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Pharmacology > Exam 1: Study Guide > Flashcards

Exam 1: Study Guide Flashcards

1
Q

Define pharmacology

A

The study of substances that interact with living systems through chemical processes

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2
Q

What did Paracelsus famously state? What is he known as?

A

“The dose makes the poison”
He is known as the father of Toxicology

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3
Q

Define Phamacodynamics

A

“Actions of the chemical on the organism”

What the drug does to the body

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4
Q

Define Pharmacokinetics

A

Absorption
Distribution
Metabolism
Excretion
What the body does to the drug

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5
Q

Pharmacogenomics

A

The relation of a person’s genetic makeup to his or her response to a specific drug

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6
Q

Define Agonist

A

A drug or endogenous substance that binds to a receptor and initiates a response (activates receptor)

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7
Q

Define Antagonist and give and example

A

Drug or endogenous substance that compete to bind with receptor sites to block or prevent agonist from accessing receptor
Can be reversible or irreversible depending on the strength of the bond
Ex: Atropine prevents the binding of acetylcholine to receptor sites

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8
Q

Define Allosteric site

A

Site of bonds that occur somewhere on the protein outside of the receptor site
Can help activate (allosteric activator) or inhibit (allosteric inhibitor)

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9
Q

Define Orthosteric site

A

Site on the receptor that a drug classically binds to by the endogenous agonist

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10
Q

What is the difference between TOXIN and POISON and what are 2 examples of each?

A

Toxins are organic or biological substances from living organisms while poisons are non biologic substances
Toxins: puffer fish, mushrooms
Poisons: lead, cadmium, arsenic

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11
Q

What physical characteristics of a drug influence how they act on receptors?

A

Size, shape, charge, atomic composition

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12
Q

Describe relative bond strengths

A

Covalent > electrostatic > hydrophobic

Covalent are often irreversible
Electrostatic bonds are more common (ionic, hydrogen, or dipole)
Hydrophobic are weak, uncharged, and require

Bond strength is inversely related to specificity

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13
Q

What is a racemic mixture? Correlate stereoisomerism and difference in drug effects.

A

Solutions of 2 or more (stereo)isomers (mirror images) with similar formulas that are combined and administered as a single drug. One stereoisomer may cause a desired effect when bound while another may not bind or bind differently to cause unwanted effects.

Ex-
S (Left hand) Ketamine= more potent, so produces more SE
R (Right hand) Ketamine= less potent, more pure, produces less SE

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14
Q

What is the difference between a competitive inhibitor and an allosteric inhibitor?

A

Competitive inhibitor- binds directly to the receptor site that the agonist binds to, can be surmountable (weaker bonds or lower doses) or insurmountable (covalent or large doses)

Allosteric inhibitor- binds to a receptor protein somewhere other than receptor site, making the agonist incapable of competing or surmounting the inhibition

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15
Q

What does EC 50 measure?

A

The point in which 50% of the drug effect is seen

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16
Q

What does Kd represent?

A

The point in which 50% of receptors are occupied

This value never changes within individual drugs, but differs between drugs
The lower the Kd the higher affinity the drug has to the receptor

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17
Q

Physiologic Antagonism

A

When a substance produces effects that counteract those of another substance by binding to different receptors
Ex: epinephrine raises HR and beta blockers lower HR by working on different receptors

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18
Q

What is a partial agonist?

A

Drug that binds to receptor with less affinity than a full agonist, eliciting a lesser response even when 100% of receptors are bound
These are competitive
and will act as antagonist in the presence of a full agonist because it will take up receptors that could be occupied by full agonist, therefore lowering the response

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19
Q

What is an inverse agonist?

A

Drug that binds to receptors and turns them “off”, effectively blocking the receptors from being turned on.
Lowers constitutive activity
Examples of receptor sites that these can effect: GABA, Histamine (H1, H2)

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20
Q

What is Emax? Can this value change?

A

The maximum drug effect
No, this value does not change

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21
Q

Define Toxicology

A

Undesirable effects that drugs have on a living system

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22
Q

Who is Imhotep?

A

First recorded physician

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23
Q

What is the Materia Medica?

A

Collection of works through history, a precursor to pharmacology

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24
Q

List the different types of drugs and what causes them to interact with their receptors.

