Transcript Foundation Knowledge and Skills

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
 First-pass metabolism
 Bioavailability
 Half-life
 Biopharmaceutics
 Loading dose
 Clearance
 Metabolism
 Cytochrome P450
 Metabolite
 Dissolution
 Pharmacodynamics
 Drug interaction
 Pharmacokinetics
 Elimination
 Therapeutic level
 Excretion
 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 cellbile ductsmall 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 outputdecreased 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 patient’s 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/manufacturer’s 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 drug’s response