Drug Distribution Flashcards
DRUG DISTRIBUTION
The four membranes which affect drug
distribution in body are:
– Cell membranes
– Capillary walls
– Blood-brain barrier
– Placenta
Cell Membrane:
a bi-lipid layer
embedded with large protein
molecules
- have to be small enough to fit through gates in membrane or be compatible with an active transport mechanism (bind and move across membrane) OR lipid soluble, they can go through the lipid layer
NOTES RE: LIPID SOLUBILITY
Large amounts of highly lipid soluble drugs
tend to accumulate outside CNS
- high lipid soluble drug molecules accumulate outside of CNS (fat tissue in body act as a sponge and suck up the drug
–> then slowly released from the fatty tissue into the blood (ex THC still releasing into the bloodstream)
CAPILLARIES
Tiny Blood Vessels with walls
formed by a single layer of tightly
packed cells
- small openings b/t cells called pores which are generally larger than most drug molecules –> drugs can exit outside the pores
- drugs can bind to protein molecules in blood –> can become too large and not move out of the capillary wall –> then gets eliminated
CAPILLARIES affect on drug intake:
Exiting of drug molecules also affected by rate
of blood flow
- faster BF = quicker drug exit and move to site of action (exercise or heat)
Blood Brain Barrier capillary features (4)
A feature of the physical structure of the brain capillaries
- brain caps have smaller pores than elsewhere in body
- drug has to be quite small
- also fewer pores in brain capillaries
- lipid layer surrounds capillaries in brain (drug has to go through fatty sheath)
BLOOD BRAIN BARRIER to combat lipid layer
Some drugs may be actively transported
across
- if not lipid soluble
- transporters are selective of molecules that bind to them
- provides barrier for less lipid soluble drugs
PLACENTA
Network of blood vessels and pools of maternal blood into which fetal capillaries protrude into (nutrients to fetus and remove waste products from fetus)
- can supply drugs as well
- Drug concentration can reach 75-100% of mothers within 5 min of admin (almost equal amount)
* Some drugs can have harmful effects on developing fetus (ex: alcohol)
DRUG ELIMINATION
Small amounts of some drugs will be eliminated
through body secretions i.e., sweat (methamphetamine), saliva (nicotine), breast milk (nicotine)
* Some drugs may be excreted in feces and bile
* Some drugs will be eliminated through the lungs (alcohol)
- Most drugs leave the body in the urine
DRUG ELIMINATION through urine mainly in two organs….
Working in concert, kidneys and liver do most
of elimination work
Nephron
arteries: capillary bed arond the nephron loop
- glomerulus –> bed of capillaries surrounded in a Bowmans capsule
- to the PCT then to DCT
- waste is in tubules and can be reabsorbed into the blood via cap bed
- most things moving back are highly lipid soluble molecules
- others are watre soluble and stay in the tubule
- go to collecting duct and are excreted in the form of urine
DRUG ELIMINATION
Kidneys remove drug molecules/drug
metabolites from blood and send to ureter,
and enzymes in the liver metabolize drug
molecules into excretable drug metabolites
* Excretable drug metabolites are more water
soluble, less lipid soluble
In addition to being less lipid soluble, drug metabolites are generally ____
less active than parent molecule
- Some drug molecules are as active or more active than parent molecule (heroine gets metabolized as morphine) (THC and mushrooms are more active)
- Some drug molecules will not be metabolized by liver; will be excreted intact (a type of mushroom)
Rate of drug metabolization affected by the number of____
enzymes in the liver
- The number of enzymes in liver c/be significantly increased with continuous use of drug –> Enzymatic action of liver responsible for drug (metabolic) tolerance (more metabolism= quicker elimination) –> increase drug intake to counteract
Orally administered drugs undergo _______ (to be less than injected/inhaled)
“first pass metabolism”
- go to the liver and kidney before they get to the brain –> accounts for less levels of the drug in blood at the site of action
- “First pass” metabolism accounts for lower blood levels of orally administered drugs
Elimination rate of drugs will be described in terms of a drug’s ________
“half life”
Ex; nicotine HL is 30mins (50% of nic is eliminated in 30mins) , in 60 min (75% gone), in 90min (87.5% gone)
- Different drugs will have different half-lives
- Half-life will also vary from person to person due to genetic make-up (insufficient enzyme) or age or disease related states of kidney or liver functioning
For most drugs, it typically takes_____ half-lives to eliminate 98% of the drug absorbed
5-6 half-lives to eliminate 98% of the drug absorbed
* An exception to the concept of half-life is alcohol
* Alcohol is metabolized in a linear fashion (rate limiting step)
Drug testing Commonly involves _____ or ______ analysis
blood or urine analysis
- Drug detected in blood suggests recent use
- Drug detected in urine indicates recent or past use (lipid soluble drug)
- Detection times substantially longer if drug metabolites can be measured by testing method
Detection time ranges generally _____ than elimination time ranges, thus
Detection time ranges generally shorter than elimination time ranges, thus
– Positive results cannot provide precise info regarding when drug used
– Negative results may not be 100% confirmation of non-use (just not high enough concentration to be detected)
* Methods used to get false negatives:
1. Substitution (Their urine for someone elses)
2. Adulteration (substances that will interfere with the detection processes)
3. Dilution: ( dilute with water so the drug is less concentrated)
once drugs go back to blood stream from nephron, they encounter the
liver, which biodegrades (metabolize) drug molecule to be not lipid soluble to water soluble
- when they reach the nephron again, they will not be reuptaken and be excreted as urine
concentration of drug in blood
IV: drug drops off quickly
IP (in stomach): bigger hill
muscular: smaller hill
Oral: less amount in blood (from going to L and K first)
want a steady affect of the drug? use ___
- steady effect of drug= oral route***
as soon as the drug is absorbed the drug begins to be _____. resultant is
eliminated
- resultant is the concentration of the drug in the body
Different drugs will have different______ ________
ranges
Different drugs will have different detection time
ranges
- Detection rates will also vary as a function of: (2)
- Length of drug use
- Individual differences in how drug handled by body
