9/23b Pharmacology (Biomedical Sciences) Flashcards
• To understand the basic principles of pharmacology so as to apply them as a clinician • To understand the fundamental concepts of pharmacodynamics, including mechanism of action and dose-responsive curve To understand the stages of pharmokinetics as the drug is processed in the body and factors affecting pharmokinetics
Drug Nomenclature
- Chemical - the chemical structure of the drug
- Generic - abbreviated version of the chemical name
- Trade Names - Motrin = NSAID = Ibuprofen = Isobutyl propanoic phenolic acid
what is the process that takes a drug to be ready to be sold on the market?
- approval from FDA
- regulation
- animal trials and human trials that last up to 20 years
- data is sent to FDA after completed
- the whole trial needs to be safe and effective - classification
- prescription (Rx) vs over the counter (OTC)
- often Rx drugs can change to be over the counter drugs as more data is stored
Are PTs allowed to prescribe drugs?
- NO, except for PTs in the military (they can prescribe analgesics)
- it is important to use information about the drugs to educate your patients and understand the big picture of their treatment
Basic Concepts of Pharmacodynamics
- site of action = location where drug exerts its effect
- mechanism of action = how a drug produces its effects
- receptor site = site on a cell wall where a drug exerts its effects
what is the dose curve and maximal efficacy related to?
pharmacodynamics
response of a drug to a proportional dose
define pharmacodynamics
the relationship between how the body interacts with a drug
Dose
- the exact amount of a drug administered to produce a specific effect
- want doses that fall on a linear curve because they actually bring about a response within the threshold
- doctors normally start with a small dose
threshold dose
lowest dose you see with an actual response
max effect/ceiling effect dose
when you increase the dose to a maximal amount, it plateaus and stops at the max/ceiling effect
Potency
measure of strength, or concentration of a drug required to produce a specific effect
–be able to determine how potent a drug is on a chart
Drug safety is determined by what?
the therapeutic index!! aka median effective and toxic doses
what is the therapeutic index?
- the amount of drug that creates a toxic response (adverse/lethal side effects) for 50% of the people = median toxic dose
- the amount of drug that creates a beneficial dose for 50% of the people = median beneficial dose
- TI = median toxic dose (TD50)/Median beneficial dose (ED50)
- the higher the therapeutic index, the safer the drug typically is
Examples of therapeutic index that is low, but still on the market
- TI is low (~1) in antihistamines because the drowsy-ness side effects are prevalent for more people than the benefits
- TI is reallllly low for chemotherapy, but if this drug isn’t approved, then a lot of people wouldn’t get these benefits
Drug selectivity
- Selective: a 100% selective drug only reacts with a specific receptor in a specific kind of cell in a specific tissue
- Non-selective: a drug that binds with every receptor in the body
give an example of a non-selective drug
aspirin based products, NSAIDS, bind with any receptor that is a cox receptor
New techniques for drug delivery
- controlled release preparations
- implanted drug delivery systems
- targeting drug delivery to specific cells and tissues
Controlled release preparations for drug delivery
coating on drugs so the liver takes care of the coating, but the drug is more slowly dispensed and more bioavailable in the system
Implanted drug delivery systems
patch that continuously releases
targeting drug delivery to specific cells and tissues for drug delivery
cell receptor senses it has been bound and the drug starts actioning right then
Factors that affect pharmokinetics
- genetics
- disease (liver disease)
- Drug interaction (additive = 2 sns drugs together OR nullifying = one drug cancels out another drug)
- age (efficiency decreases as age increases = plasma levels stay higher longer)
- diet
- sex (women are more vulnerable to processing drugs)
- other factors (alcoholism, smoking, pathology)
Importance of drug interaction that affects pharmacokinetics
Drug interaction
- additive = 2 sns drugs together
- nullifying = one drug cancels out another drug
Importance of diet on pharmacokinetics
- MAO inhibitors for hypertension bind to the same receptors as grapefruit juice. SO, if you drink a lot of grapefruit juice when taking a MAO drug, it ends up being more bioavailable
- wine and cheese with antidepressants can cause an adverse effect
how does pathology affect pharmacokinetics
GI motility is affected by spinal cord injuries, so processing is not the same
define pharmacokinetics
how the body processes drugs
what are the different routes of administration for pharmacokinetics?
