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Pharmacokinetics and Pharmacodynamics

Terms in this set (102)

PharmacoKinetics =
Medicine + Movement
How drugs pass through the body
Concentration of a drug in the body depends on 4 things
AD ME
Absorption
Distribution
Metabolism
Excretion
Absorption is...
How the drug moves from site of administration across a membrane into the blood
Distribution is...
Once in the blood, how the drug is distributed throughout the body
Metabolism is...
How the drug is altered/changed in the body
Excretion is...
How the drug is removed from the body
Absorption is problematic due to its...
Unpredictability!
Primary method of moving drugs across membranes is
Diffusion
Absorption is affected by
- Concentration of drug (each drug has its own PH)

- Chemical properties of drug

- Bioavailability of drug

- Fillers, Route, GI tract

- Chemical Properties of environment : PH of body, Blood, Urine, lipid soluble or insoluble etc.
To readily cross membranes, a drug must be....
LIPID soluble (lipophilic)
NON-IONIZED drugs
Why are LIPID-SOLUBLE drugs more easily absorbed?
How do LIPID-INSOLUBLE drugs absorb?
- Lipid soluble drugs can dissolve directly into the lipid portion of the membrane of a cell and diffuse into that cell.
-Lipid INsoluble drugs require a water filled PORE, CHANNEL or PORTAL which they can pass through.
Ionized drugs are lipid ______________
INsoluble
Bioavailability is
The amount of the drug that reaches the CIRCULATION
Diffusion of a drug across a membrane depends on 4 MAJOR CIRCUMSTANCES:
- SURFACE AREA of the guts (with all the lumen)
- THICKNESS of the guts (membrane)
- DWELL TIME of the guts (peristalsis, how full, transit of bowels)
- BLOOD FLOW to the guts
Diffusion of a drug across a membrane depends on 4 MINOR methods
- AQUEOUS CHANNELS (holes/ports in cellular membrane)
- ACTIVE TRANSPORT (Kidney specific, certain drugs)
- FACILITATED DIFFUSION (PgP)
- DRUG SOLUBILITY (hydro- or lipo-philic)
Acidic drugs are usually absorbed in the
STOMACH
Alkali drugs are generally absorbed in the
INTESTINES
P-Glycoprotein (PgP) aka "Efflux Protein" or "Multi-Drug Transporter Protein" is what?
Special protein that MOVES DRUGS BACK ACROSS MEMBRANES (back OUT) to try and excrete it as a foreign body, via GI, Urine etc
P-Glycoprotein (PgP) is found where?
Intestines
Liver
Kidneys
Brain
Placenta
Most important minor method of diffusion across membranes
DRUG SOLUBILITY (is it hydro or lipo philic/ water or fat soluble)
What is the BIOAVAILABILITY SCALE (aka F-SCALE)...
The higher the number =
the more EQUIVALENT a generic drug will be
Most absorption occurs in
SMALL INTESTINE
some in STOMACH
SLOW stomach emptying means __________absorption
DECREASED absorption
(takes LONGER for drug to enter Small Intestine)
QUICK stomach emptying means _________absorption
INCREASED absorption
(drug enters Small Intestine QUICKER)
SLOW Intestinal emptying means ___________absorption
INCREASED absorption
(Longer DWELL TIME allows more more diffusion)
The amount of a drug that actually reaches the circulation is referred to as a drug's ___________________
BIOAVAILABILITY
QUICK Intestinal emptying means ______________absorption
DECREASED absorption
(Less DWELL TIME = less chance for diffusion)
Characteristics of Sublingual/Buccal drugs
(where is it used heavily?)
- Diffuses DIRECTLY to circulation
- Good alternative to injections in home settings
( used HEAVILY in HOSPICE)
Characteristics of Rectal drugs
- May have local OR systemic effects
- Rectum is VASCULAR, baby
