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PHRM828 > Final Exam Study Guide > Flashcards

Final Exam Study Guide Flashcards

1
Q

Chloramphenicol is used in what type of medication?

A

Eye drops

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2
Q

What type of reaction does chloramphenicol go through? And what does this cause the molecule to do?

A

This molecule goes through hydrolysis and it cleaves off the 2 chloro groups

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3
Q

Where should you never store your medicine?

A

In a humid environment

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4
Q

What happens to a drug at an elevated temperature?

A

The breakdown of the drug in an aqueous solution is accelerated

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5
Q

What are the 4 ways a solution drug will be stable in….?

A
  1. At a given concentration
  2. For a certain time
  3. At a certain temperature
  4. At a certain degree of light exposure
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6
Q

What are the 4 ways a solution drug will be stable in…..?

A
  1. For a certain time
  2. At a certain temperature
  3. At a certain degree of light exposure
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7
Q

Do solutions or solids decompose faster?

A

Solutions decompose faster

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8
Q

True or false?…. Compatibility is a problem for longer infusions times

A

True, but this is not a problem with shorter infusion times

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9
Q

Most antibiotics like piperacillin/tazobactam, azithromycin, ciprofloxacin, tobramycin, and vancomycin all have issues with slow infusions because of compatibility. There is also issues with vasoconstrictors and insulin. True or false

A

True

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10
Q

What speeds up chemical reactions to break down the drug and its proteins?

A

High temperatures

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11
Q

The majority of IV drugs are stored in the refrigerator….which 2 medications are not kept in a fridge because they would crystalize?

A

Furosemide and phenytoin

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12
Q

What drugs did we talk about in class that are kept in the fridge?

A

Metronidazole, moxifloxacin, acetaminophen, acyclovir, pentamidine, and valproate

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13
Q

What does light exposure do to drugs?

A

They cause photodegradation, and in some cases they can increase toxicity

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14
Q

Why are medications administered in amber vials?

A

This is to reduce the light exposure

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15
Q

What are the 3 drugs we talked about in class that must be protected from light during administration?

A

Vitamin-K, nitroprusside, and doxycycline

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16
Q

How should you make sure a drug isnt changed from photosensitivity?

A

Make sure to check the color of the drug to see if there are any color changes

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17
Q

What is the definition of stability?

A

Stability is the extent to which a product retains the same properties and characteristics throughout its period of storage and shelf life

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18
Q

What happens if some of the functional groups are prone to lower stability?

A

The functional groups will be easily degraded and can make the drug ineffective or toxic

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19
Q

What are the three chemical reactions that cause drug degredation?

A

Oxidation-reduction
Hydrolysis
Photolysis

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20
Q

What is oxidation?

A

Oxidation is when oxygen groups are added like either to epinephrine or another example used was when you cut and onion and it becomes caramelized from the -OH groups becoming just oxygens

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21
Q

What are the 6 ways that oxidation can be prevented?

A

Protection from changes in the temperature
Control the pH with buffers
Light protection - like pharmacy amber vials
Lower the temperature to slow down these reactions
Chelating agents such as EDTA to remove metal ions which cause oxidation
Antioxidants can remove free radicals produced by oxidation

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22
Q

When does hydrolysis occur?

A

Hydrolysis occurs when water causes cleavage of a bond in the molecule

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23
Q

What are the 3 compounds we talked about in class that are likely to get hydrolyzed?

A
  1. Carbonyl group
  2. Amide group
  3. Cyclic amide
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24
Q

What are 6 functions of dosage forms?

