Lecture 3 Flashcards
What is Pharmacokinetics?
What the body does with the drug
What is Pharmacodynamics?
What the drug does to the body
What are the 4 processes of Pharamcokinetics (ADME)?
- Absorption
- Distribution
3.Metabolism
4.Excretion
How is the route of administration determined (2 things)?
- properties of the drug
- the therapeutic objective
What are the TWO major routes of administering?
- Enteral
- Parental
What routes make up the enteral section?
- oral (has first pass metabolism in intestine and liver)
-sublingual (DIRECT systemic absorption)
-rectal (DIRECT systemic absorption)
What routes make up the parenteral section?
- IV (avoids first pass, once given difficult to remove)
-IM (intramuscular, abosrbs aq solutions quick so prepared as a “depot” to promote slow absorption)
-subcutaneous (like IM, rapid or slow, localize drug effect)
how do they move molecules across the membrane?
- diffusion
- active transport
What is drug ABSORPTION?
- from the site of administration that allows the agent access to the plasma
- depends on drug’s ability to cross cell membrane and resist presystemic metabolism
- bioavailibility involved
What is bioavailibility?
amount of drug that reaches systemic circulation intact
if anything goes wrong in absorption, you can get MORE drug than anticipated
What factors affect absorption?
- acidity of stomach (*do NOT take an antacid before)
- physiochemical properties
- route of administration (100% bioavailibity for IV)
- lipid solubility
- blood flow
- surface area
What is drug DISTRIBUTION?
passage of agent through blood or lymph to various body sites and into interstitial tissue and intracellular fluids
What factors affect drug DISTRIBUTION?
- Blood flow –> want HIGH flow tissues
- (brain, liver, kidney) = handle LARGE volumes of drugs - Capillary permeability –> based on structure
- CNS blood brain barrier –> stops drug penetration if they are not lipid soluble or have a specific transport mechanism - drug structure
-hydrophobic, non polar, uniform electron distribution, no net charge = move DIRECTLY through endothelial membrane
- the opposite of above = pass through endothelial slit junctions - binding to plasma proteins
- talk later
When is a drug active or inactive?
Drugs are only ACTIVE when they are FREE!
Therefore, when bound to plasma proteins , they are INACTIVE
What is the binding and binding capacity of albumin like?
- low (1:1) or high
- bind REVERSIBLY
- 2 categories:
1. Class 1 –> low dose/albumin binding ratio
2. Class 2 –> high dose/albumin capacity ratio , majority of drug exists in its FREE state, can displace Class 1 from albumin (competition for binding sites!!!)
What is drug METABOLISM?
- mostly occurs in LIVER
-consists of “first pass-effect” - involves the “hepatic portal circulation”
- P450 enzymes
- biotransformation occurs
What are the Phases of metabolism reactions?
Phase 1:
- modify chemical by adding a functional group
- helps substrate to “fit” into phase 2 enzyme
- consists of Oxidation, Reduction, and Hydrolysis
Phase 2:
- conguation occurs –> adding a group (glucuronic or sulfuric acid) to make it water soluble
What are P450 enzymes?
-isoenzymes
- in GI and liver
- helps with metabolism
What is Biotransformation?
conversion of drug into 4 stages
Phase 1:
- oxidation
- reduction
- hydrolysis
Phase 2 :
- conjugation –> adding a group (glucuronic or sulfuric acid) to make it water soluble
What can modify biotransformation?
- age
-body weight
-gender - race
-genetic variability - body rhythms
- poor nutrition
- acid-base, fluid, electrolyte balance
-enzyme deduction
-dose level - diseases (liver and kidneys)
- immunoolgy –> drug allergies
- psychology –> placebo affect
- Environment
- tolerance
What is drug EXCRETION ?
- occurs in the kidneys (spaghetti and meatballs organs)
-elimination of drugs and toxicants
What is the process of renal excretion?
- Passive glomerular filtration
- active tubular secretion in the proximal tubules
- passive distal tubular reabsorption
What can affect renal excretion? (2 things)
- golumerular filtration rate
- change in urinary pH after excretion of weak acid and base drugs
What is a Drug half-life and how can it be affected?
- time taken for the drug’s blood or plasme concentration to decrease from full to one-half
- LONGER the half-life, the LONGER the drug remains in your body
- if you cant metabolize or excrete drug properly, the half life INCREASES
