Chap 3 Pharmacokinetics

Question 1

Volume of distribution (apparent)

Answer 1

The ratio of the amount of drug in the body to the drug concentration in the plasma or blood. Units: liters

Question 2

Clearance

Answer 2

The ratio of the rate of elimination of a drug to the concentration of the drug in the plasma or blood. Units: volume/time, eg, mL/min or L/h

Question 3

Half-life

Answer 3

The time required for the amount of drug in the body or blood to fall by 50%. For drugs eliminated by first-order kinetics, this number is a constant regardless of the concentration. Units: time

Question 4

Bioavailability

Answer 4

The fraction (or percentage) of the administered dose of drug that reaches the systemic circulation

Question 5

Area under the curve (AUC)

Answer 5

The graphic area under a plot of drug concentration versus time after a single dose or during a single dosing interval. Units: concentration × time; eg, mg min/mL

Question 6

Peak and trough concentrations

Answer 6

The maximum and minimum drug concentrations achieved during repeated dosing cycles

Question 7

Minimum effective concentration (MEC)

Answer 7

The plasma drug concentration below which a patient’s response is too small for clinical benefit

Question 8

First-pass effect, presystemic elimination

Answer 8

The elimination of drug that occurs after administration but before it enters the systemic circulation (eg, during passage through the gut wall, portal circulation, or liver for an orally administered drug)

Question 9

Steady state

Answer 9

In pharmacokinetics, the condition in which the average total amount of drug in the body does not change over multiple dosing cycles (ie, the condition in which the rate of drug elimination equals the rate of administration)

Question 10

Biodisposition

Answer 10

Often used as a synonym for pharmacokinetics;

-the processes of drug absorption, distribution, and elimination.

Sometimes used more narrowly to describe elimination

Question 11

The effective drug concentration is the concentration of a drug at the _______

Answer 11

receptor site

Question 12

(Vd)

Answer 12

apparent volume of distribution (Vd)

Question 13

(CL)

Answer 13

clearance (CL)

Question 14

The volume of distribution (Vd) relates the amount of _____ to the ____ according to the following equation:

Answer 14

drug in the body

plasma concentration

Vd= Amount of drug in the body

Plasma drug concentration (Units =Volume)

Question 15

Clearance equation

Answer 15

Clearance (CL) relates the rate of elimination to the plasma concentration:

CL= Rate of elimination of drug (divided) by Plasma drug Concentration

Units: Volume per unit time

Note: For a drug eliminated with first-order kinetics, clearance is a constant;

Question 16

CLerence depends of what factors

Answer 16

Clearance depends on the drug, blood flow, and the condition of the organs of elimination in the patient.

Question 17

Most drugs in clinical use obey the first-order kinetics rule described in the text.

Name 3 important drugs that do not?

Answer 17

1. ethanol
2. aspirin
3. phenytoin

Question 18

What is 1/2 life

Answer 18

Half-life (t 1/2) is a derived parameter, completely determined by Vd and CL.

Like clearance, half-life is a constant for drugs that follow first-order kinetics.

Half-life can be determined graphically from a plot of the blood level versus time

Question 19

1/2 life equation

Answer 19

t 1/2 = 0.693×Vd

CL (Units = Time)

Question 20

bioavailability

Note:

Answer 20

bioavailability of a drug is the fraction (F) of the adminis- tered dose that reaches the systemic circulation

Note: bioavailability is generally reduced by incomplete absorption (and in the intestine, expulsion of drug by intestinal transporters), first-pass metabolism, and any distribution into other tissues

Question 21

The area under the curve (AUC)

Graph

Answer 21

The area under the curve (AUC) is used to calculate the bioavailability of a drug. The AUC can be derived from either single- dose studies (left) or multiple-dose measurements (right). Bioavailability is calculated from AUC(route)/AUC(IV).

Question 22

The oral route of administration is the most likely to have a large first-pass effect and therefore low bioavailability. What tissues contribute to this effect?

Answer 22

The oral route of administration entails passage of the drug through the gastric and intestinal contents, the epithelium and other tissues of the intestinal wall, the portal blood, and the liver before it enters the systemic circulation for distribution to the body. Metabolism by enzymes in any of these tissues, expul- sion by drug transporters, and excretion into the bile all may contribute to the first-pass effect of oral administration.

