Lecture 4 Part 1 Flashcards
what is the goal of therapeutics
to achieve the desired beneficial effect with minimal adverse effects
as mentioned, the goal of therapeutics is to achieve the desired benefit with minimal adverse effects.
clinicians accomplish this by determining the proper dose of a drug.
HOW IS THE DOSE DETERMINED
determined by combining the principles of pharmacokinetics and pharmacodynamics
combining these principles helps to understand the dose-effect relationship
pharmacokinetics gives ___-___
pharmacodynamics gives ___-___
kinetics = dose-concentration
dynamics = concentration-effect
when the drug is absorbed, where does it go?
into systemic circulation
once a drug is absorbed into the systemic circulation, what are its potential fates?
-drug is eliminated (metabolized or excreted)
-drug is reversibly distributed into the tissues
-drug at the site of action
when a drug is at the site of action, what happens?
it produces its pharmacological effect (either a clinical response or toxicity or both)
true or false
the drug concentration at the site of action producing a pharmacological effect is related to pharmacodynamics
true
pharmacokinetics is involved with ADME.
what does ADME determine?
how rapidly and how long the drug will be at the target organ
pharmacodynamics involves what 2 properties?
the pharmacological effect and maximal efficacy
pharmacodynamics involves the pharmacological effect and the maximum efficacy.
this characterizes the relationship between….
the drug concentration and the effects it produces
true or false
a relationship does not exist between the beneficial or toxic effect of a drug and the concentration
false - a relationship does exist
the importance of pharmacokinetics and pharmacodynamics in patient care rests on the improvement in….
therapeutic benefit and REDUCTION in toxicity
pharmacokinetics is a _____ study and characterization of the time course of drug concentrations in the body
qualitative or quantitative?
quantitative
pharmacokinetics allows us to answer what 2 questions
when will the drug reach steady state levels
when will the drug be eliminated
what helps to establish dosage regiments that will result in improved drug utilization in patients?
pharmacokinetics
what physiological factors will modify pharmacokinetic properties of a patient?
sex
age
disease stage
genomics
what 2 disease states in particular will require dosage adjustment
heart failure and renal failure
the “standard” dose of a drug is obtained from what
studies on healthy volunteers with average ability to absorb distribute and eliminate the drug
pharmacokinetics is a discipline that uses mathematical formula to ____ the relationship between….
delineate the relationship between the dose of the drug administered and the final concentration of the drug at the site of action
define parenteral administration
administration by some route other than the GI tract
name the 3 major parenteral routes of administration
IV
SUBQ
IM
name 4 “other” parenteral routes of administration
epidural
inhalation
topical
intrathecal
define enteral administration
via the GI tract
name 3 major enteral routes of administration
oral
sublingual
rectal
true or false
the rectal route of administration could be considered parenteral or enteral
true
enemas are for local effect and don’t go through the GI but systemic suppositories do
which route of administration has the MOST RAPID onset?
what is the bioavailability?
IV
100% (by definition)
which route of administration has a bioavailability of 75 to less than or equal to 100%
IM and SC(SUBQ)
what is the most convenient route of administration? what is it’s bioavailability ?
oral
5 to less than 100%
which route of administration usually has very slow absorption and used for its lack of first pass effect? has a prolonged duration of action.
what is it’s bioavailability ?
transdermal patch
80- less than or equal to 100%
what is the bioavailability of inhalation? what is it’s onset?
5 - less than 100%
often very rapid onset
true or false
the rectal route of administration has less first pass effect than oral
also give the bioavailability of the rectal route of administration
true
30- less than 100%
which has larger volume - IM or SC
IM has larger volumes
both may be painful
true or false
first pass effect is not very important for oral drugs
false - may be important
give the definition of bioavailability
the fraction of UNCHANGED DRUG that reaches systemic circulation following administration (by ANY route of administration)
IV administration: bioavailability=___
other routes of administration=____
IV = 1
other routes = less than 1
name the 2 major factors that reduce the bioavailability to less than 100%
incomplete absorption
first pass effect (liver metabolizes drug before it reaches systemic circulation)
give the 3 steps of the drug absorption sequence.
bioavailability may be affected by which steps?
