Exam II Basic Pharm Principles Flashcards
pharmacotherapeutics
the use of specific drugs in the prevention, treatment, or diagnosis of disease
pharmacodynamics
what the drug does to the body
the quantitative effects of a drug on the body
pharmacokinetics
what the body does to the drug
quantitative, time dependent changes of both plasma drug concentration and the total amount of drug in the body, following the drug’s administration by various routes
-ADME
absorption
drug and its intake/absorption at site of administration
- lipid or water soluble
- ionized
- speed of action desired
- systemic or local action
- enteral vs. parenteral
- some drugs can change based on the pH inside the body
- bioavailability is based on drug absorption:
- plasma concentration/dose
distribution
- occurs mainly via circulation
- wide variance in organs and tissues ability to take up a drug
- non-vascular tissues and plasma proteins can take up or bind drugs
- rate at which tissues take up a drug depends on vascularity of region that absorbs it
sites of metabolism
liver* (primary) kidneys lungs skin GI tract
biotransformation (aka drug metabolism)
capable of altering drugs in 4 ways:
1-conversion of active drug to inactive drug
2-conversion of active drug to active or toxic metabolite (prolongs activity of drug)
3-conversion of inactive prodrug to active drug (prodrug activated in the liver - cytoxin)
4-conversion of unexcretable drug to excretable metabolite (non-water soluble to water soluble)
Metabolic Pathways
phase I reaction: usually precedes Phase II but not always
-chem mod. through oxidation, reduction, or hydrolysis,
-cytochrome P450 system is most common oxidative pathway (CYP3A4 (usually in liver)
phase II reaction: intend to make things nonwater soluble into water soluble
-conjugate drug to form large polar molecule
-enhance solubility and excretion in urine or bile
elimination
renal* primary
renal excretion relies on water solubility
drugs also excreted in small amounts via bile, feces, sweat, lungs
-elimination halflife: amount of time over which the drug concentration in the plasma decreases to one-half of its original value
-ranges from days (diazepam- 80 hr half life bc metabolites have similar activity, digoxin) to minutes (NE)
longer halflives can be more troublesome bc they stay around longer
enteral
administration type: uses GI tract to enter body, not many risks upon entry
- includes ORAL, SUBLINGUAL/BUCCAL, RECTAL
- advantages of oral type that it’s simple, safe, convenient, inexpensive, no pain, no infection, no rapid spikes in plasma levels (the # rises and tapers off slowly), larger vascular network available in oral and rectal mucosa.
- disadvantages this is extremely variable administration of a drug bc transporters and receptors are proteins and so vary by person, this is the most variable and complex pathway of admin, slow delivery, requires GI absorption and function, First Pass Effect means sometimes the liver can and will metabolize the drug before it gets moved into the systemic circulation so it may end up having a much lower availability, GI environment is harsh, GI irritation can occur.
parenteral
administration type: does NOT use GI tract for entry into body
- includes IV, INTRAMUSCULAR, SUBCUTANEOUS, also meds can be implanted (ie insulin pump)
- advantages: rapid delivery, high bioavailability, avoid first-pass metabolism, avoid GI environment, good control of delivered dose
- disadvantages: irreversible, infection risk @ injection sites, pain and fear, need for skilled delivery, limited drug delivery with SC and IM
other routes of administration
- inhalation (large surface area rapid delivery, complicated for self-delivery not easy to do correctly)
- intranasal
- intrathecal (some chemo drugs baclofen within a sheath, directly into subarachnoid space)
- topical
- phonophoresis (sound waves to drive meds into skin)
- ionophoresis (electricity to drive into skin)
intrathecal
**some chemo drugs ex: baclofen
med is inserted within a sheath in the body, directly into subarachnoid space specifically of spinal column
-in neural membranes
transdermal
application of medicine across dermis skin
first pass effect
First Pass Effect means sometimes the liver can and will metabolize the drug before it gets moved into the systemic circulation so it may end up having a much lower availability
volume of distribution
dose/[drug]plasma
-volume of distribution=vd is low for drugs contained in plasma, high for drugs distributed in muscle or adipose… low # means drug is contained in plasma and primarily water soluble:
