Drug disposition and fate of drugs Flashcards
General Principles of Drug Absorption (Routes of Administration)
- Drug dissolve in body fluid (water).
- Drugs enter the circulatory system as fluid enters the circulatory system.
- Drugs must enter the circulatory system before they can distributed to sites of
action. - Therefore, drugs are not IN the body until they are IN the bloodstream.
It is convenient, cheap, no need for sterilization, variety of dose forms
Oral administration
Disadvantages of Oral administration
- Variability due to physiology, feeding, disease, etc.
- Intractable patients
- First-pass effect
- Efficiently metabolized drugs eliminated by the liver before they reach the
systematic circulation.
It can be given by the owner (small patients); vasoconstrictor can be added to prolong effect at site of interest
subcutaneous administration
When applied, patients groom themselves
topical
Patient and pharmaceutical factors of oral admin.
- Pill compression, coatings, suspending agents, etc.
- GI transit time (too slow or too fast), inflammation, malabsorption, syndromes
patient and pharmaceutical factors of SC administration
- More autonomic control over blood flow (than muscle)
- dehydration, heat, cold, stress
its patient and pharmaceutical factors include lipid solubility and molecule size, skin hydration and abrasion, area of application, ambient an patient temperature
topical
Larger absorptive surface are than IM / Subcutaneous
intraperitoneal
may cause peritonitis and damage to organs by needles
intraperitoneal
Generally restricted to laboratory animals
intraperitoneal
route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF)
Intrathecal
administered in the joint
intra-articular
Produce extremely high concentrations “pointed at” the tissue of interest.
intra-arterial
Used primarily for anti-tumor therapy and infectious disease therapy when blood supply is questionable
intra-arterial
Access to GI absorption in unconscious or vomiting patients
per rectum
any chemical substance which modify the functions of a biological
system and primarily intended for the treatment, prevention or diagnosis of
disease to man or animals
drug
the pharmacopeia of the United States of America (1820)
USP
British Pharmacopeia
B.P
B.P.C
the British Pharmaceutical Codex (1907
N.F.
national formulary
study the actions of drugs on living things
pharmacology
C.F
canadian formulary
Ph. I.
International Pharmacopeia
C.F.
codex francis
drug mixtures prepared from crude drugs and containing several organic ingredients
galencials
a blank preparation containing only innocuous ingredients
placebo
extent to which the active ingredient in a drug product can be taken up by the body in a form which is physiologically active in order to exert the desired therapeutic effect
bioavailability
in order to be absorbed, reach sites of action drugs must have the ability dissolve in?
water
drugs can leave and enter capillaries,
and enter and leave cells, through?
lipid solubility
measured in either serum or plasma
drug concentration in blood stream
easy painless application of topical drug
systemic therapy
reduced systemic effects/enhanced skin effects of topical drug
skin therapy
disadvantages of topical
- Patients groom themselves (topically applied, orally absorbed)
- Toxic skin reactions
- Variable blood flow to skin
- Complex relationship between drug, vehicle , skin physiology
Diffusion through stratified epithelium
“Passage” through adnexal structures
topical administration
True or false.
“like” vehicles retain drug on skin surface while drugs in “unlike” vehicles leave the vehicle to move on to skin
true
Its disadvantages are:
- Difficult dose calculation
- CSF volume is not proportional to body weight
- Toxicity likely, and toxicity may be unusual
- Introduce infection into a VERY bad location
Intrathecal
One of the disadvantages are limited number of efficacy studies (especially in animals)
intra-arterial
Animals may not willingly retain the drug
per rectum
Its process is like oral without mechanical preparation by stomach
per rectum
7% of body weight
Vascular space
Extracellular Space size
15 - 20% of bw
distribution of drug in vascular space
10 - 30 minutes
Extracellular Space distribution
30 minutes - 1.5 hours
intracellular space size
35 – 45% of body weight
distribution in intracellular space
30 minutes to 12+hours
Give three reserved spaces.
- Special barriers between plasma and tissue fluid CSF
- aqueous humor
- prostatic fluid
Distribution in minutes to never
reserved spaces
three processes in renal excretion
- Glomerular filtration
- tubular secretion
- passive reabsorption
renal elimination of aspirin can go from _____ of total elimination
2% to 30%
volume of fluid that “appears” to contain the amount of drug in the
body
volume of distribution
volume of plasma water cleared of the drug during a specified time period
clearance
sum of all organ clearances
Total body clearance (Clt)
fraction of the volume of distribution cleared per unit time
rate constant elimination
time for elimination of one half of the total amount in the body
elimination half-life
initial dose of drug given to shorten the time to reach the steady-state concentrations
loading dose
describes the rate of drug movement (oral, IM, SC, etc.) from the dose to the circulatory system
absorption rate constant
Two drug products are ______ if the nature and extent of therapeutic and
toxic effects are equal following administration
bioequivalent
Attempt to describe the actual events which control drug absorption,
distribution, and elimination
physiologic model/pharmacokinetics model
absorption rate decrease as the dose increases
dose-dependent absorption
clearance and the elimination rate constant decrease as the dose
increases
dose-dependent elimination
The sum of all individual organ
clearances. Usually determined by
plasma sampling
total clearance (CLT)
The clearance “performed” by the
kidney.
renal clearance (CLR)
The clearance “performed’ by the
liver.
hepatic clearance (CLH)
highest plasma concentration
achieved following a single non-intravenous dose of a drug.
peak plasma concentration (cmax)
portion of a non-intravenous dose of
drug that reaches the systemic
circulation.
fraction of dose absorbed
Time required to eliminate 50% of
any amount of drug from the body
half life elimination
