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Pharm 2024 > Exam 1 Study Guide > Flashcards

Exam 1 Study Guide Flashcards

1
Q

List receptor type based on molecular structure

A

Intracellular
Enzymatic/Catalytic receptors
Ion channels
GPCR
Orphan receptors

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2
Q

Define the structure of GPCRs and RTKs, including their components

A

GPCR spans membrane 7 times. Extracellular NH3 end is receptor, intracellular carboxyl terminal end attached to alpha portion of the trimeric G-protein.

Receptor tyrosine kinase (RTK)- RTK is a monomer enzyme in the cell membrane with extracellular receptor and intracellular end with tyrosine. needs 2 monomers, each needs ligand to bind to merge into dimerization to activate.

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2
Q

Describe the cell signaling process

A

signaling cell releases endogenous ligand from vesicles of pre-synaptic terminal -> EL binds to receptor on post-synaptic terminal -> receptor undergoes conformational change that either opens ion channel or activates enzyme that creates secondary messenger cascade -> secondary messengers activate effector proteins that results in physiologic response

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2
Q

Name 4 transmembrane signaling methods by which drug-receptor interactions exert their effects.

A

GPCR
Catalytic receptor
Ligand gated channel
intracellular- lipid diffusion

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3
Q

elucidate the mechanism of GPCR signaling

A

When receptor activates, receptor has conformation change that causes alpha G-protein to release GDP and bind with GTP and moves to activate enzyme. That enzyme uses ATP to activate an inactive 2ndary messenger. phosphorylation cascade occurs (2ndary messenger activates another enzyme which activates another inactive 2ndary messenger and so on…) until 2ndary messenger activates effector protein that results in physiologic effect.

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4
Q

Describe the role of second messengers and list the most common

A

cAMP, IP3 and DAG, Ca++
secondary messengers activate phosphorylation cascade that amplifies a response from a single receptor binding. They can also cause multiple responses within the cell, resulting in a multitude of responses from a single extracellular receptor.

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5
Q

Define desensitization and describe the molecular components of desensitization in the GPCR

A

Desensitization occurs from prolonged binding of a ligand to receptor. B-arrestin binds to the -OH groups on the receptor and stops signaling further. It also pulls it to Clathrin coated pit to endocytose receptor into the cell. Once in the cell, the ligand can either unbind and receptor can bind to new alpha G-protein and return to the cell surface, or it can be phagocytized by a lysosome and broken down into recycled proteins.

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5
Q

Differentiate ligand gated and voltage gated ion channels

A

Ligand gated channels requires ligand binding to open channel to allow ions to move down concentration gradient. example= nACh receptors in skeletal muscle

voltage gated channels function based on cell’s resting membrane potential (Vrm). Has M gate and H gates. Cell has to repolarize to be able to reset ion channel

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6
Q

Distinguish ionotropic and metabotropic ion channels

A

ionotropic ion channels are where the receptor is also the ion channel.

metabotropic is receptor activates a GPCR that then functions to open separate ion channel

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7
Q

List the types of ligands that bind to receptors inside the cell

A

gases like nitrous oxide(NO) and lipid soluble steroid hormones (estrogen, cortisol, etc.)

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8
Q

List the pharmacokinetic variables

A

ADME

Absorption
Distribution
Metabolism
Excretion

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9
Q

Describe the four ways a drug gets across barriers

A

simple diffusion
facilitated diffusion
Active transport
endocytosis

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9
Q

Define volume of distribution (Vd)

A

the theoretical volume in which a drug would need to be uniformly distributed to achieve the same concentration as it is in the blood/plasma. It helps us predict how a drug behaves, whether it stays in the bloodstream or distributes widely into body tissue.

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9
Q

define Clearance

A

The rate at which a drug is removed from the body.

