FOCUS ?'s Flashcards
(155 cards)
1
Q
What served an important purpose in early pharmacy?
A
Our instinct to survive
2
Q
What was the early evidence of drug use?
A
Cool water alleviated pain
Leaves from plants treat infected skin areas
Mud to close and heal wounds
3
Q
What was the trial and error approach that shaped early pharmacy?
A
Drug therapy
4
Q
Why did people become sick in early history?
A
Evil spirits
5
Q
What treated sickness in early history?*
A
- compassion of a god
- observance of ceremonies
- absence of evil spirits
- healing intent of the dispenser (bribe if you want to be healed properly)
6
Q
What were the failures and successes of the tribal apothecaries?
A
Failures: inactive agents, underdosing, overdosing, poisoning
Successes: coincidence, inconsequential effect of drug, placebo effect
7
Q
Who discovered biological acids?*
A
Karl Wilhelm Scheele
8
Q
Who isolated morphine from opium?*
A
Friedrich Serturner
9
Q
What did Joseph Caventou and Joseph Pelletier do?*
A
Combined their talents to isolate drugs from tree bark
10
Q
Why were the USP and NF created? What are they?*
A
Need for uniform standards to ensure quality
They are organized sets of monographs or books of standards (written in high degree of clarity and specificity)
11
Q
*What are the two major goals of pharmaceutical care for pharmacists?
A
prevent related morbidity (drug induced disease)
prevent drug related mortality (drug induced death)
12
Q
What are some factors necessary for being successful at pharmaceutical care?*
A
- current knowledge on drugs and drug therapy
- good information skills
- good communication skills
- caring
- socio- economics (business contacts and health)
- * health related quality of life most important
13
Q
What was the goal of the food and drug act of 1906?
A
Drugs must comply with standards for strength, purity, and quality
14
Q
What did the Sherley amendment say?*
A
No more false claims
Declared products misbranded
(1912 manufacturers claims of therapeutic benefit)
15
Q
What caused the federal food, drug and cosmetic act of 1938 to come about? What did the act provide?*
A
Sulfanilamide tragedy
Required drugs be tested for SAFETY, required tests to be submitted to the gov’t via NDA, mandated drugs be labeled with adequate directions, authorized FDA to conduct unannounced inspections
16
Q
*Who played a key role in the thalidomide tragedy in the U.S.??
A
Dr. Frances Kelsey - recognized drug was acting differently in people than animals
17
Q
*What act did the thalidomide tragedy result in?
What did the act do?
A
Kefauver Harris Amendments of 1962 which required drug needed to be safe AND efficacious before approval
Drugs from 1906- 1938 grandfathered in
18
Q
What did the Durham Humphrey act do?
A
No refills w/o valid prescription
OTC vs prescription
Refilling necessary only if authorized in prescription
19
Q
The comprehensive drug abuse prevention and control act of 1970 further supported the Durham Humphrey act by doing what?
A
Establishing 5 schedules for drug classification for those that were more likely to be abused
20
Q
Differentiate between schedules I - IV
A
I - high potential (marijauna)
II - high potential (codeine, oxycodone, fentanyl)
III - moderate potential (vicodin, suboxone)
IV - low potential (diazepam, clonazepam)
V - low potential (phenergan with codeine)
21
Q
*What are the pregnancy categories? Worst to best?
A
Category A: studies failed to demonstrate risk to fetus
Category B
Category C
Category D
Category X: animal studies of humans demonstrated fetal abnormalities - serious risk
22
Q
*What are black box warnings?
A
FDAs strongest labeling requirements used for high risk meds.
- stresses importance of close patient monitoring, no reminder ads allowed
23
Q
*What did the drug listing act of 1972 create? What are the components?
A
The NDC - permanent registration code to identify manufacturer or distributor. (10-11 digits)
The first 4 digits are the labeler code (identify manufacturer or distributor)
The next 3-4 digits are the product code (identify drug formulation)
The last 3-2 are the package code (size and type)
24
Q
what did the drug price competition and patent terms restoration act say?
A
any originally approved new drug can be filed through ANDA, bypassing animal and human study testing
Speed up time to market generics
25
* What did the 1987 prescription drug marketing act do?
| Dingell bill
- prohibit reimportation of drugs, prohibit sales, trading and purchasing of drugs
* Protect supply of prescription agents and prevent repackaged and mislabeled drugs from entering market
26
*Dietary supplement health and education of 1994 said what?
