lecture 3 - pharmicokinetics Flashcards
what is the drive theory?
the idea that body has innate urges that increase until they are temporarily met
how does the drive theory relate to drug use?
repeated drug use generates the “drive” to seek the effects of the drug even more
what is drive theory based on?
the disruption of homeostasis due to urges
what occurs if you ignore an urge?
it intensifies until you satisfy it
what is opponent-process theory?
the effects of a drug are counteracted by the body in an attempt to maintain homeostasis
what occurs if the counteracting effects outweigh the drug’s effects ( you stop using drugs)?
the person experiences withdrawal - which is why an addict uses more to avoid the withdrawal
when does drug addiction begin?
the shift from how much a drug is liked to how much the drug is wanted
what does the incentive salience model tell about drug use?
drug use command the user’s attention through cravings - people continue to use drugs not because it is pleasant, but because they have intense cravings
where is the liking and wanting parts of drugs in the brain?
liking and wanting are both in limbic system
liking: orbitofrontal cortex
wanting: striatum
what is drug dependence?
the physiological change where the body is adapted to repeated drug use
what does drug dependence affect?
it affects your tolerance of the drug causing you to require more for a higher effect
what is the conditioned compensatory response?
the idea that your body has automatic responses that it learns following repeated drug use
what is addiction?
compulsive drug use despite harmful consequences
what is the 3 stage cycle of addiction?
- intoxication
- withdrawal
- preoccupation/anticipation
what is intoxication?
when the drug creates an impaired state
why is addiction continued ?
taking the drug to avoid the unpleasant aspects of withdrawal
what is the preoccupation and anticipation of drugs?
preoccupation with obtaining persistent physical/physiological problems
what are ways to treat substance use disorders?
- detox - removing drug from system
- manage withdrawal symptoms
- prevent relapse through therapy and pharmaceuticals
into what groups are pharmaceutical sciences divided?
- pharmaceutics
- pharmacokinetics
- pharmacodynamics
what is pharmacokinetics?
how drugs are absorbed and passed through the body
what is bioavailability?
amount of drug administered that enters blood circulation & can reach target site
what is dose?
specified amount of medication/ substance administered at one time
what is dosage?
amount, number, & frequency of doses over a specific period
what is absorption in pharmacokinetics?
the movement of drug from the site of administration to the bloodstream/ circulatory system
what drug properties can influence absoption?
- molecule size
- pH & Ionization status pH
- lipid/ water solubility
- drug concentration
are all drugs absorbed into blood stream?
no
do all drugs absorb into the bloodstream at the same rate?
no, it is at different rates
what can affect the strength of the drug effects?
how quickly it is absorbed
how do lipid soluble drugs pass through cell membrane?
by passive diffusion (high to low )
how do larger molecules or drugs against the membrane?
through active transport by carrier proteins
what factor related to a person’s body can influence absorption?
- rout of administration
- area of absorbing surface
- individual differences in size, sex, age (a smaller person will dilute the drug LESS)
- presence of food in GI tract\
- disease state/liver functionality
what is mostly true about drugs that are absorbed more slowly?
they have a longer duration of action
what affects the bioavailability and rate of diffusion?
depends on how well the drug diffuses from administration site into bloodstream
what are the 2 main routes of administration?
- enteral route - through GI tract (oral/rectal)
- parenteral - injection, pulmonary, topical
for oral administration, what organs absorb the drug?
small intestines - basic drugs are absorbed
what is important about the oral drugs that are administered?
they must be resistant to destruction by stomach acid and enzymes
for rectal administration, what is bypassed?
the first pass metabolism so more bioavailability
in first pass metabolism, what occurs?
- you eat the drug
- the drug is broken down in the stomach
- the drug is transferred from our intestines to the liver by the hepatic portal vein
- the liver breaks them down and filters them
- the smaller quantity of the drug is released into circulation
why is a portal vein a safety mechanism?
drugs absorbed by the gut can be carried directly to the liver
what are the types of injections?
- intravenous
- intramuscular
- subcutaneous
what is an IV?
injection directly into vein and enters bloodstream immediately.
most rapid and accurate method
why can IV admin be dangerous?
if you overdo it, there is little time to correct overdoses so the drug cannot be removed from the body as fast as throwing up.
what is an IM?
injection into muscle area like upper arm, thigh, butt; more prolonged absorption
what is an SC?
injection into space beneath the skin; more prolonged absorption
what is the inhalation administration method?
generally absorbed by the lungs (and to some extent through the mucous membranes of the mouth, throat, and nose)
why is inhalation a rapid response?
the lungs have large surface area and many capillaries so the drug can be transferred into the circulatory system rapidly
what is topical administration?
drug is applied to mucous membranes
local affects - take LONG
transdermal: through the skin through patches
what is sublingual admin?
drug is placed under tongue
what is buccal admin?
drug is placed in your cheek
what is intranasal admin?
nasal passage contains mucosal membranes that can absorb drugs into the capillaries, similar to sublingual or transdermal routes.
avoids first pass metabolism so more is in blood stream
bypassed blood brain barrier
what factors do route of administration affect?
