Narrow Therapeutic Drug Index (NTDIs)

Question 1

Narrow Therapeutic Index Drugs

Answer 1

-Drugs in which small changes in dose or serum concentration can lead to significant changes in effectiveness or toxicity.
-aka critical dose drugs

Question 2

Subtherapeutic

Answer 2

Drug dose or concentration is below what is needed for the drug to be effective (too little drug)

Question 3

Supratherpeutic

Answer 3

Drug dose or concentration is above the point at which the drug is safe, posing risk of toxicity (too much drug)

Question 4

Characteristics of Narrow Therapeutic Index Drugs

Answer 4

1. Little difference between subtherapeutic and supratherapeutic doses or concentrations
2. Subtherapeutic concentrations result from marked therapeutic failure
3. Serum concentrations or other markers of drug activity are monitored
4. Dose changes tend to be done in small increments

Question 5

Cyclosporine & Tacrolimus (Immunosuppressive Agents) Drugs Deemed as NTID

Answer 5

-Both are immune suppressive drugs used to prevent transplanted organ rejection

Question 6

Consequences of subtherapeutic and supratherapeutic concentations of cyclosporine or tacrolimus

Answer 6

-Sub therapeutic concentrations can lead to transplant rejection
-Supra therapeutic concentrations can lead to toxicity, characterized by kidney failure

Question 7

Digoxin -Drugs Deemed as NTID

Answer 7

-Serum concentration monitoring is required

Question 8

Consequences of digoxin toxicity

Answer 8

-Drug interactions or reduced kidney function increase risk for supratherapeutic levels
-Side effects include nausea, vomiting, bradycardia, & life threatening arrhythmias

Question 9

Carbamazepine, Phenytoin, Valproic Acid (Anti-Epileptics)- Deemed as NTIDs

Answer 9

-Serum concentration monitoring is required
-Doses & target levels may also depend on the individual patient seizure threshold

Question 10

Consequences of subtherapeutic doses or levels of carbamazepin, phenytoin, or valproic acid

Answer 10

-Subtherapeutic concentrations can lead to break-through seizures,
-Whereas Subtherapeutic can lead to numerous toxicities

Question 11

Levothrroxine (Thyroid Hormone Replacement)-Deemed NTIDs

Answer 11

-Monitoring of thyroid stimulating hormone (TSH) required

Question 12

Consequences of Levothrroxine (Thyroid Hormone Replacement)

Answer 12

-Increase in TSH indicate lower drug effect & vice versa
-Low TSH levels indicate high drug effect (infer toxicity)

Question 13

Lithium Carbonate (Mood Stabilizers)-Deemed NTIDs

Answer 13

-Serum concentration monitoring required

Question 14

Consequences of lithium toxicity

Answer 14

-Toxicity includes tremors, altered mental status, and kidney failure-can be long lasting

Question 15

Theophylline- Deemed NTIDs

Answer 15

-Drug used for asthma & COPD
-Serum Concentration monitoring is required

Question 16

Consequences of theophylline toxicity

Answer 16

-Toxicity includes: arrhythmias, seizures, and metabolic disorders

Question 17

Warfarin- Deemed NTIDs

Answer 17

-Requires monitoring of INR, which is a measure of the ability of the blood to clot

Question 18

How is Warfarin INR levels monitored?

Answer 18

-high INR levels indicate slower clotting times
-low INR levels indicate faster clotting times

Question 19

Consequences of Subtherapeutic and Supratherapeutic Warfarin concentrations

Answer 19

Sub therapeutic concentrations can lead to strokes or other blood clots
-Supra therapeutic concentrations can lead to bleeding, ranging from mild to life threatening (brain hemorrhage
-Numerous drug & food interactions & genetic differences make this drug particularly problematic

Question 20

LIST OF NARROW THERAPEUTIC INDEX DRUGS (10)

Answer 20

-Calporic acid
-Carbamazepine
-Cyclosporine
-Digoxin
-Levothyroxine
-Llithium carbonate
-Phenytoin
-Tacrolimus
-Theophylline
-Warfarin