The dietary supplement labels needed to say "This product is not intended to diagnose, treat, cure or prevent any disease"
body function influences were ok
27
What did FDAMA do? (FDA modernization act)
- expand patient's access to investigational treatment for serious life - threatening diseases
- accelerate approval of new drugs
- pediatric use of investigational drugs now made possible
28
*What are the classes of drug product recall?
Class I: exposure will cause serious adverse health consequences, or even death
Class II: exposure will cause temporary or medically reversible adverse health consequences
Class III: exposure not likely to result in adverse health effects
29
Why was the synthesis of antipyrene important?
It was done in a test tube which changed the way drugs were made from this point forward.
30
*What did Alexander Flemming do?
Discover penicillin
31
*What did James- Watson Crick do?
Solve DNA structure
32
```
Where did the following come from? What is the issue with plant poisons?
Morphine
Quinine
Digitalis
Belladonna
```
```
Batch to batch consistency is a problem with plants.
Morphine - opium poppy
Quinine - cinchona bark
Digitalis - foxglove
Belladonna - deadly night shade
```
33
What does vinca rosea treat?
Melanoma
34
What tree is involved with creating 3/4 of treatment for a cancer patient?
Pacific yew (taxus brevifolia)
35
*Who performs services involved with drug discovery?
Chemists
Pharmacologists
Toxicologists
Formulation developers (pharmaceuticals)
36
What is the purpose of drug development? Who usually does it and where?
Drug development is used to provide superior dosage forms and a way of delivering effective drugs throughout the body.
Mostly done by scientists with a phD at a pharmaceutical company or school of pharmacy
37
What are the properties investigated in early formulation studies?
Drug solubility, partition coefficient, dissolution rate, physical form, stability
38
*Drug solubility
less than 10mg/ml is considered poorly soluble
39
* Partition coefficient
preference for lipid vs. aqueous phase
40
*Dissolution rate
speed at which a drug substance dissolves in a medium (at physiological temperatures)
41
*Physical form
crystal vs amorphous vs powder will alter rate and extent of absorption
42
*Stability
retention of drug substances within dosage forms
43
What are characteristics of the "goal drug"?
Can produce a desired effect
Can be administered @ the most desirable route (orally)
Can be administered @ minimal dosage and frequency
After exerting necessary effect should be eliminated from the body efficiently and w/o negative side effects
44
What is a "lead compound"?
Compound that is the closes agent to the goal drug possessing the fundamental desired biologic of pharmacologic activity.
45
*Pharmacology (drug researcher)
Determines biologic activity and mechanism of drug action in vivo and in vitro
46
*Drug metabolism (drug researcher)
determines the absorption, distribution, metabolism and elimination (ADME)
47
*Toxicology (drug researcher)
deals with adverse and undesirable effects of the drug
| - what is the maximum tolerated dose? lethal dose?
48
What is the main reason for drug related side effects?
Non specific delivery to intended targets
49
What is CDER, what does it do?
Center for drug and evaluation research
- - assess benefit to risk relationship (is a particular drug safe and effective enough?)
- make drugs available to the public sooner
- provide clear standards for drug evaluation
- high priority drugs (significant advantage over current therapies)
50
Investigational New Drug Application is used for what?
Once a drug has been developed, before it can be tested in humans it must be filed with the FDA via an IND application
- protects rights and safety of subjects and makes certain the research objectives can be achieved with the investigational plan
*Main purpose was to provide the FDA with sufficient info to make a meaningful eval of a new drug
51
*What happens in the Phase I clinical trials?
drug should show promise as a useful drug
- What is the safe does in 20-100 patients?
- Usually less than one year
- to determine toxicology, metabolism and pharmacologic actions
- patients tested don't need to have the disease
52
What is the application in phase I clinical trials?
The plan for the study, chemical structure, animal testing results, manufacturing info
53
CTM for phase one studies?
- biopharmaceutical properties
- practical considerations (supply of bulk, time it takes to prepare bulk stock)
Advantages and disadvantages of extemporaneous formulations
54
What are advantages and disadvantages of extemporaneous formulations?