- across gut wall into portal circulation
- portal blood transports drug to liver
- drug may then reach systemic circulation
bioavailability may be affected by all 3 steps
true or false
drug metabolism may occur:
-in the intestinal wall
-in the blood
-in the liver
true
a basic drug will be better absorbed in the stomach or small intestine?
small intestine because it will be unionized
the liver may excrete the drug ___
in the bike
true or false
the oral route is most preferred and most common
true
name 3 reasons why oral bioavailability may be reduced
-the drug may not be soluble enough in aqueous environment (no dissolution= no absorption)
-the absorption may be incomplete due to biological barriers OR drug metabolism in the gut (drug may be inactivated in the gut)
-1st pass effect
true or false
a drug cannot be inactivated in the gut
false - it can
due to biological barriers or drug metabolism in the gut
how can absorption vary in different areas of the gut?
due to:
-pH
-food present in the gut
-gastric emptying
-IN GENERAL, drugs tend to be more readily absorbed from the small intestine than stomach due to large surface area and villi
explain the surface area of the small intestine
with no villi would be 3300 cm squared
it has microvilli so it’s 2,000,000cm squared
ALLOWS FOR BETTER ABSORPTION THAN THE STOMACH
true or false
drugs tend to be more readily absorbed in the stomach than the small intestine
false - more readily absorbed in small intestine due to large surface area
true or false
the intravenous route of administration is when the drug is introduced directly into the bloodstream
true
give the advantages of IV route of administration
-most rapid onset
-bioavailability is 100%
-safe for narrow therapeutic index drug bc a control injection can be made slowly and stopped quickly
-good for a highly metabolized drug bc 1st pass is bypassed
give disadvantages of the IV route
-drug can’t be recalled once injected-
-embolism risk
-catastrophic effects may happen
-if excessive fluid is injected will lead to congestive heart failure
how does absorption occur in the IM and SC routes of administration?
by simple diffusion
from the extra cellular site of injection into the circulation
in IM and SC, what is the rate of absorption limited by
the area of absorption
the solubility of the drug in the interstitial fluid (no dissolution=no absorption)
where is the drug injected in IM
into skeletal muscle
where is the drug injected in subcutaneous
under the skin
what are the advantages of IM
absorbed rapidly
large amounts are often feasible
what are the disadvantages of IM
inconvenient most of the time
not good for those with poor circulation
painful
name advantages of SUBQ
good for small amount of drug and long term drugs
name disadvantages of subq
absorbed slowly
not good for those with poor circulation
may be painful
necrosis
explain the intra-arterial route of administration
occasionally a drug is injected into an artery to localize its effect in a particular tissue or organ (TREATMENT OF LIVER TUMORS/head/neck cancers)
diagnostic agents sometimes administered intra arterial (technetium-labeled serum albumin)
explain the intrathecal route of administration
local and rapid effects on the meneinges or cerebrospinal axis(spinal anesthesia, treatment of acute CNS infections and brain tumors)
sometimes injected directly into subarachnoid spaces
give 2 advantages of oral route
easy to administer
economic (cheap)
give disadvantages of oral
many factors affect its absorption
stomach situation (pH, presence or absence of food)
first pass effects
emesis (vomit) may occur
is sublingual enteral or parental
can be considered both? does bypass hepatic metabolism but on slides says enteral
explain how the sublingual route of administration works
direct absorption into systemic circulation.
bypasses hepatic portal and first pass
prevents the destruction of the drug by intestinal enzymes or low pH
what is the environment like in the sublingual route of administration? is this an advantage?
slightly acidic with a high water composition - advantage
state advantages of the sublingual route of administration
-bypasses the liver
-a drug that is absorbed from the oral cavity gains access to the systemic circulation
-slightly acidic environment with high water composition
-thin and highly vascularized epithelium
-drugs are kept in this kind of environment when placed under the tongue
true or false
sublingual drugs must be kept under the tongue until they are dissolved
true
what may be limiting in the sublingual route of administration
relatively large doses
name advantages of rectal route
-partly avoids first pass (drugs absorbed from lower part of the rectum bypass liver – ~50%)
-drug cannot be destroyed by intestinal enzymes or low stomach pH
-patients who are unconscious or vomiting
-drugs with bad taste or odor
name some disadvantages of rectal route
absorption can be irregular, incomplete, and may irritate the mucosal membrane
what is the most rapid absorption route
inhalation
inhaled as a gas and enters circulation through diffusion across the alveolar
name advantage and disadvantage of inhalation
advantage - fast access to circulation dc of large surface area and AVOIDS FIRST PASS
-disadvantage: only a few drugs can be used by inhalation
name 2 drugs that are available via intranasal
salmon calcitonin - peptide hormone used to treat osteoporosis - nasal spray
cocaine is sniffed
topical drugs are used when what kind of effects are desired? give an example
local effects
atropine is instilled directly into the eye to dilate the pupil
explain the transdermal route
achieves systemic effects
-drug applied to skin
-used for SUSTAINED delivery - such as nitroglycerin - an antianginal
true or false
transdermal route of administration is for local effects
false - systemci
