Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Pharmacology FA26 E1
| Question | Answer |
|---|---|
| What is PK? | Pharmacokinetics, ADME, what the body does to the drug |
| What is PD? | Pharmacodynamics, MOA, what the drug does to the body |
| MOA is | PD |
| ADME is | PK |
| What is the underlying principle for why a drug works? | Receptor theory |
| What is the drug target? | receptors, usually macromolecules like proteins, DNA, and RNA |
| What is a drug bound to a target called? | A drug-receptor complex |
| T or F? Any molecule of functional importance can be a drug receptor. | True |
| T or F? Classical and drug receptors are the same thing. | False. Not all drug receptors are classical receptors |
| Which is a bigger class or molecule? Classical receptors or Drug receptors? | Drug receptors |
| Drug forms bond with a receptor via... | IMF/Intermolecular Forces |
| Covalent bonds are unique because... | they are RARE but they are irreversible |
| What is the common irreversibly binding drug that people often take for pain? | Aspirin |
| Covalent bonds are SUPER strong. Why? | Because the drug and the receptor share electrons |
| Why are non-covalent bonds weaker? | Because the drug and the receptor do not share electrons |
| Hydrophobic means... | Water HATING |
| Hydrophilic means... | Water LOVING |
| What molecules typically clump together in water? | Hydrophobic |
| What is the strongest reversible drug to receptor binding force? | Ionic bonds |
| Why are ionic bonds strong? | because they are the attraction of two opposite charges |
| Hydrophobic bonds are what polarity? | Nonpolar |
| Hydrophilic bonds are what polarity? | Polar |
| Organic solvents are hydro... | phobic |
| Strongest non-covalent interaction? | Ionic bond |
| Medium strength non-covalent interaction? | Hydrogen bond |
| Weakest non-covalent interaction? | Hydrophobic bonds |
| The phosphate backbone of DNA is negatively charged, how does that work?? | Pi stacking forces overpower negative bonds in the phosphate backbone |
| Polar molecules do not like | hydrophobic residues |
| More bonds means | stronger binding affinity |
| Less bonds means | weaker binding affinity |
| T or F? Bonds can form over a long distance. | False. Bonds can only form over a short distance |
| T or F? It is important that a drug fit its receptor structurally. | True |
| If the drug makes it to the receptor, binds, and still doesn't have the strongest bond, why might that be? | The molecule is unable to bind with the receptor because the shape causes miniscule but notable distance, or there are bad matches in terms of charge |
| Another way to say binding affinity is | tightness of bonding |
| Fit is not everything, binding affinity also relies on this to match... | charges, + to - |
| A good drug has what relationship to its receptor? | many IMF bonds, good fit, and non-repulsive electrostatic forces |
| What is Bumetanide? | A diuretic |
| How does Bumetanide work? | The drug sits in the binding pocket of the NKCC receptor and blocks it from transporting K+ |
| What enzyme does aspirin inhibit? | COX-1 |
| What does Aspirin do? (basic function) | It inhibits platelet activation and blood clotting |
| How does the body recover from taking irreversibly binding drugs? | By synthesizing new proteins |
| Why can't platelets make new proteins? | Because they have no nucleus |
| Most drug receptors are | proteins |
| The binding pocket in a protein is full of | amino acid side chains |
| What are the two broad names of reversible bonds? | electrostatic and hydrophobic bonds |
| The little eyelashes in Hong's drawings represent what? | Hydrophobic residues |
| Rings of carbon or long chains of carbon are usually | Hydrophobic |
| Hydrophobic molecules preferentially bind to | Other hydrophobic molecules |
| A normal cell can produce COX-1 to overcome the inhibitory action of aspirin. T or F? | True |
| Platelets can produce proteins T or F? | False |
| Chemotherapeutic drugs are also called | Alkylating agents |
| Where do most alkylating agents bond? | The bases of DNA |
| Why do alkylating agents/chemo drugs work on cancer cells? | The presence of the drug molecule covalently linked to DNA interferes with gene transcription and DNA replication |
| How do you increase the likelyhood of a drug finding its receptor? | Increase drug concentration or the receptor concentration |
| Kd tells us the | Binding affinity for a specific drug-receptor pair, level of drug where at least 50% of receptors are bound |
| High binding affinity correlates to what Kd? | Low Kd |
