Basic Principles of Pharmacology Flashcards
Exam 1
Differentiate the following: Pharmacodynamics, Pharmacokinetics, Pharmacogenomics, & Toxicology
-Pharmacodynamics: Describes what the drug does to the body.
-Pharmacokinetics: Describes what the body does to the drug; absorption, distribution, metabolism, excretion
-Pharmacogenomics: Looking at a genetic profile to determine how effective a drug will be
-Toxicology: Specifically relates to poison, toxins, and how they relate to the body
Agonistic vs Antagonist
Agonistic: Elicits a response from a receptor when it binds to the receptor
-Effect may be lesser or greater than the native ligand (endogenous hormone or catecholymine)
Antagonistic: Blocks the endogenous/native ligand from binding to the receptor
-Does not activate a response
Allosteric vs Orthosteric
Specific Binding vs Non Specific Binding
Allosteric: Binds anywhere but the active site on the receptor
-Is a non competitive inhibitor because it does compete for the active site
Orthosteric: Binds directly to active site on the receptor
Specific Binding: Binds specifically to the receptor. There is a max dose because receptors are not infinite
Non-specific Binding: The more drug that is given, the more non-specific the binding becomes. The drug saturates the receptors and must bind somewhere else.
Ex: Albumin
Describe the difference between toxins and poisons
Poison: A nonbiological substance such as arsenic, cadmium, lead
Toxins: A biological substance such as toxic mushrooms, a puffer fish
Describe the Relative Bond Strengths
Covalent Bond: Share electrons. Strongest bond, but least specificity. Irreversible
Electrostatic: Ionic Bonds;
-Charged molecules
- Hydrogen bonds
- Van der waals forces
Hydrophobic, lipid soluble drugs: Weakest bond, highest specificity
Bond strength and specificity are inversely related
Racemic Mixtures, Stereoisomerism, Isomers
-Isomers of a drug have the same chemical equation, but different shape.
-Stereoisomerism (Optical Isomers) is when isomers are mirror images of each other, but do not behave the same way. This applies to more than half of all drugs
-Racemic Mixtures are optical isomers
Ex: (R) Ketamine- More toxic than (S) Ketamine, increased unwanted side effects
(S) Ketamine: 4x more potent, less unwanted side effects
Competitive & Allosteric Inhibitors
Competitive Inhibitor: Binds to the active site in place of agonist. If a high enough dose of the agonist is given, it can “out-compete” the competitive inhibitor
Allosteric Inhibitors: Bind somewhere other than the active site on the receptor, so they are not competitive. Agonist response is always muted when given with an Allosteric inhibitor
Active Receptors vs Inactive Receptors
Receptors live in equilibrium between the active and inactive state. These configurations can switch back and forth between active and inactive without a drug/endogenous ligand present. When a drug favors the active form of a receptor, a downstream response will be elicited
Other Mechanisms of Antagonism: Physiologic Antagonism
Two or more physiologic processes that have an opposite effect
Ex: SNS vs PNS; epinephrine secreted acts on the B1 receptors, increases heart rate. Acetylcholine acting on the muscarinic receptors decreases heart rate
Pharmacodynamics: What happens when an Agonist is given with a single dose of 1) Allosteric Agonist, 2) Competitive Inhibitor, or 3) Allosteric Inhibitor?
-Agonist + Allosteric Agonist/Activator: We will see an increased/maximal drug response here compared to giving an agonist alone
-Agonist + Competitive Inhibitor: We can initially have a muted response; however, giving more of the agonist will allow it to out-compete the competitive inhibitor and we will have an increased response
-Agonist + Allosteric Inhibitor: We will have a muted response here. There is no way to out-compete the Allosteric inhibitor because they do not bind to the same area on the receptor
Agonist Mimic, Indirect Agonist
Agonist mimics or Indirect Agonists are downstream inhibitors. You have a receptor activated that causes a cascade of effects: A—> B—>C. Let’s say there is an enzyme that is supposed to break down “C”. You give the agonist mimic and it breaks down that enzyme, increasing your amounts of “C”
Receptor- Antagonist Interactions; Competitive Inhibitors & Non-Competitive Inhibitors, insurmountable vs surmountable
Competitive inhibitors/antagonists: They are SURMOUNTABLE because you can continue to give increasing doses of the antagonist to overcome the competitive inhibitor as long as they do not form covalent bonds
Competitive Orthosteric inhibitors/antagonists: Compete for the active site, but if they form covalent, irreversible bonds, it makes make them INSURMOUNTABLE
Non-competitive Allosteric inhibitors/antagonists: They are INSURMOUNTABLE because they are not directly competing for the same site. These are irreversible
Partial Agonist, Inverse Agonist vs. Full Agonist
- A partial agonist, when given alone, will always have a muted/lessened response
-When given with full agonist; acts as antagonist
-Inverse Agonist: Favors the receptor in its inactive form. It lowers the receptors’ activity below its constituitive activity, causing it to be less active with the drug present than without. Clinically, these act as antagonists but stronger
-A full agonist elicits a full downstream response once given
Other Mechanisms of Antagonism: Administration of opposite charge
Ex: Protamine (+) binds to and inhibits the effect of Heparin (-)
Which axis is this reflected on?
