Pharmacokinetics Flashcards
pharmacokinetics
study of how the body affects a drug over time
-what the body does to the drug
roles & responsibilities in prescribing
-take history
-perform physical
-formulate diagnosis
-develop tx plan that is person centered:
nonpharmacologic vs. pharmacologic`
pharmacodynamics
how the body reacts to the drug itself
-effect of the drug on the body cellularly
pharmacotherapeutics
disease being treated by drug
non-pharmacologic treatment plan
first tx plan to consider, least invasive
- dietary change
- PT
pharmacologic treatment
medication that can be prescription or OTC
methods to avoid medication error
asking if pt can read
asking what other meds pt is on
considerations for therapy
previous treatments/allergies to medications interactions- if pt is on herbal supplements and/or OTC meds side effects comorbidities age cost if pt is pregnant gender weight ease of use- pt's schedule, how often med must be taken religious/cultural needs nationality living environment/support system
parameters of pharmacokinetics
absorption distribution metabolism excretion half-life
Absorption
what occurs after drug is administered at site: GI tract —–> blood plasma
-drug may or may not bind to protein
» free drug: effective
» bound drug: non-effective
relative drug contradiction
using drug with caution in setting of other diseases
ex) Tylenol and the liver
alcoholic pt cannot metabolize Tylenol in large amounts
pharmacology of Metformin
kinetics: ingested orally into stomach & metabolized in liver and kidney
dynamics: stimulating the body to release insulin
therapeutics: treating type II DM
characteristics of drug effect and relationship to therapeutic window
- onset of effect for PO meds = when absorption occurs -> will reach peak effect = equilibrium concentration in tissue is the same as plasma
- minimal effective concentration for desired response
- time period between onset and MEC = duration of action (therapeutic window)
lag period
when medication is administered and prior to onset of effect of drug
true drug contraindication
true drug allergy
ex) allergic rxn to PCN
factors to consider in administration of drug
- barriers that drug will need to pass through
- setting that med will be administered
ex) at home vs. inpatient - urgency of need for med
ex) pt in the ER - stability of drug
- first pass effect
first pass effect
when drug is metabolized in the liver, the drug loses some potency before it is dispersed in circulation
parenteral administration
routes of administration that DO NOT involve drug absorption via the GI tract
- IV
- IM
- SQ
- transdermal
oral administration (PO)
most common route of administration that is absorbed via GI tract -> liver -> blood
- variable absorption pattern that is affected by many factors
advantage: most common, convenient, and economical
disadvantages of oral administration
- limited absorption of some drugs
- food may affect absorption
- pt compliance is necessary
- drugs may be metabolized before systemic absorption
intravenous administration (IV)
parenteral administration in which absorption is not required
- occurs in hospital setting, valuable in emergent situations
- can have immediate effects
- ideal if dosed in large volumes
advantages of IV administration
immediate effects
- suitable for irritating substances and complex mixtures
- valuable in emergencies
- dosage titration permissible
- ideal for high molecular weight proteins & peptide drugs
disadvantages of IV administration
unsuitable for oily substances
- bolus injection may result in adverse effects
- most substances must be slowly injected
- strict aseptic techniques needed
Subcutaneous administration (SC or SQ)
parenteral administration injected in subq tissue in which absorption depends on drug diluents
- aqueous solution: prompt
- depot preparations: slow & sustained
ex) insulin
advantages of subcutaneous administration
suitable for slow release drugs
-ideal for some poorly soluble suspensions
disadvantages of subcutaneous administration
pain or necrosis if drug is irritating
-unsuitable for drugs administered in large volumes
intramuscular administration (IM)
parenteral administration injected into muscle in which absorption depends on drug diluents
-aqueous solution: prompt
-depot preparations: slow & sustained
ex) Toradol
preferable to IV if pt must self-administer
advantages of intramuscular administration
suitable if drug volume is moderate
- suitable for oily vehicles and certain irritating substances
- preferable to IV if pt must self-administer
