactions are caused by light?
Oxidation
Photolysis
What can excipents do to cause instability?
Increase water content
What can the pH of an environment do to a drug for instability?
Hydrolysis, oxidation, isomerization