- Speed of drug action (onset)
- Length of response
- Bioavailability
- Strength of drug response
what administration has 100% bioavailability?
intravenous
what is distribution in pharmacokinetics?
the passage of a drug from the bloodstream to various sites in the body.
what barriers affect how a drug is distrubuted?
- blood brain barrier
- placental barrier
- nonspecific binding
what are blood vessels?
all the things that carry blood through the body (arteries, capillaries, veins)
what are the job of arteries?
delivers oxygen and nutrients to tissues; sympathetic stimulation
what are the job of veins?
drains blood back to heart; parasympathetic stimulation
what are the jobs of capillaries?
transport oxygen and nutrients to cells ; remove waste
how much of blood from the heart goes to brain?
20%
what is the BBB?
a selectively permeable membrane that regulates nutrient/ drug passage into the brain and separates blood supply from direct contact with brain tissue
prevents pathogen and toxins from entering brain
what components make up BBB?
- endothelial cells
- astrocytes
- pericytes
- active transport channels
what do endothelial cells do?
lines inside of blood vessels. Adjoining edges fuse to form tight junctions which prevents flow of most substances into & out of the brain
what do astrocytes do?
glial cells responsible for formation & maintenance of BBB. astrocytic end feed wrap around endothelial cells to restrict entry of pathogens from bloodstream into brain.
release secretion factors to maintain tight junctions.
what do pericytes do?
Wrap around endothelial cells
Contract to regulate blood flow
what are the types of active transport channels that span the bbb?
glucose
essential amino acids
do large molecules pass easily through the bbb? if not, what do they require?
they do not; they require active transport channels
what is another molecule that does not pass through the bbb well?
molecules with high electrical charge
what substances do pass through the bbb well?
lipid soluble, certain gases, and water
what is a barrier unique to females?
placental barrier
what is the purpose of the placenta?
it is the membrane that separates the fetal and maternal blood. nutrients from the mother travel to the fetus and the waste from the fetus travels back to the mother.
what substances diffuse rapidly across placental barrier?
fat soluble
what are teratogens?
stimuli that cause developmental abnormalities in the fetus like x-rays, drugs, pathogens. there is an increased susceptibility during 1st trimester.
what are drug depots?
inactive binding sites with silent receptors that when the drug binds to them no biological effect is produced
where are the silent receptors found at drug depots?
plasma proteins in blood, fat, bones, etc
what happens when the drug is stuck in the depot?
it cannot reach the active sits or be metabolized by the liver
what does depot binding affect?
- it affects the magnitude and duration of drug action
- there is delayed drug effects
- reduces bioavailability
- varies across individuals and may account for drug sensitivity differences
how long can drugs remain in the body due to depot binding? give an example.
for extended periods of time even after you quit using the drug
ex. THC in marijuana
what is metabolism (biotransformation)?
breaking a drug down into its metabolites via the activity of various enzymes
where does metabolism occur most of the time?
liver – it transforms the drugs to make them more water soluble
what are cytochrome p450 enzymes?
main enzyme family responsible for breaking down most psychoactive drugs in phase 1 metabolism (MAKES THEM MORE WATER SOLUBLE)
what are transferase enzymes?
responsible for also breaking down drugs in phase 2 metabolism (in a different way)
what is the starting compound of the drug called?
the parent drug
when the drug reaches the liver, what is it broken down into?
- inactive metabolites: excreted via kidney or bile
- active metabolites : return to blood and has its own biological actions in the body - its effect can be weaker or stronger than the parent drug
what are pro drugs?
when the parent drug is inactive and then only becomes active after the drug is metabolized
what is enzyme induction?
drug use increases enzyme number/activity
- speeds metabolism of other drugs that enzyme acts on
- drug loses effectiveness with repeated use
- drug gets out of your system faster
what is enzyme inhibition?
drug use inhibits enzyme number/activity
- drug effects are more intense or prolonged
- toxicity / overdose is possible
what occurs when there is drug competition for an enzyme?
elevated levels of one drug reduced the metabolism of the second
ex. alcohol and valium compete for cytochrome p450
what are factors that affect drug metabolism?
- genetic polymorphism : asians have a reduced capacity to break down acetaldehyde so thats why they have a red face, nausea, and vomiting with alcohol
- age, sex, nutrition levels
what is excretion?
process by which drugs are removed from the body
once drugs are metabolized and made more water soluble by the liver, what happens next?
the kidneys filter them from the blood with exception if they are too large or bound to plasma proteins
what is elimination rate?
amount of drug that is removed from the body over time
what is true about elimination routes?
several routes
(sweat, breast milk, ect.)
what describes the pattern of drug elimination?
first order kinetics : a constant fraction of drug in the blood is removed during each time interval (proportional to the amount of drug in the system)
what is half life?
the amount of time required to remove 50% of the drug from the blood
(takes about 6 half lifes to remove the drug from blood)
some drugs are not eliminated by first order kinetics, what is the other way?
zero order kinetics: drug is cleared at a constant rate regardless of amount of drug consumes or concentration of drug in blood
(ex. alcohol)
what is the goal of drug in your blood?
to maintain concentration and achieve a steady state plasma level
what helps determine the time needed to reach steady state plasma level?
half life
