pharmacokinetics - ADME Flashcards
pharmacokinetics
what the body does to the drug
pharmacodynamics
what the drug does to the body (mechanism of action)
3 purposes of drugs
- preventive
- diagnostic
- therapeutic
what oral conditions results from most commonly prescribed drugs
xerostomia and salivary gland dysfunction
3 different ways to classify drugs
- mechanism of action
- organ or system target
- therapeutic use
absorption is defined as
presence of drug in plasma
metabolism of drugs occurs mainly in the
liver
elimination of the drug occurs mainly by
kidney and eliminated usually via urine
what is the goal for drug administration
adjust drug delivery to optimize drug availability at the therapeutic target
topical administration
local application of drug to body surface (intended for effect that that site)
systemic administration
drug enters circulatory system and moves throughout the whole body. it is not directed to site of action
enteral drug administration
through the GI system
parenteral drug administration
not through the GI system
drug formulation
form of the drug (cream, patch, pill, etc.); relates to route of admin.
types of drug routes where absorption is through mucosa
oral, rectal, inhalation
types of drug routes where absorption is on or through skin
- subcutaneous, intramuscular, intraperitoneal
- topical and transdermal
- intravenous, intraarterial
- intrathecal
what is an exception to topical route
patches: the drug is absorbed through the skin and intended to have an effect in areas of the body away from the site of application
3 types of enteral routes
- oral
- sublingual
- rectal
oral administration (PO) advantages
- convenient
- high compliance
- variety of release forms
first-pass effect
drug gets metabolized in liver first, causing reduced concentration of the active drug upon reaching its site of action
oral administration (PO) disadvantages
- MAX FIRST PASS EFFECT
- variable absorption
sublingual (SL) advantages
- rapid absorption
- NO FIRST PASS EFFECT
sublingual (SL) disadvantages
-limited to non-irritant drugs
rectal (PR) indications
pts with nausea or unable to swallow
rectal (PR) disadvantages
- limited to non-irritant drugs
- variable absorption
- LIMITED/VARIABLE FIRST PASS EFFECT
route for lower 1/3 rectum
vena cava *NO FIRST PASS EFFECT
route for middle 1/3 rectum
both vena cava and portal vein *SOME FIRST PASS EFFECT
route for upper 1/3 rectum
portal vein then liver (FIRST PASS EFFECT)
intra-articular injection is a type of ____ route
topical, because the injection is directly into site
advantages of parenteral drug delivery
- rapid and predictable administration
- accurate dosage
- IV bypasses absorption
- IV bypasses first pass effect
disadvantages of parenteral drug delivery
- need for asepsis
- discomfort/pain
- difficult self-administration
- risk of tissue damage
- risk of medical complications
- cost
what are 3 routes of admin that are fast
- parenteral
- intranasal
- inhalation
is oral (PO) fast or slow
slow
is IV injection slow or fast when first administered
fast, because it bypasses GI and liver and doesn’t require time for absorption
intervals between doses where concentration is zero is bad for which groups of pts
- pts in chronic pain
- pts on Abx
Css (concentration steady state)
mean concentration of drug at plateau level where rate of drug input = rate of drug elimination
bolus
discrete amount of drug over a discrete/short time period
example of type of continuous drug administration
IV infusion (using drip line)
compare the graphs for repeated vs continuous
same but continuous is smoother
drug absorption
transfer of drug from site of admin to bloodstream
6 factors affecting drug absorption
- tissue barriers
- mechanism of drug absorption
- molecular size of drug
- drug protonation/charge
- drug solubility (P o/w coeff)
- drug binding to plasma protein
examples of tissue barriers
cell membranes, tight junctions, and capillary permeability
systemic capillaries
- unrestricted movement
- lots of space (fenestrations) to allow passive diffusion
- pinocytosis
renal capillaries
- restricted movement
- cannot pass through fenestrations
- could pass through in damaged kidney
brain capillaries (BBB)
- restricted movement
- no fenestrations
- solutes must diffuse through 2 membranes
3 things that make the BBB impermeable
- glial cells
- continuous basement membrane
- continuous endothelial cells
2 methods for passive diffusion of water-soluble solutes
- gap junctions (connexins)
- aquaporins
non-ionized drugs (neutral drugs) cross membranes ___ (more/less) efficiently
more efficiently
why should basic drugs not be absorbed orally
bc they get protonated in the stomach and have an overall + charge, which is harder to be absorbed
acids have a __absorption at low pH and a ___absorption at high pH
high absorption at low pH
low absorption at high pH
the gradual pH increase from stomach -> plasma-> urine allows for
ion trapping (neutral in stomach=> charged in urine)
drugs with high lipid solubility will have a ___ (high/low) accumulation in cell membranes
high
drugs with low lipid solubility will have a ___(high/low) accumulation in cell membranes
low
the bond between drugs and plasma proteins is __ (weak/strong)
weak
drug binding to proteins is
dynamic and reversible
what happens when drug is bound by protein
nothing! it is not active, metabolized, and eliminated
is the protein-bound drug fraction dependent on drug concentration
no. it is only drug specific
high protein-drug = ___ drug distribution
low. only free drug moves in/out bloodstream
drugs that bind to proteins may have competition from
other protein-binding drugs, causing the drug to remain active
what do acidic and neutral drugs bind to
albumin or lipoproteins
what do basic drugs bind to
alpha-1 acid glycoprotein
why might it be hard for drugs to bind to proteins in a sick person
- plasma protein levels are altered in disease
- less protein = more free drug = gets active, metabolized, eliminated
distribution of water in the body
- 40-44% intracellular
- 16-20% extracellular (intersticial 12-16%, plamsa 4%)
volume of distribution
amount of drug in body / plasma conc of drug
high Vd = ____ (stay/leave) plasma
leave
low Vd = ____ (stay/leave) plasma
stay
high Vd will require ___ (high/low) dose to reach a certain conc
high
apparent Vd uses concentration of drug in
plasma (NOT BODY)
assumptions of using apparent Vd
- drug is distributed uniformly and in a single compartment
- concentration of plasma is representative
describe the order of drug distribution over time (VRG, MG, VPG)
VRG=>MG=>VPG
biological response modifiers
- antibodies, cell signal mediators, blood products, vaccines, and gene therapy
- produced by biological organisms
radiopharmaceuticals
drugs that are intentionally made radioactive (radionuclides) and used for research, diagnostic, and therapeutic purposes