- Butt Absorption is ERRATIC & UNPREDICTABLE
- Psychologically, people generally don't like stuff going in their butt
Characteristics of SubCutaneous (SQ/SC) drugs
- Faster than ORAL
- Still RELATIVELY SLOW absorption
- FAT tissue is a RESERVOIR for the drug
- Can't use IRRITATING drugs SQ
Affected by:
Circulation to tissue
Volume injected
Lipid solubility
Amount of Ionization
amount of adipose tissue
heat/cold
Absorption rate of SQ drug can be slowed how?
By adding a vehicle.... (ex: insulin + zinc)
Characteristics of IntraMuscular (IM) drugs
- possibly faster than SQ (IM vs SQ = controversial)
-Affected by:
Circulation to tissue
Volume injected
Lipid Solubility
Amount of Ionization
Absorption rate of IM drug can be slowed how?
By adding a vehicle.... (ex: PCN + Procaine)
Characteristics of IntraVenous (IV) drugs
[major risk?]
- Potential for IMMEDIATE ACTION TO Cardiac system
- rate of administration affects rate of action
- Cardiac OUTPUT affects distribution
- MISTAKES f@cking suck and can't be taken back, yo!
[Risk of INTRODUCING PATHOGENS systemically]
Characteristics of Epidural ("above/upon/around" + "dura mater") drugs
[major risk?...other than paralyzing someone]
- Injection into area outside Dura Mater
- Less medication needed
[risk of INTRODUCING PATHOGENS into CNS!]
Characteristics of IntraThecal ("within" + "spinal theca") drugs
[major risk?]
- go directly INTO spinal subarachnoid space
- BYPASSES BLOOD BRAIN BARRIER!!!!!
- Less medication, longer effect
[risk of INTRODUCING PATHOGENS into CNS!]
Characteristics of Pulmonary drugs
- LOCAL effects: occur along Bronchial passages
- SYSTEMIC effects: drug must reach deeply into ALVEOLI
- Volatile liquids/gases (ex: general anesthesia) RAPIDLY absorbed in mucosa of Respiratory tract
Characteristics of Topical drugs
- SYSTEMIC absorption if LIPID SOLUBLE drugs (can pass through cells of epidermis)
- LOCAL absorption if LIPID INSOLUBLE drugs (can't easily pass through cell lipid bilayers...can pass through glands)
Affected by:
- Blood supply
- Temperature
- enivornment
What are TOPICAL drugs not appropriate for (3 things)?
- PRNs (not fast enough)
- as a "Breakthrough" medication (not fast enough)
- usually not appropriate for INFANTS: Body surface area to weight ratio don't kill babies!
Characteristics of Optic and Ear Drugs?
- LOCAL action only, NOT systemic actions
Characteristics of Nasal drugs?
- MAINLY LOCAL.... a veryfew systemic drugs
Cytochrome P450 ("CYP") Enzymes
- MAJOR drug metabolizing ENZYME
- Responsible for ~80% of OXIDATIVE drug Metabolism
- Can metabolize ~90% of Drugs we use today
Found in:
- LIVER
- GI tract
- KIDNEY
"Drug to Drug" Interactions can __________ Absorption of one or both of the drugs
DECREASE or DELAY absorption
"Food to Drug" Interactions can __________ Absorption of the drug
DECREASE or DELAY absorption
(Fatty foods can LOWER GI motility, DELAYING absorption)
define DISTRIBUTION
Movement of a drug from BLOOD --> TISSUES --> TARGET SITE
DISTRIBUTION relies heavily on _______________ status of Pt.
CARDIOVASCULAR status...
- BP?
- Cardiac output?
- Ischemia?
- Diabetes?
- Cold temperatures...shunting of bloodflow?
etc
Rate of DISTRIBUTION of a drug depends on
-BLOOD FLOW to and from tissues
-BINDING CAPACITY to specific tissues
-PLASMA PROTEIN BINDING CAPACITY
-Specific BARRIERS to Distribution (placenta, Blood-Brain)
Explain TISSUE BINDING CAPACITY...
- Some drugs prefer to bind to SPECIFIC tissues, may bind to these tissues in LARGE amounts. This is REVERSIBLE! As BLOOD concentration of drug DECREASES, tissues will RELEASE the drug.

