exam 4 Flashcards

1
Q

hydrolysis

A

drug interacts with water to cleave and break into two fragments
water reacts to degrade drug so do not store in humid environments
ex - chloramephenicol

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2
Q

chemical kinetics and stability

A

drug degrades faster at higher temps

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3
Q

stability NAPLEX

A

solution stable: at given concentration, for certain time, temperature, degree of light exposure. decompose faster than solids
solid stable: for certain time, temperature, degree of light exposure

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4
Q

drug compatability

A

compatability issues for longer infusion times like piperacillin/tazobactam, antibiotics like z-pack, cipro, tobramycin, vancomycin, insulin and vasopressors

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5
Q

temperature and stability

A

higher temps break down proteins and speed up chemical reactions
most IV drugs are refrigerated for longer stability
exceptions: furosemide and phenytoin crystallize if kept cold
IV drugs like flagyl, moxifloxacin, acetominophen, acyclovir, pentamidine, valproate can be kept at room temp

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6
Q

light exposure NAPLEX

A

light exposure causes photodegradation and can increase toxicity
amber vials protect from light
Vit. K , nitroprusside, doxycycline must be protected from light during admin
check drug for color changes

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7
Q

stability and degradation NAPLEX

A

stability: product retains properties and characteristics throughout its period of storage
certain functional groups are susceptible to degradation
degradation: oxidation-reduction, hydrolysis, photolysis

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8
Q

oxidation - naplex

A

ex - oxidation of epinephrine
other known oxidations include carmelization of onions where OH groups oxidize and turn brown
prevent oxidation - protect temp changes, control pH, light protection, low temp, chelating agents (ETDA), antioxidants to remove free radicals

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9
Q

hydrolysis NAPLEX

A

water causes cleavage of a bond in molecule
likely hydrolyzed: carbonyl, amide, cyclic amide

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10
Q

function of dosage forms

A

provide accurate dose
promote drug dissolution
promote delivery to site of action
ensure drug stability
control drug deliver to body
determine dosing intervals

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11
Q

hydrolysis mechanism in basic conditions

amide hydtrolysis

A

nucleophillic attack of hydroxide anion (OH-) on ester of carbonyl group
this forms carboxylic acid and alcohol

nucleophillic attack of hydroxide anion on amide carbonyl group
carboxylic acid and amine formation

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12
Q

how can hydrolysis of esters and lactones be prevented

how can hydrolysis of amides and lactams be prevented

A

protect from moisture (solid dosage forms like tabs and caps)
protect from heat (hydrolysis is faster at higher temps)
control pH in solution formulations (ester/lactone hydrol is ph-dependent)

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13
Q

oxidation summary

A

oxidation is a common, complicated route of drug degradation
photolysis is drug degradation caused by exposure to light
many functional groups oxidize
oxidation can be minimized by protecting from air, light, metals and excipients added to formulation

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14
Q

zero order kinetics

A

degradation of drug in suspension
when the drug concentration in solution is constant like in a suspension
independent of concentration
in the solid state

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15
Q

stability issues for biologics (proteins)

A

proteins tend to be more fragile than small molecule drugs
biologics are bigger so they have more bonds that can break
biologics can lose activity if they unfold
biologics can aggregate: increase or decrease potency and increase potential for adverse immune response

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16
Q

proteins summary

A

recombinant proteins like vaccines, stem cells, gene therapy
made from AA and have folded structure
tend to be more fragile than small molecule drugs
one of fastest growing drug classes

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17
Q

protein degradation

A

chemical degradation: breaks covalent bonds and forms incorrect ones, hydrolytic reactions, oxidation reactions
physical degradation: changes in protein structure without breaking bonds, unfolding, aggregation

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18
Q

hydrolytic reactions
oxidation reactions
aggregation

A

hydrolytic (chemical): asparagine deamination, peptide bond hydrolysis
oxidation (chemical): methionine oxidation
disulfide bond scrambling
aggregation (physical)