-aspirin: 11L (low)
-digoxin: 500L (high)
uniform distribution is AT or NEAR 42L
-most drugs circulate with plasma proteins (ex: albumin, and others, which makes this not available to do other things in the body since it’s occupied by acting as a transfer ptn), drugs can be taken up into tissues and tissue compartments oher than**
conjugation
ways to change drugs once they;re inside the body. during metabolic pathway, during Phase II, drug can be conjugated to form a large polar molecule
therapeutic dosing
amplification effects can occur if dosing is too high, therapeutic window exists for all drugs, smaller doses mean theyll last shorter amount of time, look@therapeutic dosing graph
enzymatic induction
liver enzymes inducted: tobacco smoke increases drug activiy -phenlytoin and carbemazeprine (anti-seizure) -rifampin (antibiotic) -ethanol (alcohol) -benzopyrene
enzymatic inhibition
liver enzymes inhibited:
- prilosec (omeprazole)
- erthryromycin- antibiotic
- cimetidine
- amiodarone (heart rhtyhm)
- grapefruit juice (slow down rate of activity of meds, gets on enzymes in the sm intestine)
half-life
period of time required for the concentration or amount of drug in the body to be reduced by one-half. We usually consider the half life of a drug in relation to the amount of the drug in plasma
G protein coupled receptor
“guanine-protein coupled receptor”
-constitute a large protein family of receptors that sense molecules outside the cell and activate inside signal transduction
most common receptor in humans, 70% of interactions use these receptors
second messenger
molecules that relay signals received at receptors on the cell surface — such as the arrival of protein hormones, growth factors, etc. — to target molecules in the cytosol and/or nucleus
desensitization
decreased affinity
inactivation, changes to receptor activity that’s in place (enzymatic activity and phosphorilation) - can happen quickly. modification of substances already in the cells
ligand doesn’t bind as frequently or readily to the receptor
supersensitivity
increased affinity
changes to receptor activity that’s in place (enzymatic activity and phosphorilation) - can happen quickly. modification of substances already in the cells
ligand binds more freuqnelty and readily to receptor
up/down regulation
changes in # of receptors
An increase of a cellular component is called upregulation. An example of downregulation is the cellular decrease in the number of receptors to a molecule, such as a hormone or neurotransmitter, which reduces the cell’s sensitivity to the molecule
refractory
Resistant to treatment, as of a disease
agonist
a molecule that binds a receptor and causes a response
antagonist
“blockers” - inhibits the action of the agonist but has no effect… inhibition
chemical antagonist
non-receptor antagonist
physiologic antagonist
non-receptor antagonist
opposite effect of another drug, for ex: thryoid issues and the beta blocker role
competitive antagonist
ligand binds where another could bind, compeing with agonist for same site.
noncompetitive antagonist
for ex: a channel doesn’t open, even when agonist is bound.
partial agonist
activates receptor but produces only a partial response, even when all sites are bound. affinity for receptor (often high), response observed isn’t observed; opioid pain relievers…morphine is considered a strong agonist, though)
graded dose-response curve
response of one individual to a drug, small dosage means no response observed, then after threshold dose there’s an increase in response, at ceiling effect, no more receptors to interact with- saturated.
efficacy
capacity for a drug producing a desired result or effect
potency
lower dose of drug has higher impact
quantal dose-response curve
you measure based on what occurs during drug administration, on or off response,
for ex: yes or no, or 50% is the effective dose.
Therapeutic / toxic / lethal effect
therapeutic window
range of doses that fall within range (cumulative % exhibiting therapeutic effect), beneath the toxic effect
therapeutic index
TI=TD50/ED50… bigger implies a safer med (further toxic dose is away from effective dose). tylenol has a high index, chemo drugs have a TI close to 1 since they’re inherently toxic.
TD=toxic dose/ ED=Effective Dose
absorption
nonpolar substance will diffuse through more readily than a polar substance. pH of GI tract changes drastically from stomach to sm intestine and this can affect where and how drugs are absorbed.