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10
Q

define concentration

A

the amount of drug present in a specific volume of fluid

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10
Q

define Rate of Elimination

A

The speed at which a drug is removed from the body (metabolized or excreted)

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10
Q

define target concentration

A

the desired concentration of a drug in the bloodstream that is required to achieve a specific therapeutic effect without causing toxicity

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11
Q

define half life

A

the time is takes for the concentration of a drug in the body to decrease by 50%

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11
Q

define bioavailability

A

the percentage of a drug that reaches systemic circulation in its active form

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11
Q

What is meant by a high Vd or low Vd

A

higher Vd means the drug is more likely to be distributed outside the bloodstream, low is more likely to stay in bloodstream

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12
Q

What is meant by a drug having high CL

A

it means the body is rapidly removing the drug from the bloodstream.

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13
Q

define capacity limited elimination and the variables in the equation

A

Capacity limited elimination (saturation kinetics) refers to the situation where process responsible for drug elimination has been saturated and rate of elimination will be constant, while CL rate will be variable

variables:
Vmax= maximum rate of elimination
concentration

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14
Q

Analyze flow dependent elimination as it relates to extraction ratio

A

Refers to situation where rate of elimination is primarily determined by the blood flow to the organ responsible for metabolizing or excreting the drug, rather than the organ’s ability to remove the drug. Extraction ratio is a measure of the efficiency with which an organ removes a drug from the bloodstream

Drugs with high extraction ratio means rate of elimination is largely flow-dependent.

Drugs with high hepatic extraction ratio are dependent on hepatic blood flow rate

ER = (C in-C out)/ C in

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14
Q

Estimate the half life of a drug based on its clearance and volume of distribution

A

T1/2 = (0.7 x Vd) / CL

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15
Q

Describe the blood level versus time for drugs subject to zero-order elimination and for drugs subject to first order elimination. What remains constant (CL or RoE)?

A

first order elimination: CL is constant, RoE is variable

zero order elimination: fully saturated so RoE is constant and CL is variable, until concentration no longer saturates all means of elimination, then goes to first order

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15
Q

List the 7 routes of drug administration

A

IV
IM
subQ
oral
rectal
transdermal
sublingual

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15
Q

How would you calculate dosage adjustment for obese patients?

A

use Ideal body weight

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16
Q

Describe therapeutic drug monitoring (peak and trough)

A

Peak- measuring the highest amount of drug shortly after administered.
Trough- measuring the amount of drug present at the lowest amount, measured right before another dose is due

Help ensure safe and effective therapy, dose not too high or not too low

17
Q

List the test used to determine kidney function

A

creatinine clearance

18
Q

who is the father of western medicine

A

Hippocrates

19
Q

First recorded physician

A

Imhotep 3000BCE

20
Q

What is Materia Medica

A

first pharmacology encyclopedia that listed use of botanicals for pharmaceutical purposes. Precursor to pharmacology

20
Q

Define the following terms: agonist, antagonist, allosteric, orthosteric.

A
  • Agonist- drug that binds to a receptor to illicit a response similar to endogenous ligand
  • Antagonist- ligand binds to a receptor to block a response or dampen response/action of the agonist
  • Orthosteric- ligand that binds directly to active site/primary active site on receptor
  • Allosteric- ligand that binds site other than the primary active site. This binding can enhance or inhibit effects of the primary active site
21
Q

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

A

Agonist- drugs that bind to and activate receptors, mimicking the effect of the body’s natural signaling molecules

Partial agonist- bind to and activate receptors but produce weaker response to full agonist (can act as antagonist in presence of full agonist).

Antagonist- Drugs that bind to receptor but don’t activate it, blocking agonist from binding

Inverse Agonist- drugs that bind to receptor but illicit opposite response of endogenous ligand

Competitive antagonist- drug that competes with agonist for same primary active binding sites. Can be out competed

Non-competitive antagonist- Antagonist that can’t be out competed. Either irreversibly binds to receptor or changes receptor’s conformation

Allosteric activator- drug that binds to separate binding site that enhances effects of agonist

Allosteric inhibitor- drug that binds to separate binding site that reduces or prevents the effects of an agonist at the active binding site

21
Q

State the difference between toxins and poisons.

