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
(Drug+Herbal) What interaction will happen with MAOIs, PPA, epinephrine,
caffeine and ma huang
increased blood pressure; irregular heart rate
(Drug+food) CNS depressants and caffeine
antagonism
warfarin and green leafy veggies
antagonism
tetracycline,
quinolone + dairy products
chelation/complexation causing decreased
tetracycline absorption
MAOIs + tyramine-rich food (beer,
cheese, wine, chicken
liver)
decreased metabolism of norepinephrine causing
hypertensive crisis
INH + histamine-rich food
(cheese, tropical fish,
tuna)
flushing reaction with headache, difficulty of
breathing, nausea, tachycardia
bisacodyl + milk
alteration of pH causing premature liberation of
bisacodyl
ASA + caffeine
alteration of pH causing increased ASA
absorption
metronidazole + alcohol (wine, beer)
disulfiram-like effect
spironolactone + banana
hyperkalemia
digoxin + oatmeal
decreased A of digoxin
bisphosphonates + any food
decreased BA
drugs increased by food
acarbose griseofulvin itraconazole metoprolol theophylline phenytoin metolazone
drugs decreased by food
alendronate captopril erythromycin stearate isoniazid penicillamine penicillins tetracycline quinolones
drugs that absorption can be increased by high fat-containing food
griseofulvin, theophylline, phenytoin, and metolazone
___ and ___are affected only to a lesser extent
doxycycline and minocycline
(Drug + Lab) penicillin, chloramphenicol, vitamin C, INH, streptomycin and glucose in urine (Benedict's test)
false positive result
(Drug + Lab) chlordiazepoxide and thyroid function test (I131)
false negative result
(Drug + Lab) rifampicin
vitamin B2
chloroquine
metronidazole and urinalysis
change in color: red-orange intense yellow brown ash gray
(Drug + Lab) allopurinol and blood cholesterol levels
false positive result
- processes of ADME of drugs
- “what the body does to the drugs”
Pharmacokinetics
Alterations in Absorption (A)
- Alteration of pH
- Complex Formation
- Decreased Gastric Emptying Time
- Increased Gastric Emptying Time
- Increased GI Motility
- Adsorption of Drug
- Interruption of Enterohepatic Circulation
- Inhibition of GI Microbial Flora
(Alteration of pH) antacid + bisacodyl
premature liberation of bisacodyl
(Alteration of pH)antacid + ketoconazole
decreased ketoconazole A
(Alteration of pH) antacid + salicylates
decreased salicylate A
(Complex Formation) tetracycline + metal-containing drugs
decreased tetracycline A
(Complex Formation) fluoroquinolones + metal-containing drugs
decreased fluoroquinolone A
(Complex Formation) cholestyramine + digoxin
decreased digoxin A
(Complex Formation) cholestyramine + warfarin
decreased warfarin A
(Complex Formation) penicillamine + metal-containing drugs
decreased penicillamine A
(Complex Formation) sucralfate + levothyroxine
decreased thyroxine A
(Decreased Gastric Emptying Time) atropine + antacid
increased antacid A
(Decreased Gastric Emptying Time) atropine +amphetamine
decreased amphetamine A
(Increased Gastric Emptying Time)
nicotine + antacid
decreased antacid A
(Increased GI Motility) laxative or cathartic + any drug
decreased drug A
(Adsorption of Drug) adsorbent + any drug
decreased drug A
(Interruption of Enterohepatic Circulation) antibiotics + OCP
decreased OCP A
(Inhibition of GI Microbial Flora) antibiotics + digoxin
increased digoxin A
erythromycin decreases bacterial inactivation of digoxin. true or false.
