Lecture 1: Basics of Pharmacology Flashcards
What is stereochemistry?
3D structural orientation of molecules
What are the two possible clinical responses of drugs?
Toxicity or effectiveness
What is a common tachyphylactic drug?
Ephedrine
Which type of drug (ionized or nonionized) is able to diffuse and equilibrate into other tissues?
Nonionized, though it may become ionized once it diffuses
Intravascular fluid is part of what compartment in the two compartment model?
Central compartment
What is biotransformation?
A chemical process where a drug is altered in the body
What are the two types of membrane receptors?
Agonists and antagonists
What is a racemic mixture?
A mixture that has equal parts left and right-handed enantiomers of a chiral molecule
The process by which drugs in the systemic circulation are converted into metabolites or exit the body
Elimination (Metabolism)
Which method of administering drugs would be represented by a graph that demonstrates a steep incline followed by a slow decay? Why is the decay progressively slower and slower?
Direct injection of drug into blood with route of elimination (think of a drain in a sink)
The slope becomes less and less steep because the level of volume in the blood falls as it is eliminated (“drained”), so the pressure gradient that drives the process of elimination becomes less and less (exponential decay curve)
What are three factors that lead to decreased amounts of plasma protein in the blood?
Age
Liver failure
Pregnancy
What is the average plasma volume?
3 L
In a pH higher than its pK, an acidic drug will be ionized or nonionized?
Ionized
What is the difference between pharmacological effect and clinical response?
Pharmacological effect occurs at the molecular level; clinical response is evident in the things we can measure via sight, touch, smell, hearing, smell, etc.
The term “parenteral” means that drugs are administered:
“aside from” the alimentary tract
Which type of receptor triggers a cascade when bound by a drug?
Enzyme receptor
Subcutaneous tissue lies below which level of skin?
Dermis
Ionized drug + nonionized drug: which type crosses cell membranes?
Nonionized drugs cross cell membranes.
A noncompetitive inhibitor of acetylcholinesterase would have what major side effects?
Build up Ach concentrations in the body with no relief; cause SLUDGE-BBM Salivation Lacrimation Urination Defecation GI distress Emesis Bronchoconstriction Bradycardia Miosis, Muscle spasm
Which type of channel involves a conformational shift to open a channel and let ions flow through?
Ligand-gated ion channel
What is tachyphylaxis?
An exhaustive situation in which after dosing a drug, you must administer a higher dose to get the same initial response
Drugs leave the systemic circulations and enter the tissues of the body via?
Distribution
How can the binding of a competitive antagonist be overcome?
Increase the concentration of the agonist at the receptor site
Which enantiomer of Bupivicaine is cardiotoxic? Which is not?
L-isomer is cardiotoxic.
R-isomer (Rhopivicaine) is not.
How do drugs effect voltage-gated ion channels?
Example?
They bind and block the channel so that ions cannot pass through to cell, altering the electrical activity of the cell.
Lidocaine and Na+ channels
What is the major converter of drugs to metabolites in the liver?
Cytochrine P450
What is an antagonist?
A drug that produces its clinical effect by binding to a receptor without activating it and simultaneously prevents an agonist from stimulating it
What type of antagonism cannot be overcome by increasing the concentration of the agonist?
Irreversible blockade
What are two ways drugs exit the central compartment in the compartment model?
Biotransformation + excretion
In the compartmental model, from the central compartment free drug can travel to what three areas of the body?
Therapeutic site of action (positive effects)
Tissue reservoirs
Unwanted site of action (negative effects)
In a pH lower than its pK, a basic drug will be ionized or nonionized?
Ionized
Which method of administering drugs would be represented by a graph that demonstrates a steep incline followed by a steep and then more gradual decline?
Most realistic model; takes into account both the elimination mechanism and extravascular equilibration. Rapid equilibration (steep decline) and then slower elimination (more gradual decline)
In the compartment model, we examine the pharmacokinetics of drugs in terms of:
What compartments they travel to + what happens when they reach those compartments
By what mechanism does the liver remove drug from plasma?
Hoffman elimination
In the central compartment, some drug is bound to:
proteins
In which compartment (central or peripheral) will lipophilic drugs tend to sequester?
Peripheral compartment; likes to cross cell membranes and remain in fatty tissues
Phenylephrine is an example of what kind of membrane receptor?
Agonist: stimulates sympathetic response on a-1 receptor
How many phases of metabolic biotransformation are there?
Two
What is a prodrug? Give an example.
A drug that itself is not an active effector, but once it is metabolized in the body, those metabolites are active effectors
Morphine itself isn’t active, but its metabolite morphine-6-glucoronite is active
Which type of drug (ionized or nonionized) is soluble in water?
Ionized
What are the four major types of reactions in metabolism?
1) Oxidation
2) Reduction
3) Conjugation
4) Hydrolysis
Interstitial fluid is a component of
Extracellular fluid, along with plasma
What is the R-isomer (type of enantiomer) of Bupivicaine?
