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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
Q

What is the mechanism of hydrolysis?

A

A nucleophilic attack of hydroxide anion on ester carbonyl group, the oxygen attacks the hydrogen as it happens fast

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26
Q

How do you prevent the hydrolysis of esters and lactones?

A
  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)
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27
Q

When you open an aspirin bottle what do you smell?

A

Vinegar

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28
Q

What does amide hydrolysis make in basic conditions?

A

A tetrahedral intermediate which can eventually create a carboxylic acid and an amine

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29
Q

What is O2-?

A

A superoxide

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30
Q

What is O2-2?

A

A peroxide

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31
Q

How many steps are there in the auto-oxidation of captopril?

A

5 steps

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32
Q

What is the RS- in the auto-oxidation of captopril?

A

A thiolate anion

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33
Q

What is the 2RS* in the auto-oxidation of captopril?

A

Thiyl radical

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34
Q

Summary of oxidation and photolysis?

A

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

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35
Q

What are the 2 ways that oxidation can be minimalized?

A

Protecting from air, light and minerals
Excipients added to the formulation

36
Q

What type of kinetics is degradation of a drug in solution?

A

Zero-order, the rate of drug degradation is also constant

37
Q

How to determine the slope of the rate of degredation in a zero-order kinetics graph?

A

Concentration / time = -k
-k is = to the slope

38
Q

What is the rate of the drug degradation in a zero-order kinetic graph?

A

The rate of drug degradation is constant, independent of concentration

39
Q

What are some of the stability issues for proteins?

A

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
Q

What happens when proteins (biologics) aggregate

A

It an increase or increase potency
There is increased potential for adverse immune response

41
Q

Summary of biologics…

A

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
Q

How do protein drugs degrade? (chemical degradation)

A

Chemical degradation
-breaks the “correct” covalent bonds and/or forms “incorrect” ones
-Hydrolytic reactions
-Oxidation reactions

43
Q

How do protein drugs degrade? (physical degradation)

A

Physical degradation
-changes protein structure, usually without breaking covalent bonds
-unfolding
-aggregation

44
Q

What are the 3 common routes of protein degradation?

A

Hydrolytic reactions (chemical)
Oxidative reactions (chemical)
Aggregation (physical)

45
Q

In protein degradation what happens during hydrolysis reactions?

A

Asparagine deamidation
Peptide bond hydrolysis “clipping” or breaking of the chain

46
Q

In protein degradation what happens during oxidative reactions?

A

Methionine oxidation
Disulfide bond scrambling

47
Q

In the methylphenidate vs madidate graph in 12a, which of the following is not true?

A

The methylphenidate has a higher total release is not true because the the madidate CD will last along time

48
Q

When a tablet is dropped in 250ml of water at 37*C and all of it dissolves what is this drug considered?

A

“High-solubility”

49
Q

When a tablet is dropped in 250ml of water at 37*C and not all of it dissolves what is this drug considered?

A

“Low-solubility”

50
Q

What are the 4 non-enteric polymer cellulose film coatings that get sprayed onto tablets (THESE DISSOLVE IN THE STOMACH)

A
  1. hydroxy-propyl-methyl-cellulose
  2. methyl-hydroxy-ethyl-cellulose
  3. ethyl-cellulose
  4. hydroxy-propyl-cellulose
51
Q

What are enteric polymers?

A

A coating that makes it dissolve in the small intestine unlike the non-enteric which dissolves in the stomach

52
Q

What is the omeprazole story?

A

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
Q

What is a matrix tablet?

A

A drug embedded in polymer matrix (a plastic coating)

54
Q

What is erosion and diffusion in the polymer matrix?

A

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
Q

How does the EOP (elementary osmotic pump) work in concerta?

A

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
Q

With the EOP there are two delivery delivery devices the single chamber and the double chamber how do these work?

A

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
Q

What do matrix and oros tablets have in common?

A

They can both show controlled release

58
Q

What does a coated tablet do?

A

They provide a sustained release

59
Q

What does the ad for converta vs metadate show?

A

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
Q

Why were extended release tablets of oxycontin released?

A

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
Q

What are the pharmacokinetics of OROS vs IR oxybutynin

A

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
Q

What are some of the techniques for innovation?

A

Brainstorming, storyboarding, mind mapping, excursion method, product improvement method, osborn’s checklist, scenario planning, TRIZ, and stage gate

63
Q

What are the 3 types of innovation?

A

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
Q

What is mind manager?

A

a concept map to get ideas out and get them into groups as a way to find a brainstorming approach

65
Q

What is the model for inventive ideation?

A

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
Q

What is the inventive ideation for ritalin proposed in class?

A

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
Q

What is the blue ocean strategy?

A

A graph where you can compare all the needs to figure out what the best option is

68
Q

What are the fitbits in an innovation standpoint?

A

It was a huge breakthrough or disruptive innovation that no one can see coming

69
Q

What are some disruptive products?

A

Topple industry leaders
Simpler
Best approach is to spin off a new company to introduce these
-IBM in florida

70
Q

With the new innovation in antiviral drugs what have been some of the consequences?

A

The U.S. Life expectancy has increased over the past 50 years with a women’s life expectancy to be higher than men

71
Q

Why has the life expectancy gone down the past couple of years?

A

Covid-19

72
Q

HIV/AIDS in the united state and its mortality?

A

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
Q

What are some of the problems of antiviral drugs? and how can we solve them?

A

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
Q

Sofosbuvir is an antiviral drug what is it?

A

Sofosbuvir is a prodrug

75
Q

What % of antiviral drugs makes it to phase 1 clinical trials

A

Only 25% because of its very poor bioavailability

76
Q

How can you improve bioavailability and solubility in antiviral drugs?

A

To make an amorphous dosage form by melt extrusion

77
Q

Itraconazole example? antiviral drug

A

Depending on what polymer you use it can drastically increase the solubility

78
Q

The pellets made by the melt extrusion for itraconazole do what?

A

They can get put into a capsule which will make it more soluble and able to have therapeutic effect

79
Q

By spray drying a drug what is the outcome?

A

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
Q

How do you start a design for new antiviral medications?

A

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
Q

What are some of the pharmaceutical strategies to help abuse with medications

A

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
Q

What is the original theory of oxycontin and oxycontin and oxycodone blood levels?

A

Oxycodone IR dose will go high enough to give you some euphoria at the start

83
Q

What is the oxycontin abuse deterrent formulation

A

they added a polyethylene polymer into the formula so that it cannot be crushed or chewed to help fight abuse

84
Q

What is the gel content of of PEO polymer mixtures?

A

When water gets added it becomes a gel so that it cannot be used in a syringe

85
Q

What is true about PEO?

A

PEO forms a net structure with water to produce a gel

PHRM828 (3 decks)

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