Lecture 1 General Principles of Pharmacology Flashcards
List the routes of drug administration
Enteral (by the GI tract): Oral, Sublingual, Buccal, and Rectal
Parenteral (injections): Intravenous (IV), Intramuscular (IM), and Subcutaneous (SC)
Other: Inhalation, Transdermal patches, Topical (eye drops, ear drops, skin creams/etc.)
First pass effect
initial metabolism of the drug in the liver before the drug reaches systemic circulation.
This reduces the amount of active drug that can reach the bloodstream.
The first pass effect affects the oral route of administration the most because drugs go straight from the stomach/intestines to the liver via the portal vein.
Other routes can be partially affected by it such as inhalation or rectal.
Which routes undergo first pass effect?
Oral, rectal and inhalation (partial first pass effect)
Which route allows 100% bioavailability of the drug?
Intravenous (IV) – immediate onset of action, works most rapidly in emergencies
Pharmacokinetics vs pharmacodynamics
how the drug passes through the body (ADME) vs how the drug interacts with the body (at its targeted receptor)
ADME = Absorption, Distribution, Metabolism, Excretion
Metabolism: how the body chemically modifies the drug into metabolites (active or inactive molecules); occurs primarily in the liver when talking about systemic drugs
Excretion: kidney is the most common, but can also occur in bile/defecation, sweat, breast milk, tears, saliva, lungs
List the factors that allow drugs to move most easily through cell membranes to get into the bloodstream
Size (smaller more easily pass) Ionization (non-ionized/non-polar more easily pass) Lipophilicity (lipophilic, hydrophobic, lipid soluble more easily pass) Concentration gradient (higher dose/concentration allows easier/faster rate of diffusion) Surface area (increased surface area, easier to pass)
Note: ionized forms are polar/hydrophilic/water soluble, so they do NOT pass through cell membranes (lipid membranes do NOT let molecules through that are large or charged).
What mechanism do most drugs move through membranes (passive diffusion, active transport, facilitated diffusion, or endocytosis/bulk flow – uses ATP)?
Passive diffusion
Explain why most systemic drugs are weak organic acids and weak organic bases
chemically, this allows the drug to exist in two different forms: ionizedd and non-ionized forms, with the amount of each form depending on the pH of the environment they are in.
ex. a drug that is a weak acid will have a higher ratio of non-ionized form in an acidic environment to pass the stomach membranes
ex. a drug that is a weak base will have a higher ratio of non-ionized form in a basic environment to pass the intestine membranes.
Endogenous, Exogenous, Bioavailability, Prodrug
Endogenous–substances made outside of the body; exogenous–substances made outside the body
Bioavailability–amount of administered dose of a drug that reaches the systemic bloodstream
Prodrug–inactive compound that can be converted to an active form by enzymes
What is the calculation representing the drug’s propensity to remain in the bloodstream (plasma) or to redistribute to extravascular compartments?
Volume of Distribution
What does a low and high Vd (volume of distribution) suggest?
Low indicates the drug is staying in the bloodstream
High indicates the drug is distributed to other extravascular compartments in the body
Which order of kinetics is dependent on drug concentration? Note: a higher drug concentration will result in a higher elimination rate.
This first order elimination kinetics is also the most common in drugs.
First Order Elimination Kinetics
Which order of kinetics is not dependent on drug concentration–resulting in a constant elimination rate?
Zero-Order Kinetics
ex. Alcohol
A measure of the body’s efficiency in eliminating the drug from systemic circulation–takes into account Vd and t 1/2 (half-life)
Clearance
List the organs with a high blood flow
GI tract, kidneys, liver, lungs, brain, and eye
Define the Blood-Brain-Barrier (BBB)
contains capillary endothelial cells with tight junctions which are surrounded by astrocytes, creating an extra semi-permeable barrier that protects the brain from foreign/toxic substances. This makes the BBB less permeable to drugs than most other parts unless they are very fat soluble.
List 5 tissues/places where some drugs can accumulate in the body
Muscles, fat, teeth, bones, and blood
What is the main goal of metabolism? In what organ does metabolism of systemic drugs primarily take place?
The main goal of metabolism is to make the drug hydrophilic for filtration/excretion in the kidneys.
The liver.
Pharmacodynamics: Define Agonist, Full Agonist, Partial Agonist, Antagonist
Agonist – drug that binds and activates a receptor
Full Agonist – drug that binds and activates a receptor that produces a maximal response
Partial Agonist – drug that binds and activates a receptor lower than the maximal response, no matter how much of the drug is given
Antagonist – drug that binds to a receptor but doesn’t activate it. The antagonist drug blocks/inhibits/prevents the binding and actions of agonists.
Describes the tendency for a drug to bind to a receptor, or how tightly a drug binds to the receptor.
Note: BOTH agonists and antagonists have this toward a receptor
Affinity
A measure of the amount (concentration/dose) of a drug that is required to achieve a desired effect.
The less drug that is needed to produce an effect, the more _____the drug.
Potency ; potent
Effective Dose 50 (ED 50) Toxic Dose (TD 50) Lethal Dose (LD 50)
the dose of a drug that produces 50% of its maximum response
the dose of a drug at which 50% of the population experiences a toxic effect
the dose of a drug that is expected to produceg 50% mortality in a population
The margin of safety between the dose which can provide the maximum therapeutic effect and when unwanted adverse effects begin. The wider the range, the safer the drug is to administer. The narrower the range, the more dangerous the drug.
Therapeutic Index
Therapeutic Index Formula
TD / ED
Does an agonist have both affinity and efficacy? What about an antagonist?
Yes;
An antagonist ONLY has affinity, but NOT efficacy because an antagonist doesn’t activate a receptor.
Describes the maximum response (effect) of a drug when it binds to a receptor
Efficacy
