Chap 3 Pharmacokinetics Flashcards
Volume of distribution (apparent)
The ratio of the amount of drug in the body to the drug concentration in the plasma or blood. Units: liters
Clearance
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
Half-life
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
Bioavailability
The fraction (or percentage) of the administered dose of drug that reaches the systemic circulation
Area under the curve (AUC)
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
Peak and trough concentrations
The maximum and minimum drug concentrations achieved during repeated dosing cycles
Minimum effective concentration (MEC)
The plasma drug concentration below which a patient’s response is too small for clinical benefit
First-pass effect, presystemic elimination
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)
Steady state
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)
Biodisposition
Often used as a synonym for pharmacokinetics;
-the processes of drug absorption, distribution, and elimination.
Sometimes used more narrowly to describe elimination
The effective drug concentration is the concentration of a drug at the _______
receptor site
(Vd)
apparent volume of distribution (Vd)
(CL)
clearance (CL)
The volume of distribution (Vd) relates the amount of _____ to the ____ according to the following equation:
drug in the body
plasma concentration
Vd= Amount of drug in the body
Plasma drug concentration (Units =Volume)
Clearance equation
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;
CLerence depends of what factors
Clearance depends on the drug, blood flow, and the condition of the organs of elimination in the patient.
Most drugs in clinical use obey the first-order kinetics rule described in the text.
Name 3 important drugs that do not?
- ethanol
- aspirin
- phenytoin
What is 1/2 life
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
1/2 life equation
t 1/2 = 0.693×Vd
CL (Units = Time)
bioavailability
Note:
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
The area under the curve (AUC)
Graph
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).
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?
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.
Maintenance Dosage
Equation:
Note:
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
Loading Dose equation:
note:
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.
therapeutic window
graph:
The therapeutic window is the safe range between the minimum therapeutic concentration and the minimum toxic concentration of a drug.
The most important renal variable in drug elimination is ____ ___ ____, and ____ ___ is a convenient approximation of GFR
Equation:
glomerular filtration rate (GFR)
creatinine clearance (CLcr)
Equation:
Corrected dosage = Average dosage ×
Patient’s CLcr
100 mL/min
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
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.
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
Diseases
serum creatinine concentration
total urine creatininine
24
Metformin
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.
Biguanide
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
How is Metformin prescibed:
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),
Explain how Biguanides work?
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.
Tobramycin
- 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
Verapamil
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
Phenytoin (PHT)
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.
Benzodiazepines
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.
Lidocaine
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
Theophylline
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
Procainamide
Procainamide is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias.
Gentamicin
(aminoglycoside antibiotic)
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
