Pharmacology Basics Flashcards
Basic Principles of Pharmocology, Pharmacokinetics, and Drug Receptors
List the 3 different ways to name medications
Chemical
Generic
Trade
Explain the differences between generic and brand name medications
Generic: Less expensive, same bioavailability, different inactive ingredients
List the steps in the drug approval process
- In Vitro
- In animals
- Humans
a. Phase I: Healthy adults
b. Phase II: Small target pop
c. Phase III: Larger target pop - Marketing
a. Phase IV: Postmarketing surveillance
Describe Scheduled medications and implications of patient use
There are 5 schedules of medications that the FDA classifies and regulates with V being the least potential for abuse and I being the most potential of abuse
Potency vs maximum efficacy
Potency is how much medication needs to be given to produce a specific effect whereas maximum efficacy is how large of an effect can be created (the ceiling effect)
Connect therapeutic index to drug safety and adverse effects
Therapeutic index is the toxic dose divided by the effective dose –> the higher it is, the greater its safety
Which name is the official name of a drug?
Generic name
Which schedule of medication cannot be used for treatment or research?
Schedule 1
median effective dose vs median toxic dose
The median effective dose is the amount where 50% of the population starts seeing some benefit from the drug whereas the median toxic dose is the amount where 50% of the population exhibits adverse effects
What do dose-response curves tell you?
They show the threshold dose and the ceiling effect for a given medication in a log scale
Sites of drug storage in the body
- adipose: primary site because many medications are lipid soluble
- bone: toxic agents
- muscle
- organs: liver and kidney
primary site of drug elimination in the body
Liver
What are the routes of administration?
- Enteral
a. oral
b. Sublingual and bucc
c. Rectal - Parental
a. Inhalation
b. Injection
c. Topical
d. Transdermal
Advantages of Oral Administration
- easiest
- self- administer
- controlled manner of entry
- small intestine absorption
Disadvantages of Oral Administration
- need to have high degree of lipid solubility
- may irritate stomach
- first pass effect
- eventual amount and rate of drug reaching target is less predictable
- acidic environment of the sromach
What is the first pass effect
- after absorption via small intestine, drug sent to liver and may be metabolized there before reaching target tissue, causing less of a dose at the target tissue
Advantages of sublingual and bucal administration
- avoid first pass effect (transmucosal absorption in mouth)
- good if pt had swallowing difficulty
- faster effect than swallowing
Disadvantages of sublingual and bucal administration
- drug must be able to easily pass into venous system
- amount taken is limited
Advantages of Rectal Administration
- if vomiting prevents drug from being given orally
- do not have to swallow it (pt unconscious)
- local effect on recital tissue (hemorrhoids, constipation, etc)
Disadvantages of rectal administration
- drug absorbed poorly or incompletely
- irritation of rectal mucosa
Advantages of Inhalation for administration
- large alveolar SA promotes diffusion into pulmonary circulation (ex. Anesthesia medications)
- direct delivery to bronchial and alveolar tissue for pulmonary diseases
Disadvantages of inhalation
- irritate alveoli
- drug particles can get trapped by cilia and mucous making it difficult to predict the exact amount of drug delivered
List the types of injection
Intravenous Intra-arterial Subcutaneous Intramuscular Intrathecal
What is the risk for all types of injection
Infection
Advantages of IV Injection
- accurate and known quantity of a drug entering bloodstream
- reaches target tissue rapidly (good for emergent situations)
- 100% bioavailable
- steady infusion overtime to prevent large fluctuations in plasma concentrations
Disadvantages of IV Inju
Difficult to counter side effects if full dose injected
Advantages of IA Injection
Large dose of medication can reach target tissue (chemo & radiopaque dyes)
Disadvantages of IA Injection
Difficult and dangerous procedure
Advantages of Subcutaneous Injections (SQ or SC)
- slower, more prolonged release into systemic circulation (hormonal contraceptives)
- easy for pt to learn to self-administer (insulin)
Disadvantages of SQ/SC Injection
- can only deliver small amount of medication
- could irritate subcutaneous tissue
- Bruising
Advantages of intramuscular injections
- to treat a problem directly in injected muscle (Botox)
- Steady prolonged release of drug into systemic circulation (vaccines, antipsychotics)
- plasma concentrations achieved rapidly (a few minutes)
Disadvantages of intramuscular injections
Cause a significant amount of pain and muscle soreness
Advantages of intrathecal injections
- better access to spinal cord
- bypass the blood brain barrier
- directly administered to area
Disadvantages of intrathecal injections
Very technical
Advantages of topical administration
- primarily to treat skin conditions (absorbs poorly through the upper dermis into the systemic circulation - wound healing products and steroids for inflammation)
- Application to mucous membrane can lead to systemic absorption (eye drops and ear drops)
Disadvantages of topical administration
- applying the correct amount can be difficult
- only effective in treating outer layers of the skin
Advantages of transdermal administration
- introduces drug into body without breaking the skin
- Can provide steady prolonged delivery via medicated patches
Disadvantages of transdermal administration
- Drug must be able to pass through dermal layers intact
What are the two type of transdermal medication’s physical therapist can use
Iontophoresis and phonophoresis via estim (ionto) and ultrasound (phono) to subcutaneous tissue
Define bioavailability
The extent to which the drug reaches the systemic circulation
IV vs Oral administration and plasma concentrations
IV administration has a higher and faster plasma concentration whereas oral is slower and has a lower peak
Which routes have a highly variable bioavailability
Oral and Inhaltion: 5 to <100%
Rectal: 30 to <100%
Which four routes have a 75 to less than or equal to 100% bioavailability
Sublingual/buccal
IM
SQ
Transdermal
List the movement across cell membrane barriers & state:
- Cost E?