Potency; Dose-Response Curve
-Potency is reflected on the dose axis (horizontal)
-Potency refers to the EC50 or ED50. Concentration or dose required to produce 50% of the drugs maximal effect
-Inversely related to the EC50/ED50 on the response curve
-As potency decreases, the EC50 increases and shifts to the RIGHT
-As potency increases, the EC50 decreases and shifts to the LEFT
-If graph is shifting horizontally, we are seeing a change in POTENCY
-Drugs can have different potency, but efficacy can be the same
Which axis is this reflected on?
Efficacy: Dose-Response Curve
-This parameter is reflected on the response axis (vertical)
-Also depends on intrinsic activity, are these drugs agonists, antagonists, partial agonists, etc..
-If curve is shifting vertically, there is a change in efficacy
-Drugs can have different potency, but efficacy can be the same
Efficacy is more important than potency
Role of Drug Carriers; Most Common in the blood
-The role of drug carriers is to bind to the drug and carry it through the cardiovascular system. Plasma proteins have inert binding sites that the drug will bind to, causes no change
-Albumin is the most important/prevalent carrier
-Drugs cannot cross any carriers when bound to plasma proteins because of size
-Drugs can diffuse into tissues in their free form
-Conditions that decrease your levels of albumin affect drug distribution
-Dose is dependent on how much drug is bound and how much is free floating
-Multiple drugs can also compete for the inert binding site
Types of carriers:
1) Albumin; mostly acidic drugs
2) A1-Acid Glycoprotein; mostly basic drugs
3) Lipoproteins; mostly neutral drugs
Therapeutic Index
The larger the therapeutic index, the safe the drug is.
TD50= Median toxic dose
ED50= Median effective dose
Calculate therapeutic index: TD50/ED50
(LD50 for animals, not used in humans)
Drug pH & pKa
-Most drugs are weak acids or weak bases. pKa is the pH at which ionized & unionized concentrations are equal.
-Drugs need to be uncharged in order to cross the cell membrane; pKa affects the charge
-pH < pKa; favors protonated form
-pH > pKa; favors unprotonated form
Weak acids: protonated form is uncharged, unprotonated is charged
Weak bases: protonated form is charged, unprotonated form is uncharged
Drug Variations in response
- Can be idiosyncratic
- Patient is hyporeactive, hyperreactive
- Hypersensitivity
- Tolerance or tachyphylaxis
Causes of Drug Variations in Individuals
- Alteration in drug concentration that reachese the receptor
- Variation in concentration of the endogenous ligand; not everyone has the same amount of receptor sites
- Functionality of receptors
- Changes in the downstream cascade (most likely) due to proteins altering the response
-Body has a natural ability to compensate for this
Define monoclonal antibodies and how they are produced
-Biologics, drugs created from living organisms
-Extracted from living organisms such as abx, blood, transplants, microbiota and produced by recombinant DNA technology
-Mice are immunized with an antigen, and antibodies are made. Once the mice’s serum titer level is sufficient, they are euthanized and their spleen is removed as a source of cells for cell fusion
Naming for monoclonal antibodies, pathologic conditions
Ends in -mab
Rheumatoid Arthritis, Eczema (Dupixent), Psoriasis, Hidradinitis suppurativa
Role of the FDA
-Oversee the development process of drugs in the US
-Grants approval for marketing
-Reviews claims and makes recommendations
Difference in regulation between prescription and OTC drugs
-Prescription drugs have a higher potential for harm w/ misuse
-Only available under the care of an authorized health professional
-Must be safe AND effective
-OTC drugs are freely available to the public
-Lower risk for harm, but does not mean they’re safe. OTC herbal supplements do not have to be effective, only safe
The steps to bring a prescription drug to market
- In vitro studies, ~ 2years
- Apply for patent at year 2
- Animal testing begins, 2-4 years, apply for IND
- Phase I begins- small group of healthy adults test the drug
- Phase II- Small group (100’s) of adults with said disease condition. Usually double blind studies
- Phase III- Clinical testing on 1000’s of sick adults, market formulation, submit NDA (Year 9-10)
- Phase 4- Marketing. Patent will expire sometime shortly after this phase and generic will become available