A
  • Toxin- biologic, produced by living organisms
    • animal venom, Botulinum toxin, Ricin
  • Poison- non-biologic produced
    • lead, cyanide, arsenic
21
Q

Who is father of toxicology

A

Paracelsus- “the dose makes the poison”

22
Q

Differentiate the following terms: pharmacodynamics, pharmacokinetics, pharmacogenomics, and toxicology

A
  • Pharmacology - The study of how drugs interact with living systems, including their effects, mechanisms of action, and therapeutic uses.
  • Pharmacodynamics- how the drug affects the body
  • Pharmacokinetics- how the body affects the drug
  • Pharmacogenomics- study of how our genes affect our body’s response to medication
  • Toxicology – study of unintended/undesirable side effects of chemicals on the body
23
Q

Describe the relative bond strengths

A

Bond strength is inversely proportional to receptor specificity

Stronger bond are less

Covalent bond- strongest bond

Ionic bonds - moderate

Hydrogen

Van der waal- lowest

24
Q

Define racemic mixtures, and correlate stereoisomerism and differences in drug effects.

A

a mixture that contains equal amounts of two enantiomers of a chiral molecule. 2 isomers that are NON-superimposable mirror images of each other.

One enantiomer typically has stronger effect, and the other associated with toxic side effects.

25
Q

Analyze drug response curves to determine Bmax, Emax, Kd, and EC50.

A

Bmax = drug concentration where 100% of receptors are bound
Emax= drug concentration where 100% of effect is seen
Kd (dissociation constant)= drug concentration where 50% of receptors are bound
EC50= drug concentration where 50% of effect is seen

Kd tells us drug’s binding affinity

EC50 measures potency

25
Q

Define and describe the terms receptor and receptor site.

A

A receptor is a specialized protein molecule located on the surface of a cell or within a cell that binds to specific molecules

A receptor site refers to the specific region or binding site on the receptor where a ligand/drug attaches to the receptor.

26
Q

Describe physiologic antagonism.

A

the body’s natural system that inhibits an agonist

example: Epinephrine is an agonist to stimulate HR, acts as a physiologic antagonist of histamine which lowers HR, even though they bind to different receptors.

27
Q

define constitutive activity

A

the ability for a receptor to be active in the absence of a ligand, produces a baseline level of activity when no agonist present

28
Q

Describe the role of drug carriers, and list the most common ones in the blood.

A

Plasma proteins that bind to drugs (but not activate them) and help transport them in the bloodstream.

Albumin- most important- binds to acidic drugs

alpha1-acid glycoprotein- binds to basic drugs

lipoproteins- bind to lipid soluble drugs

These carrier proteins are essential for the distribution of drugs in the body and help regulate the free drug concentration, which is the active portion responsible for interacting with receptors and producing therapeutic effects.

29
Q

Calculate the therapeutic index of an unknown drug.

A

(LD50 or TD50)/ ED50 = TI

higher TI is safer

30
Q

Predict the charge on a drug based on its pH and pKa.

A
  • If ph < pKa – favors protonated form
  • If ph > pKa – favors unprotonated form
  • Weak acids- protonated = uncharged, unprotonated = charged
  • Weak bases- protonated = charged, unprotonated = uncharged
31
Q

Discuss the four main causes of drug variation.

A

Changes in component of response downstream to receptor- post receptor process. most important

Variation in the number of functioning receptors
Variation in the distribution of the drug
Variation in concentration of endogenous ligand.

32
Q

Define monoclonal antibodies and how they are produced.

A

Clone of single isolated immune cell

Target antigen injected into mouse
Once mice creates enough antibodies, harvest spleen cells
spleen cells fused with myeloma cells to make them immortal, allowing them to grow indefinitely in culture
Humanization if necessary, involves replacing portions of the mouse antibody structure with human antibody sequences. Done to prevent human immune system from seeing antibody as foreign

33
Q

Appreciate the naming conventions in monoclonal antibodies.

A

end in -mab

34
Q

List uses for monoclonal antibodies in pathologic conditions.

