pharmacokinetics Flashcards
Pharmacokinetics
what body does to drug
Pharmacodynamics
what drugs do to body
4 phases of Pharmakinetics
(1) Absorption - administration–> blood
(2) Distribution - blood –> cells
(3) Metabolism - enzymatic alteration
(4) Excretion - metabolites –> out of body
Major barrier for drugs to pass through cell
Cytoplasmic membrane
How can drugs pass through cytoplasmic membrane
(1) membrane transport system (Generally Selective)
(2) Lipophilic drugs: penetrate membrane
(3) Polar drugs/ Ions - not able to cross
Absorption Rate
How SOON effects begin
Absorption Amount
how INTENSE effects are
Enteral
GI tract/ absorption via mouth/anus
Paraenteral
outside of GI tract
Topical
applied outside body
What affects Drug Absorption?
(1) Rate of dissolution - fater = increased absprotion rate
(2) Surface Area - larger SA = faster absorption rate
(3) Blood Flow- high blood flow = faster absorption rate
(4) Lipid solubility - increased solubility = rapid absorption
(5) Plasma pH- enhanced with greater difference between plasma and administration site
- drug molecules have greater tendency to be ionized in plasma
What are the different ways absorption can happen
(1) By mouth
(2) IV
(3) IM
(4) Topical
(5) Inhaled
(6) Rectal Suppositories
(7) Vaginal Suppositories
(8) Direct Injections
Barriers to Absorption by mouth
(1) GI tract epithelium - main
(2) Capillary wall
What causes fluctuations in absorption by mouth
(1) drug solubility
(2) GI tract ph.
(3) food in gut
(4) coadministration of other drugs
(5) special coatings on drugs
Advantages of oral route
(1) easy/ convenient
(2) safe
(3) potentially reversable
Disadvantages of Oral route
(1) high variability of absorption
(2) inactivation of certain drugs
(3) patient requirements (cooperation, consciousness)
What is the general route of by mouth
GI tract –> portal vein –> liver
What are the possible outcomes of drugs when they go through the liver
(1) uneventful
(2) extensive hepatic metabolism
(3) enterohepatic recirculation
Barriers to absorptionIV route
NONE
- goes directly into blood
What are the fluctuations in IV absorption
NONE
-instant and complete
IV advantages
(1) rapid, precise, permits use of large volume
(2) permits use of irritant drugs
IV Disadvantages
(1) inconvenient
(2) irreversible
(3) Infection
(4) Embolism
Parenteral Routes
Intramuscular (IM)
Barriers to Parenteral absorption
Only the capillary wall
Parenteral Advantages for absorption
(1) administration of poorly soluble drugs
(2) depot preparations –> drug is slowly absorbed
Disadvantagesof IM injections
(1) Inconvenient
(2) Discomfort
(3) Local tissue Injury
(4) Nerve damage
Subcutaneous (SubQ)
under the skin
almost identical to IM
Topical administration
local therapy
transdermal absorption into systemic circulation
Inhaled Administration
local effects on lungs
Rectal Suppositories administration effects
local or general
Vaginal suppositories effects
treat local disorders
Direct Injections
directly in heart, joints, or nerves
What factors effect Distribution
(1) Blood Flow
(2) Drug’s ability to exit vascular system
(3) Drugs ability to enter cells
How do drugs exit the vascular system
(1) Capillary beds
(2) Blood Brain Barrier (BBB)
(3) Placental Drug Transfer
(4) Protein Binding
How do drugs exit the BBB
-lipid soluble drugs can pass through the membrane
-some drugs can use transport system
BBB protective component
PGP
What is PGP
a transporter that pumps drugs out of cells back into blood
- limits access to brain
How do drugs pass through the placenta
Lipid-soluble, non-ionized compounds pass from maternal blood to fetus.
- ionized, highly polar, and protein bound are excluded
What is the main drug binding protein?
Albumin
How are drugs attached to albumin affected?
Cannot leave blood
Increases drugs half-life
Why do drugs enter cells
Some to reach site of action.
All drugs must enter for metabolism and excretion.
How do drugs cross the cell membrane?
(1) Either lipid-soluble
(2) able to activate a transport system
Define Metabolism
chemical alteration of drug structure
Where does most drug metabolism occur
Liver
What enzyme is most drug liver metabolism performed by
hepatic microsomal enzyme system P450 (CYP)
Therapeutic Consequence of Drug Metabolism
- what can happen when the liver metabolizes a drug
(1) Promotion of renal excretion of drugs
(2) Drug Inactivation
(3) Increased effectiveness of drug
(4) Activation of prodrugs
(5) Increased/ decreased toxicity
Most Important consequence of metabolism
promotion of renal drug excretion
How does the liver excrete highly lipid soluble drugs
Converts into hydrophilic drugs
How does liver convert lipid-soluble drugs to hydrophilic drugs?
(1) Structural change –> less lipid soluble
(2) Glucuronidation= lipophilic converted to hydrophilic
What is a Prodrug?
a compound pharmacologically inactive when administered but is converted to active form via metabolism
Toxicity
Converting drugs into inactive forms
How does age affect Drug metabolism?