true
Alterations in Distribution (D)
-Displacement from Protein Binding Sites
warfarin + phenylbutazone
hemorrhage
glibenclamide + phenylbutazone
hypoglycemia
OHA + ASA
hypoglycemia
bilirubin + salicylates
kernicterus
phenytoin + warfarin
gingival hyperplasia
tolbutamide + sulfonamide
hypoglycemia
epinephrine + lidocaine
restricted blood flow
Alterations in Metabolism (M)
Enzyme INDUCERS and Enzyme INHIBITORS
Enzyme INDUCERS
(GSMPRC) Griseofulvin St. John’s Wort Meprobamate Phenytoin Phenobarbital Rifampicin Carbamazepine Chronic Alcoholism Cigarette Smoking
or (BS CRAP GPS) Barbiturates St. John’s Wort Carbamazepine Rifampicin Alcoholism (chronic) Phenytoin Griseofulvin Phenobarbital Sulfonylureas
Enzyme INHIBITORS
(MEDVICKSGAO) Metronidazole Erythromycin Disulfiram, Diltiazem Valproic acid, Verapamil Isoniazid, Indinavir Cimetidine Chloramphenicol Ciprofloxacin Clarithromycin Ketoconazole Saquinavir Grapefruit juice Acute Alcoholism Omeprazole
or
(SICKFACES.COM) Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Acute Alcoholism Chloramphenicol Erythromycin Sulfonamides Ciprofloxacin Omeprazole Metronidazole Grapefruit juice
potent enzyme inhibitor
Grapefruit
- regular beer =
12 fl. oz.
- malt liquor =
8-9 fl. oz.
- table wine =
5 fl. oz.
Alterations in Excretion (E)
- Alteration of Urinary pH
- Alteration of Active Transport
(Alteration of Urinary pH) salicylates + NaHCO3 →
increased renal E of salicylates
(Alteration of Urinary pH) amphetamine + NH4Cl →
increased renal E of amphetamine
(Alteration of Active Transport) probenecid + penicillin
decreased renal E of penicillin
(Alteration of Active Transport) probenecid + indomethacin
decreased renal E of indomethacin
(Alteration of Active Transport) NSAIDs + lithium salts
decreased renal E of lithium salts
(Alteration of Active Transport) NSAIDs + methotrexate
decreased renal E of methotrexate
(Alteration of Active Transport) quinidine + digoxin
decreased renal and non-renal E of digoxin
(Alteration of Active Transport) amiodarone + digoxin
decreased renal and non-renal E of digoxin
(Alteration of Active Transport) corticosteroids + ASA
increased renal E of ASA
– the MOA and pharmacologic effects of drugs
- “what the drug does to the body”
Pharmacodynamics
- 1 + 1 = 2
- response is equal to the combined effects of individual drugs
Additive Effects
- 1 + 1 = 3 or > 2
- response is greater than the combined effects of the individual drugs
Synergistic Effects
- 1 + 0 = 2
- a drug with no inherent activity will enhance the effect of another drug
Potentiation
- 1 + 1 = 0
- a drug inhibits the effect of the other
Antagonism
- alcohol + barbiturates →
- alcohol + antihistamines →
- alcohol + CNS depressants →
- alcohol + chloral hydrate →
- benzodiazepine + antihistamine →
increased sedation
alcohol + chlorpropamide
increased hypoglycemic effects
flecainide + verapamil
increased negative inotropic and chronotropic effects
prazosin + beta-blocker
orthostatic hypotension
beta-blockers + non-DHP CCBs
heart block
antidepressants + azithromycin
QT interval prolongation
sulfamethoxazole + trimethoprim
co-trimoxazole
sulfadoxine + pyrimethamine
Fansidar
amoxicillin + clavulanic acid
increased amoxicillin’s antibiotic effect
ampicillin + sulbactam
increased ampicillin’s antibiotic effect
piperacillin + tazobactam
increased piperacillin’s antibiotic effect
levodopa + carbidopa
increased levodopa’s effect
(antagonism) phenoxybenzamine +
catecholamines
(antagonism) warfarin +
vitamin K
(antagonism) heparin +
protamine sulfate
(antagonism) opioids +
naloxone
(antagonism) benzodiazepine +
flumazenil
(antagonism) atropine +
physostigmine
(antagonism) procaine +
sulfonamides
(antagonism) epinephrine +
acetylcholine
(antagonism) propranolol +
albuterol
(antagonism) OHAs +
glucocorticoids
(antagonism) levodopa +
antipsychotics or neuroleptics
(antagonism) tetracycline +
