Interactions and Incompatibilites Flashcards
- occurs inside the body
- cannot be seen
Interaction
- problem which could arise when two or more substances interact during, before, or after drug administration
- occurs outside the body
- usually visible
Incompatibility
Forms of Incompatibilities
- Pharmaceutical Incompatibilities
a. Physical Incompatibilities
b. Chemical Incompatibilities
c. Pharmaceutic - Therapeutic Incompatibilities
a. Drug Interactions
interaction between two or more ingredients that leads to a visibly
recognizable change
- same drug is present
- state is altered
Physical Incompatibilities
- insolubility
- immiscibility
Example:
• gum and alcohol
• pectin and alcohol
• resin and water
• oil and water
Incomplete Solution
- salting-out process
- solute which is originally dissolved in the solvent is thrown out of solution
- factors affecting solubility: solvent, pH, temperature
Example:
• aromatic water and salt
• spirits and salt solution
• camphor solution and water
Precipitation
Management of precipitation
- know the drug’s solubility
- use the salt or ester form
- know or calculate for the drug’s pH
- add solubilizers or co-solvents
Four types of Liquefaction of a Solid Ingredient
- deliquescence
- efflorescence
- eutexia
- hygroscopicity
A liquefaction of solid ingredient that absorbs moisture and dissolves.
deliquescence
A liquefaction of solid ingredient that release of water of crystallization.
efflorescence
A liquefaction of solid ingredient that lowering of melting point. Occurs at room temperature.
eutexia
A liquefaction of solid ingredient that absorbs moisture but does not dissolve.
hygroscopicity
Solid ingredients that can undergo deliquescence.
NaCl
Solid ingredients that can undergo efflorescence.
- citric acid
- atropine sulfate
- ferric sulfate
- alum
Solid ingredients that can undergo eutexia.
- menthol
- phenol
- thymol
- camphor
Solid ingredients that can undergo hygroscopicity.
• silica gel
Management of liquifaction.
- solvates and hydrates must be stored and dispensed in tight containers
- substitute anhydrous form
- add adsorbent
- place product in a low humidity environment
- separate and protect potential eutectic mixtures
collective term for absorption and adsorption of drugs onto containers, IV tubing, devices,
closures
Sorption
Management for sorption
- shorten contact time
- liberation of the active ingredient
- compounds with high vapor pressure
Vaporization (or Volatilization)
Another term for vaporization
Volatilization
An example of a compound with high vapor pressure based on maam ka’s reviewer lols
nitroglycerin (Monday disease)
Management for Vaporization
- store in tight containers
- reduce the vapor pressure
existence of one or more crystalline and/or amorphous forms
Polymorphism
Examples of compounds are amorphous based on maam ka’s reviewer lols
- aspirin
- Theobroma cacao
- chloramphenicol
- sulfanilamide
Cubic
NaCl
Monoclinic
sucrose, ritonavir (form I)
Tetragonal
urea
Hexagonal
iodoform
Triclinic
boric acid
Rhombic
iodine
Orthorhombic
ritonavir (form II)
- reverse of liquefaction
- dehydration due to extreme conditions in the environment
Loss of Water
loss of water for emulsions
phase inversion in o/w emulsions; cracking
loss of water for suspensions and solutions
increased potency
loss of water for ointments
crumbling
loss of water for gels
syneresis
Management for Loss of water
- store in tight containers
- store in correct conditions
- add humectant
reaction between two or more ingredients that leads to a change in its
chemical properties
- a visible change is not necessarily observed
- original drug is no longer present
- may or may not retain form or state
Chemical Incompatibilities
- loss of electrons
- reducing agents
- dehydrogenation
- increase in oxidation state
- triggered by oxygen, light, metals
- manifests as change in color
Oxidation
Example of drugs that may undergo oxidation based on maam ka’s reviewer
- ascorbic acid
* epinephrine
Management of oxidation
- protect from oxygen and light
- add antioxidants
- keep oxidizing agents and reducing agents away from each other
- gain of electrons
- oxidizing agents
- hydrogenation
- decrease in oxidation state
Reduction
Test for reducing sugars
Tollen’s test
- neutralization
- evolution of gas
- changes in color
Acid-Base Reaction
An evolution of gas applied in drug dosage forms
effervescence
effervescent tablets composes of