A

-Solids, liquids, gasses, organic (carbs, lipids, proteins, nucleic acids) and non organic compounds (Lithium, iron, heavy metals)
-Drug size (100-1000MW), electrical charge, shape, atomic composition

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25
What is the difference between a receptor and a receptor site?
A receptors is typically a protein located inside the cell or on its surface designed to signal a response while a receptor site is the unique region of the receptor that has distinct shape and chemical properties allowing it to interact with corresponding ligand(s)
26
What is the difference between a competitive inhibitor and an allosteric inhibitor?
Competitive inhibitors bind directly to the active site and can be reversible or irreversible or insurmountable. Allosteric inhibitors bind to a site on the receptor other than the active site and are always insurmountable, so more agonist will not create a response. See fig 1-2 in text
27
Describe physiological antagonism. Give an example.
Physiological antagonism occurs when a substance produces effects that counteract those of another substance without binding to the same receptor site. ex: epinephrine acts on beta1 receptors to increase the heart rate. Acetylcholine may bind to a different receptor site and result in a decrease in the heart rate.
28
Differentiate potency and efficacy.
Potency describes how much of a drug is required to get to Kd (50% receptors bound) or EC50 (50% effect seen). Efficacy describes the ability of the drug to get to a certain response level (Emax or Max) See Fig 2-15 Ex: Fentanyl is more potent than morphine but can achieve the same efficacy while Tylenol is not as efficacious as either of these drugs for pain control.
29
Describe the role of drug carriers, list most common ones in the blood.
Drug carriers help enhance the pharmacokinetic properties of drugs that cannot readily be metabolized. Can be bound or free form. Albumin is the most common in the blood. Others: alpha-1 acid glycoprotein, lipoprotein
30
How would you calculate the therapeutic index of an unknown drug?
Take the TD50 and divide by ED50
31
Predict the form and charge for a weak acid when pH
protonated, uncharged
32
Predict the form and charge for a weak base when the pH
protonated, charged
33
Predict the form and charge for a weak acid when pH> Pka
non protonated, charged
34
What are the 4 main causes of drug variation?
1. Alterations in drug concentration that reaches receptor 2. Variation in concentration of endogenous receptor ligand 3. Alterations in number of functioning receptors 4. Changes in components of response distal to receptor (most common cause of variation)
35
Correlate the Henderson Hasselbach equation with the charge on acidic and basic drugs.
It relates the pH of the surrounding solution to the dissociation constant (pKa)
36
Predict the form and charge for a weak base when pH> Pka
non protonated, uncharged
37
Define monoclonal antibodies and how they are produced.
A single clone of a cell that produces antibodies. The antigen (protein) is isolated then injected into a mouse. The mouse will recognize this a foreign and make antibodies against it. Those antibody's cells in spleen are then fused with myeloma cells that will produce those antibodies forever.
38
How do you recognize a monoclonal antibody from it's name?
-mab
39
List uses for monoclonal antibodies and pathologic conditions.
-Monoclonal Antibodies are for targeted therapy treatments of disease. These are good at treating diseases that have a singular root cause as they target a specific receptor or growth factors of the cell. Can also cause cell death if indicated - Treats conditions like cancer, viruses, cardiovascular disease, etc.
40
Describe the role of the FDA
Oversee the approval process for drugs, grants approval for the sale of a drug, and makes recommendations for drug developments and indications. They ensure that drugs that are both safe and effective. They also determine whether a drug needs a prescription or not.
41
What are the regulatory differences in prescription vs OTC drugs?
Prescription requires guidance of physician, they tend to have a higher risk for abuse or harm OTC are available to the public without physician guidance, tend to have a wider therapeutic index and therefore assumed lower risk of harm or abuse All are regulated by FDA
42
List the receptor types based on molecular structure
Seven- transmembrane receptors- GPCR Ligand gated channels- opens when ligand binds Ion channels- opens with ligand or voltage change Catalytic receptors- enzymatic internal reactions Nuclear receptors- inside nucleus Transporters- move substance across the membrane Enzymes- can be targets for particular drug types
43
What 4 ways can drugs get across barriers?
1. Aqueous diffusion- channels 2. Lipid diffusion- directly across membrane 3. Carrier Proteins- active transport 4. Endo/ Exocytosis- encapsulating a drug at the cell membrane and bringing in or out
44
What types of ligands bind to receptors inside the cell?
Gasses Lipid soluble agents
45
What is the difference between Ionotropic and metabotropic ion channels?
With inotropic channels, the ligand and receptor are the same protein while metabotropic channels have a ligand receptor that activates a G protein that sends a signal to an effector protein that activates a second messenger that opens the channel (GPCR)