Rhopivicaine
Phenylephrine is a/an ____________ -acting agonist. Its mechanism is:
directly-acting: binds to alpha and beta receptors to cause an effect
Why do patients feel hungover after having been administered thiopental as compared to propofol?
Longer elimination phase; hangs around in the body
Narcan is an ___________ of which membrane receptors?
Antagonist of opioid receptors
Drugs sequestered in tissues where they are ionized or nonionized?
Ionized; they freely travel in tissues where they are nonionized, but once they are ionized they cannot cross into other tissues
What occurs in phase II of metabolic biotransformation?
Polar metabolite conjugates with an endogenous substrate to become water soluble
What are the two components of extracellular fluid?
Plasma + Interstitial fluid
Drugs that are not distributed or eliminated go where? This marks the transfer from pharmacokinetics to?
Site of action; pharmacodynamics
If pK of substrate (drug) = pH of surrounding fluid, what portion of substrate is ionized?
50% is ionized.
The term “mimetic” relates to what type of drug that acts on membrane receptors?
Agonist
What is an agonist?
A drug that produces its clinical effect by binding to a receptor and activating it
What are enantiomers?
Two molecules having the same chemical composition but different orientations around a central atoms; these molecules are mirror images of each other
The term “blocking” relates to what type of drug that acts on membrane receptors?
Antagonist
Why do patients with liver failure have a more exaggerated response to drugs?
They have low levels of albumin in the blood, so there is a higher concentration of free drug in the body that produces a more exaggerated effect.
What is pharmacokinetics?
What the BODY does to the drug
What is defined as an enzymatic alteration of a drug’s chemical structure?
Metabolism
Indirectly-acting agonists increase the concentration of endogenous substrate at a receptor site: what are examples of endogenous substrate?
Neurotransmitters or hormones
From the drug dose, what process determines how much will enter the central compartment?
Absorption
The two compartment model demonstrates what two main compartments in the body?
Central + peripheral compartments
Intracellular fluid accounts for what proportion of total body fluid?
2/3
What are the four main components of pharmacokinetics?
Absorption, distribution, metabolism, and excretion
Competitive antagonist is irreversible or reversible?
Reversible blockade
Across the lipid mucosal barrier, a steep concentration gradient exists between levels of which drug type (ionized or nonionized)?
Ionized
EXAMPLE: Plasma has a more basic pH, so an acidic drug is going to be largely ionized in that environment, meaning only the small portion of basic drug can cross the lipid membrane barrier. Once the nonionized drug crosses the lipid membrane barrier into very acidic gastric juice, the drug is more likely to exist in its nonionized form than ionized. Therefore, the nonionized forms can equilibrate across the membrane, but the nonionized form cannot, and there’s a much greater concentration of nonionized drug in the plasma than in the gastric juice.
Of any administered dose, what percentage of midazolam is active?
5% is active; 95% is bound to proteins
GABA is an example of what kind of receptor?
Ligand-gated ion channel
Fentanyl is an __________ of which membrane receptors?
Agonist of opioid receptors, specifically mu receptors
Ephedrine is a/an ______________ -acting agonist. Its mechanism is:
indirectly-acting: releases stores of norepi and norepi binds at receptors to cause effect
How does degree of protein binding relate to volume of distribution?
Degree of protein binding is inversely proportional to volume of distribution
Extracellular fluid accounts for what proportion of total body fluid?
1/3
Volume of distribution relates what two values?
The amount of drug in the body to the concentration of drug in the blood or plasma
For which receptor must the drug first cross the cell membrane?
Enzyme receptors
The term “enteral” means that drugs are administered:
via the alimentary tract
Highly perfused tissues include:
Of the two compartment model, in which compartment are these tissues included?
Brain, liver, kidney, lungs, heart…
Central compartment
Which compartment of the two compartment model exhibits slower uptake?
Peripheral compartment
What is an example of a non-competitive antagonist? How do you correct for its action?
Plavix; its active metabolite prevents the binding of ADP to platelet P2Y12 receptors, therefore preventing the activation of the glycoprotein GPIIb/IIIa complex and in doing so, inhibiting the aggregation of platelets
To correct for it, you must give more platelets
Which method of administering drugs would be represented by a graph that demonstrates a steep incline followed by an exponential decay to a steady state?
Direct injection of drug into blood with route of equilibration; the blood volume equilibrates quickly with the extravascular volume, causing a drop in concentration of drug in the blood until that steady state is reached; then the amount of drug in the blood and in the extravascular volume are equal and constant
Which method of administering drugs would be represented by a graph that demonstrates a steep incline followed by a plateau?
Direct injection of drug into blood with no route of eliminiation
Basic drugs travel on what type of protein in the body?
alpha-1-acid glycoprotein
Name two drugs that act on GABA receptors:
1) Propofol (all induction drugs)
2) Benzodiazepines
What type of antagonist is rocuronium– competitive or noncompetitive? By what mechanism?
