Lecture 4: How Drugs Are Eliminated Flashcards
What are the characteristics of competitive drug?
site targeted: orthosteric
effect on potency: weakens potency of agonist
effect on Emax: no effect
What are the characteristics of irreversible competitive drug?
site targeted: orthosteric
effect on potency: weakens potency of agonist
effect on Emax: reduces Emax
What are the characteristics of non-competitive drugs?
site targeted: allosteric
effect on potency: no effect
effect on Emax: reduces Emax
What are the characteristics of positive modulator drugs?
site targeted: allosteric
effect on potency: normally strengthens potency
effect on Emax: no effect, or increase
What happens after you administer a drug?
the drug needs to be absorbed and travel in the body to reach its target issue
over time the effects of the drug “wear off” because the drug is eliminated from the body
Why is pharmacokinetics important?
understanding what controls absorption and elimination is extremely important in order to maximize the amount of time that the drug is present in an optimal concentration
these parameters influence important questions: how much drug should be taken? how often? how long will it take for me to perceive an effect of the drug?
usually a medication is taken more than once, so these considerations are important to optimize performance of a medication
What are factors that can affect steady state concentration and fluctuations?
dose, time between doses, bioavailability, clearance, half-time
What is steady state?
attained after approximately four half-times
time to steady state independent of dosage
What are steady-state concentrations?
proportional to dose/dosage interval
proportional to F/CL
What are fluctuations?
proportional to dose interval/half-time
blunted by slow absorption
What are important considerations about the routes of administration?
convenience - it is easy to take a medication orally (vs. injection/IV, other routes)
bioavailability - different drugs may be absorbed with different efficiency from the gut
processing - Hepatic portal circulation is a major consideration, drugs that are absorbed from the gut first encounter the liver BEFORE entering systemic circulation… so there can be significant processing/breakdown
What is first pass metabolism?
if ingested orally, drugs absorbed in the gut then pass through the hepatic circulation before entering the systemic circulation
this is a major site of metabolism that strongly influences the bioavailability of many drugs
What is the oral route of drug administration?
most common route of prescription drugs
rate of absorption is slow and affected by intake of food
exposure of drug may be influenced by breakdown in the gut, processing in the liver (variable between individuals)
What is the intravenous route of drug administration?
delivery directly into the systemic circulation, so very rapid onset of action
inconvenient and requires expertise
high control over circulation level by controlling the rate of infusion, or amount injected
What is the intramuscular/subcutaneous route of drug administration?
injection into muscle, or just below the skin
rate of absorption depends on blood flow to site
common to use “depot” preparations (slowly dissolving) for sustained release
What is the inhalation route of drug administration?
absorption is through epithelium in the lungs, and can be very rapid
What is the sublingual route of drug administration?
rapid absorption route, also bypasses “first pass” effects despite taking orally, rapid delivery
What is the transdermal (ointment or patch) route of drug administration?
convenient, slow absorption and sustained exposure
What is bioavailability?
fraction of unprocessed/unaltered drug that reaches the systemic circulation after administration by a particular route
how much of the delivered drug reaches systemic circulation?
What is distribution?
in pharmacokinetics, distribution refers to how a drug/substance is partitioned into different body “compartments” after it is absorbed
the distribution of a drug can have a big influence on the effective concentration of a drug in the body, as well as the lifetime of the drug in the body
Why is binding to plasma proteins important to the distribution of drugs in the body?
drugs will circulate in an equilibrium between “free” and “bound”
usually only the “free” fraction is considered to be pharmacologically active
some drugs are highly bound (so small effect even if a lot is present in body)
Why is drug accumulation in tissues important to the distribution of drugs in the body?
accumulation is favored for drugs that are lipophilic
more highly perfused tissues can accumulate a drug more readily than tissues with poor perfusion
key parameter is “volume of distribution”
What is volume of distribution?
this is a “concept”, not meant to represent a real volume
this provides a relative comparison of how well different drugs are distributed into tissues
drugs with a high volume of distribution are well distributed
drugs with a low volume of distribution are poorly distributed
What is the formula for volume of distribution?
volume of distribution = (total amount of drug in the body)/[drug]