+ : short development time, minimal drug substance requirements (few hundred grams), minimal formulation development, minimal analytical work
- : unpleasant taste, patient compliance issue, dosing inconvenience for multiple dose studies
55
*Phase II clinical trials
To determine compound's effectiveness
- drug tested in ~100-300 people
- patients have the disease
- extensive pharmacologic, toxicologoical and pharmacological testing
- many clinical agents don't make it to this point
56
CTM for phase II
- capsules or tablets typically necessary
- generally same form used as in phase I EXCEPT when required dosage strength is not supported, when medium large scale is not feasible
- can introduce a new formulation closer to desired commercial dosage form
- covers a large range dose so # of strengths may be large. - dose range determined by pharmaceutical scientists, pharmacokineticists, and clinical study and clinical supply coordinators
57
In CTM II what are limitations of high and low dose strengths?
High: dissolution and processability
Low: content uniformity and stability issues
58
*Phase III Clinical Trials
To demonstrate long-term safety and efficacy of drug product; to discover drug's efficacy standards
- 1000- 3000 patients in many centers
- carried out over several years
- how good is the drug in treating the disease or condition?
- short term side effects and risks in patients with impaired health?
- used in several randomized, controlled studies in clinical research facilities, veterans administration, university teaching hospitals
59
CTM for phase III
- stability data needed on at least 3 primary batches of drug products
- stability testing must cover minimum period of 12 months typically @ 25C
- changes in dosage strengths and manufacturability of CTM may be necessary to achieve specific goals
- same formulation, processing and packaging procedures as with commercial product is recommended
60
How long can the development of a drug take?
up to 15 years, most of the time spent in clinical trials
61
*Usual adult dose
starting dose for a patient
62
* Usual dosage range
safety dose range for administering drug product
63
* dosage regimen
schedule of dosage
64
* maintenance doses
maintain clinically relevant drug levels in blood
65
** prophylactic dose
administered to prevent patients from contracting the disesase
66
** therapeutic dose
administered once disease has been contracted
67
* minimum effective dose (MEC)
the minimum dose required to get a desired effect
68
* minimum toxic concentration (MTC)
administering drugs above this level will produce dose related toxicities
69
*median effective dose (MED)
this dose will produce a desired intensity of a drug effect in 50% of the individuals tested
70
metronomic scheduling
gives epithelial cells constant exposure to the drug - effective because epithelial cells are constantly circulating and the drug does not need to go through the cells *better than MEC
71
What are therapeutic, toxic, and lethal doses?
Therapeutic is the level at which the drug is properly functioning - this dose can be relatively close to the toxic dose or very far, the lethal dose is deadly, may be very slight range between the three
72
age
neonatal pediatric and geriatric patients
73
body weight
mg (of drug)/ per kg of body weight
74
BSA
1mg/M^2 BSA - nomogram
75
sex
men and women have different responses to certain drugs due to biochemical and physiologic factors
76
pathologic state
disease state
77
times of administration
before or after meals
78
tolerance
ability to endure influence of drug
79
**How do you use a nomogram to solve this question: An adult measuring 67 inches in height and weighing 132 pounds would have a BSA of approximately how many square meters?
Make sure you look at the right age group (adult or children) and find the correct height and weight , use a ruler to connect the two points and find the point where the line touches the surface area.
80
What is the purpose for good cGMPs?
set minimum standards for product quality
81
cGMPs for finished pharmaceuticals
batch ->validation
| see pharmaceutics terms cards
82
* Batch
specific quantity of drug of uniform specified quality produced according to a single manufacturing order during the same cycle of manufacture
83
* batchwise control
use of validated in- process sampling and testing methods in such a way that the results prove the process has done what it claims to do for the specific batch concerned
84
*quality control unit
any person or organizational element designated by the firm to be responsible for the duties relating to quality control
85
*theoretical yield
quantity that would be produced at any appropriate phase of manufacture, in the absence of any loss of error
86
*actual yield
quantity that is actually produced at any appropriate phase of manufacture
87
*When bulk chemical ingredients of drug products are received what must be logged in?
- purchase order number
- date of receipt
- suppliers stock of control number
- quantity received
88
*To control process and production controls written documentation is required to make sure each drug component has what?
