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0. Foundations of Medicine > Drug Therapy : Distribution > Flashcards

Drug Therapy : Distribution Flashcards

1
Q

<p>What needs to happen to a drug once it has been absorbed?</p>

A

<p>Needs to be distributed to the tissue</p>

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2
Q

<p>What is drug distribution?</p>

A

<p>Refers to the reversible transfer of a drug between the blood and the extra-vascular fluids and tissues of the body</p>

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3
Q

<p>What is tissue distribution impacted by?</p>

A

<p>Plasma protein binding</p>

<p>Tissue perfusion</p>

<p>Membrane characteristics (blood brain barrier, blood-testis/ovary barrier)</p>

<p>Transport mechanisms</p>

<p>Diseases and other drugs</p>

<p>Eliminations</p>

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4
Q

<p>What do many drugs bind to?</p>

A

<p>Proteins such as albumin or alpha1-glycoprotein</p>

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5
Q

<p>When is the drug biologically active?</p>

A

<p>When it is unbound</p>

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6
Q

<p>What can drugs binding to proteins be described as?</p>

A

<p>Reversible</p>

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7
Q

<p>What is the amount of drug bound changed by?</p>

A

<p>Renal failure</p>

<p>Hypaalbuminaemia</p>

<p>Pregnancy</p>

<p>Other drugs</p>

<p>Saturability of binding</p>

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8
Q

<p>What does a small change in the amount of unbound drug lead to?</p>

A

<p>A massive change in the drug action, for example:</p>

<p>A drug that is 96% bound changes to 92%, so the amount of active drug has doubled</p>

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9
Q

<p>What is the therapeutic range?</p>

A

<p>Concentration of drug to achieve the desired therapeutic effect</p>

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10
Q

<p>What is the ability to achieve the therapeutic range affected by?</p>

A

<p>Volume of distribution</p>

<p>Clearance</p>

<p>Half life</p>

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11
Q

<p>What is apparent volume of distribution (V<span>d</span>)?</p>

A

<p>Volume of plasma that would be necassary to account for the total amount of drug in a patient's body, if that drug was present throughout the body at the same concentration as found in the plasma (expressed as L/kg)</p>

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12
Q

<p>What is the apparent volume of distribution (Vd) expressed as?</p>

A

<p>L/kg</p>

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13
Q

<p>What is a formula that describes the apparent volume of distribution?</p>

A

<p>Vd= (total amount of drug in the body) / (drug blood plasma concentration)</p>

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14
Q

<p>What does it mean if a drug has a high volume of distribution?</p>

A

<p>It will go to the tissue</p>

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15
Q

<p>What does it mean if a drug has a low volume of distribution?</p>

A

<p>It will stay in the plasma</p>

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16
Q

<p>If the drug spread through every membrane what would the volume of distribution be (Vd)?</p>

A

<p>42L (because there are 42L of fluid in the average body)</p>

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17
Q

<p>What would the volume of distribution be if the blood cannot penetrate cells?</p>

A

<p>12L</p>

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18
Q

<p>What would the volume of distribution be if the drug is highly protein bound?</p>

A

<p>3L</p>

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19
Q

<p>What is clearance (Cl)?</p>

A

<p>Theoretical volume from which a drug is completely removed over a period of time (measure in units of time ml/min)</p>

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20
Q

<p>What is clearance expressed as?</p>

A

<p>ml/min</p>

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21
Q

<p>What are the two kinds of clearance?</p>

A

<p>Hepatic clearance</p>

<p>Renal clearance</p>

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22
Q

<p>What is clearance a measure of?</p>

A

<p>Elimination</p>

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23
Q

<p>What does clearance depend on?</p>

A

<p>Concentration and urin flow rate for renal clearance</p>

<p>Metabolism and bilary excretion for hepatic clearance</p>

24
Q

<p>What is half life (t1/2)?</p>

A

<p>Time taken for the drug concentration in the blood to decline to half of the current value</p>

