2. Pharmacokinetics Flashcards
Pharmacokinetics
= What does the Body do to the drug
Pharmacodynamics
= What the drug does to the body
Stages of a drug…
absorption
distribution
metabolism
excretion
What is absorption
= passage of drug from its site of administration into the plasma
- drug must enter plasma before reaching site of action
Where does oral absorption occur?
= through GIT tract
- stomach
- Small intestine (Mainly)
- large intestine
Factors affecting oral administration?
- gastric emptying
- GI motility
- Splanchnic blood flow –> decreased splanchnic blood flow decreased absorption
- particle size
- formulation
What is distribution?
= distribution around the body occurs when the drug reaches the circulation
– Drugs are distributed throughout body fluids and fats
Factors affecting distrubition?
The distribution pattern between various body compartments depends on
• Characteristics of the drug
o Permeability across tissue barriers
o Binding with compartments
o Oil: water partition coefficient
o Physiochemical properties of drugs
• Physiological factors
o Regional blood flow
o Cardiac output
o Capillary permeability
o Tissue volume (except the CNS - protected by the BBB)
What is metabolism?
Biotransformation of a drug by enzymes
- – Drug is made more polar (hydrophilic) that hastens excretion by the kidneys, because the polar metabolite is not readily reabsorbed in the renal tubules
– The metabolites are usually less active than parent drug – Liver is primary site of metabolism
where does elimination?
• Metabolism (metabolic biotransformation)
o Liver (main source of metabolism)
o Intestine, kidney, lung
• Excretion
o Renal (urine)
o Biliary (faeces)
o Exhalation
o Other routes (e.g. lactation)
Name the phases in Hepatic Metabolism
Phase 1 Metabolism
- biotransformation reactions introduce orr expose functional groups on the dug with the goal of increasing the polarity of the compound
- grouped into three categories, oxidation, reduction, and hydrolysis
- convert a parent drug to be more polar
Phase II metabolism
- o glucuronidation, acetylation, and sulfation reactions
“conjugation reactions” that increase water solubility of drug with a polar moiety
What is half life and why is it important?
Half-life = time taken for plasma concentration or the amount of drug in the body to decrease by 50%
Less half-life = less side effects, therefore longer half-life = more side effects
Describes how long a drug or metabolite
stays in the body
Determines frequenting of dosing
What is the CYP450?
= main family of enzymes where drug interactions occur
Most enzyme can metabolise a range of dugs
Substrate – metabolised by and may compete for metabolic sites
Inhibitor – competes for and ‘blocks’ metabolic site (not always a substrate)
Inducer – increases metabolic activity by increasing amount of enzyme
Ie. drug can be a substrate, inhibitor, or inducer of CYP enzyme system
What are pharmacokinetic drug interactions?
• Absorption
o Normally food interactions
• Distribution
o Including protein binding
• Metabolism
o Cytochrome P450
• Renal elimination
o Competition for active efflux/ tubular reabsorption
What is volume of distribution?
= the volume of fluid required to contain the total amount of drug in the body at the same concentration as that present in the plasma
Determined by
- Plasma protein binding
- Tissue binding
Importance of Volume of distrubition?
Drugs with large volumes of distribution tend to:
- Have longer half lives
- Accumulate in the body with repeated dosing
- Cross the placenta and into breast milk
- Cross the blood brain barrier
- Require loading doses
Drugs with small volumes of distribution tend to:
- Have shorter half lives
- Accumulate less in the body
- Be safer to use in pregnancy and breastfeeding
- Be free of CNS effects
What is Bioavailability and why is it important?
- Bioavailability (F) is the fraction of the dose that is absorbed into the systemic circulation
- Values of F may be between 0 and 1 (or 0% to 100%)
- Bioavailability is 100% (F = 1) following an intravenous injection, less following oral administration
- Determining bioavailability is important for calculating drug dosages for non-intravenous routes of administration.
What is bioequivalence?
The term bioequivalence is often used to describe that two products have the same rates of absorption and bioavailability
Bioequivalence is important to determine whether different brands of a drug can be interchanged
What is first pass metabolism?
= Metabolism of a drug before it reaches the systemic circulation
- Oral route of administration is most affected by first pass
What are the three fundamental process of elimination via the kidney?
- Glomerular filtration
- Tubular reabsorption (usually lipophilic drugs)
- Tubular secretion
Steps in urine formation?
- Filtration
Only takes place in renal corpuscle - Reabsorption
Occurs when filtered material is moved back into the blood - Secretion
Removes selected material from the blood and places it in the filtrate
What is the relevance of renal elimination?
- Urinary pH and renal blood flow also affect renal elimination
- In renal impairment, consider dosage reduction of drugs cleared predominantly by kidneys
