M1s4 Pharmacokinetics Flashcards
Briefly describe how a drug must produce its desired effect
-drug must reach the cellular side of action at right concentration, exert its effect and then be removed from body
Pharmacokinetics
-movement of a drug into throughout and out of body
-derived from “pharmaco” meaning drug and “kinetics” meaning movement
Processes involved in pharmacokinetics
-starts with admission of drug which can happen through: topical, enteral and parenteral
After admission: 1. Absorption 2. Distribution 3. Metabolism 4. Excretion
Commonly called ADME
-acting together, 4 factors determine concentration of drug in blood with determine drug at site of action
Tropical administration
-drugs applied directly to a particular place on or in the body
Typical routes of administration include:
On skin
-Lots of drugs can be applied to skin to treat mild to moderate severity skin conditions like eczema, acne, and infections
-drugs applied to skin for local effect can be absorbed and produce a systemic (effects whole body or multiple organ systems) effect. Ex. Some topical steroids used to treat skin condition can be absorbed and cause toxicities elsewhere in body
through the skin
-Transdermal drug delivery is application of drug to the skin for absorption into general circulation for systemic effect ex. Nicotine path allows nicotine to pass into general circulation to eventually act on the brain.
-This method of drug delivery: convenient, delivers steady drug supply for several days, eliminating frequent oral dosing, bypasses enzymes of stomach, intensive, liver
-expensive tho and cause local irritation
inhalation (into lungs)
-common in prescription and recreational drugs
-rapidly absorbed from lungs
-administrated through lungs for both local and systemic effects: gaseous anaesthetics provide systemic effect and steroids and other drugs for lung disease administered for local effect in lungs
Advantage for local effect: quantities small and less than required for systemic effect thus avoiding toxicity associated with oral admission
Disadvantage: requires proper use by patient
Systemic effect
Events occurring in tissues distant from site of contact between the body and the medical device
Enteral administration
-admission via gastrointestinal (GI) tract through mouth or artificial openings (surgical procedure between organ and outside of body)
-when drug absorbed into blood from GI, first delivered to liver which contains enzymes that decrease amount of active drug left to enter the general circulation. This called first pass effect
Routes of administration include:
-mouth
Advantages:
-commonly used, >90% of drugs taken this route
-most convenient
-least expensive
-non-invasive
-can be self-administered
Disadvantages:
-variable absorption between patients due to differences in intestinal motility and disease
-rectum
Advantages:
-can be for systemic or local effect
-can be used in patients who are nauseated or vomiting, less invasive route for those who are comatose (unconsciousness for long period)
-digestive enzymes of stomach and intestine are bypassed
Disadvantages:
-limited number of medications are available or suitable for rectal administration
-absorption from rectal mucosa is slow, incomplete and variable depending on time of medication is retained
-sublingual (under the tongue) and buccal (in the cheek)
Advantages:
-enzymes of stomach, intestines and liver are bypassed
Disadvantages:
-not all drugs adequately absorbed from this route
-drugs may be swallowed and then drug behaves as if taken orally
Parenteral administration
-admission by passing the GL tract.
-ejected into body and enter bloodstream directly
Routes:
intravenous
-drug placed directly into blood
-immediate effects
-used for drugs that poorly absorbed, provided can be made into solution in purified water for injection
-response irreversible, causing route to have highest drug reactions
-administration requires significant Human Resources ex. Nurses
-preparation must be sterile and free of fever producing substances (pyrogens)
intramuscular
-drug injected deep into muscle
-volume of drug limited to 2 to 3 mL in adults
subcutaneous
-drug injected into deepest layer of skin
-allow for modification of drug preparations to control timing of release of the drug from injection site
Bioavailability
-fraction of an administered dose that reaches the systemic circulation (blood) in an active form
-defers between drugs as during absorption not all drug ends up in blood
Ex. A drug dose given intravenously is places directly into blood and considered to be 100% bioavailable as no absorption
-drug given any other route will not be 100% absorbed into blood
Routes of administration for organ/ tissue administered to compared to onset of action and bioavailability
Route:
Tropical
Skin, eye, ear, nose and lung - rapid to slow (depends on organ) - 5% to 100%
Enteral
Mouth - slow (30 min to >1 hour) - 5% to 100%
Rectum - slow and incomplete - 30% to 100%
Under the tongue - rapid (1 to 2 minutes) - 30% to 100%
In the cheek - intermediate (3 to 4 minutes) - 30% to 100%
Parenteral
Veins (I.v.) - 15 to 30 sec - 100%
Muscle (I.m.) - 10 to 20 min - 75% to 100%
Under the skin (s.c.) 0 15 to 30 min - 75% to 100%
Explain process absorption (1 of 4) when drug enters body
ADME
Absorption:
-movement of a drug from the site of administration into the blood
-for drug to be absorbed and distributed into sites of action, storage and excretion, it must be able to cross biological membranes
-this occurs from moving across the lumen to the other side the interstitium through many ways
One method- diffusion through aqueous pores. Drugs with small molecular weights that are water soluble can move across membranes by dissolving in aqueous fluids surrounding in cells then passing through small openings between cells. High conc to low conc
Another method- Most important as is diffusion through lipids. Most drugs have molecular weight greater 150 daltons so can’t pass through aqueous pares so go through membrane by dissolving in lipid portion of membrane. Flow high conc to low and availability of drug to cross membrane via this method and be absorbed depends on lipid soliubility
Final method-activated or carrier mediated transportation. Number of drugs bind to proteins or transporters which carry molecules across membrane. Once bound, carrier protein-drug complex moves across the membrane and releases the drug on the other side of membrane. Can but down a concentration but can also be an active process require it energy to move drug against conc gradient.