NaHCO3 + tartaric acid/citric acid
Example of drugs with effervescence based on reviewer that starts with p
p-aminosalicylic acid
- involving water as solvent
- breaking-up of bonds with water
- most common type of incompatibility
- most common mechanism of drug degradation
Hydrolysis
Examples of drugs that involves degradation through hydrolysis based on reviewer
- lactams (penicillins, cephalosporins)
- esters (cocaine, physostigmine, aspirin, tetracaine, procaine, methyldopa)
- amides (dibucaine)
- imines (diazepam)
- glycosides
Management of hydrolysis
- store in tight containers
- add desiccants
- control pH
- refrigeration
- interaction of drug with solvent other than water
Solvolysis
- action or process of changing from an optically active compound into a racemic compound
or an optically inactive mixture - racemic mixture: equal amounts of dextro- (+) and levo- (-) isomers
Racemization
Examples of drugs involved in racemization based on reviewer
- thalidomide
- catecholamines
- local anesthetics
- formation of epimers
- interconversion of one epimer to another epimer
Epimerization
compounds with two or more chiral centers
Epimer
Examples of drugs that undergo interconversion of one epimer to another epimer
- tetracycline
* pilocarpine
- salting-out process
- two or more drugs interacting to form a new substance
Precipitation
Ca(OH)2 + CO2 → CaCO3↓ + H2O
Precipitation nani lols
-reducing agent (RA) + oxidizing agent (OA)
Explosive Mixture
Name two examples of an explosive mixture based on reviewer!!!!!!!!
• sugar + KMnO4 • glycerin + KMnO4
-cake formation
Cementation
An example of cementation
acacia + Bi salts
An example of gelatinization
acacia + Fe salts
-gel formation
Gelatinization
- formation of 5-hydroxymethylfurfural from dextrose
Polymerization
- degradation by light
- photooxidation
- photolysis
- remedy: protect from light; given at night; cover IV line with carbon paper
- manifests as change in color
Photochemical Degradation
Examples of drugs that can undergo photochemical degradation
- nifedipine
- nitroprusside
- riboflavin
- phenothiazines
- Adriamycin
- cisplatin
- amphotericin B
management of photchemical degradation
protect from light
- caused by a chemical or physical incompatibility when two or more drugs are mixed together
- occurs when drugs are mixed inappropriately in syringes or infusion fluids prior to administration
Pharmaceutic (in general najud ni sis. physicochemical instability najud)
phenytoin sodium will precipitate in an acidic pH. true or false?
true
aminophylline (basic pH) should be mixed with epinephrine which decomposes at
alkaline pH
false. it should not be mixed with epinephrine sis. daot jud na kay alkaline si aminophylline.
two or more drugs are administered, and response is different from
what is expected
- undesirable pharmacological interaction between two or more ingredients that leads to:
• potentiation of the therapeutic effects of the ingredients
• destruction of the effectiveness of one or more of the ingredients
• occurrence of a toxic manifestation within the patient
THERAPEUTIC INCOMPATIBILITIES
increase or decrease in pharmacological response due to the presence of another
drug, herbal medicine, food or drink, treatment, or environmental chemical agent
DRUG INTERACTIONS
drug, chemical, or food causing the interaction
Precipitant drug
drug affected by the interaction
Object drug
supported by well-proven clinical studies
Established
very likely but might not be proven clinically
Probable
might occur and some data might be available
Suspected
could occur and limited data are available
Possible
- doubtful
- no good evidence of an altered clinical effects is available
Unlikely
Drug interactions include:
- Drug-herbal
- Drug-food
- Drug-laboratory test
- Drug-drug
• pharmacokinetic
• pharmacodynamic
(Drug+Herbal) What interaction will happen with digoxin and st. john’s wort
decreased conc. of digoxin
(Drug+Herbal) What interaction will happen with warfarin, LMWH, heparin and garlic
bleeding or hemorrhage!!!!!!!!!!!
(Drug+Herbal) What interaction will happen with warfarin and asian ginseng?
decreased conc. of warfarin
(Drug+Herbal) What interaction will happen with barbiturates, BZDs and valerian
“double sedation”
(Drug+Herbal) What interaction will happen with hypoglycemic agents and ginseng
increased hypoglycemic effect
(Drug+Herbal) What interaction will happen with anti-HTN and licorice
antagonism