- FAT tissue tends to store LIPID SOLUBLE, and its RELUCTANT to RELEASE the drug, as Blood supply to FAT is LOW = "stable reservoir"
If a drug BINDS to tissues, the ONSET of the drug is __________.
The LEVELS of the drug in the body remain fairly ____________, and the ACTION of the drug is ____________________
- SLOWER
- STABLE/EVEN
- PROLONGED
A BOUND drug is ___________________ to activate a receptor
is UNAVAILABLE
(its stuck!)
an UNBOUND drug is _____________________ to activate a receptor
AVAILABLE
(its free!)
Drugs like to ________ to sites on PROTEINS. ALBUMIN is most influential in this process
BIND!
FREE DRUG + PLASMA PROTEIN (albumen) =
DRUG/PROTEIN COMPLEX
Only a/n ______________ drug can reach its target cell
UNBOUND
The less ALBUMEN in one's blood stream, the _______________ Free Drug reaches target cells = the __________________ Drug RESPONSE
MORE
MORE
SOme drugs (like coumadin/"warfarin") have 99% binding capacity, so dosage must be calculated to ensure that the remaining 1% of unbound drug is enough to be ________________
THERAPEUTIC
Explain the Drug-Protein Complex
When a free drug BINDS with a plasma protein like Albumen, it becomes bound to that protein and thus forms a DRUG-PROTEIN COMPLEX
If drug "A" is reversible and bound to proteins, and you add a drug "B" (which has a HIGHER affinity for protein binding than "A"), what can occur?
COMPETITION FOR BINDING SITES!

Drug "B" can BUMP drug "A" off the limited number of protein binding sites and take its place. This suddenly INCREASES the amount of free drug "A" in the bloodstream, and INCREASES drug "A's" effect on target sites
Ratio of "Free" to "Bound" drug in the body will _____________ for every individual drug
Differ/Be different
- Drug XXXX and YYYY are both equally bound to albumen, saturating all the albumen.
- More of drug YYYY is taken, it can't bind to the saturated Albumen, so it binds to its target receptor sites and has its effect.
- You STOP taking drug XXXX, the XXXX that is already bound to the albumen gradually deteriorates, reopeneing available binding sites.
- Those newly available binding sites ATTRACT the target receptor bound drug YYYY to leave their target site and attach to the ALBUMEN.

what does this mean for the effect of drug YYYY?
Drug YYYY which WAS bound to it starget receptor site, got pulled back into the bloodstream to bind with the newly oipened ALBUMEN receptor sites.

Drug YYYY stops working after XXXX was discontinued.
stopping or starting a drug that binds to free proteins, can change the free drug levels of...?
OTHER protein bound drugs!!!
Blood Brain Barrier does what to 90% of drugs?
Brain capillaries are less permeable than other capillaries.

BBB Doesn't allow HYDROPHILIC drugs to pass from Blood to Brain
Placental Barrier
Placental Enzymes INACTIVATE drugs as they cross from Maternal to Fetal circulation
Placental Barrier is less effective than Blood Brain Barrier, it often lets what types of drugs through? ("SANA" gonna get your baby!)
- STEROIDS
- ANESTHETICS
- NARCS
- ANTIBIOTICS
BIO-TRANSFORMATION is also known as
METABOLISM
Define Metabolism
The CONVERSION of a DRUG to a more WATER SOLUBLE (IONIZED) compound ("metabolite") that can be REMOVED from the body easily.
Main site of METABOLISM?
LIVER
(mainly hepatic enzymes: P450 system
Other sites of drug METABOLISM (other than liver...hint: all the f#ck over!)
- SPLEEN
- KIDNEYS
- LUNGS
- BRAIN
- PLASMA
- GI
HEPATIC ENZYMES can perform 4 functions
- INACTIVATE a drug
- ACTIVE an inactive drug
- Make drug MORE WATER SOLUBLE
- Convert a Drug into a Drug Metabolite
Proper metabolism requires....
A HEALTHY HEPATIC SYSTEM!
The body sees a drug as __________________, and tries to _________________
as a FOREIGN OBJECT
tries to GET RID OF IT (usually via liver).
BIG question to ask when it comes to METABOLISM?
What is the _______________ status? What is the ______________ ___________ to the Liver?
What is the CARDIOVASCULAR status?

What is the BLOOD FLOW to the liver?
Define "FIRST PASS EFFECT"
-ORAL drugs move from stomach --> Small Intestine --> Liver

-Drug Concentration is greatly decreased

- What drug is left after liver metabolization is then released back into general circulation

THIS CAN OCCUR MORE THAN ONE TIME --> 2nd pass, 3rd pass etc.
Drugs that utilize first pass metabolism to convert from inactive to an active form via first pass are called:
PRO-DRUGS
ORAL drugs are subject to first pass (SL, Buccal, SQ, IM, IV are not).