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19
Q

solubility

A

solubility should be considered with dose
poorly soluble drug can completely dissolve under physiological conditions if dose is small, so dose solubility may be more important

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20
Q

bioavailability

A

depends not only on having drug in solution but also on drugs permeability
if drug cannot get into solution it will not be bio available

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21
Q

enteric coating polymers

A

release drug in small intestine

22
Q

matrix tablet

A

drug embedded in polymer matrix

23
Q

errosion and diffusion

A

errosion: where polymer is degraded and drug is released

diffusion: polymer remains and drug swells and diffuses out

24
Q

elementary osmotic pump (OROS) in Concerta

A

semipermeable membranes
drug containing osmotic core
water enters membrane but drug cannot escape
there is a delivery orifice that allows drug to enter body

25
single chamber and double chamber
single: drug just diffuses out double: water fills up chamber and pushes drug out
26
GI transit time of OROS
stomach (fasted): .5 hr .25 - 4 hr stomach (fed): 2-3 hr .75 - 10hr small intestine: 3 hr 2-4 hr colon: 32 hr 4 - 96 hr
27
dissolution of methylphenidate vs oros
methylphenidate: taken three times spikes than levels out oros: more consistent dissolution
28
drug release forms
immediate release: drug peaks immediately delayed release: has same peak but release is delayed extended release: does not peak as high but release is longer. can also allow us to not peak as high or dip as low
29
problems with generic concerta
giving immediate release can cause more side effects compared to extended release
30
types of innovation
group A: most are group a. involve incremental tweaking of existing products - change tablet shape group B: based on analogy group C: wild ideas
31
mind manager
concept map model for inventive ideation - convert, change, copy, separate, combine
32
ritalin innovation
want to change BID to QD change: formulation copy: use OROS combine: beads of different release seperate: use beads of different release
33
innovation pipeline
idea concept experiment pilot launch
34
blue ocean strategy
map needs and differentiate which needs you meet
35
lean startup
build products or services that meet needs of early customers try, test, fail quickly don't overplan go for minimum viable product customer feedback and do not invest time in designing features
36
disruptive innovation
no one sees it coming early prototypes were not very functional, but niche consumer segment won over topple industry leaders simpler best approach is to spin off new compant to introduce these - IBM in florida
37
us life expectancy
from 1950-2014 it has been increasing males - 76.4 y.o females - 81.2 y.o
38
us life expectancy with covid
both male and female life expectancies dropped due to COVID
39
antiviral drugs
very insoluble, so difficult to get into bloodstream
40
solutions for insoluble antiviral drugs
prodrug: drug that is inactive and then converted to active form due to physico-chemical transformation in the body formulation: melt extrusion and spray drying
41
sofosbuvir
prodrug that is converted to triphosphate and inhibits the NS5B polymerase
42
antiviral drugs poor solubility reasons for failing
39% poor bioavailability 30% low efficacy 11% high toxicity 10% adverse effects 10% others
43
melt extrusion
make amorphous dosage from by melt extrusion improve solubility and bioavailability
44
itraconazole
not soluble in crystalline form more soluble as pellets or melted
45
spray drying
improves solubility and bioavailability spray solution into hot dryer particles fall down and become processed into fine powder
46
antiviral molecules
makes molecules that will inhibit virus molecules has little effect on normal cells and is non toxic formulation is important in making these molecules soluble
47
abuse prevention
abuse-deterant tech makes product manipulation more difficult improve tamper resistance incorporate deterrent abuse-deterrent must be referenced by comparator
48
abuse deterrent formulations
oxycontin has polyethylene oxide (PEO) that is very hard and does not break that makes it very hard to inject.
49
polyethylene glycol
PEO turns into gel when water is added and hard to inject
50
reformulation to decrease drug diversion
before reformulation it was higher after reformulation it was much lower