A
  1. Provide an accurate dose
  2. Promote drugs dissolution
  3. Promote delivery to the site of action
  4. Ensure drug stability
  5. Control drug delivery to the body
  6. Determine dosing interval
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25
What is the mechanism of hydrolysis?
A nucleophilic attack of hydroxide anion on ester carbonyl group, the oxygen attacks the hydrogen as it happens fast
26
How do you prevent the hydrolysis of esters and lactones?
1. Protect from moisture (in solid dosage forms (tablets and capsules)) 2. Protect from heat (hydrolysis is faster in higher temperatures) 3. Control the pH in solution formulations (ester/lactone hydrolysis is pH-dependent)
27
When you open an aspirin bottle what do you smell?
Vinegar
28
What does amide hydrolysis make in basic conditions?
A tetrahedral intermediate which can eventually create a carboxylic acid and an amine
29
What is O2-?
A superoxide
30
What is O2-2?
A peroxide
31
How many steps are there in the auto-oxidation of captopril?
5 steps
32
What is the RS- in the auto-oxidation of captopril?
A thiolate anion
33
What is the 2RS* in the auto-oxidation of captopril?
Thiyl radical
34
Summary of oxidation and photolysis?
Oxidation is a common, and complicated route of drug degredation Photolysis is a drug degredation caused by exposure to light Many different functional groups are subject to oxidation
35
What are the 2 ways that oxidation can be minimalized?
Protecting from air, light and minerals Excipients added to the formulation
36
What type of kinetics is degradation of a drug in solution?
Zero-order, the rate of drug degradation is also constant
37
How to determine the slope of the rate of degredation in a zero-order kinetics graph?
Concentration / time = -k -k is = to the slope
38
What is the rate of the drug degradation in a zero-order kinetic graph?
The rate of drug degradation is constant, independent of concentration
39
What are some of the stability issues for proteins?
They are more fragile than small molecule drugs Biologics are larger than small molecule drugs, so there are more bonds that can break They can lose activity if they unfold or disassemble in any way
40
What happens when proteins (biologics) aggregate
It an increase or increase potency There is increased potential for adverse immune response
41
Summary of biologics...
One of the fastest growing drug classes Includes recombinant proteins, vaccines, stem cells, and gene therapy Proteins are made of amino acids and have a folded structure Protein drugs tend to be more fragile than small molecule drugs
42
How do protein drugs degrade? (chemical degradation)
Chemical degradation -breaks the "correct" covalent bonds and/or forms "incorrect" ones -Hydrolytic reactions -Oxidation reactions
43
How do protein drugs degrade? (physical degradation)
Physical degradation -changes protein structure, usually without breaking covalent bonds -unfolding -aggregation
44
What are the 3 common routes of protein degradation?
Hydrolytic reactions (chemical) Oxidative reactions (chemical) Aggregation (physical)
45
In protein degradation what happens during hydrolysis reactions?
Asparagine deamidation Peptide bond hydrolysis "clipping" or breaking of the chain
46
In protein degradation what happens during oxidative reactions?
Methionine oxidation Disulfide bond scrambling
47
In the methylphenidate vs madidate graph in 12a, which of the following is not true?
The methylphenidate has a higher total release is not true because the the madidate CD will last along time
48
When a tablet is dropped in 250ml of water at 37*C and all of it dissolves what is this drug considered?
"High-solubility"
49
When a tablet is dropped in 250ml of water at 37*C and not all of it dissolves what is this drug considered?
"Low-solubility"
50
What are the 4 non-enteric polymer cellulose film coatings that get sprayed onto tablets (THESE DISSOLVE IN THE STOMACH)
1. hydroxy-propyl-methyl-cellulose 2. methyl-hydroxy-ethyl-cellulose 3. ethyl-cellulose 4. hydroxy-propyl-cellulose
51
What are enteric polymers?
A coating that makes it dissolve in the small intestine unlike the non-enteric which dissolves in the stomach
52
What is the omeprazole story?
When they were testing omeprazole they made patients take sodium bicarb with it to neutralize the stomach acid, this then gave them blood levels which they then knew to put an enteric coating on it to make sure it dissolves in the small intestine
53
What is a matrix tablet?
A drug embedded in polymer matrix (a plastic coating)
54
What is erosion and diffusion in the polymer matrix?
Erosion happens when the tablet just completely dissolves and all the drug gets released Diffusion happens when the outer layer of the polymer matrix is swell-able and when it swells with water the drug is able to easily diffuse and leave the polymer matrix
55
How does the EOP (elementary osmotic pump) work in concerta?
There is a semipermeable membrane with a drug containing core, when it gets absorbed water comes in and the drug leaves through a small hole letting it have an ER effect all day
56
With the EOP there are two delivery delivery devices the single chamber and the double chamber how do these work?
