Exam 1, ch. 1 review Flashcards
Father of western/modern medicine
Hippocrates
First recorded physician? Where?
Imhotep, in ancient egypt
First Medical textbook
Materia Medica
Who is paracelsus? What is their famous quote?
Father of toxicology; The dose makes the poison
Pharmocodynamics
What the drug does to the body
Pharmacogenomics
Looks at genetic profile, how you’ll respond to the drug, some drugs require genomic testing. E.g. her-2 positive
Toxicology
Poisons and toxins and how they affect your body
Pharmacokinetics
What the body does to the drug i.e. What organ metabolizes it, half-life, how it crosses barriers
Define the following terms: agonist, antagonist, allosteric, orthosteric
- Agonist: Will bind to receptor (receptor is on cell surface)
- Antagonist: Blocks the receptors from receiving/functioning, prevents it from happening or dampers it
- Allosteric: binds somewhere outside active site
- Orthosteric: Binds at active site
State the difference between toxins and poisons
- Poisons are non-biologic, arsenic or lead.
- Toxins are biological substances that are from living organisms like pufferfish, mushrooms, etc.
List the different types of drugs, and what causes them to interact with their receptor
Solid, liquid or gas. The causes are similar to a lock and key analogy, molecular weight, and types of bonds.
Describe the relative bond strengths
Covalent is the strongest, then electrostatic, and the weakest is hydrophobic because there isn’t a charge. The stronger the bond, the less the specificity, and the weaker the bond, the more specific it is.
Define racemic mixtures, and correlate stereoisomerism and differences in drug effects
Racemic mixtures are 2 different optical isomers. They can be the same molecular formula but create different effects/results.
Define and describe the terms receptor and receptor site.
Receptor is mostly on the outside of the cell and is where a drug can bind to the receptor to be transported inside the cells. A receptor site is the specific site the drug binds to, and there are multiple kinds of sites. You have orthosteric and allosteric sites. Some are active and competing, some aren’t.
Analyze drug response curves to determine Bmax, Emax, Kd, and EC50
study graphs!
EC50
When 50% of the desired effect is achieved. i.e. when propranolol drops the heart rate from 120 to 60
Kd
Kd is when 50% of the receptors are bound, does NOT equal EC50
Emax
Emax is the the drug concentration needed to achieve full maximum effect of the drug.
Bmax
The highest concentration needed to achieve 100% receptor-bound drug.
Distinguish between a competitive inhibitor and an allosteric inhibitor.
A competitive inhibitor will compete with the active site and block other drugs from binding and starting a reaction. An allosteric inhibitor is non competing and bonds to the receptor outside the active site, and since its non-competing, it is more effective.
Describe physiologic antagonism.
When 2 different types of receptors that are doing opposite tasks. It’s when drugs act at different receptors to squelch effects of other drugs. I.e. acetylcholine agonizes Muscarinic receptors to lower heart rate while norepinephrine is agonizing beta receptors to raise heart rate.
Differentiate potency and efficacy. Compare the efficacy and the potency of 2 drugs on
the basis of their graded dose-response curves
Potency is the concentration of the drug required to produce 50% of the maximal effect.
Efficacy is greatest possible response a drug can deliver, and must take into account toxicity.
Describe the following terms: partial agonist, inverse agonist
Partial agonist is an agonist when acting alone, but becomes an antagonist when in presence of a full agonist
Inverse agonist in practice is an antagonist, but they are agonizing a receptor in order to block effects. It works by shutting down downstream response.
Evaluate haw a partial agonist can also be an antagonist
It’s an antagonist when a full agonist is present. It bonds to the receptor and keeps the full agonist from binding, which in turns weakens the reaction, becoming an antagonist.
Describe the role of drug carriers, and list the most common ones in the blood.
Bind to drug but do not affect the body. BOUND drug cant cross barriers. Albumin binds to acidic drugs, alpha-1 acid glycoprotein bind to basic drugs, and lipoproteins bind to neutral drugs.
What happens if albumin is low?
Less of the drug is bound to albumin, therefore the drug becomes more toxic in its free form.
Does albumin cross barriers easily?
No, albumin bound with drugs do not cross barriers easily. Drugs in free form cross much easier.
What happens if the patient receives multiple drugs that bind to albumin?
They compete for albumin receptor sites, resulting in a higher concentration of free form drugs, increasing the effect of the drug on the body.
Calculate the therapeutic index of an unknown drug
For animals: LD50 divided by ED50
For humans: TD50 divided by ED50
Predict the charge on a drug based on its pH and pKa
If the ph < pKa, then it is protonated (hydrogen ion attached). If it is a weak acid, its uncharged. If its a weak base, its charged.
If the pH > pKa, then it is unprotonated (no hydrogen ion attached). A weak acid is charged, and the base is uncharged.
Correlate the Henderson Hasselbach equation with the charge on acidic and basic drugs.
It relates pKa to pH. pKa tells us at what pH you’ll have charged and non-charged at equilibrium.
Discuss the four main causes of drug variation
- Alteration in concentration of drug that actually reaches the receptor (Rate, age, weight, sex, disease state, genetics, illness)
- Variation in concentration of endogenous receptor ligand (everyone has different amount of receptors on cell surface, can be affected by health status)
- Alteration in number of FUNCTIONAL receptors (may be blocked unknowningly)
- MOST IMPORTANT Changes in components of response distal to receptor. i.e. post receptor process, bodies natural ability to compensate.
In order to cross barriers, drugs need to be
Uncharged.
Define monoclonal antibodies and how they are produced
Drugs created by living organisms, may be direct or modified in lab. They are extracted from living systems (blood, transplants, microbiota) and produced by Recombinant DNA technology. They are produced by clones of a single parent cell.
Draw the basic structure of a monoclonal antibody
Slide 75 of lecture 1 notes
Appreciate the naming conventions in monoclonal antibodies
Prefix is the variable (target system for body, and source e.g. mice) with -mab as the suffix.
List uses for monoclonal antibodies in pathologic conditions
Extremely specific to targeted cells, therefore resulting in less side effects and increase in efficacy. Can cause cell death by various mechanisms, such as for cancer cells.
Describe the role of the FDA
They oversee development process of drugs in US, and demand that drug must be safe AND effective (vitamins dont have to be effective).
List the difference in regulation between prescription and OTC drugs
Rx: only available by authorization of health professional, viewed as “more effective” by public. (Safety does not always equal efficacy).
OTC: freely available to public, low risk for harm/abuse, does NOT equate to safe.
Define steps to bring a prescription drug to market.
vitro/animal testing for 4 years, apply for IND (investigative new drug)
Broken into 4 phases.
Phase 1: 20-100 healthy volunteers for dosing, safety, and may include patients IF they are high risk.
Phase 2: 100-200 patients, double blind study, testing efficacy. This does include patients with the actual disease the drug is treating.
Phase 3: 1000s of patients, market formulation, route.
NDA: new drug application
Phase 4: finally make money back, drug is on the market. patent expires after 20 years.