| Low binding affinity correlates to what Kd? | High Kd |
| What is potency? | The amount of a drug required to produce an effect |
| What is efficacy? | The maximum intensity of a response produced by a drug |
| T or F? Higher potency = better drug. | False. Higher potency does not mean a better drug |
| T of F? Higher efficacy = better drug. | True. Higher efficacy generally does mean a better drug |
| In order for a drug to produce an effect, the drug must do what to a receptor when bound? | Cause a conformational change or block a conformational change |
| T or F? Conformational change is reversible. | True |
| Some drugs bind and turn receptor activity on. These are called: | activators/agonists |
| Some drugs bind and turn receptor activity off. These are called: | inhibitors/antagonists |
| What is it called when a substrate binds to a remote site that is not the active site and induces a conformational change? | Allosteric modulation |
| A competitive antagonist... | Binds and turns off the receptor by blocking binding site |
| A non-competitive antagonist... | Binds at a spot other than the active site and allosterically inhibits receptor function |
| With estrogen, in the presence of an agonist, it takes ____ estrogen to produce the same level of effect | less |
| True or False? Drug developers want Kd small for unintended receptors. | False. They want Kd low for intended receptors necause lower Kd = higher binding affinity |
| True or False? Some drugs can lose selectivity at high concentrations | True, too much drug, too many chances to bind off target |
| A chemical from outside of the body is called a | xenobiotic |
| Your body naturally wants to do this to xenobiotics | make them more water soluble to extrete in the urine |
| Your body changes the characteristics of a chemical substance, this is called | Biotransformation |
| Biotransformation includes two parts, these are: | Phase I and Phase II metabolism |
| In Phase I and II, _________ goes up and _________ goes down | hydrophilicity, lipophilicity (think oil) |
| What group does Phase I metabolism typically add to a molecule? | an oxygen as an OH group |
| Phase II attaches what to drug molecules? | Big functional groups |
| CYP enzymes are most prevalent in what phase of metabolism? | Phase I |
| SULT, UGT enzymes are used in what phase of metabolism? | Phase II |
| What is the most abundant CYP enzyme in the liver that accounts for over 50% of drugs metabolized? | CYP3A4 |
| Dr. Hong's favorite phase II enzyme is | NAT2 |
| T or F? Metabolism can both prolong and limit drug action in the body | True |
| What is it called when metabolism activates a drug? | Prodrug |
| T or F? First pass metabolism only applies to orally administered drugs | True |
| The first pass effect often does what to drug serum levels? | Limits it |
| Why can't you take Tylenol with alcohol? | Because it induces CYP2E1 which is the enzyme that bioactivates Tylenol into a toxic metabolite |
| Give an example of a CYP inducer | Rifampin the TB drug |
| Give an example of a CYP inhibitor | Grapefruit juice |
| How does rifampin induce CYP2C9 enzymes? | CYP2C9 enzyme level increases in the liver, this can lead to an increase in metabolism, therefore less therapeutic effects |
| How does grapefruit juice inhibit CYP3A4 enzymes? | It contains compounds that irreversibly inhibit CYP3A4, this would cause drugs metabolized by CYP3A4 to be high, toxicity |
| Tamoxifen acts as an ______ in the breast and a ______ in the bones | antagonist in breast, agonist in bone |
| Tamoxifen is a SERM. What does SERM mean? | selective estrogen receptor modulators |
| When estrogen binds to an estrogen receptor, it cannot activate gene transcription by itself. It needs what? | a co-activator |
| How does the Tamoxifen ER complex prohibit growth in the breast? | it does not allow for the conformational change that allows a co-factor to bind, so ERS cannot activate downstream target genes |
| Why does Tamoxifen induce bone growth? | There is a bone-specific co-activator called NCOA1 that can still bind after Tamoxifen binds causing growth promoting genes to be turned on |
| What is a drug that someone can take instead of Tamoxifen so that there is no unintended uterine growth in treating breast cancer? | Raloxifene |
| Hypothetically, if you introduced NCOA1's into breast tissue of a woman treated with Tamoxifen, what would happen? | Breast growth would be promoted! |
| If two drugs are metabolized by the same enzyme and had the same binding affinity, which drug wins? | The drug with the higher serum concentration |
