Pharmacokinetics + Dynamics

1. What does phar- knowledge pertaining to drugs macology mean? 2. What is studthe action of drugs + their metabolite in the body ied in pharmacology? 3. What is pharma- what the body does to the drug cokinetics? 4. What is pharma- what the drug does to the body codynamics? 5. What is adminis- delivery of drug to the body tration? 6. What is absorp- movement of a drug across membranes tion? 7. What is distribu- description of the compartment of the body the drug tion? enters 8. What is metabo- chemical alteration of the drug lism? 9. What is elimina- transfer of the drug from inside the body to the outside tion? 10. What does pharmacokinetics help to describe? - absorption from the site of administration - delivery to the site of action - elimination - time to onset / duration of effect - accumulation on repeat dosage - drug interactions 11. Where is a drug from the intestines to the liver likely to be absorbed if given orally / via the rectal route? 1 / 14 12. What is the main avoid passing through the GI tract advantage of administration by injection? 13. Describe first pass metabolism: If a drug is given enterally, then it is likely to be absorbed from the intestine + pass to the liver + then be metabolised to a less effective form 14. What does given given orally / rectally enterally mean? 15. What is a the concentration of drug in plasma good indication of drug present in the body? 16. Unless givmust cross membranes to reach the systemic circulation en intravenously, what must drugs do? 17. What is the transition of drugs through the membrane barriers determined by? - lipid solubility - area available for absorption - possible specific carriers - amount that reaches the target may be compromised by first-pass metabolism 18. How are oral - faeces and rectal drugs - urine sweat eliminated from - milk the body? 19. How are parenteral + topical drugs eliminated: sweat + milk 2 / 14 20. Why do some drugs enter under the tongue (sublingual administration)? under the tongue is a well vascularised area, so the drug can enter into the blood vessels 21. Describe the rec- the drug enters the intestinal tract tal route: 22. Describe what drug goes into areas near to blood vessels, so the drug membranes the has to pass through smooth muscle + endothelial lining in order to enter the plasma intramuscular and subcutaneous route pass through to get to the plasma: 23. Describe what the subcutaneous route is useful for: useful for insulin + heparin administration 24. Describe what in emergencies the intramuscular route is useful for: 25. Describe the in- - injection into the spinal cord trathecal route: - directly into the CNS - very high risk 26. Why does oral Drug has to pass through the GI tract, then through the have an initial hepatic portal vein to the liver where first pass metabolism high plasma con- occurs centration compared to IV? 27. What is bioavail- defines how well a drug is absorbed + reaches its site of ability? action 3 / 14 28. How is bioavail- comparison of drug absorption orally and via IV ability measured? 29. What is the equa- F = amount of drug absorbed in systemic circulation foltion for bioavail- lowing oral administration/amount of drug absorbed when ability? the same dose is administered intravenously 30. What 2 measure- half-life ments give us an clearance idea of how the body is dealing with the drug? 31. What is half-life (T0.5)? time taken for the plasma drug conc to fall to half its original value 32. Why is half-life important? it gives info on the length of time that a drug will remain in the body 33. What is the equa- clearance = rate of elimination/plasma drug concentration tion for clearance> 34. What is zero-or- - rate of elimination is constant + independent of drug der kinetics? concentration - few drugs behave in this way 35. Describe plasma - half life is directly proportional to the amount of drug half-life in zero taken order kinetics: - T0.5 is longer when a higher dose is given 36. Describe the - the plot of plasma conc (cp) against time is a straight line graph in zero or- - half life is directly related to the amount of drug given der kinetics: 4 / 14 37. What is pseudo - at high concentration, the kinetics are 0 order (straight zero order kinet- line) ics? - at low concentration, it's first order (exponential curve) 38. What is pseudo its concentration-dependent + depends on the pathway zero order kinet- for drug metabolism ic dependent on? 39. Give an example ethanol of a drug that has pseudo zero order kinetics: 40. What is pseudo zero order kinetics dependent on? concentration 41. What is first order kinetics? - most drugs are eliminated with first-order kinetics - constant fraction is removed in unit time 5 / 14 42. What is rate of depends on how much drug are present elimination dependent on in first order kinetics? 