- Low—> high or high —> low
- Passive: No E, H->L
- Active: E, L->H
- Facilitated diffusion: No E, L->H
- Endocytosis and exocytosis: allows for large non-lipid soluble molecules to enter and exit
List the factors affecting distribution
- Tissue permeability
- blood flow (high perfusion —> reaches tissue faster)
- Binding to plasma proteins (only free drugs can exert pharmacological effect)
- Binding to subcellar components (if bound in a cell, cannot be distributed to other compartments)
What is the volume of distribution and why do we care
Amount of drug administered divided by concentration of drug and plasma. It tells us how well the drug is distributed through the body and can impact elimination.
Interpret:
Vd = 42 L
Vd < 42 L
Vd > 42 L
- drug is distributed uniformly throughout body fluids
- Drug is retained in the bloodstream
- Drug is being concentrated in the tissue
List the adverse consequences of drug storage
- high concentration of drug/drug metabolites/toxic compounds can cause damage to the tissues they are stored in (lead poisoning )
- High concentrations of therapeutic drugs (can become toxic and cause damage)
- Can soak up the drug preventing it from reaching target tissue
- can lead to redistribution of drugs after desired effects
What is oxidation
- Oxygen added or hydrogen removed from the OG compound.
- predominant method of drug transformation in the body
List some of the methods of bio transformation in the body
- oxidation (predominant)
- reduction
- hydrolysis
- conjugation
Where does biotransformation (metabolism) occur for most drugs
In the liver
How does tolerance develop
Prolonged use of drugs alters enzymes:
- More metabolizing enzymes are being produced
- Fewer metabolizing enzymes are being broken down
Where is the primary site for drug excretion
The kidneys
What happens when:
- Administration > elimination
- Elimination > administration
- Drug accumulation/toxicity
2. Drug concentration is too low
What is clearance
The measure of a single organ or tissue’s ability to eliminate a drug
What contributes to an organ being able to eliminate a drug
- blood flow to the organ (perfusion)
- how much of the drug is extracted (organ function)
What is half-life
The amount of time required for 50% of the drug remaining in the body to be eliminated
- impacted by Volume distribution and clearance changes
List some things that can cause variations in drug response and metabolism
- genetics
- disease
- drug interactions
- age
- diet
- sex
What is affinity
The amount of attraction between a drug and receptor.
- high affinity = easily able to bind to open receptors
- low affinity = need more of the drug in order to fill up receptors
Agonist vs Antagonist
An agonist binds to a receptor to imitate a change in cell function, has affinity, and has efficacy whereas an antagonist will bind and not create a change in cell function (lacks efficacy), even though it has affinity for a receptor.
Define receptor desensitization
Brief and transient decrease in receptor responsiveness
What are drug receptors
A component on or within a cell that a substance can bind to
- most commonly located on the surface
Mechanism for surface receptors linked directly to ion channels
The receptors act as an ion pore changing the membrane permeability (to open or close channel)
Mechanism of action for surface receptors linked directly to enzymes
The receptor spans the whole membrane, w/molecule attaching on the surface, that then triggers an enzymatic reaction (activation or inactivation) on the other side of the cell membrane
Mechanism of action for surface receptors linked to regulatory (G) proteins and the role of the second messenger
Membrane receptor affects cell function by linking to an intermediate regulatory protein located on the inner surface of the cell (creates a cascade effect)
List the 2 types of G proteins
Stimulatory (increase response of cell)
Inhibitory (decrease cell activity)
Process for drug that influences a second messenger
- Drug as first messenger -> binds outside and causes biochemical change inside the cell
- Substance produced inside the cell from the biochemical change is what then mediates the change in cell function
What are intracellular receptors
Located within the cell so the drug has to diffuse through the bilateral
- steroids
What is drug selectivity
When a drug only influences one type of cell or tissue and produces a specific response (relative)
Differentiate concepts of affinity and selectivity
Affinity is how well the drug is able to bind to the receptors and selectivity delineates which receptors the drug will bind to
What is efficacy
How much of a change a drug causes
Competitive vs Noncompetitive Antagonists
In competitive antagonists, whichever of the two drugs has the higher concentration will win & bind whereas noncompetitive antagonists form strong, permanent bonds to receptor and will lock it down until the receptor expires.
What is a partial agonist
Drug that does not produce a maximal response compared to a strong agonist, even if all available receptors are occupied
What is the hierarchy of efficacy
- strong agonist
- partial agonist
- strong noncompetitive antagonist
What is a mixed agonist-antagonist
- stimulate certain receptor subtypes AND block the effects of endogenous substances or other receptor subtypes (do both simultaneously)
What is an inverse agonist and what is its goal
- Drugs that bind to the same receptor as the agonist but have the opposite effect of the agonist on cellular function
- decreased activity in situations where the receptor is too active or overstimulated
Define receptor downregulation
Decrease in number of receptors available (slower and prolonged process; few days)
What is receptor supersensitivity
Prolonged decrease in stimulation of receptors results in an increase in receptor sensitive to substances
Ex - more sensitive to caffeine since they haven’t had it in a while
What is receptor upregulation
Increase in number of receptors, resulting in an increase in function
(Instead of having 100% of receptors, 150% receptors)
True or false: all drugs act on receptors
False - some drugs change DNA or create a chemical reaction or other