| Dominating drugs are often called __________ drugs while the losing drug is called _________ drugs. | Perpetrator vs Victim |
| What happens in competitive inhibition? | One drug binds and inhibits the binding of the other |
| In competitive inhibition, which drug would be higher in the serum? | the drug that loses/can't bind to the receptor/the victim drug |
| What happens in non-competitive inhibition? | A substrate binds to a remote regulatory (allosteric) site that causes a conformational change that alters the main active site |
| What happens in mechanism based inhibition? | the enzyme treats a drug as a substrate and metabolism can create a reactive intermediate that can form a covalent bond with the active site |
| How does the body "recover" from mechanism based inhibition? | synthesis of new enzymes |
| What is PXR (pregnane X)? | it is a xenobiotic sensor (pxr) |
| How does PXR (pregnane X) work? | A ligand activates PXR, it forms a complex with RXR and recruits co-factors and upregulates the production of metabolizing enzymes |
| What is CAR (constitutive androsane receptor)? | It is a xenobiotic sensor (car) |
| Which xenobiotic sensor is most important in environmental toxicology? | AhR, or the aryl hydrocarbon receptor |
| Endogenous means | created in the body |
| If you see EC50, it means what? | Kd, drug concentration at half effect |
| A High EC50 means that you need what drug concentration to have an effect? | High concentration |
| A Low EC50 means that you need what drug concentration to have an effect? | Low concentration |
| Linear scale is distorted, so the best presentation of Kd/Drug concentration curves is | Log scale |
| What shape is a linear scale drug concentration curve? | Hyperbolic |
| What shape is a log scale drug concentration curve? | Sigmoid |
| The dose response curve does what when the drug is an agonist? | Moves left on graph (dose response increase) |
| The dose response curve does what when the drug is an antagonist? | Moves right on graph (dose response decrease) |
| What happens to the drug concentration curve when the receptor is exposed to a competitive antagonist? | It moves right on the graph, but can be reversed by increasing substrate levels (ie, increasing estrogen w/ Tamoxifen) |
| What happens to the drug concentration curve when the receptor is exposed to a non-competitive antagonist? | The maximum effect is reduced and cannot be overcome by increasing the substrate levels |
| A smaller drug is worse for specific binding because... | it has fewer opportunities (moieties) to make unique bonds with the receptor |
| What acts quicker? a G-Protein coupled receptor, or a Steroid hormone receptor? | G-Protein Coupled receptors |
| Some drugs need second messengers to | amplify the signal and allow for crosstalk between signaling pathways |
| Why cascade? | Because no new proteins need to be made |
| What major receptor is inside the cell? | Steroid Hormone Receptors |
| Steroids are slow acting... but | long lasting |
| Why are steroids "long lasting?" | because they promote the growth of new proteins |
| In order for a drug to reach a steroid hormone receptor, it must | be hydrophilic and capable of passing the lipid bilayer |
| What is your body trying to maintain when it degrades drugs? | Homeostasis |
| In drug tolerance, repeated stimulation leads to | decreased maximal effect over time |
| You can be de-stimulated by discontinuing a tolerated drug | yeah, duh, rehab exists for this reason |
| Drug metabolism is defined as | the enzymatic alteration of a drug structure |
| Drug metabolism most often takes place where in the body? | the liver |
| CYP3A4 is the enzyme that | metabolizes 50% of drugs on the market! |
| What are the consequences of drug metabolism? | accelerated renal excretion, increased or decreased therapeutic action and/or toxicity, activation of prodrugs |
| What is pharmacogenomics | how a patient responds to a medication based on their genotype |
| T or F? Poor metabolizers (PMs) for a drug will likely display decreased serum concentrations for that drug. | False |
| T or F? Ultra rapid metabolizers (UMs) for a drug will likely display decreased serum concentrations for that drug. | True |
| T or F? Poor metabolizers (PMs) for a drug will likely display decreased serum concentrations for a prodrug. | True |
| T or F? Ultrarapid metabolizers (UMs) for a drug will likely display decreased serum concentrations for a prodrug. | False |
| What is the primary concern with reduced function of SLCO1B1? | Toxicity affecting adherence |