penicillin
aminoglycoside + loop diuretic
increased nephrotoxicity and ototoxicity
aminoglycoside + neuromuscular blocker
increased muscle relaxation or paralysis
diuretic + neuromuscular blocker
increased hypokalemia causing increased muscle
relaxation or paralysis
diuretic + digitalis
increased hypokalemia causing digitalis toxicity
diuretic + tetracycline
increased BUN levels
Risk for drug interactions:
- Multiple drugs – more drugs, more potential for drug interactions
- Multiple prescribers
- Patient risk factors – elderly, predisposing illness (diabetes, asthma, alcoholism)
Prevention:
- Review drug history and patient risk factors
2. Avoid complex therapeutic drug regimens
Management:
- Be knowledgeable on the MOA of the drugs being used
- Suggest a different drug for significant drug interactions or consider therapeutic alternatives
- Instruct patient as to timing of the medication
- Educate the patient
- Monitor the patient for response, adverse events, and drug levels
Alcohol + sedative-hypnotics,
opioid analgesics,
TCAs,
antihistamines
- additive CNS
- depression
- sedation
- ataxia
- increased risk of accidents
aminoglycosides + loop diuretics
enhanced ototoxicity
antacids + iron supplements,
fluoroquinolones,
ketoconazole,
tetracyclines
decreased gut absorption
antibiotics + estrogens, including oral
contraceptives
many antibiotics lower estrogen levels
and reduce contraceptive effectiveness
antihistamines (H1-blockers) + antimuscarinics,
sedatives
additive effects with the drugs involved
antimuscarinic drugs + drugs absorbed from small intestine
slower onset of effect
barbiturates (esp. phenobarbital) + azoles, CCBs, propranolol, quinidine, steroids, warfarin, and many other drugs metabolized in the liver
increased clearance of the affected
drugs
beta-blockers + insulin
masking of symptoms of hypoglycemia
beta-blockers + prazosin
increased “first-dose” syncope
bile acid-binding resins + acetaminophen,
digitalis,
thiazides,
thyroxine
reduced absorption of the affected
drugs
carbamazepine + doxycycline, estrogen, haloperidol, theophylline, warfarin
reduced effect of the affected drugs
cimetidine + benzodiazepines, lidocaine, phenytoin, quinidine, theophylline, warfarin
increased effect
disulfiram,
metronidazole,
certain cephalosporins + ethanol
increased hangover effect
erythromycin + cisapride,
quinidine,
sildenafil,
theophylline
risk of toxicity
ketoconazole and other azoles + benzodiazepines, cisapride, cyclosporine, fluoxetine, lovastatin, omeprazole, quinidine, tolbutamide, warfarin
risk of toxicity
MAOIs + catecholamine releasers
amphetamine, ephedrine
increased NE in the sympathetic nerve
endings
MAOIs + tyramine-containing food and
beverages
hypertensive crisis
NSAIDs + anticoagulants
increased bleeding tendency
NSAIDs + ACE inhibitors
decreased antihypertensive efficacy
NSAIDs + loop diuretics,
thiazides
reduced diuretic efficacy
phenytoin + doxycycline, methadone, quinidine, steroids, verapamil
increased metabolism of drugs involved
quinidine + digoxin
increased digoxin levels
rifampicin + azole antifungals, corticosteroids, methadone, theophylline, tolbutamide
decreased efficacy of the drugs involved
salicylates + corticosteroids
additive toxicity to gastric mucosa
salicylates + heparin,
warfarin
increased bleeding tendency
salicylates + methotrexate
decreased clearance of drug involved
salicylates + sulfinpyrazone
decreased uricosuric effect
SSRIs + MAOIs,
meperidine,
TCAs
Serotonin syndrome
thiazides + digitalis
increased risk of digitalis toxicity
thiazides + lithium
increased plasma levels of lithium
warfarin + cimetidine,
erythromycin,
lovastatin,
metronidazole
increased anticoagulant activity
warfarin + anabolic steroids, aspirin, NSAIDs, quinidine, thyroxine
increased anticoagulant effect
warfarin + barbiturates,
carbamazepine,
phenytoin,
rifampicin
decreased anticoagulant effect