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PHRM 828 Exam 4 > Lecture 9 > Flashcards

Lecture 9 Flashcards

1
Q

Hydrolysis of Chloramphenicol

A
  • attack of water on the molecule
  • molecule cleaves and breaks into 2 fragments
  • Common compounds likely to be hydrolyzed: carbonyl, amide, cyclic amide
  • water can react and degrade drugs
  • humid environments are not storable places to keep drugs
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2
Q

Accelerated Stability

A
  • test to see how bad degradation and stability is
  • rate of breakdown is increased at a high temperature
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3
Q

Stability of Solution Drug

A
  • at a given concentration
  • for certain time
  • at a certain temperature
  • at a certain degree of light exposure
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4
Q

Stability of Solid Drug

A
  • for certain time
  • at a certain temperature
  • at a certain degree of light
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5
Q

NAPLEX Stability

A
  • solutions decompose 10x faster than solids
  • compatibility is a problem for LONG infusion times with piperacillin/tazobactam and will degrade over time
  • compatibility is an issue with antibiotics such as azithromycin, ciprofloxacin, tobramycin, vancomycin
  • compatibility is an issue with insulin and some vasopressors
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6
Q

Temperature and Stability NAPLEX

A
  • high temperatures speed up chemical reactions and break down drugs
  • most IV drugs are refrigerated for longer stability

EXCEPTION: furosemide and phenytoin are crystallized is kept cold

Metronidazole, moxifloxacin, acetaminophen, acyclovir, pentamidine, and valproate are kept at room temperature as well

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7
Q

Light Exposure NAPLEX

A
  • light exposure caues photodegradation and can cause formulations to be toxic (drug changes color)
  • medications are kept in amber vials to protect from light
  • Vitamin K, Nitroprusside, and Doxycycline cannot be ran through regular light systems
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8
Q

Shelf Life

A

stability is the extent to which a product retains the same properties and characteristics throughout its period of storage and use

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9
Q

Chemical Reactions that cause Degradation

A

Redox
Hydrolysis
Photolysis

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10
Q

Oxidation

A

-OH groups of a drug are oxidized into carbonyl groups

  • Example: caramelization of onions as the OH groups are oxidized and onions turn brown
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11
Q

Prevention of Oxidation

A
  • protect from changes in temperature
  • control pH with buffers
  • Light protection (amber vials)
  • Lower temperature slows reactions
  • Chelating agents (EDTA) remove metal ions that can cause oxidation
  • antioxidants can remove free radicals produced by oxidation
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12
Q

Function of Dosage Forms

A
  • provide accurate dose
  • promote drug dissolution
  • promote delivery to site of action
  • ensure drug stability
  • control drug delivery
  • determine dosing interval
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13
Q

Hydrolysis Based Mechanism

A

Slide 36

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14
Q

Prevention of Esters Hydrolysis

A
  • protect from moisture
  • protect from heat (hydrolysis is faster at high temp)
  • control pH of formulations (pH dependent)
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15
Q

Amide Hydrolysis Mechanism

A

Slide 49

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16
Q

Prevention of Amide/Lactam Hydrolysis

A
  • protect from moisture
  • protect from heat
  • control pH of formulations
17
Q

Auto-oxidation Mechanism

A

Slide 64

18
Q

Summary of Drug Reactions

A
  • oxidation is a common, complicated, route of drug degradation
  • many functional groups are subject to oxidation
  • oxidation can be prevented by protecting from air, light, and metals as well as certain excipients added
  • photolysis is drug degradation caused by exposure of light
19
Q

Zero Order Kinetics

A
  • rate of drug degradation is constant and independent of concentration
  • graph is a straight linear line downward

dCa/dt = - k

20
Q

Stability issues for biologics

A
  • proteins are more fragile than small molecules
  • biologics are larger and have more bonds
  • biologics can lose activity if they unfold or degrade
  • biologics can aggregate: increase/decrease potency & increased potential for adverse reaction
21
Q

Summary of Biologics

A
  • fastest growing drug class
  • include recombinant proteins, vaccines, stem cells, and gene therapy
  • proteins are made of amino acids that have folded structure
  • proteins are more fragile than small molecule drugs
22
Q

Biologic Degradation

A

Chemical Degradation
- breaks correct covalent bonds and forms incorrect ones
- hydrolytic reaction
- oxidation reaction

Physical Degradation
- changes protein structure with breaking bonds
- unfolding
- aggregation

23
Q

Hydrolytic Reaction of Biologics

A
  • asparagine deamidation
  • peptide bond hydrolysis (clipping)
24
Q

Oxidative Reaction of Biologics

A
  • methionine oxidation
  • disulfide bond scrambling

PHRM 828 Exam 4 (5 decks)

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