A

cancer, autoimmune disease, multiple sclerosis, inflammatory bowel disease, COVID, a lot of uses….

35
Q

Describe the role of the FDA.

A

Protect the public from unsafe and ineffective drugs. GRASE- “generally recognized as safe & effective
Oversees drug development process
Categorizes drug based on risk: Rx, OTC/BTC, herbal/vitamin (must be safe, doesn’t have to be effective)

36
Q

Define steps to bring a prescription drug to market.

A
  • Must first identify a lead compound
  • Needs to be animal tested for safety
  • Apply for investigational drug (IDA) and enter clinical testing
    • Phase 1: is it safe? Pharmacokinetics
      • Healthy young individuals
    • Phase 2: double blind. does it work? More effective than placebo? On patients with actual disease
    • Phase 3: larger double blind on larger amounts of patients
  • After/During phase 3 can apply for NDA (New drug application) with the FDA to be approved for marketing
  • IDA and NDA are both regulated by the FDA - allow you to progress to the next step
37
Q

Describe drug biotransformation and the difference between a prodrug and an active drug.

A
  • Drugs get metabolized and changed into other metabolites, some are active or inactive. (goal to make them more hydrophilic to be able to excrete easier)
  • Ex. Codeine is prodrug to morphine. Codeine itself provides no pain relief. Has to get converted to morphine in the body. Some codeine may also get metabolized into other inactive metabolites as well. Not all gets converted to active metabolite (morphine).
    • Codeine turning into morphine via CYP2D6 (phase I)
      • If mutation in CYP2D6 - morphine won’t be effective
    • Morphine metabolism via glucuronidation (phase II) can make it inactive or active
38
Q

List the major phase I and phase II metabolic reactions. Know which P450 isoforms are responsible for the greatest number of important reactions.

A

Phase 1: introducing or unmasking a functional group (-OH, -SH, -NH2) Increase polarity of drug making it hydrophilic and easier to excrete. Done through oxidation, reduction and hydrolysis. Done through Cytochrome P450 enzymes.

CYP3A4 (50% all drugs)
CYP2D6(20% all drugs)
CYP2B6(8% all drugs)

Phase 2: conjugation reactions that add bigger compounds.
Glucuronidation, sulfation, glutathione conjugation, acetylation

38
Q

Describe the first pass effect, and the route of blood through the liver.

A

drug after being absorbed by GI tract is metabolized by the liver before it reaches systemic circulation. This reduces the concentration of drug that reaches the bloodstream. Affects BIOAVAILABILITY.

Oral drugs: GI tract -> local veins -> hepatic portal vein -> sinusoids/hepatocytes -> hepatic vein -> inferior vena cava

All drugs- systemic circulation -> hepatic artery -> sinusoids/hepatocytes-> hepatic vein -> inferior vena cava

39
Q

Define what is meant by “wild type” CYP enzymes, and how they are notated.

A

*1

most common CYP variant seen in nature

39
Q

Describe the pathways by which acetaminophen is metabolized (1) to harmless products if normal doses are taken and (2) to hepatotoxic products if an overdose is taken.

A

Acetaminophen normally metabolized by phase 2 reaction through glucuronidation and sulfation. In higher doses can be metabolized by phase 1 CYP34A and create reactive intermediates. An additional phase 2 reaction can neutralize the reactive intermediate through glutathione conjugation. If limited stores of glutathione exhausted the reactive intermediates can bind to cell macromolecules of hepatocytes and cause liver cell death

39
Q

Delineate the generic pathway of Cyp450 metabolism.

A

drug binds to CYP450 active site (iron containing Fe3+ state), induces a conformational change in CYP450 enzyme that facilitates reduction of electron transfer from NADPH reductase to the Fe3+ to Fe2+. Oxygen binds to the reduced iron. Second electron reduces the oxygen molecule, one oxygen atom is incorporated into the drug and water is produced.

The drug is now oxidized and more polar, making it more hydrophilic

40
Q

Describe the mechanism of hepatic enzyme induction and inhibition.