25
Q

<p>What does half life depend on?</p>

A

<p>Volume of distribution</p>

<p>Rate of clearance</p>

26
Q

<p>How many half lifes does it generally take to clear a drug?</p>

A

<p>5</p>

27
Q

<p>What does prolongation of half life increase?</p>

A

<p>Drug toxicity</p>

28
Q

<p>What could prolongation of half life be due to?</p>

A

<p>Reduction in clearance</p>

<p>Large volume of distribution</p>

29
Q

<p>What does knowledge of a drugs half life allow?</p>

A

<p>Us to work out how often a drug needs to be administered</p>

30
Q

<p>How are most drugs given to achieve their therapeutic effect?</p>

A

<p>Chronically</p>

31
Q

<p>When is the steady state of a drug normally obtained?</p>

A

<p>After 4 half lifes</p>

32
Q

<p>What is time to the steady state independant of?</p>

A

<p>Dosage</p>

33
Q

<p>What is proportional to a drugs dosage?</p>

A

<p>Steady state concentration</p>

34
Q

<p>What are fluctuations in concentration proportionate to?</p>

A

<p>Dosage and half life</p>

35
Q

<p>What is drug elimination?</p>

A

<p>Removal of active drug from the body</p>

36
Q

<p>What does drug elimination determine?</p>

A

<p>The length of action of the drug</p>

37
Q

<p>What are the 2 parts of drug elimination?</p>

A

<p>Drug metabolism</p>

<p>Drug excretion</p>

38
Q

<p>Where does drug metabolism usually occur?</p>

A

<p>In the liver</p>

39
Q

<p>Where does drug excretion normally occur?</p>

A

<p>Usually in the kidney, but also in bilary systems, lungs and milk</p>

40
Q

<p>What are the 3 mechanisms that the kidneys use for excretion?</p>

A

<p>Glomerular filtration</p>

<p>Passive tubular reabsorption</p>

<p>Active tubular secretion</p>

41
Q

<p>Why is renal damage important for causing drug toxicity?</p>

A

<p>The kidneys are important for excretion</p>

42
Q

<p>How much fluid does glomerular filtration filter per day?</p>

A

<p>190L</p>

43
Q

<p>What drug are filtered by glomerular filtration?</p>

A

<p>All unbound drugs as long as their size, charge or shape are not excessively large</p>

44
Q

<p>What do factors that affect glomerular filtration reduce?</p>

A

<p>Clearance of the drug</p>

45
Q

<p>What happens during tubular reabsorption?</p>

A

<p>1) As filtrate moves down the renal tubule any drug present is concentrated</p>

<p>2) Passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation</p>

46
Q

<p>Where does passive tubular reabsorption occur?</p>

A

<p>Distal tubule and collecting duct</p>

47
Q

<p>What kinds of drugs are reabsorbed in passive tubular reabsorption?</p>

A

<p>Only unionised drugs such as weak acids</p>

48
Q

<p>What can passive tubular reabsorption be affected by?</p>

A

<p>Renal failure</p>

49
Q

<p>What happens to acidic/basic compounds?</p>

A

<p>They are actively secreted into the proximal tubule by active tubular secretion</p>

50
Q

<p>What is active tubular secretion the most important system for?</p>

A

<p>Eliminating protein bound cationic and anionic drugs</p>

51
Q

<p>How much bile does the liver secrete per day?</p>

A

<p>1L</p>

52
Q

<p>What are the two ways that drugs can be secreted into the bile?</p>

A

<p>Actively or passively</p>

53
Q

<p>What happens to many drugs from the bile?</p>

A

<p>They are reabsorbed into circulation which continues until the drug is metabolised in the liver or excreted by the kidneys</p>

54
Q

<p>What is drugs being reabsorbed from the bile into circulation known as?</p>

A

<p>Entero-hepatic circulation</p>

55
Q

<p>What does metabolism in the liver lead to?</p>

A

<p>Conjugation of the drug, the conjugated drug not being reabsorbed from the intestine</p>

56
Q

<p>What doesn't happen to the conjugated drug proced during metabolism in the liver?</p>

A

<p>It is not reabsorbed from the intestine</p>

57
Q

<p>What does damage to the liver reduce?</p>

A

<p>The rates of conjugation and bilary secretion and so allows the build up or reabsorption of the drug resulting in toxicity</p>

0. Foundations of Medicine (167 decks)

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