Section 12 - Drug Incompatibilities Flashcards
____ can be a major hazard w/ pharmaceutical solutions
Unintended precipitation or degradation
What can insoluble particles in intravenous solutions lead to?
- Adverse effects
- Potential under-treatment
- Occlusion of infusion lines
- Possible occlusion of patient capillaries
Is it easy to predict precipitation of a pharmaceutical solution?
No
What is important to note when interpreting compatibility reports?
- Drug manufacturers
- Drug concentrations
- Base solution, diluents, and manufacturer
- Order of mixing
- Time frames
- Temperature
- Test methods
What will occur when a drug is dissolved in a cosolvent system and the product is diluted w/ water?
Drug will precipitate
What will occur if digoxin injection is diluted w/ an aqueous injectable solution?
Precipitation
What is the equation for the approximate relationship btwn solubility and solvent volume-fraction?
LogSt = vf(water) * logS(water) + vf (solvent) * logS(sol)
- Vf(water) = volume fraction of water
- S(water) = solubility of drug in water
- Vf(sol) = volume fraction of cosolvent
- S(sol) = solubility of drug in solvent
What can happen when a solution contains 2 drugs w/ a large difference in the solubilities of the 2 forms?
One or both drugs may come out of solution
What can happen when a drug that generates a different pH is added to the original drug solution?
One or both drugs may come out of solution
What steps should be done when combining, diluting, or manipulating ionizable drugs?
- Check solubilities of all drugs in solvents involved (both the salt and free forms)
- If solvent system contains sufficient alcohol, precipitation may not occur even w/ a pH change
- Determine the salt type of the drug
- Estimate the resultant pH of the solution
What must be done to the salt form a drug for precipitation to occur in an aqueous solution?
Salt form must be converted to neutral free form by changing pH
How can you determine the resultant pH of a solution?
Check an appropriate reference or measure it
Which drug solutions have acid pH’s?
- Phenothiazines
- Tetracycline HCl
- Ascorbic acid
- Glycopyrrolate
- Metaraminol bitartrate
- Morphine sulfate
Which drug solutions have basic pH’s?
- Phenytoin sodium
- Aminophylline
- Sodium bicarbonate
- Sodium barbiturates
How do you calculate the pH of precipitation for salts of weak bases?
- pH = pKa + log (So/St-So)
- St = final [ ] of drug in solution
- So = solubility of neutral free form of drug
How do you calculate the pH of precipitation for salts of weak acids?
pH = pKa + log (St-So/So)
What can be done to weak electrolyte solutions?
- Control pH by adding a buffer
- Keep drug solutions w/ incompatible pH’s separate
- Dilute final solution so that concentration is below the precipitation concentration
What can be done for weak electrolyte solutions for IM injections?
Draw in separate syringes and give in different sites
What can be done for weak electrolyte IV solutions?
Give at different times and flush the IV line btwn injections of the incompatible solutions
What can happen when an added drug forms a sparingly soluble salt w/ the first drug?
Precipitation can occur
What are some unusual counter ions found in drugs?
Mesylate, lactate, and succinate
What should be done for a drug w/ an unusual counter ion?
Be cautious when adding another salt (more combinations are compatible, but better to be safe); often more common salt forms are less soluble
What are examples of alkaloids?
Amine drugs of plant origin (atropine, cocaine, codeine, colchicine, morphine, and ephedrine)
Alkaloids are ___ w/ ___ water solubility
Bases; poor
What are examples of compounds that may cause alkaloids to precipitate? What do these compounds do to cause precipitation?
- Citrate salts
- Tannins (from wild cherry syrup)
- Iodide
- Picric acid
- Most precipitation is caused by change in pH of the solution
What can prevent precipitation of an alkaloid?
Sometimes, addition of alcohol or glycerin
Solubility of most drugs ____ as temp decreases
Decreases
What is recommended w/ respect to temp to retard microbial growth?
Refrigeration
What is a disadvantage to refrigeration?
May cause problems w/ precipitation
What are some examples of parenteral drugs where refrigeration isn’t recommended b/c of precipitation?
- Fluorouracil
- Cisplatin
- Cotrimoxazole
- Metronidazole
- Some brands of aminophylline
Which reactions can occur when drugs are mixed together and can result in drug instability?
- Hydration
- Decarboxylation
- Additions
- Schiff’s base formation
What is an example of drug incompatibilities?
Reaction btwn beta-lactam group of penicillins/cephalosporins and amino group of aminoglycoside antibiotics (forms inactive amide)
How is a Schiff’s base formed?
Reaction btwn primary amine and aldehyde or ketone functional groups
What is a Maillard reaction?
Reaction btwn amine group and hydroxyl group of a sugar
