Pharmacokinetics Flashcards
PHARMACOKINETICS
• “pharmakon” - drugs • “kinesis” - movement • Movement of drugs in the body • Study of the time course of drug absorption, distribution, metabolism and excretion • “what the body does to the drug”
Clinical Pharmacokinetics
Application of pharmacokinetic principles
to the safe and effective therapeutic
management of drugs in an individual
patient
COMPONENT PROCESSES
“ADME”
• Absorption
o Entry of the drug into the plasma
• Distribution
o Into interstitial and intracellular fluids
• Metabolism
o Biotransformation by the liver of other tissues
• Excretion
o drug and metabolites in the urine, feces, bile
OBJECTIVES OF PK
- The prediction of therapeutic doses and suitable dosage regimen
- The adjustment of individual drug dosage forms for optimal efficacy and safety
- The correlation between therapeutic blood concentration of the drug with pharmacologic effects
ABSORPTION
Process by which the unchanged drug proceeds from the
site of administration to the site of measurement (plasma)
FACTORS THAT INFLUENCE ABSORPTION
- Physical State of the drug
- Route of administration
- Blood flow to the absorption site
- Total surface area available for absorption
- Contact time at the absorption surface
- Expression of p-glycoprotein
PHYSICAL STATE
• Solid dosage form, solution, suspension
• Drug in product → Drug in solution → Absorbed drug
• Speed of absorption:
Solution > Suspension > Solid dosage form
ROUTE OF ADMINISTRATION
IV, IM, OR, SUbQ, INH, TOPI
Most common, safest and most economical method of absorbtion
Enteral (oral)
List some limitations of Enteric route
Limited absorbtion
Bioavailabilty
first pass
reaction with other foods
What is sublingual admin
o Placement under the tongue allows a drug to diffuse into the capillary network and enter the systemic circulation directly. (bypassing firstpass effect) o Between the cheek and gum. Advantages: § Ease of administration § Rapid absorption § No first-pass effect
Fick’s law for absorbtion
higher blood flow to the stomach, better absorption
TOTAL SURFACE AREA AVAILABLE FOR ABSORPTION
With a surface rich in brush borders containing
microvilli, the intestine has a surface area about 1000-fold that of the stomach, making the absorption of the drug across the intestine more efficient.
Does Gastric motility effect absorbtion
yes
why is faster motility bad?
less absorption, eg: diarrhea
How is gastric emptying significant?
Less absorption
RECTAL ROUTE
- Irregular and incomplete absorption
- Can cause irritation of the rectal mucosa
- Inconvenient (particularly for pediatric patients)
- 50% of the drug bypass the liver, reducing hepatic first-pass metabolism
Hepatic First-pass Metabolism
When a drug is absorbed from the GI tract, it enters the portal circulation before entering the systemic circulation. If the drug is rapidly metabolized in the liver or gut wall during this initial passage, the amount of unchanged drug entering the systemic circulation is decreased
PARENTERAL ROUTE
• Administration directly into the systemic circulation • Poorly absorbed from the GI tract • Unstable in the GI tract • Unable to take oral medications (ICU and neonate patients) • Rapid onset of action • Highest bioavailability No first pass control over dosing
Types of paraentral route
IV- ->25° § Most common parenteral route § Rapid onset § Maximum degree of control over the amount of drug delivered
IM->90°
§ Aqueous solution = rapidly absorbed
§ Depot preparations = slowly absorption
SubQ- )->45°
§ Absorption via simple diffusion and is slower
than IV
§ Provide constant, slow and sustained effects
Intradermal- 10-15°
. ORAL INHALATIONAL
- Provide rapid delivery of a drug across the large surface area of the mucous membrane of the respiratory tract and pulmonary epithelium.
- Rapid onset of action.
- Effective and convenient for patients with respiratory disorders (e.g. for patients with asthma)
Nasal inhalation
Directly to the nose (Otrovin)
Intrathecal/Intraventricular
Direct to CSF- epidural anasthesia
Topical
local effect of the drug- Fungal creams