disadvantages of intramuscular administration
affects certain lab tests ( creatine kinase)
- can be painful
- can cause IM hemorrhage (precluded during AC therapy)
transdermal administration
parenteral administration with patch in which absorption of drug is slow and sustained
ex) nicotine
advantages of transdermal administration
bypasses first-pass effect
- convenient & painless
- ideal for drugs that are lipophilic and have poor oral bioavailability
- ideal for drugs that are quickly eliminated by the body
disadvantages of transdermal administration
some pts are allergic to this which can cause rxn
- drug must be highly lipophilic
- may cause delayed delivery of drug to pharmacological site of action
- limited to drugs that can be taken in small daily doses
rectal administration
administration in which absorption is erratic & variable
- partially bypasses first-pass effect
- ideal if drug causes vomiting
- not a well accepted route
advantages of rectal administration
partially bypasses first-pass effect
- bypasses destruction by stomach acid
- ideal if drug causes vomiting
- ideal in pt that are vomiting or comatose
disadvantages of rectal administration
drugs may irritate mucosa
-not a well accepted route
inhalation
administration in which absorption is fast and may be systemic; not always desirable
- ideal for gases
- effective for pts with respiratory problems
- dose can be titrated
- localized effect to target lungs
- lower doses used compared to oral or parenteral administration
- fewer systemic side effects
disadvantages of inhalation
most addictive route of administration as drug can enter brain quickly
- pt may have difficulty regulating dose
- pt may have difficulty of use
sublingual
route of administration in which absorption depends on the drug
ex) NTG: rapid, systemic absorption
- most drugs erratically or incompletely absorbed
advantages of sublingual administration
bypasses first-pass effect and destruction by stomach acid
- drug stability maintained because the pH of saliva is relatively neutral
- may cause immediate effects
disadvantages of sublingual administration
limited to certain types of drugs
- limited to drugs that can be taken in small doses
- may lose part of the drug dose if swallowed
most common routes of drug administration
IV
IM
SC/SQ
oral tablets
entero-coated (protect stomach lining) that dissolves after passing through stomach
a. extended release: timed release that is once a day dosing (XL)
b. immediate release: absorbed into stomach and effective immediately
oral vs. IV
oral drugs enter stomach first -> metabolize in liver -> portal circulation -> systemic circulation
» many opportunities to become ineffective
IV drugs enter directly into systemic circulation -> direct access to rest of body -> effective immediately
subcutaneous injection
administered into tissue
flu shot
insulin
intramuscular injection
administered into muscle which is deeper
ex> DEPO injection stays in muscle for longer time and gradually dissipate/released from muscle over time
absorption
how drugs are absorbed from GI tract into cells
-influenced by:
> route of administration
> blood flow (places with more blood flow will access drug more easily)
> surface area available (optimal for meds to be absorbed in intestines rather than stomach)
> solubility (must be in lipid soluble state
> drug-drug interactions
> pH
passive diffusion
most common pathway for how meds are absorbed
- molecules move down concentration gradient from higher to lower concentration
1. water soluble drug -> aqueous channel or pore
2. lipid soluble drug - dissolved in membrane - no cellular energy expended/no carriers
- stops when concentration is equal
active transport
energy dependent absorption pathway where meds must use ATP to move across concentration gradient (lower to higher)
- specific carrier proteins move drug molecules across gradient
- can become saturated
- may be competitively inhibited by other co-transported substances
facilitated diffusion
carrier proteins allow drug molecules to piggy-back through membrane
- can become saturated -> some drug will be lost
- can be inhibited by competitive compounds as drugs may be similar to compounds in the body
endocytosis
used for large molecules where membrane engulfs drug and pinches off in a drug filled vesicle
fast absorption
IV
inhalation
sublingual
slow absorption
oral
IM
subcutaneous
increased blood flow
results in increased absorption of drug
decreased surface area
results in decreased absorption of drug
ex) stomach vs. intestines
distribution
