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77 Cards in this Set
- Front
- Back
Places that drugs are metabolised (excluding the liver). |
° Lungs ° Plasma ° Intestinal Flora |
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What is meant by the term 'truly absorbed'? |
° When a drug has entered lymphatic or vascular system. |
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What is Pharmacokinetics? |
° The study of absorption, distribution, metabolism and excretion (ADME) of a drug/xenobiotic. ° Evolutionary advantage to void potentially dangerous substances from the body.
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What is meant by the term 'voiding'? |
° A term used to describe how a drug leaves the body, and it used as the GI tract is said to be on the outside of the body. ° Excretion occurs via urine, faeces, bile or breath (low concentrations sometimes in sweat e.g fish odour syndrome). |
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Enteral Routes: |
° Sublingual/Buccal ° Oral ° Rectal |
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Parenteral Routes: |
° Intravenous (IV) ° Intramuscular (IM) ° Subcutaneous (SC) ° Epidural ° Spinal Tap |
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What is meant by the term 'absorption'? |
° The extent to which an intact drug is absorbed from the intestinal lumen into the portal circulation. ° Expressed as f(G), meaning the fraction of drug absorbed from the gut. |
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What are the factors affecting absorption? |
° Formulation of the drug. ° Surface area for absorption at drug target. ° Physicochemical properties (pKa, pH, P values etc). ° Blood circulation of absorption site. ° Amount of enzymes/efflux proteins present. ° Gastric emptying rate.
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What is meant by 'first pass metabolism'? |
° Amount of drug that is lost due to liver metabolism via hepatic portal vein. ° Expressed as f(H), fraction of the drug lost to first pass metabolism. |
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How do drugs enter hepatic circulation? |
Via the Hepatic Portal Vein |
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Name two formulations of the same drug that give different therapeutic responses. |
° Modified/Sustained release tablets. ° Gastro-resistant/Enteric coated tablets. |
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What is meant by the term 'bioavailablity'? |
° F = f(G) + f (H) ° The sum of the fraction absorbed and the fraction lost due to first pass effect. ° Measured against the bioavailablity of IV administrations as this is always 100%. •Plot 2 graphs and calculate the area under the curve for each one •F (other route)= AUC(other)/AUC(IV) × 100.
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When is first pass metabolism beneficial? |
° When administering drugs that require metabolising to become active, known as pro-drugs. ° Activated due to the actions of certain enzymes known as cytochromes P450. ° Codeine -------> Morphine CYP2D6 |
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What are some implications of first pass metabolism? |
° Reduces drug bioavailability. ° Higher dose required to give therapeutic effect (therapeutic window). ° May cause problems with poor metabolisers (PM) as the drug may accumulate and become toxic. |
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Why are most drugs weak acids or weak bases? |
° Weak acids/bases tend to exist in an unionised state so can be absorbed easier than they can in their ionised form. ° Have a log P value between 3-6. |
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What is a p-glycoprotein? |
° ATP-dependent efflux pump used as an evolutionary defence mechanism to expel xenobiotics. ° If a drug target contains are large concentration of p-glycoproteins then a higher dose is required to ensure complete absorption. |
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What is 'depot therapy'? |
° Injection (usually intramuscular) of a drug together with a substance that slows the release and prolongs the action of the drug. ° Good for drugs such as contraceptives e.g Depo Provera and drugs with low patient compliance to regular doses e.g antipshycotic Haloperidol. |
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What are the factors affecting bioavailablity? |
° Drug formulation e.g sustained release. ° Physicochemical properties (pKa, pH, P values etc). ° Route of administration. ° First pass metabolism. |
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What is Fick's Law? |
° Absorption of the drug is proportional to the concentration gradient (C1 - C2) across cell membranes. ° Faster with lipid soluble drugs. |
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What is facilitated diffusion for absorption? |
° Occurs via carrier proteins across cell membranes (passive). ° Requires a concentration gradient. ° Saturable due to the finite number of carrier proteins present. |
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What is meant by 'filtration' as a method of drug absorption? |
° The movement of a drug across a membrane due to a hydrostatic pressure gradient created by the cardiovascular system. ° Drugs may move through spaces between cells (paracellular). |
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What is meant by 'Volume of Distribution' (Vd)? |
° Vd is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. ° Indicative of the extent of distribution of a drug. ° Low Vd value indicates a high amount of plasma protein binding. |
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What would it meant if a Vd value was greater than total body water? |
° The drug is widely distributed through tissues. |
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What would a high distribution rate mean? |
° The drug is highly lipid soluble so able to enter cells rapidly. ° Includes entry across the blood brain barrier. |
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Why does Iodine have a high Vd? |
° It is highly concentrated to one area (the thyroid gland). |
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Following intravenous administration, drugs are distributed fastest to? |
° The liver, kidney and brain. |
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What characteristic is the most important determinant of the pharmacological activity of a drug which is administered orally? |
°Susceptibility to metabolic enzymes |
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What is the half-life of adrug with a volume of distribution of 100L/70kg and a clearance of 7L/hr/70kg? |
° Method: |
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What is the description of Phase II metabolism? |
°Reactions which add a polar molecule to a functional group already present on a drug or one of its metabolites. |
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What dose of i.v. amoxycillin would give a plasma concentration of 7mg/L assuming S=1 Vd = 0.25L and a 70kg patient? |
°Method: |
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What does drug transport by lipid diffusion NOT depend on? |
°Density of transporters |
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Transdermal drug administration: |
b) is not subject to first-pass hepatic metabolism |
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Which of the following characteristics is most likely to be associated with a very high apparent volume of distribution? |
