Lecture 4 Flashcards
What happens after you administer a drug?
- drug needs to be absorbed and travel to reach its target
- over time the effects will wear off, as the drug is eliminated from body
What is the therapeutic window?
conc range where drug will have its desired outcome
What is the steady state?
- attained after 4 half-times
- time to steady state depends on the dosage
What are steady state concentrations?
- proportional to dose/dosage interval
- proportional to F/CL (bioavailability)
What are fluctuations
- proportional to dose interval/half-time
- blunted by slow absorption
What are some important things to consider when thinking of routes of adminstration
- Convenience (easy to take medicine orally then injection)
- Bioavailability - different drugs are 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
What is first pass metabolism?
when drugs are ingested orally, drugs are absorbed in the gut then pass through the hepatic circulation before entering the systemic circulation
- strongly influences the bioavailability of many drugs
What is the extraction ratio?
the amount of drug cleared from the liver divided by the amount of drug in the blood
What are the different routes of administration?
- oral
- intravenous
- intramuscular
- inhalation
- sublingual
- transdermal
What is the oral mode of administration
- most common route for drugs
- rate of absorption is slow and can be affected by food
- exposure is influenced by breakdown in the gut
What is the intravenous mode of administration?
- rapid onset of action
- inconvenient and requires expertise
- high control over circulating level by controlling the rate of infusion, or amount injected
What is the intramuscular mode of administration?
- injection to muscle
- rate of absorption depends on blood flow to site
What is the inhalation mode of administration
absorption is through the epithelium in the lungs, and can be rapid
What is the sublingual mode of administration
rapid absorption, also bypasses first pass despite oral delivery, rapid delivery
What is the transdermal mode of administration
convenient, slow absorption and sustained exposure
What is bioavailability?
fraction of unprocessed drug that reaches the systemic circulation after administration by a particular route
What is distribution?
- refers to how a drug is partitioned into different body compartment after it is absorbed
- distribution 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
What are the two key factors related to distribution?
- binding to plasma proteins
- drug accumulation in tissues
What is drugs binding to plasma proteins
- drugs circulate in equilibrium between free and bound
- only the free fraction is pharmacologically active
- some drugs are highly bound (so small effect even if a lot is present in body)
What is drug accumulation in tissues
- accumulation is favoured for drugs that are lipophilic.
- perfused tissues can accumulate a drug more readily than tissues with poor perfusion
- key parameter is volume of distribution
What is the volume of distribution?
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
- volume of distribution = total amount of drug in the body/[drug]
What is single compartment distribution?
- drug is contained within a single compartment
- if elimination pathway is present, drug concentration decreased with exponential decay kinetics (rate of elimination depends on concentration of drug)
What is multiple compartment distribution
- after administration, drug distributes into multiple compartments
- elimination pathway is present, drug concentration in the blood determines the rate of elimination, but the reservoir of drug in the tissues can prolong the lifetime of the drug in the body
How are drugs eliminated?
- metabolism in the liver (Biotransformation), and excretion (kidney, gut)
- metabolism in the liver involves Phase 1 and 2