43. What is T0.5 in constant first order kinetics? 44. How do we mea- we measure the amount of drug in the blood (difficult to sure the amount measure the amount at site of action) of drug at the site of action? 45. What is the ther- the right amount of drug to be effective apeutic window? 46. What are the only types of drugs able to diffuse across membranes? drugs that are free / unbound 47. What does drugs reversibly distributing into various tissues of the body depend upon? - perfusion rate of the tissue (blood flow) = the greater the blood flow, the more drug that will pass through the tissues - the physiochemical ability of the drug to cross membranes - nature of the membranes - the extent to which the drug is bound 48. Why do the liv- - the tissues in the liver + kidneys are well vascularised ( er + kidneys re- have plenty of blood ceive more of a drug compared to other parts of the body? 49. 6 / 14 What is the im- - achieve a steady state (for regular dosing) pact of distribu- - peak plasma conc followed by removal from the body tion? (2) (single doses) 50. What is distrib- amount of drug entering the blood compartment is balution equilibrium anced by the amount of drug leaving the compartment (steady state)? 51. Define partition uptake of a drug co-efficient (Kp): 52. What is the equa- Kp = drug conc in tissues / drug conc in blood tion for partition co-efficient? 53. What does a big- it takes longer to reach distribution equilibrium ger value of Kp mean? 54. What molecules ionised / polar molecules don't cross membranes as readily? 55. What allows larg- muscle er polar molecules to pass through? 56. What does it - lipid soluble mean if a drug is - it it becomes more unionised, it's less lipid soluble + unionised? more water soluble What if it becomes more unionised? 57. In order to elim- the ability to dissolve in water inate drugs via urine, what prop7 / 14 erty will the drug need? 58. Describe basic drugs in a high pH: lipid soluble so readily transported 59. Describe acidic drugs in a low pH: lipid soluble + readily transported 60. Describe basic drugs in a low pH: far less lipid soluble + so not readily transported 61. Describe acidic drugs in a high pH: far less lipid soluble + so not readily transported 62. What is drug-protein binding? - drug binds to the protein (mainly albumin) + can no longer cross the membrane (it's too big) - can be reversible/irreversible 63. Describe what cannot cross membrane so any drug bound to them will happens to drug not be distributed bound to high molecular weight proteins: 64. What does R1 - delivery of drug to the tissue stand for? What - depends on perfusion rate does R1 depend on? 65. What does R2 - passage of drug across the membrane stand for? What - depend on physiochemical properties + nature of the does R2 depend membrane on? 66. R1 and R2 8 / 14 What is overall rate of distribution determined on? 67. What does a Vd tell us? how the drug has been distributed in terms of large components 68. What is the equa- Vd = amount of drug in body / conc of drug in blood tion for Vd? 69. How do we mea- urine + blood is used to measure drug levels in the body sure Vd? 70. Where are lipid plasma + interstitial fluids insoluble drugs confined to? 71. Where do can reach all compartments + may accumulate in fat lipid-soluble drugs distribute to? 72. Where might Vd when there are more soluble drugs that accumulate outexceed body vol- side the plasma compartment by being fat/ bound to ume? tissues 73. How does a drug - becomes less lipid soluble + more water soluble enter the renal - achieved by a process of metabolism in the liver system? 74. What can drug metabolism be defined as? an enzyme mediated conversion of a lipophilic compound into a more water soluble one 75. Describe phase I tends to make drugs more water soluble but its main of drug metabo- purpose is to prepare the drug molecule for phase II lism: 76. 9 / 14 What are the phase I reactions? includes oxidation, reduction + hydrolysis uncovers functional groups 77. Describe phase II conjugations whereby the drug is coupled to a second, of drug metabo- fairly large water-soluble molecule lism: 78. What reactions - glucuronidation are in Phase II re- - methylation actions? - sulphation - acetylation - glutathione 79. What is a prodrug? A compound that is metabolised in the body to yield a pharmacologically active compound but is devoid of such toxicity 80. Where is cytochrome P450 located? ER of the liver 81. What is induction of metabolism? increase the amount of enzyme present = drug is metabolised more quickly + its half-life will be less 82. What is inhibition of metabolism? less active enzyme is available so the drug is metabolised more slowly, and the half-life of the drug will increase 83. What happens the drug is broken down quicker to a drug if there's more enzyme present? 