Drug Transport & Absorption -Dr. Issar Flashcards
what are types of transport mechanisms
- passive mechanism: simple diffusion
- active mechanisms: active transport
- specialized mechanisms: fascilitated diffusion
what are the types of simple diffusion
- filtration
- ion pair transport
- paracellular
what is a type of active transport
pinocytosis
what is lipid water partitioning
partition coefficient used in
simple diffision happens from high to low:
along concentration gradient.
What is Fick’s law of diffusion
Diff factors that inf the rate of diffusion across the bilayer membrane.
h= membrane thickness and the thicker the membrane the ____ the rate of diffusion.
lesser;
The only thing that changes is ____ gradient and is only dependent on conc of drug at the site and is very small thus follows ____ order diffusion pattern.
diffusion; first
The role of fascilitated diffusion is pretty small in absorption of drugs and follows Michaelis Menten kinetics. Low drug concentrations. Cabs
first
when conc of drug becomes high the Cabs»_space; Km and this follows ___ order diffusion. It doesnt depend on how much drug is at site, it depends on fixed ____
zero; rate
Some characteristics of active transport are
- against conc gradient (low to high)
- requires energy
- can be competitive
- saturable( when you go to high conc can go from 1st order to 0 order rate of transport)
- present in intenstine, kidneys, liver
- constant (0 order) absorption at higher drug conc.
____diffusion is most common with pharmaceutical drugs
Passive
____diffusion has no saturation. But fascilitated diffusion and active transport does have saturation
Passive
what does the extent of ionization of a weak electrolyte depend on
- pKa of the drug
2. pH of the solvent
for weak acids assume that we have a weak acid, HA which ionizes into its counterpart ions. Ratio of nonionized to ____.
ionized
What is ion trapping
If taking an aspirin with pka of 3.2. The aspirin in the non ionized form placed in acidic medium exists mainly as non ionized spcies. Will have a small portion being ionized. This has a tendency to go into blood with pH of 7.4. An acid sitting in alkaline medium gets ______. Majority gets transferred to ionized form and cannot cross and go back onto other side and gets trapped into circulation.
-ionized
Non ionized species on both targets will always be _____
equal
If molecule has ability to ionize and there is differential to pH it will:
move to other side
Weak ____ or acid will ionize to ___ degrees on the respective sides and have ____ drug conc on either side of the membrane and the compartment containing greater proportion of ____ drug will contain greater total drug concentration
base; different; unequal; ionized
when weak base is being ionized it will form its counterpart ions and the ratio flips in the case of a base. In weak acid, non ionized species on top, in the numerator. So in weak base the ratio is ionized species to ____
non ionized (more in stomach it will ionize)
anything thats ionized is hydrophillic and hydrophillic molecules have difficulty going across the _____
membrane.
weak acids in plasma are usually in ___ ____ form
non ionized
for weak base, you will acidify urine by giving ___ ___. Weak base wil be in ionized species and will have difficulty going back and will get excreted.
ammonium chloride
for weak acid you basify it…raise pH of urine. Phenobarb is weak acid and will ionize when pH is much higher and will get _____ out
excreted
Drugs with similar pKa can be affected differently by changes in pH of body fluids. Even though amphetamine has a similar pKa to chlorpromazine, why is there greater amphetamine excretion compared to chlorpromazine?
Bc chlorpramize is more lipophilic in nature. Liphophilicty overrides whatever pKa is doing in pH environment. A lipophilic drug will precede and will still be able to go back and get reabsorbed even if their being ionized.
what is another factor that affects drug elimination?
affinity/binding of the drug to a tissue component
weakly basic drugs can go into breast tissue and get trapped and ionize bec breast milk is ____
acidic
For an acid, the pH is very strong, so their pKa is going to be very ____
low
pKa for weak base is going to be very
high
what are the 4 parts of pharmacokinetics?
what body does to the drug
- absorption
- distribution
- metabolism
- excretion
major organ of drug elimination is
kidneys
peptides are not given _____. Non peptide drug will get absorbed. a Peptide drug will get chewed up
orally
what are physiological factors affecting absorption
- route of administration
- area of absorbing surface
- blood flow or perfusion at site of administration
- disease states
- drugs affecting absorption of other drugs
what drugs are given orally
- insulin
- EPO
- growth hormone
a larger surface area, the greater the absorption of the drug will be. Absorption will be very rapid in ____and lung as opposed to stomach
intestine
subcutaneous tissue is poorly vascularized compared to _____. So you have greater absorption in muscle.