- correct identity
- correct strength
- correct quality
- correct purity
89
What documentation is required for packaging and labeling control? Why?
receipt, storage, handling, sampling, and testing of products
- prevent mislabeling of products
- check for expiration date
- tamper evident packaging required
90
*What are types of tamper evident packaging?
```
film wrapper
blister/ strip pack,
shrink seal, band,
foil, paper, plastic pouch
bottle seal
tape seal
breakable cap
sealed tube
sealed carton
aerosol container
```
91
*How long must production records and reports be kept for? What is on the records?
1 year following expiration date of batch
- name and strength of product dosage form, components and dosage units, control procedures, equipment used, in process controls, results of analysis, calibration of instruments
92
How does the FDA recognize the importance of compounding under the FDA modernization act of 1997?
- ensured patient's access to compounded products
- prevented unnecessary FDA regulation of health professional (pharmacy) practice, but did not exempt the drug manufacturing company
93
*Why do plastic containers have advantage over glass containers?
They are lighter in terms of weight
They have greater flexibility in design and appearance
Plastic squeeze bottle
94
* Issues with plastic containers over glass
- permeability of containers (want to make sure drug won't pass in and out)
- leaching of constituents of container
- absorption of drug to container ( affect optimal dose)
- transmission of light through container
- change in container material over time
95
What age is child resistant packaging used for? What are examples?
Must be difficult to open by children under 5 years of age
- line the arrows
- press and turn
- squeeze and turn
- latch top
96
What must be included on a prescription label?
- Pharmacy name and address
- serial # of prescription
- date of prescription
- name of prescriber
- name of patient
- directions for use
97
*What is necessary with OTC labeling?
headings and subheadings must be easy to understand
| - package labeling must contain warning statements if misuse can lead to serious complications
98
* What is required on an OTC label?
- product name, net quantity of contents, pharmacologic category, cautions and warnings to protect customer, storage conditions
* **- sodium content (for oral products) when necessary
- 5 mg or more per single dose
- 140 mg or more in maximum dose
99
How does the shirley amendment relate to dietary supplement labeling?
- the claims must be accurate and truthful
| - no disease claims are allowed
100
```
*****Storage temperatures defined by USP:
What is cold?
Cool?
Room temp?
Warm?
Excessive heat?
```
```
Cold: 8 degrees C
Cool: between 8 and 15 degrees C
Room temp: 20 to 25 degrees C
Warm: between 30 and 40 degrees C
Excessive heat: above 40 degrees C
```
101
What are characteristics about the ideal dosage form?
- should be biocompatible
- drug and dosage form should be compatible
- formulation should be:
Stable, easily administered, safely administered, efficacious
102
Reasons we need dosage forms?
- protection from gastric pH
- address offensive taste or odors
- improve drug action
- provide for insertion into body's orifices
- provide protection from destructive chemical influences-
- control rate of drug release
103
**Dosage forms must be matched with appropriate illnesses, and address patient specific needs: give an example relative to children and elderly
Liquid form is preferred for children under 5
| Elderly need help with self medication procedures (opening lids)
104
Chemical, physical and biologic drug properties
Chemical: structure, form, reactivity
Physical: particle size, crystalline structure, melting point and solubility
Biologic: ability to get to site of drug action and elicit response
105
What is important about the particles of a drug during microscopic examination?
The particles need to stay as individuals because they need to dissolve
106
*How is melting point depression related to differential scanning calorimetry?
DSC - measures thermal phase behavior which can be used to determine purity of a substance because if you know the melting point of pure A, you can tell whether it is contaminated with pure B if the melting point lowers
107
* How is DSC used?
- sample chamber with dosage form w/o drug and experimental chamber with dosage form with drug
- creates a thermogram for the melting point of lipids to prepare dosage forms
thermogram = plot of E absorbed as the temp of the system is raised - peak is caused by absorption of energy required to melt the lipid bilayer
108
**What does a phase diagram (temperature composition diagram) reveal? What are the phases? What is each section? I, II, III, IV? What is the minimum melting point?