Question 23

Maintenance Dosage

Equation:

Note:

Answer 23

Because the maintenance rate of drug administration is equal to the rate of elimination at steady state (this is the definition of steady state), the maintenance dosage is a function of clearance

Equation:

Dosing rate = CL × Desired plasma concentratition Bioavailability

Note: If it is important to maintain a concentration above the mini- mum therapeutic level at all times, either a larger dose is given at long intervals or smaller doses at more frequent intervals

Question 24

Loading Dose equation:

note:

Answer 24

Loading dose = Vd × Desired plasma concentration Bioavailability

Note:

clearance does not enter into this computation. If the loading dose is large (Vd much larger than blood volume), the dose should be given slowly to prevent toxicity due to excessively high plasma levels during the distribution phase.

Question 25

therapeutic window

graph:

Answer 25

The therapeutic window is the safe range between the minimum therapeutic concentration and the minimum toxic concentration of a drug.

Question 26

The most important renal variable in drug elimination is ____ ___ ____, and ____ ___ is a convenient approximation of GFR

Equation:

Answer 26

glomerular filtration rate (GFR)

creatinine clearance (CLcr)

Equation:

Corrected dosage = Average dosage ×

Patient’s CLcr

100 mL/min

Question 27

If drug is cleard partly by the kidney and partly by othre routes…..the Corrected dosage equation shold be applied to the part of the dose that is eliminated by the kidney

Ex: cleared by which organs and how

Answer 27

For example, if a drug is 50% cleared by the kidney and 50% by the liver and the normal dosage is 200 mg/d, the hepatic and renal elimination rates are each 100 mg/d.

Question 28

Note: renal functions is alreted by many _____ and is often decreases in older patients. CLcr can be meansred directly however requires careful measurements of both _____ ____ ____ and ____ ____ ____ over 12 or ____ hrs

Answer 28

Diseases

serum creatinine concentration

total urine creatininine

24

Question 29

Metformin

Answer 29

Type of Medicine known as a biguanide.

This works to lower the amount of sugar in the blood of people with diabetes. It does this by lowering the amount of sugar produced in the liver, and also increasing the sensitivity of muscle cells to insulin.

Question 30

Biguanide

Answer 30

The term biguanide refers to a group of oral type 2 diabetes drugs that work by preventing the production of glucose in the liver, improving the body’s sensitivity towards insulin and reducing the amount of sugar absorbed by the intestines

Question 31

How is Metformin prescibed:

Answer 31

Metformin is usually prescribed as a single treatment (monotherpay), but it can also be combined with other medication in a single tablet -

Ex: metformin + pioglitazone (Competact),

Question 32

Explain how Biguanides work?

Answer 32

Biguanides work by preventing the liver from converting fats and amino-acids into glucose from the blood

They also activate an enzyme (AMPK) which helps cells to respond more effectively to insulin and take in glucose from the blood.

Question 33

Tobramycin

Answer 33

• Tobramycin* is an aminoglycoside antibiotic derived from Streptomyces tenebrarius that is used to treat various types of bacterial infections, particularly Gram-negative infections.
• Tobramycin* treats only bacterial eye infections and does not work for other types of eye infections
• Tobramycin* does not pass the gastro-intestinal tract, so for systemic use it can only be given intravenously or by injection into a muscle

Question 34

Verapamil

Answer 34

Medication used for the treatment of high blood pressure

Angina (chest pain from not enough blood flow to the heart) supraventricular tachycardia

It may also be used for the prevention of migraines and cluster headaches

Given by mouth or by injection into a vein

Question 35

Phenytoin (PHT)

Answer 35

Phenytoin (PHT), sold under the brand name Dilantin

• an anti-seizure medication.

It is useful for the prevention of tonic-clonic seizures and focal seizures, but not absence seizures.

The intravenous form is used for status epilepticus that does not improve with benzodiazepines.

Question 36

Benzodiazepines

Answer 36

Benzodiazepines are a class of psychoactive drugs used to treat a range of conditions, including anxiety and insomnia and seizures, relax the muscles, and induce sleep.

Question 37

Lidocaine

Answer 37

Lidocaine, also known as lignocaine, is a medication used to numb tissue in a specific area (local anesthetic). It is also used to treat ventricular tachycardia and to perform nerve blocks.

10 min to 20 min

Question 38

Theophylline

Answer 38

Theophylline, also known as 1,3-dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma

Question 39

Procainamide

Answer 39

Procainamide is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias.

Question 40

Gentamicin

(aminoglycoside antibiotic)

Answer 40

Antibiotic used to treat several types of bacterial infections

include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis

Note: not effective for gonorrhea or chlamydia infections

Gentamicin can cause inner ear problems and kidney problems