muscle
what inc absorption
- larger surface area
2. increased blood flow/vascularity
what is achlorydria
when stomach doesn’t produce enough gastric acid
what do acid reflux drugs do
prevents production of gastric acid
What happens when you block cholinergic receptors. What is an ex of drugs that do this
slow down gut motility
-tricyclic antidepressants
what does metoclopramide stimulate
stomach contraction, relaxes the pyloric sphincter –> promotes intestinal peristalsis which could affect drug 2 which might need more time absorb
what are the routes of administration
- parenteral
- enteral
- topical
what are characteristics of parenteral route of admin
going beyond alimentary canal. Like an injection. Bypassing first pass effect bc bypassing gut and liver directly first
what are characteristics of enteral
- GI tract
- sublingual
- buccal
- oral
- rectal
what are characteristics of topical/transdermal/inhaled
- no first pass effect
2. lungs, skin
What is intravenous
going directly into the circulation system. No first pass effect because not going to liver first. this is used in emergency situations and bypasses absorption and entire drug quantity enters vasculature.
What is intravenous advantageous for
- narrow therapeutic index
- poor, erratic or NO absorption
- rapid metabolism; irritation
- poor blood circulation at site of administration
what happens to drugs that have a thinner index
drugs that have thinner index, (small) then if you give it to another administration it might be below or above the range, which is why iv is advantageous
what drugs are good to use via iv
1, drugs that are charged
- drugs that metabolize quick
- drugs that poorly absorbed in gut
- peptides
what are disadvantages to intravenous?
- drug overdose
- introduce bacteria if not sterile
- disrupt hemodynamics
____ drugs or oils should not be given by iv
insoluble
what are characteristics of why drugs are administed via subcutaneous tissue (skin)
- less vascular than muscle
- no first pass effect
- only for non irritating drugs
ex: insulin preparations
what are advantages of intramuscular drug administration
- rate of absorption is good
- more irritating drugs, larger volume
* rate of absorption depends on vasculature and other properties
what is the buccal route of administration
between cheek and gum line:
- No first pass effect; goes directly into systemic circulation
- Has high lipid water partition coefficient
what is difference between buccal and sublingual
sublingual dissolves very fast. Ideal candidate! Very lipophilic, small and non ionized. extensive blood supply in region so absorption is fast.
does stomach absorb things?
stomach function: no absorption! Breaks down food and drugs into smaller substances.
what is characteristic of oral route of administration in stomach
- good blood supply
- surface area < intestine
- passive diffusion for most drugs
- small molecules, lipid soluble non ionized electrolytes - low pH aids in absorption of many drugs (but not good for weak bases bc they are ionized)
what are characteristics of small intestine
- large surface area
- high blood perfussion
- high capacity for absorption
what are important considerations for oral route
- common safest, conveneint and economical
- first pass effect
- morphine and propranolol: get taken up by systemic circulation. Liver chews up drug molecules. Acts as barrier to specific drugs. - enterocytes lining small intestine
- efflux transporters: (Pgp) permeability glycoprotein; usually inf the rate of asborption of drugs
- Acid secretion on drug stability
- Presence of food
what are characteristics of rectal method
- irregular and incomplete absorption
- partial avoidance of first pass effect; superior rectal vein
- drugs can irritate the rectal mucosa
what are advantages of rectal route
administer labile drugs and compliance with unconsious patients, infants, or patients with swallowing issues
different regions of body have prodound affects of rate absorption. Least permeable is ____ ___ ____. Most permeable is mucous membrane. Skin conditions that affect drug absorption through skin include skin ____ and ____
palms, soles, nails; temperature; eczema
what are ch’s of stratum corneum
- less water, phospholipids; packed with keratin
- lipid soluble drugs diffuse slowly
- water soluble drugs excluded
what are ch’s of dermis
- good lymph and blood supply
2. permeable to lipid and water soluble drugs
Absorption through ___ is rapid. Absorption through ___is slow
mucosa; skin
Rate of diffusion across skin is directly proportional to ____ ___ and inversely proportional to ___ of stratum corneum
surface area; thickness
what are advantages of pulmonary delivery
- extensive surface area - rapid absorption
- local or sytemic delivery
- rapid pharm response
- bypass first pass effect
- similar therapeutic effect with lower dose
what are disadvantages of pulmonary deliver
- efficient aeodynamic filter
- mucociliary transporter
- low pulmonary deposition