| Somatic DNA changes are not passed on to a person's offspring and are involved in _________. | cancer |
| Pharmacogenomics can affect what pharmacological processes? | transport, metabolism, drug effect on the patient |
| What is the major site of drug metabolism? | Liver |
| What is the goal of drug metabolism by your body? | To make the drug more water-soluble |
| If you induce/increase an enzyme that metabolizes your drug, what happens to plasma concentration of the original drug? | It would go down |
| What kind of messenger are g-protein coupled receptors? | 2nd messengers |
| What is homeostasis? | The ability to maintain a stable status despite external changes? |
| Continuous activation of a receptor may result in _______ receptor sensitivity due to the development of tolerance | decreased |
| Why does desensitization occur? | Because the body wants to return to the state it was in before the drug |
| What does Tachyphylaxis mean? | very quick |
| In desensitization, what happens when the receptor is stimulated constantly long term? | receptor down regulation therefore decreased receptor gene expression |
| T or F? A signaling cascade that occurs downstream of an active receptor is designed to slow down the signal transmission | False |
| T or F? All drug receptors work through a down stream effector. | False |
| T or F? Drug selectivity depends on drug concentration | True |
| T or F? In general, the smaller the drug, the better its specificity. | False |
| Drug A inhibits CYP3A4 which metabolizes Drub B. How would Drug A affect the plasma concentration of Drug B | It would increase drug B concentration |
| What is the affect of tamoxifen on the uterus? | Growth promotion |
| Drug C induces CYP3A4 which metabolizes Drug D. How would the drug C affect the plasma drug concentration of Drug D? | decrease the concentration of drug D |
| Which nuclear receptor is known to be involved in the induction of drug metabolizing enzymes? | PXR |
| What happens when a drug binds to PXR? | PXR binds with RXR and metabolic enzyme production increases |
| This receptor is the molecular sensor | PXR |
| When PXR is inactive, what happens? | Metabolic enzymes decrease production |
| How does PXR know when to stop and start producing enzymes? | Its a negative feedback loop. no drug no enzyme. lots of drug lots of enzyme |
| This receptor acts as a molecular sensor for environmental toxicants | AhR receptor |
| ABC transporters are always | efflux |
| SLC transporters are | efflux and influx |
| Which transporter uses ATP? Why? | ABC because it requires more energy because always pumping out has potential to go against the concentration gradient |
| How can the microbiome be involved in drug metabolism? | It can affect the ionization of drugs due to pH |
| T or F? Smoking can increase the drug serum concentration of a CYP1A2 drug. | False, smoking decreases drug serum concentration of CYP1A2 drugs |
| T or F? Vaping can increase the drug serum concentration of a CYP1A2 drug. | True. Effect likely because of the flavoring agents |
| If smoking decreases drug serum concentration of CYP1A2 drugs, does this demonstrate increased or decreased metabolism? | Increased |
| If smoking increases drug serum concentration of CYP1A2 drugs, does this demonstrate increased or decreased metabolism? | Decreased |
| In elderly patients, what is the main concern with drug dosing? | That the amount of drug will be too high for failing organs and a lowered overall metabolism |
| Which gender is 75% more likely to have adverse drug reactions? | Women |
| Which gender (in general) metabolizes drugs more quickly? | Men |
| What is a polymorphism? | a genetic variation in greater than 1% of the population |
| What is a mutation? | a genetic variation in less than 1% of the population |
| What is a missense mutation? | a change in an amino acid |
| What is a nonsense mutation? | Codes for a premature stop |
| What is a synonymous mutation? | A change in a nucleotide sequence that does not change the amino acid sequence |
| What is a frameshift mutation? | Any nucleotide insertion or deletion not divisible by three |
| How do you calculate an activity score? | You add allele 1 and allele 2 |
| What is phenoconversion? | When a drug converts a genotypically normal metabolizer into a poor metabolizer |
| The SSRI Paroxetine is an ________ for CYP2D6 | inhibitor |
| What transporter is important for statins? | SLCO1B1 |
| What is the drug that causes stevens johnson syndrome if given to specific patients with specific HLA variants? | Carbamazepine |
Created by:
gpopop
Popular Life Science sets