Pharmacokinetics Flashcards
What are the factors affecting drug absorption? (11)
Route of administration Drug formulation Drug dosage Digestive motility Digestive tract enzymes Blood flow at administration site Degree of ionization of drug pH of surrounding environment Drug-drug interactions Food-drug interactions Dietary supplement/herbal product-drug interactions
What are the 4 components of pharmacokinetics?
Absorption - how does it get into the body
Distribution - how is it transported throughout the body
Metabolism - how do we break it down
Excretion - how do we get rid of it
What is metabolism?
Aka biotransformation
converts a drug to a form that can be more easily removed from the body
involves biochemical reactions
mostly takes place in the liver
What is the first-pass effect?
Oral drugs (drugs that go into the stomach) follow the following path: they are absorbed, enter the hepatic circulation, are metabolized to an inactive form, conjugate and then leave the liver, are distributed to general circulation
What is distribution?
Involves how drugs are transported in the body.
Occurs in the blood - the greater the blood flow to the area, the higher concentration of drug is delivered.
Lipid-soluble agents are not limited by barriers therefore are completely distributed to body tisses
What is drug distribution?
Initially drugs are carried in largest amounts to the most richly perfused tissues (e.g., adrenals, brain, heart, lungs, kidneys, muscles)
Later drugs undergo redistribution within the body being retained in tissues for which they have affinity (e.g., fat for lipophilic drugs)
Plasma protein binding
Drug molecules may be bound to plasma proteins
while bound to plasma proteins - drugs are inactivated because they cannot leave vascular system and enter tissues
Once free level of drug falls, drug molecules diffuse off the plasma proteins to maintain a constant bound/free ratio
What is affinity?
How much the drug likes the receptor
What is excretion?
Primary site of excretion is the kidneys
Ionized and water-soluble drugs are filtered
Drug-protein complexes are secreted into distal tubule
Secretion mechanism is less active in infants and older adults
pH of filtrate can increase excretion
How are drugs eliminated? Renal excretion
Drugs are filtered, secreted and reabsorbed
Filtration
All drugs not bound to plasma proteins are filtered.
Secretion
Some acidic and basic drugs are secreted.
This is an active process with transport maxima.
Drugs that are secreted usually have short half-lives.
Reabsorption
Drug reabsorption from the renal tubules depends on the percentage of the drug in the non-ionized form.
Non-ionized drug molecules are usually reabsorbed into the systemic circulation
Ionized molecules are not reabsorbed
Renal failure and excretion
Renal failure diminishes the excretion of medication
drugs are retained for extended times
dosages must be reduced
What other organs can be sites of excretion?
respiratory system
glands
biliary system
Enterohepatic recirculation of drugs
Drugs excreted in bile
Bile recirculates to liver
Percentage of drug recirculated numerous times
Prolongs activity of drug - activity of drug may last after discontinuation
What is half-life?
Length of time needed to decrease drug plasma concentration by one half
The greater the half-life the longer it takes to excrete
Determines frequency and dosages
What is steady state?
3-5 half lifes
amount of drug in = amount of drug out
The amount of drug being absorbed is equal to the amount being eliminated.
How drug reaches and maintains therapeutic range
Repeated doses of drug given
Drug accumulates in bloodstream
Plateau reached
Amount administered equals amount eliminated
What is loading dose?
Higher amount of drug is given
Plateau is reached faster
Quickly produces therapeutic response
Sometimes called bolus dosing
Helps to get to therapeutic range or steady state faster
Not everything gets a loading dose. Designed to by-pass the 3-5 half-lifes of steady state.
What is maintenance dose?
Keeps plasma drug concentration in therapeutic range
Keeps person at steady state
Not for life and death situation, if first dose.
What are the routes of drug administration?
Sublingual - (SL) Oral - (PO, enteral) Rectal - (Supp, PR) Parenteral - injections - Intravenous (IV) - Intramuscular (IM) - Subcutaneous (SC) - Intra-articular (IA) Inhalation Topical
What is sublingual?
Under the tongue Used for drugs that: 1. irritate the stomach 2. are destroyed in the stomach 3. are destroyed during the first pass through the liver Use for drugs that: 1. rapidly dissolve in saliva 2. are to irritating to the oral mucosa, and 3. are lipophile
what is oral?
- drugs are absorbed from the stomach and the duodenum
- drug absorption is better from the duodenum because of the larger absorbing surface
- the stomach can absorb acidic drugs and weakly basic drugs
- the duodenum can absorb the same drugs as the stomach plus most basic drugs
For a drug to be absorbed from the stomach and/or duodenum, it must: be dissolved in the GI tract, have sufficient non-ionized drug molecules, and have non-ionized molecules with sufficient lipid solubility to pass through the GI mucosa
