test 2 part 2

Question 1

Continuous Infusion Regimen

Answer 1

• Rate of drug entry into body is constant

* Plasma concentration of drug rises until steady state is reached

Question 2

Steady-state Plasma

Concentration (Css)

Answer 2

•Drug elimination equals the rate of administration

Question 3

Relationship between infusion rate and concentration steady-state (Css)

Answer 3

• Css is directly proportional to infusion rate

* Example: infusion rate doubled, then Css is doubled

Question 4

Relationship between clearance and concentration steady-state (Css)

Answer 4

• Inversely proportional to clearance of drug
• Anything that decreases clearance will increase Css (liver/renal disease)
• Anything that increases clearance will decrease Css (high metabolism, diarrhea)

Question 5

What is the Length of Time to Reach Css?

Answer 5

• Rate constant to reach steady state is equal to the rate constant for total body elimination of drug (t1/2)
• Sole determinate of the rate that a drug achieves steady state is the half-life

Question 6

Steady-state concentration based on half-life

Answer 6

•Drug concentration approaches 50% of Css after the first half-life

• 75% at two half-lives
• 87.5% at three half-lives
• 93.75% at four half-lives
• 96.875% at five half-lives
• usually will reach steady state between 4 and 5 half-lives

Question 7

Fixed-dose/fixed-time Regimens (IV)

Answer 7

• More convenient than IV infusion

* Results in fluctuating levels of drug

Question 8

Intravenous Fixed-time Regimens

Answer 8

• Drug given at intervals shorter than 5 half-lives
• Some drug from the first dose remains in body when the second dose is administered, some drug from the second dose remains when the third dose is given, and so on

Question 9

Oral Fixed-dose Regimens

Answer 9

•Css is influenced by the rate of absorption and rate of elimination

Question 10

Optimization of Dose

Answer 10

•Goal is to maintain drug plasma concentration within the therapeutic window

Question 11

Therapeutic Window

Answer 11

•Safe range between the minimum therapeutic concentration and the minimum toxic concentration

Question 12

Two Ways to Achieve Optimization of Dose

Answer 12

• Loading dose

* Maintenance dose

Question 13

Loading Dose

Answer 13

•Administered to achieve rapid desired plasma levels of drug
•Single dose or series of doses
•Used with drug that have longer half-lives
•Long time to reach Css
•Followed by maintenance dose
-dependent on volume and distribution

Question 14

Loading Dose Equation (IV)

Answer 14

Loading Dose (LD) = Vd
x Css

Question 15

A patient weighs 60 kg and a target plasma concentration of 7.5 mg/L of Theophylline is required. The Vd of Theophylline is 0.5L/kg. What is the IV loading dose for this patient?

Answer 15

LD = 0.5 L/kg x 7.5 mg/L = 3.75 mg/kg x 60 kg = 225 mg

Question 16

Maintenance Dose (MD)

Answer 16

•Maintain plasma concentration of drug within the therapeutic range

Question 17

Maintenance Dose Equation (IV)

Answer 17

Maintenance Dose (MD) = CL x Css

Question 18

A patient weighs 60 kg, the target Theophylline plasma concentration is 10 mg/L. Clearance of Theophylline is 2.8 L/hr. A loading dose of Theophylline has been given to relieve acute bronchial asthma in this patient. What would be the maintenance dose for this patient?

Answer 18

2.8 L/hr x 10 mg/L = 28 mg/hr / 60 kg = 0.47 mg/kg/hr

Question 19

Dosage Adjustment

Answer 19

• Diminished renal or hepatic blood flow
  
  • Hemorrhage, heart failure
• Renal/hepatic disease
  
  • Cirrhosis, kidney failure
• Children
• Elderly
• Increased hepatic blood flow, increased metabolism, and decreased protein binding

Question 20

Drug Approval Process

Answer 20

1. in vitro studies
2. animal testing
3. clinical testing
4. marketing

Question 21

Investigation New Drug Exemption Application (IND)

Answer 21

• Submitted by the manufacturer to the FDA
• Includes all the preclinical data collected up to time of submission
  
  • Pharmacological effects
  • Hepatic and renal monitoring
  • Blood and urine test
  • Reproductive effects
  • carcinogenicity
• Includes detailed proposal for clinical trials

Question 22

Clinical Trials

Answer 22

• Divided into three phases
• Provides information for a New Drug Application (NDA)
• NDA includes all results of preclinical and clinical testing and provides the request for FDA approval

Question 23

Phase 1 (clinical trial)

Answer 23

• Evaluates dose-response relationship
• Performed on small number of healthy volunteers
  
  • (20-100)

Question 24

Phase 2 (clinical trial)

Answer 24

• Performed on a moderate number of patients with the target disease
  
  • (100-200)
• Placebo or positive control included
• Single-blinded or double-blinded design
• Evaluates efficacy

Question 25

Phase 3 (clinical trial)

Answer 25

• Performed on many patients, in many centers, with many clinicians
  
  • 1000-5000
• Includes placebo and positive controls
• Double-blinded design
• Further evaluation of therapeutic effect and discovery new toxicities
• Comparison with older drug therapies
• If successful completion, NDA is submitted to the FDA
• If NDA approved, drug can be marketed and Phase 4 begins

Question 26

Phase 4 (clinical trial)

Answer 26

• Post-marketing surveillance
• Evaluate any toxicities that occur
• Manufacturers are required to report any adverse drug reactions to the FDA on a regular basis
• Not as rigidly regulated as the other phases