NURS 05505 Final Draft Pharm 1 Exam Review
Therapeutic Index (TI)
- The ratio of the dose that produces toxicity in half the population to the dose that
... [Show More] produces a clinically desired or effective response in half the population.
• A measure of a drug’s safety, because a large value indicates a wide margin between doses that are effective and doses that are toxic.
• High TI values are required for most drugs, some drugs with low therapeutic indices are routinely used to treat serious diseases.
• The risk of experiencing adverse effects is not as great as the risk of leaving the disease untreated.
- Example:
• Warfarin (Small therapeutic index): As dose of warfarin is increased, a greater fraction of the patients respond until eventually all patients respond. For this drug, the desired response is a two-to-threefold increase in the INR. However at higher doses, anticoagulation results in hemorrhage which occurs in a small percent of patients.
• Penicillin: (Large therapeutic index): Safe and common to give doses in excess of that which is minimally required to achieve a desired response without the risk of adverse effects.
• Other examples:
- Lithium (Narrow TI: Can be at risk for coma/brain damage or even death, can also induce serotonin syndrome)
- Vancomycin (Risk of Nephrotoxicity and Ototoxicity)
Practice Question:
1. Which is correct concerning the safety of using warfarin (with a small therapeutic index) versus penicillin (with a large therapeutic index)
a. Warfarin is a safer drug because it has a low therapeutic index.
b. Warfarin treatment has a high chance of resulting in dangerous adverse effects if bioavailability is altered.
c. The high therapeutic index makes penicillin a safe drug for all patients.
d. Penicillin treatment has a high chance of causing dangerous adverse effects if bioavailability is altered.
Rationale: Agents with a low TI (that is drugs for which dose is critically important) are those for which bioavailability critically alters the therapeutic and adverse effects.
Clinical Trials
- Phase 1
• Clinical evaluation is the first testing of a new compound in subjects for the purpose of establishing the tolerance of healthy human subjects at different doses; defining its pharmacological effects at anticipated therapeutic levels; studying its absorption, distribution, metabolism, and excretion patterns in humans.
- Phase 2:
• Performance of controlled studies on patients with the target disease or disorder to determine a compound’s potential usefulness and short-term risks. A relatively small number of patients, usually no more than several hundred subjects are enrolled.
- Phase 3:
• Trials are controlled and uncontrolled clinical trials of a drug’s safety and efficacy in hospital and out-patient settings. Gathers precise information on the drug’s efficacy for specific indications, determine whether the drug produces a broader range of adverse effects than those exhibited in the small study populations of the other two phases and identifies the best way of administering and using the drug for the purpose intended. [Show Less]