basic biopharmaceutics, pharmacokinetics, and …mycollege.zohosites.com/files/11. basic...
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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
• Cytochrome P450
• Dissolution
• Drug interaction
• Elimination
• Excretion
• First-pass metabolism
• Half-life
• Loading dose
• Metabolism
• Metabolite
• Pharmacodynamics
• Pharmacokinetics
• 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 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