Which other route is partially/minimally subjected to first pass?
RECTAL
Why is a PO morphine dose much higher than an IV morphine dose?
FIRST PASS will neutralize a % of the Oral drug, whereas IV directly enters circulation and is not subjected to a first pass
Codeine
hydrocodone
& oxycodone

are the only three ___________________ agonists
mild/moderate agonists
Morphine
Hydromorphone
Methadone
Meperidine
fentanyl
are ________________ agonists
are strong agonists
CYP1, CYP2, CYP3 are important enzymes in the
Cytochrome P450 SYSTEM
Inhibition of p450 system results in ____________________ metabolism of a drug
DECREASED
4 stated examples of known, common p450 INHIBITORS

think about:
Type of Antidepressant
Type of juice
Type of antacid
Type of Chalk blockers
- MAOIs
- GRAPEFRUIT JUICE
- CIMETIDINE (tagamet)
- Calcium Channel Blockers
Enzyme Inducers have the ability to ____________ metabolic activity in the liver
INCREASE
________________ have underdeveloped P450 systems, making Liver metabolism UNPREDICTABLE
INFANTS
_________________ have questionable responsiveness to Liver loads, often due to large amounts of drugs being taken (polypharmacy)
Elderly
Examples of p450 Enzyme Inducers
- SMOKING (will reduce therapeutic levels of drug involved)

- Charcoal broiled meats (similar to smoking)

- Phenobarbitol (increases amount fo enzymes synthesized in liver --> increases rate of metabolism)
If Liver function tests in someones diagnostic lab tests are elevated....we know that metabolism will be
DIFFERENT
(more or less? don't know...just different)
Define EXCRETION
Elimination of a drug from the body
Primary site of EXTRETION
KIDNEYS
Rate of excretion determines the _____________________ of a drug in the bloodstream..
CONCENTRATION
- FREE, UNBOUND, WATER SOLUBLE DRUGS will pass _______________ through the Golmerulus.
EASILY
Define "CLEARANCE"
Clearance = How Rapidly can the body eliminate a drug
PROTEIN/LIPID BOUND drugs...will they pass so easily? (Think Glomerulus and large albumen proteins)
NOPE. Protein Bound drugs cannot be excreted!
Probably go via GI/Feces
What 2 Labs do we want to have "within normal limits" in order to have efficient excretion?
(In order for those 2 labs to be WNL, the body needs to have three things...)
CREATININE & BUN

(Body needs to have:)
- Good CARDIAC OUTPUT
-GFR
- BP
Lipid soluble drugs that can't pass via glomerulus filtration, are reabsorbed from renal tubules and enter back into the _______________________
BLOOD STREAM
_____________________ of Urine can help determine excretion vs reabsorption of a drug in Kidneys.
PH
PH of urine can be altered to slow reabsorption of a drug in ____________________ Situatiaions
OVERDOSE
IF overdose with an acidic drug(Aspirin/ASA), then we would want to ____________________ the urine with NaHCO3 (Sodium Bicarbonate)
ALKALIZE
If overdose with an alkaline drug, we would want to _______________ urine with VIT C or Ammonium Chloride
ACIDIFY
Just like some drugs *compete* for receptor sites, drugs can also compete for __________________ by renal enzymes. THus we can give drug A to slow ___________________ of drug B and keep drug B in the blood circulation locompete some drugs *compete* for receptor sites, drugs can also *compete* for __________________ by renal enzymes. THus we can give drug A to slow ___________________ of drug B and keep drug B in the blood circulation longer...or the other way around....(think of aspirin and sodium bicarbonate)
EXCRETION
EXCRETION
Other than the kidneys, "Clearance" can occur elsewhere in the body, such as:
- GI Biliary tract I(LIPIDS)
- Lungs
- Mammary Glands (via milk)
- Sweat, Saliva
- Hemodialysis
Describe the Enterohepatic cycle
(Entero-Hepatic)
LIPIDS are broken down via BILE SALTS excreted by the LIVER into the INTESTINE.

The BILE SALTS enter the BLOOD CIRCULATION then return back into the LIVER.
What is the net effect of the enterohepatic cycle in comparison to Renal excretion?
- Enterohepatic cycle takes LONGER to excrete a drug caught up in its cycle.

PROLONGED drug action compared to a drug that si quickly excreted via the kidneys
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