```
The composition of two or three component systems
phases are non-solid and solid
I. solid A + solid B
II. Solid A + melt
III. Solid b + melt
IV. Melt
```
The minimum melting point is the eutectic point - where both a and b melt
109
Polymorpism
```
different physiochemical properties of the drug :
non crystalline (amorphous)
Crystalline (crystal structure)
```
amorphous form of drug is more soluble than the crystal form
110
What are two antibiotics inactive in the crystal form but active in the amorphous form?
novobiocin
| chloramphenicol (absorption in GI tract rapid in amorphous form)
111
What is a drug more active in the crystal form than the amorphous state?
penicillin G - crystal form results in better therapeutic response
112
Why is solubility important in a drug?
- relatively insoluble compounds can lead to incomplete absorption
- solubility can be increased by chemical modification
113
Can pH be adjusted to enhance drug solubility?
| If no, what can be manipulated?
YEs, but not always so:
use co-solvents (solvent combined w/ another can dissolve solute)
- micronization - reducing avg diameter of a solid materials particles
- dispersion - particles dispersed in continuous phase of a different composition
- emulsion - mix of liquids that normally don't form a homogenous mizture
114
*What is dissolution? How does it work?
The time it takes for a drug to dissolve in fluids at the absorption site
- absorption rate increases with decrease in particle size
- dissolution will increase with increase in solubility
- dissolution can influence duration of therapeutic effect
115
*Fick's law of diffusion
transfer of drugs form an areas of high concentration (C1) to an area of low conecntration (C2)
dQ/dt = DA/h (C1 - C2)
dQ/dt - rate of drug diffusion
D = diffusion coefficient for drug
A = surface area across which drug transfer occurs
h - thickness of the region through which diffusion occurs
116
*What is the equation for the partition coefficient?
P = concentration of drug in octanol (hydrophobic)/ concentration of drug in water (aqueous )
If the lower number is higher, it is aqueoue
*optimal balance between water and lipid solubility
117
How is partition coefficient measured?
shake a known amount of drug in a flask containing a measured amount of water and octanol.
- phosphate buffer used to mimic physiological pH & correct for ratio of [conjugated base]/[acid] in vivo
- amount of drug in one or both of the phases determined by HPLC
118
*Zero order reactions
- rate is a constant and does not change with time
- k0 is the zero order reaction rate
- the amount of drug removed over any given period of time is a constant
**** C = -k0t + C0
```
k0 = zero order rate constant
t = time
c = concentration
```
119
First order reaction
- reaction rate depends on concentration of only one reactant
- rate of rxn initially fast when C is large; as C decreases the rxn slows as the rxn proceeds
- the higher the drug concentration the faster the rate process
- most rxns dealing with pharmaceutical products follow this process
lnc = -kt +lnC0
120
**A drug suspension (125mg/ml) decays with zero order kinetics with a reaction rate constant of 0.5 mg/ml/hr. What is the concentration of intact drug remaining after 3 days? (72 hrs)
How long will it take the suspension to reach 90% of its original concentration?
```
c = -k0 (t) + C0
c = -0.5 mg/ml/hr (72hr) +125 mg/ml
c = 89 mg/mL
```
90% (125mg/ml) = 112.5mg/ml
t = c - c1/ -k0
t = (112.5mg/ml - 125mg/ml)/ -0.5 = 25 hr
121
**What are the advantages and disadvantages of bulk powders for external use?
Advantages: easy application, absorb moisture, has dry cooling effect
Disadvantages: may block pores, get inhaled by infants, not suitable for all skin-related medical problems
122
What are advantages and disadvantages of bulk powders for internal use?
Advantages: stability, easily administered, absorption by GI tract is fast
Disadvantages: accuracy of dose not guaranteed, large dose containers are difficult to carry, difficult to mask unpleasant taste
123
what are the terms very coarse, coarse, moderately coarse, fine and very fine related to?
The proportion of powder that can pass through standardized sieves of varying dimensions
124
****What are the openings of standard sieves?
```
Very coarse: No. 8 (2.36 mm)
Coarse: No 20 (850microm)
Moderately coarse No. 40 (425 um)
Fine No. 60 (250 um)
Very fine: No. 80 (180 um)
```
As sieve number increases particles size decreases
125
* Very coarse
All particles fit through a No. 8, and not more than 20% fit through a No. 60 sieve
126
** Coarse
All particles fit through a No. 20 sieve, and not more than 40% fit through a No. 60 sieve
127
**Moderately coarse
All particles fit through a No. 40 sieve, and not more than 40% fit through a No. 80 sieve
128
*Fine
All particles fit through a no. 60 sieve, and not more than 40% fit through a No. 100 sieve
129
*Very fine
All particles fit through a no. 80 sieve and there is no limit as to greater fineness
130
*What can the particle size of a powder influence?