c) Extensive binding to tissue constituents |
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What would receive a hydrophilic drug slowly? |
Fat |
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What would receive a lipophilic drug quickly? |
Fat |
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What type of substance are xenobiotics? |
Exogenous |
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Bioavailability (F) is the fraction or percentage of administered drug that reaches the systemic circulation via a given route as compared to what route? |
I.V (intravenous) |
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After a single dose of a drug which has a half-life of 8 hours, what percentage of the dose is still in the body of a 70kg patient after 1 day? |
°Method: |
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Using the Fick Law of Diffusion, how will flux change if the permeability coefficient is quadrupled? |
°It will quadruple |
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Using the Fick Law of Diffusion, how will flux change if the membrane thickness is quadrupled? |
°It will quarter |
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A drug is administered by infusion at 2 mg/min toachieve a steady state concentration of 8mg/L. Assuming S=1, and a 70kg patient, what is the clearance rate? |
° Method: |
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The binding of drugs to plasma albumin: |
e) is saturable |
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Apatient is administered 400mg of a drug to achieve a plasma concentration of20mg/L. If the clearance is 2.5L/min, calculate the half-life. |
° Method: |
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Fill in the blanks: Drug bio transformation phase I makes drugs ____ polar for metabolism and phase II makes drugs ____ polar for excretion. |
More, More |
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Apatient receives an infusion dose of penicillin 150 mg, what oral dose F(tab)=0.7 would give the same bioavailability? |
° Method: |
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Of the top 15 global pharmaceutical companies in 2015, how many relied upon pharmaceutical sales for more than 50% of their income? |
13 |
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Of the top 15 global pharmaceutical companies in 2015, how many DIDN'T rely upon pharmaceutical sales for more than 50% of their income? |
2 |
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According to Rang & Dale’s Pharmacology, thesuccess rate of a typical drug (synthetic empirical compound) progressing from identification of a drug candidate to Phase IV clinical trials is what? |
1 in 20 |
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The reason why 30% of biopharmaceuticals fail in phase III of clinical trials compared to only 20% of traditional empirical style pharmacology drugs is most likely to be a consequence of what? |
° The physiological roles of the targets for biopharmaceuticals tends to be less well characterised and understood. |
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The number of new molecular entity (drug) approvals bythe FDA for new drugs has begun to stagnate in recent years: explanations for this could include which of the following: |
e) All of the above are correct |
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What is the Kd of this Hill Plot? |
° Method: |
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What is the Hill Coefficient (nH) of this Hill Plot? |
° Method: |
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What does the value of nH suggest about these results? |
There is 1 ligand : 1 receptor stoichiometry |
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What is the approximate IC50 value ofthe displacing ligand in this displacement binding curve? |
° Method: |
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What is the Kd at the binding site (Kc)? |
° Method: |
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What is the Kd of the high affinity site of this Scatchard Plot? |
° Method: |
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What does the steep slope denote on this Scatchard Plot? |
° High affinity of binding |
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What does the shallow slope denote on this Scatchard Plot? |
° Low affinity of binding |
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What is the pA2 value of the antagonist at the receptor agonistA acts on? |
° Method: |
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What is the pA2 value of the antagonist at thereceptor agonist B acts on? |
° Method: |
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What is the pA2 value of the antagonist at the receptor agonist C acts on? |
° Method: |
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What can you conclude about the interactionbetween Agonists A, B and C and their receptors? |
°Agonists B and C are likely to be acting on the same receptor as they are antagonised with similar affinity bya single antagonist. |
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What characteristic does this Schild Plot represent? |
° Competitive Binding |
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What characteristic does this Schild Plot represent? |
° Heterogenous Receptors |
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What characteristic does this Schild Plot represent? |
° Non-Competitive Binding |
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What characteristic does this Schild Plot represent? |
° Cooperative Binding |
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What characteristic does this Schild Plot represent? |
° Non-Equilibrium |
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Regarding Fick's Law, which one of these options is True? |
d) Flux is not energy dependent |
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What are the correct definitions of clearance from these options? |
a) the volume of blood/plasma irreversibly cleared of drug per unit time |
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Which of these options are correct for describing half life? |
c) decreases as clearance increases |
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If a drug is administered repeatedly at the same dose and dosage intervals, the time required to reach steady-state plasma drug concentration is proportional to what? |
e) elimination half life |
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The main determinant(s) of the hepatic clearance of a high hepatic extraction ratio drug are: |
b) hepatic blood flow |
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The main determinant(s) of the hepatic clearance of a low hepatic extraction ratio are: |
a) intrinsic clearance |
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A drug has a hepatic clearance of 50L/hour and liver blood flow is 90L/hour. What is the maximum oral bioavailability? |
Method: |
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Phase II metabolism usually: |
c) results in inactive metabolites |
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An increase in drug-plasma protein binding will lead to which of the following? |
b) decrease in free drug |
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In first-order elimination: |
a) drug half-life is directly proportional to drug concentration |