- enteral
2. parenteral
What is the enteral route of adminstration for pharmacokinetics?
- involves the GI tract
- taken orally (subject to first pass effect)
- buccal: inside of the cheek
- sub-lingual: under the tongue (nitroglycerin)
- rectal: suppositories
- positive aspect: can be administered when unconscious and conscious
- negative aspect: some part of it is metabolized before it reaches the target tissue
First pass effect
- enteral drugs are subject to first pass effect
- this means that they are immediately shunted to the liver where they get metabolized then sent into the system for distribution
- that amount of the drug that was processed in the liver WON’T be bioavailable for absorption later
what is the parenteral route of administration for pharmacokinetics?
- inhalation
- intranasal
- injection (IV, IM, or intrathecal, epidural)
- Topical
- transdermal (across the skin)
- positive aspect: no subject to first pass effect because it gets delivered directly to target tissue
- negative aspect: need a vehicle to administer and the danger of overdose is much higher
transdermal iontophoresis
drug administration across the skin using steroids and electricity to drive across the SKIN OR lotion driven across the skin in ultrasound
3 main phases of pharmacokinetics?
- absorption/bioavailability
- distribution
- elimination
Bioavailability
how much of the drug is able to have an effect once in the systemic blood pool
–dependent on administration
absorption
cell membranes are lipid bilayers, so in order for drugs to enter the cell they have to be absorbed passively or actively OR through facilitated diffusion OR endocytosis/exocytosis
Passive diffusion
almost all drugs are lipid soluble, so they can dissolve into the lipid bilayer and be transpoted from outside to inside the cell readily
Active transport
water soluble drugs need to find a way across the cell membrane, so they most commonly enter through active transport
Importance of distribution of drugs through pharmacokinetics
- storage
- redistribution
Storage of drugs in pharmacokinetics
some portion of a drug is typically stored before it is eliminated. Most common sites of storage:
- fat/adipose tissue
- bone/bone marrow
- muscle
- organs (liver/kidney)
examples of drugs being stored in the body
anesthesia gets stored in the body’s fat tissue prior to elimination, deep breathing helps with elimination of anesthetics (second pass redistribution)
Redistribution of drugs through pharmacokinetics
when a drug is stored and re-distributed after its use
elimination processes for drugs
- metabolism - biotransformation
- lipid soluble drugs can’t be excreted on their own, so they get broken down into water soluble chunks through biotransformation in the liver - excretion - RENAL, in the kidneys through urine
- respiratory, anesthesia
- less commonly, GI (feces), sweat, saliva, and lactation
drug elimination rates
- clearance
2. half life
what is clearance
- a form of drug elimination
- the ability for the body to eliminate the drug
- based on blood flow rate and efficiency of the liver and kidneys
what is half-life
- how long it takes to get 50% of the remaining drug out of the body
- determines how often a drug is administered
Healthy pateint took a typical dose of acetominaphin with a half-life of 4 hours. How long will it take for this drug to be 95% eliminated from the body?
Between 16-20hrs 95% of the drug is eliminated ◊ 4hrs - 50% ◊ 8hrs - 25% ◊ 12hrs - 12.5% ◊ 16hrs - 6.25% ◊ 20hrs - 3.125%
Determining a dosing schedule
- based on how typically blood is eliminated
- dosing windows and therapeutic windows
- as the therapist, you want to make sure that you are seeing the patient when they are in their therapeutic window
Endogenous carriers
- receptors and class of substance produced innately within the body
- Endorphins are an example of a class substance that goes through one of the body’s natural endogenous carriers
Endogenous barriers
Blood brain barrier - epithelial cells within are attached to each other with the tight junctions and things can only come through with active transport
PT correlation with pharmacokinetics
- What causes passive diffusion/perfusion/blood flow to the tissue – anything that causes heat
- Exercise because the biproduct of motion = heat
- Heat packs
- Decrease of BF to tissue = cold