Infants- limited metabolism, liver not fully developed until 1
Older adults- decreased metabolism
p450 substrates
drugs that are metabolized by P450
P450 inducers
Drugs that cause liver to increase drug metabolism
P450 Inhibitor
drugs that cause liver to decrease drug metabolism
First Pass Effect
rapid hepatic inactivation of oral drugs
- these drugs are generally administered parenterally
Drug Competition
if 2 drugs are metabolized by the same pathway, one or both will have their metabolic rate depressed.
Enterohepatic recirculation
drugs in GI tract carried through portal vein to liver. Liver excretes bile containing drug back to GI tract. Continuous this path indefinitely.
Excretion
Removal of drugs from body
How are drugs excreted from the body?
urine, sweat, saliva, breast milk, expired air
Most important organ for drug excretion
Kidney
What organ limits the duration of drug action. and why?
Kidneys
They account for the excretion of most drugs
Steps in Renal Drug Excretion
(A) Glomerular filtration
(B) Passive Reabsorption
(3) Active Secretion
Glomerular Filtration
Moves drugs from blood to urine.
What is a limitation of Glomerular Filtration
Cannot remove drugs bound to albumin
What occurs during passive reabsorption in kidneys
PH in tubule is higher than in blood.
Concentration gradient occurs.
Lipophilic drugs reabsorb PASSIVELY back into blood.
Non-lipid-soluble drugs remain to be excreted.
what happens to many lipophilic drugs during metabolism?
liver converts to hydrophilic molecules using Glucuronidation
How does the liver convert lipophilic drugs into hydrophilic molecules?
Glucuronidation
What is active tubular secretion
active transport that pump drugs from blood into tubular
What are the two primary pumps in active tubular secretion?
(1) for organic acids
(2) for organic bases
What do PGP cells do in renal drug extraction? Location
located in tubular cells-
Pump drugs from blood into tubular lumen
What plays a significant role in excretion of drugs in kidneys
PGP pumps
pH dependent ionization in kidneys
increases renal drug excretement by
-causing passively secreted lipid-soluble drugs to be ionized and
-then they cannot leave the renal tubular and is excreted.
Explain how Aspirin poisoning is treated
an agent is given to make urine pH basic (higher ph)
Aspirin is an acid.
The basic urine ionizes the aspirin
Ionized aspirin molecules are excreted in urine
What processes are used to convert lipid- soluble drugs for excretion?
(1) Glucuronidation
- lipophilic into hydrophilic
(2) Kidney performs pH dependent ionization
- ionization decreases passive reabsorption
Nonrenal excretion
Breastmilk
- lipophilic drugs access to breast milk
Bile
- enterohepatic recirculation
Lungs
- volatile anesthetic are excreted
What determines how much drug will be available at site of action
absorption, distribution, metabolism, and excretion
what are ADME major determinants of
(1) Time drug response starts
(2) Time drug will be MONST INTENSE
(3) Time drugs action will CEASE
What are the sections of Time Course of Drug Responses
(1) Plasma drug levels
(2) single- dose time course
(3) drug half- life
(4) drug levels with repeated doses
Time course of drug action has a direct relationship to
drug in blood
What are the two very important drug levels?
(1) Minimal effective concentration
(2) Toxic concentration
What is the minimal effective concentration
the threshold of where therapeutic effects occur
What is toxic concentration?
level where toxic effects begin
-Doses should not reach this level
Therapeutic Range
range between minimum effective concentration and toxic concentration.
What does a narrow therapeutic range indicate
drug is difficult to administer safely
-narrow concentration more dangerous than wide
Give example of narrow therapeutic concentration and wide TC
narrow- lithium
wide - acetaminophen
Single- dose time course
- plasma drug levels change over time
What is the latent period
the time between the drug is administered and the onset of effects
What determines the extent of the Latent period after administration of dose
determined by the rate od absorption
What is the duration of effect determined by
Metabolism and Excretion
drug half-life
time required for amount of drug in body to decrease by 50%
- no matter what amount of the drug half of it will leave during a specified time
How does half-life determine dosing interval
Short half-life = shorter interval
long half- life = longer interval
What is drug accumulation
when multiple doses are given and the amount in the body continues to accumulate
Plaeau drug levels
where the maximum amount of drug is accumulated in the body from any subsequent doses
Steady State
where the drug eliminated is equal to drug amount administered
how long for plateau to be reached if administered repeatedly at the same dose
4 half lives
how to reduce fluctuation in drug levels
(1) administer by continuous infusion
(2) administer a depot preparation- releases drug slowly and steadily
(3) reduce both dose size and dosing interval
Depot preparation
releases slowly over time
Loading doses
large initial dose given to achieve plateau in less weeks with a drug that has a long half life
Maintenance doses
the doses given after a loading dose to maintain plateau
How long does it take for MOST (94%) of a drug to be eliminated?
4 Half-Lives
