Sie sind auf Seite 1von 23

Chapter 11: Basic Biopharmaceutics,

Pharmacokinetics, and Pharmacodynamics

Learning Outcomes
Define biopharmaceutics
Describe 4 processes of pharmacokinetics
Describe factors that affect medication

absorption
Describe process & factors of distribution phase
Describe 2 most common types of drug
interactions
Define pharmacodynamics
Describe process & factors of elimination phase

Learning Outcomes
Describe steps for medication to exert effect
Describe potential problems that can occur

when
product formulation is disrupted
absorption, distribution, metabolism, or

elimination is altered

how these alterations can affect pharmacodynamics


of medication

Key Terms
Absorption
Bioavailability
Biopharmaceutics
Clearance

First-pass metabolism
Half-life
Loading dose
Metabolism

Cytochrome P450
Dissolution

Metabolite

Drug interaction
Elimination

Pharmacokinetics

Excretion

Pharmacodynamics
Therapeutic level
Volume of distribution

Biopharmaceutics
Study of manufacture of medications
Common formulations
Choice of routes
Precursor steps of absorption
Disintegration
Dissolution

Pharmacokinetics
ADME
Absorption
Distribution
Metabolism
Elimination

Absorption
Amount of medication that enters

bloodstream
only absorbed medication has pharmacologic

effect
bioavailability is percentage of dose that
reaches bloodstream

Factors
amount of drug dissolved
dosage form
route of administration

First-pass Metabolism
Following oral ingestion
med metabolized before reaching main
bloodstream

through either intestine wall or liver

result-lower percentage reaches main systemic

circulation

Routes of Administration
Rectal, inhalation, sublingual
avoid first-pass metabolism
Medications given intravenously
100% bioavailability

Distribution Phase
Follows absorption
Medication may
leave bloodstream & enter tissues
remain in the blood, bound to protein

Medication bound to blood proteins (albumin)

is inactive
does not exert any pharmacologic effect
reversible-drug may be released from protein &

distributed into tissues

Therapeutic Level
Desired effect with minimal side effects
Concentration of drug in blood
measured to help guide appropriate therapy
determines whether a change in therapy is needed

Examples of medications whose levels are

measured
phenytoin, carbamazepine, valproic acid,

phenobarbital
digoxin
gentamicin, tobramycin, vancomycin

Volume of Distribution
Extent drug distributes to various body

tissues/spaces
Medications with large volume of distribution
have lower blood concentration

Medications with small volume of distribution


have a higher blood concentration

Factors that affect extent of distribution


highly protein bound
high affinity to body fat

Loading dose is used when medications have

large volume of distribution

Metabolism
Breakdown of drugs (not all drugs susceptible)
drug molecule is changed or altered
metabolite
Drugs may travel directly to kidneys excreted
Liver is major organ in which drug metabolism

occurs
Small intestine-significant metabolism occurs
Other organs-limited metabolism
kidneys
lungs

Enzyzmes
Protein substances (enzymes) metabolize

drugs
Cytochrome P450 (CYP) family of enzymes
Drug metabolites
Metabolites may
or may not be pharmacologically active
be used as active form of pro-drugs
be toxic

Excretion
Removal of drug or metabolite from body fluid
Kidneys
filtering process drug eliminated into urine without

being metabolized
metabolites - water soluble-susceptible to excretion
by kidneys

Bloodstream liver cellbile ductsmall intestine


Drug clearance=elimination rate
Half-life (T1/2,) is time for 50% of drug to be

eliminated

Drug Interactions
Impact of drug/food product on amount or

activity of another drug


Altered drug metabolism in liver
Inhibition of enzyme activity
Induction of enzyme activity

Common drug-food interaction


grapefruit juice (CYP enzyme inhibitor)
injested with nifedipine (metabolized by CYP)
results in hypotensive episodes

Variables in
Pharmacokinetics
Speed of gastrointestinal tract
constipation or diarrhea

Diseases of kidney and liver


cirrhosis
Reduced elimination prolonged half-life
Changes in cardiac output
changes in delivery of drugs via bloodstream
low cardiac outputdecreased blood flow to

kidneys & liver


decreased clearance of medications

Kidney Disease
Renal failure
hemodialysis
kidney transplant
Causes of kidney damage
blood pressure
high blood cholesterol
diabetes

Detection: blood levels of creatinine


Doses adjusted based on degree of renal

impairment

Liver Disease
Cirrhosis
decreased ability to metabolize certain

medications

Detected by measuring
aspartate aminotransferase (AST)
alanine aminotransferase (ALT)
bilirubin
albumin
Reduced elimination & clearance of some drugs
Albumin reduced reduced protein binding

Advanced Age
Medications must be used cautiously in elderly
Reduced kidney function
Estimate patients creatinine clearance
dose reduction may be needed for some drugs
avoid drug accumulation & toxicity
Reduced liver function
watch for toxicity

Topical medications
less drug is absorbed

Pregnancy
Increased blood volume? hypothesized
Drugs may be cleared through kidneys more

quickly
May need higher doses of some medications
Some over-the-counter (OTC) drugs are
unsafe
avoid aspirin in last 3 months of pregnancy
safety of

herbal, botanical, & dietary


supplements?

Pediatrics
Medications are often dosed based on body

weight
accurate weight important

Higher relative volume of distribution for

some drugs
Refer to pediatric references/manufacturers
guidelines
Pharmacist evaluates drug doses
adjusted based on weight & other factors

Pharmacodynamics
What drug does to body
Pharmacodynamic responses
increase in bone mass with bisphosphonates
decrease in BP with antihypertensive agents

Pharmacologic effect sequence of events


absorption
distribution
bind to targeted receptor causing cascade of
events that leads to drugs response