PHARM 4: Pharmacokinetics Flashcards
List the journey of a drug through the body:
Hint = AADMEV
AADMEV
- administration
- absorption
- distribution
- metabolism
- excretion
- voided
Routes of administration can be either systemic or local.
what does it mean by systemic or local?
SYSTEMIC = entire organism is getting exposed to the drug
LOCAL = restricted to one area of the organism
Routes of administration can also be enteral or parenteral.
what does it mean by enteral or parenteral?
ENTERAL = via GI tract
PARENTERAL = everything except the GI tract
What are the different methods of absorption?
- through GI tract (via hepatic portal system)
- ## inhalation (lung = well perfused)
Why would you administer intravenously?
- provides systemic exposure very quickly
Drug molecules move around the body in 2 ways:
a)
b)
Drug molecules move around the body in 2 ways:
a) BULK FLOW TRANSFER
- in the bloodstream, it moves in bulk to the tissues
b) DIFFUSION TRANSFER
- moves molecule by molecule over short distances.
What are the different methods of crossing barriers?
- diffuse through lipid
- diffuse though aq pores in lipid
- carrier molecules
- pinocytosis
NOTE:
- most drugs = either weak base/acid
- so drugs exist in ionised/non ionized form
- ratio of ionized : non ionized depends on PH of environment + pKa of the molecules.
-
What is the
PH Partition Hypothesis?
- aspirin = acidic
- aspirin pKa = 3.4
SO
- when aspirin enters stomach (PH1 with lower pKa compared to aspirin)
- it becomes non ionized (non polar)
- so it can readily diffuse across the lipid bilayer
- into the small intestine (more basic)
- PH of s.int is higher so aspirin becomes ionized
- once ionised –> difficult to go through memb
- so slower absorption in s.int than stomach
- once it goes from liver –> systemic circulation, aspirin = in aq environment
- so proportion of aspirin = in ionized form
- -> ION TRAPPING
What are 4 factors influencing drug distribution?
- Regional blood flow
- -> better perfusion = higher drug exposure
- -> high metabolically active tissues have more capillary density
- Extracellular binding
- -> if plasma protein = bound to drug (can’t be absorbed)
- Capillary permeability
- -> fenestrated, continuous, discontinuous
- Localisation in tissues
- -> drugs that are lipophilic tend to accumulate/ localize in fatty tissue
What are the 2 major routes of excretion?
- Liver
- -> concentrates drugs in bile + secretes into intestines
- Kidney
- -> converts drug into water soluble product
Liver tends to excrete :
Kidneys tend to excrete:
Liver tends to excrete :
- large molecular weight drugs
Kidneys tend to excrete:
- xenobiotics
Why is the majority of excreted drugs get into urine via active secretion rather than ultrafiltration?
- because you can’t filter large, protein bound drug complexes.
describe process of excretion in kidneys
a) glomerulus
b) PCT
c) PCT/ DCT
a) glomerulus
- drug protein complexes not filtered
b) PCT
- active secretion of acids + bases
c) PCT/ DCT
- lipid soluble drugs
Why might treatment with IV sodium bicarbonate increase aspirin excretion?
- IV NaHCO3 will increase urine PH
- increase urine PH –> ionizes aspirin
- makes it less lipid soluble
- less aspirin = reabsorbed by tubules
- -> increase rate of excretion
Describe the process of excretion by the liver
- biliary excretion: concentrates large molecular weight molecules that are lipophilic
- active transport systems: for transport of bile acids + glucuronides –> into the bile
How might billiary excretion cause problems?
- drug gets excreted into gut via bile
- then is reabsorbed
- taken to liver and excreted again
(ENTEROHEPATIC RECYCLING )
–> Leads to DRUG RESISTANCE
Define Bioavailability
Bioavailability = proportion of the administered drug that is available in the body to exert its pharmacological effect.
note: linked to absorption
amount of drug that gets into the systemic circulation
Define Apparent Volume of Distribution
Apparent Volume of Distribution = volume in which a drug appears to be distributed.
(indicator of pattern of distribution)
note: linked to distribution
Define Biological Half Life
Biological Half Life = time taken for conc of drug to fall to half its original value
note: linked to metabolism/excretion
Define Clearance
Clearance = volume of plasma cleared of a drug per unit time.
note: linked to excretion
Define First Order Kinetics
First Order Kinetics = rate of elimination of a drug where the amount of drug decrease at a rate proportional to the conc of drug remaining in the body
What is First order kinetics dependent on?
- conc of drug at any given time
note:
T1/2 = Vd x 0.7/Cl 0.7 = Log 2
The log of conc is proportional to_____
The log of conc is proportional to time
Volume of distribution =
Volume of distribution = dose / initial conc of drug in plasma
What is Zero Order Kinetics?
Zero Order Kinetics = amount of drug decreases at a rate independent of conc of drug remaining in the body
Note: Implies a saturable (usually enzymic) metabolic process
are antacids local/ systemic
-local
are nicotine patches systemic / local?
- systemic
is betnovate local/systemic
-local
note: drugs have to transverse both aqueous + lipid environment
-
Why is protein bound drug not very likely to penetrate lipid memb?
- because it has low bioavailability
- as it is bound to the plasma protein