process by which drug leaves bloodstream and enters the interstitium of tissues’ cells
> depends on drugs:
-ability to permeate capillaries
-vascularity of tissues
-ability to bind to plasma proteins (albumin)
-ability to bind to tissue protein via active transport
-fat or water soluble characteristic
-drug dissolution
-GI tract environment
albumin
plasma protein in which FREE drug binds to during distribution of drug
ex) dilantin has affinity for this
organs that drugs are distributed to quickly
due to more blood volume
- heart
- liver
- kidneys
organs that drugs are distributed to slower
due to les vascularity/lack of capillaries
- skin
- muscle
- fat
lipid soluble drugs
easily cross through cell membranes
-cross through blood brain barrier
water soluble drugs
cannot pass easily through cell membranes
blood brain barrier
diffusion barrier which impedes influx of most compounds from blood to _
- do not allow ionized molecules to enter
- allow non-ionized molecule not bound to plasma proteins because they are easily lipid soluble
Primary sites of metabolism
Liver
Kidney
Biliary Tract
cytochrome p450 system (CYPs)
Enzymes in liver responsible for most oxidative rxns of drugs
-metabolize most drugs and other lipophilic
mechanism of CYPs
[drug] in bloodstream is lowered by first-pass effect and induction/inhibition of drug metabolism
Ex. hx of cirrhosis, hepatitis, their ability to metabolize drugs is reduced→ higher risk for toxicity and side effects due to lack of metabolism
EX Tylenol: people with a hx of liver disease→ reduce dosage of Tylenol from 4 to 2grams
Factors that Impact Metabolism
food in stomach→ slows passing of drug through stomach
pre-existing conditions
other drugs (including alcohol)
Drug tolerance
Excretion
removal of waste substances from body fluids by the kidney
primary organ that eliminates drug via …
the kidney
- Glomerular filtration—free drug passes from blood into nephron via diffusion (high to low concen)—nonionized drugs pass more readily
- Tubular excretion by efferent arteriole into tubule via carrier /ATP
- Tubular reabsorption
Clearance
rate of elimination of substances from the blood
Renal clearance
total amount of drug excreted over time
Drug elimination by the kidney
Free drug enters glomerulus(* only the free drug can enter nephron) → active secretion of drugs into proximal tubule→ passive reabsorption of lipid-soluble, unionized drug into blood→ ionized, lipid-insoluble drug passed into urine
importance of urinary pH
increase pH to change solubility and ionization of compounds→ decrease amount of drug that is reabsorbed→ increase amount that is excreted
creatinine clearance CrCl
Used to estimate renal function or GFR→ If kidney isn’t functioning properly, you will have more accumulation of the drug
Creatinine
waste product that comes from skeletal muscle when creatine phosphate is broken down
ex) elderly pts with lower muscle mass -> level of creatinine is reduced due to lower creatine in muscle
normal serum creatinine
sCr = 1 mg/dL
Factors that influence CrCl
> Age
Gender : Female creatinine clearance is lower than male clearance
Weight (and height)—body weight
ex) if someone has a lot of water weight from edema, use height with calculation
Serum creatinine (sCr)
dosing for patients with renal impairment
based on CrCl calculations from Cockcroft-Gault formula
* CrCl decreases = decrease in renal function→ lower strength of dosage or decrease frequency of drug
» the medication is not being excreted; staying in system longer so you don’t need to dose it as frequently
Half-life (t ½)
time for the drug concentration to fall to ½ its original concentration
-Measure of how long it takes for 50% of a drug to be eliminated from bloodstream
importance of half life
helps determine: Dose Dosing intervals Clearance Time it takes to reach “steady state”—a therapeutic blood level—amount of drug being absorbed is the same amount being cleared—keeping pt inside therapeutic window
6 half-life rule
it takes 6 half-lives for the concentration of a medication to reach a point where it stops causing any effects
- how long a medication is in the body
- useful for pain management dosing
ex) IR vs. ER dosing
extended release
dose in which medication will maintain therapeutic blood level
importance of 6 half-life rule
determines frequency of dosing (to prevent toxicity)
- indicates when you can begin a procedure (ie. if pt is on an anticoagulant, pt must d/c X amount of days prior to ensure it is out of their system)
- useful for when you can start a different medication (to prevent drug-drug interactions)