Single chamber is like the concerta capsule The double chamber has 2 chambers one with drug and 1 without, the water fills up the bottom and eventually pushes put drug all day long
57
What do matrix and oros tablets have in common?
They can both show controlled release
58
What does a coated tablet do?
They provide a sustained release
59
What does the ad for converta vs metadate show?
It shows that metadate has a higher concentration faster so children will have a greater effect during their critical learning hours and it will wear off faster than methylphenidate so they will be able to go to bed easier and not be as hyperactive
60
Why were extended release tablets of oxycontin released?
So when they take immediate release they dont go outside of the theraputic window and show side effects or dip below the theraputic window and be in pain
61
What are the pharmacokinetics of OROS vs IR oxybutynin
By taking the OROS oxybutynin 15mg Q24H they get a good theraputic graph instead of taking 3, 5mg tablets Q8H, they can get dry mouth from taking it TID because of the window.
62
What are some of the techniques for innovation?
Brainstorming, storyboarding, mind mapping, excursion method, product improvement method, osborn's checklist, scenario planning, TRIZ, and stage gate
63
What are the 3 types of innovation?
Group A types- involve incremental tweaking of existing products - like changing the tablet shape Group B types- based on analogy Group C types - wild ideas
64
What is mind manager?
a concept map to get ideas out and get them into groups as a way to find a brainstorming approach
65
What is the model for inventive ideation?
when you have 5 things you want to deal with and come up with an invention (the 5 things are convert, change, copy, combine, and separate
66
What is the inventive ideation for ritalin proposed in class?
Problem: Stimulate taking 2x a day with one dose Change: The formulation Copy: use OROS to control release Combine: Beads from a different release profile Separate: Use beads with different release Convert: N/A
67
What is the blue ocean strategy?
A graph where you can compare all the needs to figure out what the best option is
68
What are the fitbits in an innovation standpoint?
It was a huge breakthrough or disruptive innovation that no one can see coming
69
What are some disruptive products?
Topple industry leaders Simpler Best approach is to spin off a new company to introduce these -IBM in florida
70
With the new innovation in antiviral drugs what have been some of the consequences?
The U.S. Life expectancy has increased over the past 50 years with a women's life expectancy to be higher than men
71
Why has the life expectancy gone down the past couple of years?
Covid-19
72
HIV/AIDS in the united state and its mortality?
Most fatal in 1996 and since then there have drugs for it causing the mortality rates in 2010 to be around 1% down 5% from the all time high of 6% mortality
73
What are some of the problems of antiviral drugs? and how can we solve them?
They are very insoluble This can be solved by making a prodrug this can be solved by also changing the formulation of the drug to melt extrusion or spray drying
74
Sofosbuvir is an antiviral drug what is it?
Sofosbuvir is a prodrug
75
What % of antiviral drugs makes it to phase 1 clinical trials
Only 25% because of its very poor bioavailability
76
How can you improve bioavailability and solubility in antiviral drugs?
To make an amorphous dosage form by melt extrusion
77
Itraconazole example? antiviral drug
Depending on what polymer you use it can drastically increase the solubility
78
The pellets made by the melt extrusion for itraconazole do what?
They can get put into a capsule which will make it more soluble and able to have therapeutic effect
79
By spray drying a drug what is the outcome?
It can become a powder and used in antiviral medications with a higher dissolution rate causing an effect unlike the crystalline powder. This powder can then be put into a capsule for ingestion
80
How do you start a design for new antiviral medications?
Make a molecule that will inhibit the virus Make sure the molecule has little effect on normal cells and is not toxic The formulation has to be right - either a melt extrusion or by spray drying to get the drug to its desired area of work
81
What are some of the pharmaceutical strategies to help abuse with medications
Improve physical tamper resistance (oxycontin) Incorporate deterrent (suboxone, embeda) Most drug designs are formulated to make it more difficult and lower the abuse of the manipulated product
82
What is the original theory of oxycontin and oxycontin and oxycodone blood levels?
Oxycodone IR dose will go high enough to give you some euphoria at the start
83
What is the oxycontin abuse deterrent formulation
they added a polyethylene polymer into the formula so that it cannot be crushed or chewed to help fight abuse
84
What is the gel content of of PEO polymer mixtures?
When water gets added it becomes a gel so that it cannot be used in a syringe
85
What is true about PEO?
PEO forms a net structure with water to produce a gel

PHRM828 (3 decks)

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