A
  • Hepatic enzyme induction and inhibition can increase or decrease the rate of metabolism of a drug. This can increase or decrease how fast drug is activated or inactivated depending on whether it is a prodrug or active drug.
  • Prodrug – induction increases rate gets converted to active. Inhibition reduces the rate it gets converted to active
  • Active- induction increases rate it gets deactivated, inhibition reduces the rate it gets inactivated leaving active drug around longer.
40
Q

List additional factors affecting drug metabolism.

A
  • Extrahepatic
    • Plasma- cholinesterase
  • Intestine
    • All hepatic enzymes (decreased)
    • Important for reabsorption/excretion
  • Kidney
    • P450, GSTs
    • Differences important for volatile anesthetics
  • Brain- P450s, psychotropic metabolites
  • Lung- major phase1 and 2
  • Diet
    • Charcoal broiling- induce CYP1A
    • Grapefruit juice- inhibit CYP3A
  • Environement
    • Cigarette smoke
    • charcoal burning
  • Age and Sex
    • Pre vs post pubescent
    • Males faster (in rats)
40
Q

Define pharmacogenomics and its importance in personalized medicine.

A
  1. Study of how an individual’s genetics affect their response to drugs. Pharmacogenomics’ goal is to predict an individual’s response to a drug before the patient actually takes the drugs. Helps us determine whether a patient may need more or less of a dose or if they will even respond to a particular drug.
    The right dose of
    The right drug for
    The right indication for
    The right patient at
    The right time
41
Q

Describe the role of drug transporters in the cell.

A

Drug transporters play a critical role in the movement of drugs across cell membranes. Bind to the drug and move across barriers. Transport endogenous substances (hormones, glucose, and amino acids), but many also transport xenobiotics. They can be drug influx transporters or efflux transporters

41
Q

Name and describe three drugs that may require dosage adjustments in specific genetic populations, the enzyme or mutation responsible, and the type of testing done to determine susceptible populations.

A

6-MP- leukemia treatment. testing for TPMT mutations to determine if patient would ultraslow metabolize medication
Warfarin- recommended to do CYP2C9 , mutation will effect how well warfarin is metabolized
Herceptin- breast cancer treatment. Tested for HER2 overexpression from tumor to see if herceptin would be effective

42
Q

Define the role of drug efflux transporters.

A

Cell survival mechanism to pump unwanted substances out of the cell. Cell can increase the amount based on exposure over time.
1. Solute carrier (SLC) proteins - Passive transport via gradient
2. ABC gene family - ATP

43
Q

Analyze the anatomic differences between drug transporters in different organs and their overall effects.

A

Liver- high amount of influx transporters, then either efflux of metabolites or excretion through bile to intestine

Intestines- larger ratio of influx transporters than efflux, because job is to absorb things

Kidney- mostly efflux into urine

Brain- lots of efflux to protect the CNS

Placenta- similar to brain, efflux to protect baby

43
Q

List the most important ABC transporters and differences in their drug affinity.

A
  1. ABC= “ATP binding cassette”; transports with Nucleotide Binding Domains (NBD)
    1. ABCB-broadest substrate specificity. Wide distribution, GI, kidney, liver, testes
      1. Antineoplastics, antibiotics, antidepressants, antiepileptics, and opiods
      2. Critical in maintenance of the BBB
    2. ABCC
      1. Mainly antineoplastic efflux
    3. ABCG
      1. Breast cancer resistance protein (BCRP)
      2. Antineoplastics, toxins, food-borne carcinogens, folate transport
44
Q

List the components of the intact blood-brain barrier.

A

tight gap junctions
ABC transporters
Glial cells- astrocytes, podocytes

45
Q

Delineate the pathway of Tylenol in the gut before and after biotransformation.

A

Tylenol ingested> dissolved in stomach > absorption through intestines > first-pass metabolism in liver > phase 2/1 > either effluxed as bile into intestines or enters systemic circulation distributed to body > excretion in urine

Pharm 2024 (32 decks)

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