3 - Incompatibilities

Question 1

What is phenytoin used for?

Answer 1

• Generalized tonic-clonic seizures
• Simple/complex partial seizures
• Status epilepticus
• Tx/prevention of seizures after trauma/surgery

Question 2

What is important about the administration of phenytoin?

Answer 2

• IV dose is 50 mg/mL and must not exceed 50 mg/min or will cause severe hypotension or cardiac arrhythmias
• Elderly and those w/ CVD, shouldn’t exceed 25 mg/min

Question 3

What is the loading dose and maintenance dose of phenytoin?

Answer 3

• Loading = 10-15 mg/kg by slow infusion

- Maintenance = 100 mg q6-8h

Question 4

What are the cosolvents used w/ phenytoin and what do they do?

Answer 4

• Alcohol 10% and propylene glycol 40%

- Help solubilize phenytoin; remove the free acid that phenytoin would produce at lower pH

Question 5

What is used to adjust the pH of phenytoin?

Answer 5

NaOH to pH 12

Question 6

Is slow IV infusion of phenytoin recommended? Why or why not?

Answer 6

• Not recommended

- Lack of solubility and precipitation

Question 7

How is phenytoin administered (how is it prepared and given)?

Answer 7

100 mg or less is mixed in 50 mL NS and given over 5-15 min

Question 8

What was the methods used for dilution of phenytoin injections?

Answer 8

• Add 0.5 mL NS to 5 tubes using a 1 mL syringe
• Add 0.5 mL of phenytoin to tube 1, mix, and withdraw 0.5 mL of this solution to add to tube 2
• Repeat until tube 5 will have a final volume of 1 mL
• Repeat entire process using D5W instead of NS

Question 9

What are the results of the phenytoin injection test?

Answer 9

• Should precipitate right away in presence of D5W b/c water solubility is low and D5W takes away water for phenytoin to interact it, so will come out of water (precipitate) faster than in presence of NS
• W/ NS should take > 2 h to precipitate

Question 10

Describe the mechanism of aminoglycosides

Answer 10

Bind 30S ribosomal subunit to cause misreading of tRNA

Question 11

Which organisms are aminoglycosides effective against?

Answer 11

• Aerobic

- GN bacteria

Question 12

What is monitored when aminoglycosides are used?

Answer 12

Blood levels and sCr to avoid ototoxicity and nephrotoxicity

Question 13

When are aminoglycosides and beta-lactams used together?

Answer 13

For synergy in severe infections (ex: endocarditis caused by group D streptococcus)

Question 14

Methods of AG and beta-lactams test

Answer 14

Mix 1 mL of reconstituted beta-lactam w/ 1 mL of AG solution

Question 15

What were the results of the AG and beta-lactam test?

Answer 15

• Ampicillin, cefazolin and pen-G are compatible w/ AGs

- Cloxacillin is not compatible w/ gent or tobra b/c has a chlorine atom making its water solubility poor

Question 16

Which “common medications” were used to test incompatibilities of commercial products?

Answer 16

• Phenytoin
• Lidocaine
• KCl
• Epinephrine
• Diphenhydramine
• Aminophylline
• 0.5 M HCl
• 0.5 M NaOH

Question 17

What can parenteral drug incompatibilities cause?

Answer 17

• SEs
• Under-tx
• Occlusion

Question 18

What should be referenced when determining if parenteral drugs can be mixed?

Answer 18

• Manufacturer
• Concentration
• Diluents
• Order of mixing
• Time frames
• Temperature
• Test methods

Question 19

What can sometimes determine whether a combo is compatible or not?

Answer 19

Order of mixing and length of time mixing

Question 20

Weak drugs (acids/bases) depend on ___ of the solution

Answer 20

pH

Question 21

What can cause precipitation w/ weak acids/bases?

Answer 21

Large difference in solubility and altered pH

Question 22

If there is enough ___ in a solution, precipitation may not occur even w/ pH changes

Answer 22

Alcohol

Question 23

When does precipitation occur?

Answer 23

When the salt form is converted to a neutral free form by a pH change

Question 24

What should be done when handling solutions of weak electrolytes?

Answer 24

• Add a buffer
• Keep incompatible pH solutions separate
• Dilute final solution so the concentration of drug is less than precipitation concentration of neutral free form
• Use short expiration times

Question 25

When a drug is dissolved and another drug added forms a _____ w/ the first drug, precipitation can occur

Answer 25

Soluble salt

Question 26

What determines precipitation if a drug has an organic salt w/ an unusual counter ion?

Answer 26

Dependent on concentration and pH