Section 12 - Drug Incompatibilities

Question 1

____ can be a major hazard w/ pharmaceutical solutions

Answer 1

Unintended precipitation or degradation

Question 2

What can insoluble particles in intravenous solutions lead to?

Answer 2

• Adverse effects
• Potential under-treatment
• Occlusion of infusion lines
• Possible occlusion of patient capillaries

Question 3

Is it easy to predict precipitation of a pharmaceutical solution?

Answer 3

No

Question 4

What is important to note when interpreting compatibility reports?

Answer 4

• Drug manufacturers
• Drug concentrations
• Base solution, diluents, and manufacturer
• Order of mixing
• Time frames
• Temperature
• Test methods

Question 5

What will occur when a drug is dissolved in a cosolvent system and the product is diluted w/ water?

Answer 5

Drug will precipitate

Question 6

What will occur if digoxin injection is diluted w/ an aqueous injectable solution?

Answer 6

Precipitation

Question 7

What is the equation for the approximate relationship btwn solubility and solvent volume-fraction?

Answer 7

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

Question 8

What can happen when a solution contains 2 drugs w/ a large difference in the solubilities of the 2 forms?

Answer 8

One or both drugs may come out of solution

Question 9

What can happen when a drug that generates a different pH is added to the original drug solution?

Answer 9

One or both drugs may come out of solution

Question 10

What steps should be done when combining, diluting, or manipulating ionizable drugs?

Answer 10

• 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

Question 11

What must be done to the salt form a drug for precipitation to occur in an aqueous solution?

Answer 11

Salt form must be converted to neutral free form by changing pH

Question 12

How can you determine the resultant pH of a solution?

Answer 12

Check an appropriate reference or measure it

Question 13

Which drug solutions have acid pH’s?

Answer 13

• Phenothiazines
• Tetracycline HCl
• Ascorbic acid
• Glycopyrrolate
• Metaraminol bitartrate
• Morphine sulfate

Question 14

Which drug solutions have basic pH’s?

Answer 14

• Phenytoin sodium
• Aminophylline
• Sodium bicarbonate
• Sodium barbiturates

Question 15

How do you calculate the pH of precipitation for salts of weak bases?

Answer 15

• pH = pKa + log (So/St-So)
• St = final [ ] of drug in solution
• So = solubility of neutral free form of drug

Question 16

How do you calculate the pH of precipitation for salts of weak acids?

Answer 16

pH = pKa + log (St-So/So)

Question 17

What can be done to weak electrolyte solutions?

Answer 17

• 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

Question 18

What can be done for weak electrolyte solutions for IM injections?

Answer 18

Draw in separate syringes and give in different sites

Question 19

What can be done for weak electrolyte IV solutions?

Answer 19

Give at different times and flush the IV line btwn injections of the incompatible solutions

Question 20

What can happen when an added drug forms a sparingly soluble salt w/ the first drug?

Answer 20

Precipitation can occur

Question 21

What are some unusual counter ions found in drugs?

Answer 21

Mesylate, lactate, and succinate

Question 22

What should be done for a drug w/ an unusual counter ion?

Answer 22

Be cautious when adding another salt (more combinations are compatible, but better to be safe); often more common salt forms are less soluble

Question 23

What are examples of alkaloids?

Answer 23

Amine drugs of plant origin (atropine, cocaine, codeine, colchicine, morphine, and ephedrine)

Question 24

Alkaloids are ___ w/ ___ water solubility

Answer 24

Bases; poor

Question 25

What are examples of compounds that may cause alkaloids to precipitate? What do these compounds do to cause precipitation?

Answer 25

• Citrate salts
• Tannins (from wild cherry syrup)
• Iodide
• Picric acid
• Most precipitation is caused by change in pH of the solution

Question 26

What can prevent precipitation of an alkaloid?

Answer 26

Sometimes, addition of alcohol or glycerin

Question 27

Solubility of most drugs ____ as temp decreases

Answer 27

Decreases

Question 28

What is recommended w/ respect to temp to retard microbial growth?

Answer 28

Refrigeration

Question 29

What is a disadvantage to refrigeration?

Answer 29

May cause problems w/ precipitation

Question 30

What are some examples of parenteral drugs where refrigeration isn’t recommended b/c of precipitation?

Answer 30

• Fluorouracil
• Cisplatin
• Cotrimoxazole
• Metronidazole
• Some brands of aminophylline

Question 31

Which reactions can occur when drugs are mixed together and can result in drug instability?

Answer 31

• Hydration
• Decarboxylation
• Additions
• Schiff’s base formation

Question 32

What is an example of drug incompatibilities?

Answer 32

Reaction btwn beta-lactam group of penicillins/cephalosporins and amino group of aminoglycoside antibiotics (forms inactive amide)

Question 33

How is a Schiff’s base formed?

Answer 33

Reaction btwn primary amine and aldehyde or ketone functional groups

Question 34

What is a Maillard reaction?

Answer 34

Reaction btwn amine group and hydroxyl group of a sugar