Principles of Drug Action Flashcards
What is pharmokinetics?
The study of drug movement throughout the body.
What should we know about pharmokinetics?
- How the body deals with medication
- Understand & predict actions, side effects of medications
- Understand obstacles a drug faces to reach target cells
- Greatest barrier for drugs is crossing many membranes
- Enteral route drugs are broken down by stomach acids and digestive enzymes
- Organs attempt to excrete medicines
What are the four categories of pharmacokinetic processes?
- Absorption
- Distribution
- Metabolism
- Excretion
What are factors affecting drug absorption?
- Dose
- Route of administration
- Size of the drug molecule
- Surface area of the absorptive site
- Digestive motility
- Blood flow
- Lipid solubility of the drug
- pH of local environment
- Drug-Drug/Food-Drug interactions
- Dietary supplement/herbal product-drug interactions
- Food
What is bioavailability?
% of the drug that reaches the circulation.
What is the primary pharmacokinetic factor that determines length of time for drug to produce effect?
Absorption
What is distribution in pharmacokinetics?
Transport of drugs throughout the body
What is the simplest factor determining distribution is the amount of blood flow to body tissues??
Distribution
What are some factors of distribution?
*Physical properties of drug have great influence
* Tissue affinity
* Protein binding
What role does the Blood-brain barrier and Fetal-placenta barrier have in distribution?
- Special anatomic barriers that prevent many chemicals and medications from entering.
- Make brain tumors difficult to treat
- Fetal-placenta barrier protects fetus; no pregnant woman should be given medication without strong consideration of condition.
What is biotransformation?
The metabolism of medications
* Chemically converts drug so it can be easily removed from body
* Involves complex biochemical reactions
* Liver - primary site
* Addition of side chains, known as conjugates, makes drugs more water soluble and more easily excreted by the kidneys.
What is Half-life of drugs?
- Time it takes for half of the medication to be metabolized by the liver.
- The greater the half-life, the longer it takes to excrete
- Determines frequency and dosage
What is the first pass affect?
- Drug is absorbed
- Drug enters hepatic circulation, goes to liver
- Drug is metabolized to inactive form
- Drug conjugates and leaves liver
- Drug is distributed to general circulation
- Many drugs are rendered inactive by first-pass effect.
What is the process of enterohepatic-recirculation of Drugs - Second pass effect?
- Drugs are excreted in bile
- Ble recirculates to liver
- Percentage of drug may be recirculated numerous times
- Prolongs activity of drug
—— Activity of drug may last after discontinuation
What are some factors in excretion of medications?
- Primary site of excretion of drugs is kidneys
- Free drugs, water-soluble agents, electrolytes, and small molecules are easily filtered.
- Drug-protein complexes and large substances are secreted into distal tubule of nephron
- Secretion mechanism is less active in infants and older adults
- pH of filtrate can increase excretion
What does renal failure have on excretion of medications?
- Drugs are retiained for extended times
- Dosages must be reduces
What other organs are sites for excretion?
- Respiratory system
- Glands
- Biliary system
What is drug plasma concentration and therapeutic response?
- Concentration of medication at target tissue is often impossible to measure, so it must be measured in plasma.
—— Minimum effect concentration - amount of drug required to produce a therapeutic effect.
—— Toxic concentration - level of drug that will result in serious adverse effects.
—— Therapeutic range - Plasma drug concentration between the minimum effective concentration and the toxic concentration.
How do drugs reach and maintain therapeutic range?
- Repeated doses of drug are given
- Drug accumulates in bloodstream
- Plateau is reached
- Amount administered equals amount eliminated
What is a loading dose?
- Higher amount of drug given
- Plateau reached faster
- Quickly produces therapeutic response
What is median lethal dose?
- Used to assess safety of a drug
- Shown on frequency distribution curves
- Determined in preclinical trials
- Is lethal dose in 50% of group of animals
- Cannot be experimentally determined in humans
What is the median toxicity dose?
- Dose that will produce given toxicity in 50% of group of patients
- Value may be extrapolated from
—— Animal data
—— Adverse effects in patient clinical trials - Needed because median lethal dose cannot be tested in humans
What happens when drugs attach to receptors?
- May trigger second messenger events
—— E.g. activation of specific G proteins and associated enzymes - Initiates drug action
- Can stimulate or inhibit normal activity
What happens with drugs that act as agonists?
- Bind to receptor to create a response
- Produce same response as endogenous chemical
- Sometimes produce greater maximal response
What happens when a drug acts as a partial agonist?
- Bind to receptor - partial
- Produce weaker, less effective response than agonists
What happens when a drug acts as an antagonist?
- Block receptor to block response
- Prevent endogenous chemical from acting
- Often compete with agonists for receptor
Specific vs Nonspecific cellular responses?
- Nonspecific
—— Affect whole body
—— Create more side effects - Specific
—— Affect target tissue
—— Less side effects
What is customized drug therapy?
- End of single-drug, one-size-fits-all policy
- DNA test before receiving drug
- Prevention of idiosyncratic (unpredictable and unexplained) drug reactions
- Pharmacogenetics
What is pharmacogenetics?
Area of pharmacology that examines role of heredity in drug response.
What other factors play a role in pharmacotherapy?
- Tolerance
- Serum drug levels
- Kidney function
Wat needs to be monitored in the kidneys?
- BUN (blood urea nitrogen)
- Creatinine
- Creatinine clearance rate