46
What the difference between ligand and voltage gated ion channels?
Voltage gated channels are controlled by a change in voltage (Vrm) that triggers opening. These have 2 gates: the first opens at activation and the second is closed immediately after opening to limit the influx of ions. ex: sodium ion channels Ligand gated channels involve the binding of a molecule directly to the binding site to open the channel.
47
Define Desensitization
The body's response to a receptor being stimulated for a prolonged period. Beta arrestin is activated and stops the signaling by blocking the G protein from binding site. The receptor is then dragged along the membrane to a clatherin coated pit where it is suspended into the cell where it can be recycled for use or broken down by the lysosomes. See Fig 2-12
48
What is the role of the second messenger?
The second messenger activates additional proteins in order to have a cellular response
49
Define volume of distribution. Give example of a drug with high Vd.
-Relates the amount of drug in the entire body to the amount that is in the blood. Higher Vd= less amount staying in the blood, lower Vd= more staying in the blood -Hydroxychloroquine
50
Define clearance
Predicts the rate of elimination in relation to concentration -CL= rate of elimination/ concentration -Varies in zero order elimination -Remains constant in 1st order elimination
51
Define concentration
Amount of drug in the bloodstream (per L)
52
Define rate of elimination (RoE)
Amount of drug removed over time (usually per hour) -Varies in 1st order -Constant in zero order
53
What are 3 drugs that use zero order elimination when in large doses?
Ethanol, phenytoin, aspirin
54
List the 7 drug administration routes
IM PO/Sublingual IV SC Inhalation Rectal Transdermal
55
What is the typical drug size (MW)? Why?
100-1000MW Drugs in this range allow for selective binding and easy movement through the body
56
What is the most common second messenger?
cAMP Other: IP3, DAG, cGMP
57
Target Concentration
The concentration in the blood when therapeutic effects are seen
58
Half Life
Time required to half the concentration of a drug in the body
59
Bioavailability
Fraction of unchanged drug reaching the systemic circulation Affected by the physical properties of the drug (pKa, solubility, drug-drug interaction, etc)
60
What does it mean if you have a high Vd?
Vd= volume of distribution Very little amount stays in the blood stream May not reach the site of action because it gets stored in other parts of the body
61
What does a high CL mean?
CL= clearance A high clearance means that the drug is removed from the body quickly Dependent on blood flow and extraction ratio
62
How does flow- dependent elimination relate to extraction ratio?
Flow dependent elimination is when blood flow through a given organ (usually liver) will determine how well it eliminates a drug. Extraction ratio can be calculated based on how much of a drug goes to an organ and how much comes back out.
63
If 10mg of a drug is given and the half life is 4 hours, how much is left in the body after 1 half life in mg? How much is left in the body after 16hrs?
- 5mg -Virtually no drug is left after 4 half lives
64
What is therapeutic drug monitoring?
Drawing blood levels at specific times (peak or trough) to be able to manipulate drug dose based on individual needs. Typically performed with drugs that can be particularly toxic (ex: vanc, tacrolimus, digoxin)
65
What test is used to determine kidney function?
Creatinine Clearance Measure of creatine breakdown in muscles that is removed in the urine
66
What is Biotransformation? What is the most common place for this to occur?
The process of the body metabolically converting a drug to be less or more active before it reaches systemic circulation. This typically occurs in the Liver, but can also occur in the GI, lungs, skin, kidneys, etc.
67
What is the difference between a prodrug and an active drug?
Prodrug is the inactive form Active drug is the metabolite after activation
68
Describe the first pass effect
First pass effect is when a toxin, food, or drug enters into the hepatic portal system and undergoes biotransformation before it is circulated out to the body
69
What is the route a drug takes through the liver during first pass?
GI capillaries→ hepatic portal vein→ splenic vein→ capillaries→Hepatic sinuses→hepatocytes where they are biotransformed→ re enter circulation into hepatic vein→ IVC→ heart→ systemic circulation
70
What is Phase I metabolism?
-When an enzyme adds or unmasks a functional group -Most drugs are inactivated once going through -Makes drug less lipophilic/ more hydrophilic/ more polar to be excreted more easily
71
What is Phase II metabolism?
-Conjugation reactions; tacking on larger molecules to the substance -This can help increase molecular weight making them harder to cross barriers -Often detoxifying, -Makes the molecule more hydrophilic
72
What is meant by "wild type" and how is it indicated?
Wild type indicates that it is the most common form of the enzyme found in the population and is notated by “*1” behind the enzyme
73

Pharmacology (15 decks)

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