Competitive: binds to Ach receptors and blocks them, preventing Ach from binding–increasing the concentration of Ach at the receptor site will out-compete rocuronium
Do drugs have positive or negative effects on enzymatic processes within the cell?
Postive (upregulation)
What two things determine ionization of a drug?
pK of drug (substrate)
pH of surrounding fluid
The total approximation of all the compartments to which the drug goes
Volume of distribution
Say your patient has a tumor that secretes catecholamines (epi/norepi), and those catecholamines act on alpha + beta receptors in the body. How does your body maintain homeostasis?
It down-regulates the number of alpha and beta receptors present.
Term for a drug that has an exaggerated response:
hyperactive
Esmolol is an __________ of what receptor?
Antagonist of beta-receptor
What are the two phases following drug administration?
Distribution phase (rapid decline) and elimination phase (more gradual decline)
Are drugs bound to protein physiologically inert?
No, these drugs have their full functions; they are just stuck in the plasma where there are no receptors to work on. Free drugs can pass from the central compartment to their site of action and have an effect.
What are the three possible actions of a drug on a receptor?
1) Bind to it + activate it
2) Bind to it + block it
3) Bind to it + spur chain of events
What kind of molecule is a receptor? Where is it located in the cell?
Protein; lipid bilayer of cell membrane
Which type of drug (ionized or nonionized) is metabolized in the kidneys?
Ionized
A term that describes an individual with an allergic response to a drug
Hypersensitive
At what point on a graph demonstrating serum concentration over time do you wake up after a dose of propofol?
After the distribution phase–redistribution to tissues on which propofol doesn’t act
The dose of the drug that you administer and the concentration of the drug that actually reaches systemic circulation differ due to what process?
Absorption
CSF, GI fluids, and synovial fluids are all examples of:
interstitial fluid
In the two compartment model, which compartment exhibits a rapid uptake of drug?
Central compartment
Plasma makes up what proportion of your total blood volume?
2/3
Biotransformation produces _____________ from free drug, and those are then:
metabolites; excreted from the body
Which type of drug (ionized or nonionized) is metabolized in the liver?
Nonionized
What is pharmacodynamics? (simple definition)
What the DRUG does to the body
Which type of drug (ionized or nonionized) is soluble in lipids?
Nonionized
Example of drug that acts on enzyme receptors?
Phosphodiesterase inhibitors
What is the Law of Mass Action in relation to pharmacology?
The rate of reaction is directly proportional to the concentration of reactants.
Acidic drugs travel on what type of protein in the body?
Albumin
By what mechanism do kidneys remove drug from plasma?
Ester hydrolysis
Which compartment includes tissues like fat, bone, and inactive skeletal muscle?
Peripheral compartment
Why might acute stoppage of beta blockers cause a hypertensive crisis?
Beta blockers block beta receptors, causing an initial decrease in beta activity. To maintain homeostasis, the body makes more beta blockers in response. When you d/c beta blockers, you are opening many more receptors than patient originally had for epi/norepi to bind and cause a massive sympathetic response.
A term that describes an individual with a tolerance for a dose of a drug that would otherwise have an effect
Hypsensitive
What causes an effect on the cell in regards to ligand-gated channels?
Changes in ion concentrations across a membrane
What are the eight routes of parenteral drug administration?
Intravenous (IV) Intramuscular (IM) Subcutaneous Topical, Transdermal Nasal Intraarterial Intrathecal (injected into CSF) Pulmonary
What are the three routes of drug administration that are enteral?
Oral (PO)
Rectal
Sublingual
What is the difference between an additive effect and a synergistic effect?
Additive: 1 + 1 = 2; the doubled dose has the exact effect you would expect
Synergistic: 1 + 1 = 3; the doubled dose has even more of an effect than you would expect
What occurs in phase I of metabolic biotransformation?
Convert drug to polar metabolite.
Describe the mechanism of a directly-acting receptor agonist.
The drug combines directly with its receptor to trigger its physiological response.
What method allows you to increase Ach concentration at Ach receptors in order to out-compete rocuronium?
Sustained tetany
Hoffman elimination doesn’t depend on liver function but instead:
pH and temperature
Of the two compartment model, from which compartment are drugs eventually eliminated?
Central compartment
The central compartment accounts for what percent of cardiac output pathway? What about body mass?
75% of CO pathway, 10% of body mass
If drugs have a large volume of distribution, are they more or less prone to protein binding?
Less prone
Three site-specific factors affecting absorption of drug:
Blood flow from site
Surface area for absorption
Solubility of drug at site
What term regarding drug response describes the situation in which you give one drug to negate another?
Antagonistic effect
Describe the mechanism of an indirectly-acting receptor agonist.
The drug produces its physiological response by increasing the concentration of endogenous substrate at a receptor site..
What is plasma?
Noncellular portion of blood
What is pharmacodynamics? (fancy definition)
Intrinsic sensitivity/responsiveness of the body’s receptors to a drug