Carrier proteins for drugs play role in removing drugs and their metabolite is from the liver and kidney
Explain the process distribution (2 of 4) when the drug enters the body
-movement of a drug from the blood to the site of action and other tissues
-most drugs reach all tissues and organs regardless of target site of action
-concentration of drug at site of distribution are in equilibrium with its concentration in the blood
-if conc in blood drops below the conc at any of the distribution sites, drug will move from that site to blood to maintain equilibrium.
-rate at which drug distributes in and out of particular organ depends on blood flow to that organ
-greater blood flow to that organ, the greater the more rapidly drugs reach that organ
Distribution example of result in termination of the therapeutic effect of drug thiopental (ultra-short acting sendative which functions to rapidly induce anesthesia)
Administrative: intravenous injection of thiopental, conc of drug in blood high
-conc of thiopental in brain (high blood perfusion) elevated and patient fall asleep
-at this point conc of thiopental in muscle and fat (low blood perfusion) is low
Distribution:
-after few minutes, conc of drug in muscle and fat increases and conc in blood decreases, causing drug to leave brain and move into blood, causing it to be a ultra-short duration of action
-as conc of drug in brain decreases, patient will awake, usually after about 15-30 minutes
Termination of effects:
-action of drug has been terminated by drug redistributing from brain unto muscle and fat, but drug has not been removed from body
Explain the process metabolism (3 of 4) when drug enters the body
-drug metabolism aka bio transformation
-conversion of a drug to a different chemical compound in order to eliminate it
-products of metabolism called metabolites and usually devoid of pharmacological action
-to be eliminated from body by kidneys, drug must be water soluble
-most drugs must be converted to more water-soluble compounds
-without metabolism, some chemicals that are very liquid soluble would never be excreted from the body
Occurs:
-mostly liver
-kidneys
-intestines
-lungs
-skin
-most other organs
Bio transformation reactions are divided into phase 1 and phase 2 reactions and basically converts drug to something else
Phase 1:
Add or unmask a functional group (substituent of molecule that responsible for molecule’s characteristics effects) on drug to prepare for addition of water-soluble molecule in phase 2 rxn
-think: adding handle to which you can attach a water-soluble molecule
P450:
Enzymes capable of bio transforming drugs
Found in most tissues but present in high concentrations in the liver thus liver responsible for majority of bio transformation
Many phase 1 biotransformation enzymes exist but cytochrome P450 family of enzymes biotransforms the vast majority of clinically used drugs
Phase 2:
-reactions add large water-soluble moiety (part or functional group of a molecule), usually glucuronic acid or sulfate to the product resulting from phase 1 biotransformation, making the metabolite water-soluble for excretion by kidney ‘
Excretion:
Water-soluble drug can now be excreted by kidneys
Last step of pharmacokinetics
Drug changes shape throughout this process
One member of the cytochrome P450s is responsible for biotransforming about 50% of all drugs used clinically. Why is this an important consideration when taking multiple medications at the same time?
An often overlooked fact is that when taking two drugs simultaneously, the drugs might compete for this enzyme, resulting in the reduced biotransformation of one or both drugs, which could lead to toxic effects
Explain excretion (4 of 4) when taking drugs
-moving drugs and it’s metabolites out of body
-all body fluids will contain drugs and their metabolites
Role of each organ in drug excretion
Kidney:
-eliminates most drugs
-drugs of sufficient water solubility will be excreted in urine
-lipid-soluble drugs can be reabsorbed from kidney back into blood
Look at goodnotes for chart of all these processes summed up
GI tract:
-some excreted by gastrointestinal tract (ie feces) after they undergo biotransformation in liver
Lungs:
-drugs that are volatile or in a gaseous form can be excreted by lungs (ex. Gaseous anaesthetics and alcohol)
Breast milk:
-drugs often found in breast milk of nursing parents
-minor route of elimination of drugs from parent, the nursing infant can be exposed to a therapeutic or toxic dose of the drug
Saliva and sweat:
-drugs can be found here
-often the presence of drugs of misuse can be detected in saliva of those who have taken it
Half life
-time needed for the liver and kidney to remove half the drug from the body
-can be used to determined how often drug needs to be administered to keep drug conc in therapeutic range
-based on person’s weight, gender, health, and many other factors
Ex. Give patient 100 mg
One have life is 50 mg
Two half lives is 25 mg