84. What does the it can increase the rate of metabolism for another drug induction of cy- causing lower plasma conc + a reduced pharmacological tochrome P450 effect isoenzymes by 1 10 / 14 drug mean for another drug? 85. What does the decreasing the metabolism of another drug = there's a inhibition of cy- higher plasma concentration + increased pharmacologitochrome P450 cal effect which can leads to toxicity isoenzymes by 1 drug mean for another drug? 86. What are the affinity 3 main words efficacy that describe the specificity properties of a drug? 87. What does affini- how well a drug binds to a receptor ty mean? 88. What initially at- - electrostatic forces tracts a drug to a - it will be held to a receptor's binding site temporarily by receptor? weak bonds 89. What determines - the number of bonds the affinity of the - how well the drug fits the binding site drug for the receptor? (the greater the number of bonds + the more perfect the fit, stronger the affinity) 90. What is efficacy? the strength of an agonist at eliciting a response 91. What is a potent - only a small amount an effect agonist? - possesses strong affinity + efficacy 92. What is a weak agonist? - requires large amounts to elicit an effect - possesses some affinity + efficacy 93. What is an antag- - blocks the receptor onist? - possesses affinity but no efficacy 11 / 14 94. What is specifici- - how selective a ligand is ty? - specificity is somewhat dependent on the doses used 95. What does high specificity mean? will only bind to certain receptors 96. What is salbuta- a beta 2 adrenoreceptor agonist used for treating asthma mol? (bronchodilation) 97. How do you find total amount binding - non-specific binding the specific binding? 98. What are bioas- used to quantitatively explain the characteristics of drugs says + binding assays used for? 99. Describe the steps of a binding assay: 1) sample of tissues are incubated with increasing conc of radiolabelled ligand, allowing equilibrium to be reached 2) the bound radioligand is separated from the unbound (using centrifugation + filtration) - measured for radioactive content 3) inhibiting specific binding of the radioligand allow non specific binding to be estimated total binding - non-specific binding = specific binding 100. How can we mea- - this can be measured by repeating the test in the pressure non-specif- ence of saturated conc of a non-radioactive ligand ic binding? - inhibiting specific binding of radioligand, allows non-specific binding to be estimated 101. Why are dose-re- plotting drug response gives a sigmoid curve where 70% sponse curves is a straight line used? 102. What is Emax? estimated max response of a drug 12 / 14 103. What is EC50? the effect conc needed to produce 50% of a response 104. How do you cal- divide Emax by half + use the dose-response curve to find culate the efit fective conc required to produce 50% of the response (EC50)? 105. Why are EC50 values useful? they allow us to compare potencies of different drugs 106. What happens - dose-response curve shifts to the right to a dose-re- EC50 values increase sponse curve as a drug becomes less potent? 107. What are spare receptors? around 99% of receptors are thought to be spare as they are not needed to elicit a response 108. What is agonist economy? less agonist has to be released to produce a response due to spare receptors 109. What do antago- reduce the action of agonists by binding to receptors, but nists do? not producing an effect 110. Define drug: chemical substance that produce a biological effect when administered 111. What is competitive antagonism? - bind selectively to receptors - block receptors - interfere with agonist-receptor interactions - affinity but no efficacy - similarity in chemical structure causes the binding 112. what is the con- conc of antagonist molecules increased = higher concencentration of ag- trations of agonist required to evoke a response 13 / 14 onist required if there are increasing concentrations of the antagonist? 113. When drug metabolism leads to a more active form than what was originally administered, what is this? Prodrug 114. Why can only un- bound drugs are TOO large bound drugs distribute into tissues? 14 / 14