Pharmacokinetics

-absorption
-distribution
-metabolism
-excretion

ADME

-Half-life
-Steady state
-Loading dose
-Maintenance dose

Lipid insoluble, water soluble

-excreted easily
-hard movement

-Lipid soluble
-water insoluble

-moves easily
-hard time excreted

-Concentration of Gradient (dosage)

-Size of Drug molecule (smaller molecues absorbed faster)

-Lipid solubility (structure of molecule, ionization of molecule, PH)

-movement of drug from site of admin
-primary factor for determining onset of drug action
-quantified as *bioavailability*
-impacted by several factors affecting rate of absorption

-Admin route
-Molecule size
-Molecule characteristics

-non ionized, -good volume for distribution
-require metabolism to be conjugated (bad)
-need conjugation to become water soluble (liver)

good for excretion, bad for absorption

good for absorption, bad for excretion

Non ionized in acid-more absorption in stomach, best without food.

non ionized in alkaline- absorption in small intestine; enteric coating means no absorption in stomach (it would become ionized bc of Acid-Base reaction)

ingestion, absorption, injection, inhalation

introduction into the subcutaneous tissues of fluids, such as normal saline solution, to help correct dehydration from inadequate intake or loss of fluid and sodium

IV

topical

-presence of food may decrease absorption
-presence of certain foods and drugs may alter rate of absorption
-motility influences time during which absorption can occur

increased blood flow= increased rate of absorption
-increased surface area= increased rate
-route of admin
-impact of temp on blood flow

-depending on PH of surrounding fluid, most drugs in either charged or uncharged state

metabolized in liver (describes passing through hepatic)

*enzymatic degradation in liver prior to drug reaching its site of action

-plasma concentration of a drug in systemic circulation

eg: IV drug has 100 percent absorption, so it has complete bio-availability

rapid, emergency, bioavailable, predictable
-Needs expert knowledge, painful
-absorbed in seconds

-bioavailability depends on prep (altered by size, PH, Charge)
-pain, irritation of site

50-75 % bypasses first pass metabolism, unpredictable and varied absorption: patient dependent

-slow and sustained, release of desired drugs over long period of time

-controlled release, extended release, sustained release, prolonged action

Prep: tablet, transdermal patch, intramuscular injection (depth prep)

The initial metabolism in the liver of a drug absorbed from the gastrointestinal tract before the drug reaches systemic circulation through the bloodstream. The amount of drug is severely decreased, because a lot of it is ionized by the liver and then excreted.

-transport of drugs throughout body to target tissue

-blood flow
-ionization
-protein binding
-barriers

increased= more drug reaching target issue

-hydrophilic drugs transported in solution

-lipophillic drugs, a portion is bound to plasma proteins (albuminin) portion of drug in solution

Drug-protein complexes cannot cross capillary membranes.
Only unbound drugs reach target tissues.
Competition of protein binding sites
Each drug has protein binding percentage.

the way proteins bind within plasma affects drug efficiency as well as how proficiently a drug diffuses through a cell membrane

-Drugs bind *reversibly* to proteins in the blood, which influences distriution

-hihg PPB can increase duration of action, decreases risks of effects

-binding is saturable

Relates the amount of drug in the body to the plasma concentration

-volume of fluid which a drug would need to be distributed to achieve a concentration equal to the concentration in plasma

free, or...
bound to plasma proteins or tissue lipids

-volume distribution
-rate of renal clearance
-drug half life
-amount of free drugs in target tissueeceptor

-plasma albumin

alpha 1 acid glycoprotein

-lipoproetins
-globulins

plasma albumininum decreases

alpha 1 acid glycoproteins increase

-stay within vascular compartment

-have limited volume of distribution

-large volume of distribution

Concentration: weight (mg)/ volume

Volume: weight/concentration (plasma)

Dose/concentation

dose: mg
concentration: measured concentration of drug in blood upon equilibrium (mg/l)

molecular structure is changed or added onto

primary metabolic organ
*first pass then everytime the drug passes through hepatic circulation*

phase 1
phase 2

Oxidation, *(CYP450) * reduction, (*YP 450 reductase) *hydrolysis *(enzymes, esterase, amidase)*

-enzyme catalyzed irreversible alteration in drug structure
-drug is more polar
-active metabolicites

(only some drugs)
-a large polar molecule is added to the drug structure to increase excretion potential via kidney or GI tract (conjugation)

-lipophillic drugs
-conjugation
-more polar
-inactive metabolism
-renaly excreted

-microsomal enzymes in liver carry out most metabolic activities

-metabolizes many drugs
-many isoenzyme systems within CYP
-determine spread at which drug is metabolized

when the effect of a medication is changed, enhanced, or diminished when taken with another drug, including herbal substances

*-due to metabolism and CYP*

CYP
-prescene of 1 drug may alter metabolism of anyother drug by competing for isoenzyme

-CYP enzyme
-inhibiting isoenzymes could reduce metabolism of another drug: toxic levels

CYP enzymes
-inducing isoenzyme could increase metabolism of another drug: reducing amount of functional drug

-amoxivillin (doesnt undergo metabolism)
-Codeine (not active until metabolized- is a prodrug)
-Acetaminophen (metabolism yields toxic metabolites: use lowest effective dose!)

Kidneys

-glomerular filtration
-active tubular secretion
-tubular reabsorption

renal insufficiency
-integrity of glomerulus

*urinary PH*
-artificially or pathophysiology

*cardiac output*
-renal blood flow

*Lipophillic*: from blood: bowman's capsule, transporters in PCT exist for acidic and basic drugs that pump from the circulation- the tubules

*Lipohillic Not Metabolized:* can be reabsorbed back into blood stream while polar drugs remain in urine and become concentrated

rate of elimination proportionate to plasma concentration

all drugs except ethanol, aspirin, phytoin

-rate of elimiation is fixed- interdependent of plasma concentration:
-ethanol, aspirin, phenytoin