Dissolution rate of particles
Suspendability of particles
Uniform distribution
Penetrability
Nongrittiness
131
*Dissolution rate
decrease particle size increase absorption and dissolution and bioavailability
132
* Suspendability
particles intended to remain undissolved but uniformly dispersed in a liquid vehicle
133
* Pentrability
of particles intended to be inhaled for deposition deep in the respiratory tract (through lungs, smaller gets deeper 1-5 microns)
134
*Uniform distribution
of a drug substance in a powder mixture or solid dosage form to ensure dose to dose content uniformity
135
*nongrittiness
of solid particles in dermal ointments and creams: decrease particle size decrease grittiness (50-100 microns)
136
What are methods for determining particle size?
Sieving, microscopy, sedimentation rate, light scattering, laser holography, cascade impaction
137
Particles pass through a series of sieves of known successively smaller sizes (40-9,500 micron)
Sieiving
138
A calibrated grid background is used to measure particle size (0.2-100um)
microscopy
139
The velocity of particles through a liquid medium in a gravitational or centrifugal environment (0.8-300um)
sedimentation rate
140
Reduction in the amount of light reaching the sensor as the particle dispersed in liquid of gas passes through the sensing zone range (0.02-2,000 um)
Light scattering
141
A pulsed laser is fired through an aerosolized particle spray and photographed in three dimensions with a camera (1.4 -100 um)
Laser holography
142
** A particle, driven by an airstream impacts on a surface in its path
particles are then separated into various size ranges by successively increasing velocity of the airstream - no specific size range
Cascade impaction
143
Drug comminution
A mortar with a rough surface (as opposed to glass mortar) is used
trituration, levigation, levigating agent
144
**Trituration
the process of rubbing, crushing, grinding or pounding materials
may be employed to comminute and mix powders
glass mortar preffered if no comminution needed
geometric dilution
145
**Levigation
the process of reducing the particle size and grittiness
146
*Levigating agent
a small amount of some liquid added to the powder to form a paste
147
**Spatulation
A spatula moves through powders on a sheet of paper or ointment tile
- not recommended for large quantities
- ideally suited for mixing solid substances that form eutectic mixtures (or liquify) when in close and prolonged contact with one another
- mixing agents : camphor, phenol, menthol
To avoid eutectic mixture formation add Magnesium oxide or magnesium carbonate
148
Sifting
powders are mixed by passing through sifters
sifting -> fluffy products
- not acceptable for incorporation of potent drugs into a diluent powder because you will lose a lot and inhale it
149
**Tumbling
Most widely used mixing strategy in the pharmaceutical industry****
- tumbling powder enclosed in a rotating container
150
Quality control for bulk powders
Pharmacist should compare the final weight of the product to the theoretical weight
- powder should be examined for uniformity of color, particle size, flowability and freedom from caking
151
Quality control for divided powders
pharmacist should individually weigh the divided papers and then compare that weight to the theoretical weight
- packets should be checked to see that they are uniform
152
What are granules? Shape?
- prepared agglomerates of smaller particles of powder
- irregularly shaped, may be forced into certain shapes mechanically
- prepared by being passed through a screen, dried in air, then pit in oven and pasty mass is formed
153
Characteristics of granules
- flow well compared to powders
- have smaller SA compared to powder of comparable volume because each side of a powder is exposed, not true for granules
- more easily wetted by liquids
- prepared to contain colorants, flavorants and other pharmaceutical ingredients
154
***Effervescent granules are coarse to very coarse powders containing a medicinal agent in a dry mixture composed of what? What happens if one is missing?
Sodium bicarbonate, citric acid, tartaric acid
- if citric acid is not present the granules will lose firmness
- if tartaric acid is not present it will be sticky
155
When water is added to effervescent granules carbon dioxide is liberated and sparkles and bubbles are produced, why is this important?
Because the carbonated solution can mask undesirable tastes associated with the drug
