what are the characteristics of transdermal patches?
these are designed to provide continuous controlled release of medication through a semipermeable membrane over a given period of time (nitroglycerin- nitrodisc, estrogen-estraderm, nicotine-nicoderm)
composed of several layers with each having a specific function
most common problems with patches are irritation, erythema and edema
this is the amount of time that passes for the concentration of a drug to fall to half its blood level at any time
half life (t1/2)
what are some examples of topical route?
skin, oral mucosa, sublingually
corticosteroids, eye drops, creams, etc.
administration of topical sterioids over a large portion of the body can result in symptoms of systemic toxcity-cushings syndrome
transdermal/patches
when a drug is given and hives develop within several hours?
hypersensitivity reaction to drugs
what are the mechanisms of metabolism?
active to inactive
inactive to active
active to active
undesirable reactions, potentially harmful and occurs at usual therapeutic doses
adverse effects
this is the application to body surfaces
topical route
hepatic microsomes
reduction
what factors affect distribution?
size of organ, blood flow to organ, solubility of drug and presence of barriers
effect on developing fetus
tetratogenic effect
this is the passage of drug related to the drugs lipid solubility and degree of ionization… a high lipid soluble, non ionized drug easily penetrates this
blood brain barrier
this mechanism of metabolism is an inactive parent drug that may be transformed into an active compound-termed prodrug
inactive to active
a specific type of reaction to a drug for example, rash or itching
allergy
under the tongue, rapid absorption into the systemic circulation (for ex, nitroglycerin and glucose)
sublingual (SL)
clinically desireable actions
therapeautic effect
unchanged drug or metabolite are filtered through glomeruli into the renal tubular fluid, most drugs, most common
glomerular filtration
drug particles must be spread thruout the stomach or intestine
dispersion
the initial disruption of a tablet coating or capsule shell is necessary
disruption
characteristics of synthetic (phase II) metabolism?
involves conjugation with; glucronic acid, sulfuric acid, acetic acid, or amino acid
transferase- an enzyme mediating the conjugation of a lipid soluble drug
Progestins (norplant) implanted under skin to release a drug over a prolonged duration (birth control) - 5 years
implants
how are adverse drug reactions categorized by?
toxic reaction
side effect
idiosyncratic reaction
drug allergy
interfere with natural defense mechanisms
what are the characteristics of non synthetic phase I metabolism?
lipid molecules are metabolized by oxidation, reduction and hydrolysis
passage across this involves simple diffusion in accordance to lipid solubility
placenta
factors altering a drug effects;
pt. compliance physiologic factors - attitude tolerance-tachyphylaxis-very rapid development of tolerance pathologic state time of admin, rout of admin. sex age/weight environment
an extension of the pharmacologic effect resulting from a drugs effect on the target organs (excess)
toxic reaction
transports the drug from the blood stream across the renal tubular epithelial cells and into renal tubular fluid
active tubular secretion
how has the FDA established drugs for pregnancy categories?
A,B,C,D,X (A least risky and X-most risky never use)
tetracyclince, NSAIDS, benzodiazepines, and metronidazole
this mechanism of metabolism is an active parent drug that may be concerted to a second active compound, which is then converted to an inactive compound. (double dose essentially)
active to active
this is the passage of drugs into various body fluid compartments such as plasma, interstitial fluids and intracellular fluids and occurs when a drug moves to various sites of the body
distribution
genetically related abnormal drug response
idiosyncratic reaction
what must be determined before a drug is used?
a risk to benefit ration
the beneficial effect must be weighted against its potential for adverse reactions
major route by which systemically absorbed drugs enter the GI tract and are eliminated in the feces
biliary excretion
long acting and slowly removed
long half life
a drug is essentially gone when only 3-6% of a drug remains after 4 or 5 half lives
for ex- if a drug has a t1/2 of 1 hour- then 4-5 hrs the drug would mostly be gone out of the body
what are the 2 forms drugs are in blood?
bound to plasma proteins, and as a free drug
whether a fetal malformation can occur
teratogenicity
elimination by kidneys involve…
glomerular filtration
active tubular secretion
passive tubular diffusion
what are the two types of metabolism?
non-synthetic (phase I)
Synthetic (Phase II)
becoming less responsive to a drug over time
tolerance
what factors influence the movement of a drug?
adsorption, distribution, metabolism and excretion (ADME)
the bodys way of changing a drug so that it can be more easily excreted by the kidneys and the most common site of this is the liver
metabolism (biotransformation)
this mechanism of metabolism is an inactive compound may be formed from an active parent, and the most common type of reaction
active to inactive
for drugs to penetrate the CNS, they must pass across what?
Blood brain barrier
what are the factors influencing the rate of absorption?
physiochemical factors, route of admin, drug sollubility
the study of how a drug enters the body, circulates within the body and is changed by the body, and then leaves the body
pharmocokinetics
addition of 02
oxidation
drug must be dissolved in GI fluid
dissolution
this type of hypersensitivity to drugs can cause arthus reactions medicated by IgG, Serum thickness and includes urticarial skin eruptions and arthralgia, arthritis, lymphadenopathy and fever
Type III
is the movement of a drug from the site of action to non specific sites of action
redistribution
this type of hypersensitivity to drugs is complement dependent reaction involving IgG or IgM for example penicillin-induced hemolytic anemia
Type II
tablet or capsule contents must break apart
disintegration
this is the process by which drug molecules are transferred from the site of administration to the circulating blood, requires the passage of biologic membranes
absorption
certain drugs can reduce the bodys ability to fight infection (adrenocorticosterioid)
interference with natural defense mechanisms
what are the 4 steps that oral route requires?
disruption
disintegration
dispersion
dissolution
dose related reaction that is not part of the desired therapeutic outcome (nausea, or upset stomach)
side effect
this regulates the amount of drug in the tubular fluid, favors the reabsorption of non ionized, lipid soluble compounds
passive tubular diffusion
what are the characterisitcs of toxicologic evaluation of drugs?
the LD50 is the dose of a drug that kills 50 percent of exp. animals
the ED50 is the dose required to produce a specified intensity of effect in 50 percent of animals
the TI of a drug is the LD50/ED50 ratio
if TI is small- toxciity is more likely
if TI is large, drug will be safer
a TI of 10 or greater is needed to produce a therapeautically useful drug
breaking down of esters with the addition of H20
hydrolysis
immunologic response resulting in a rash or anaphylaxsis, less than 5 percent of all adverse reactions
drug allergy
short action and quickly removed
short half life
This type of hypersensitivty to drugs is delayed hypersens., mediated by T lymphocytes, for example contact dermatitis or allergy to latex.
Type IV
this type of hypersensitivtiy to drugs targets bronchioles resulting in anaphylatic shock..
chracterized by hypotension, bronchospasm, laryngeal, edama and cardiac arrythmias?
type I (worst)