Pharmacokinetic Dynamic Including Metabolism

1. Is a weak base A weak base is polar and is not easily absorbed. polar and is it BH+ -> B + H+ easily absorbed across the phospholipid bilayer into the bloodstream? 2. Define what a drug is? A chemical substance of a known structure which when administered to a living organism produces a biological effect. 3. What does AADME stand for in pharmacokinetics? Administration (delivery of drug to body) Absorption (movement of drugs across membranes) Distribution Metabolism (chemical alteration of the drug) Elimination 4. What is the buc- Between the lips and the teeth cal administration route for a drug? 5. What is the Under the tonge sublingual route of administration for a drug? 6. What is the bene- Passes drug directly to bloodstream without having to fit of intravenous pass a membrane first. injections? 7. For a drug to be The gastrointestinal lining absorbed ORALLY what type of membrane does it have to pass 8. What properties SMALL does a drug HYRDOPHOBIC 1/7 have to posses the drug goes from an area of high concentration to an to be absorbed area of low concentration. through passive diffusion? 9. What properties does a drug have to possess to be absorbed through Facilitated diffusion LARE HYDROPHIOBIC Requires a protein carrier to move from high conc to low conc 10. What properties LARGE does a drug HYDROPHILIC have to posit needs to be pumped by the ATP sess to be absorbed through active transport? 11. What properties VERY LARGE does a drug it engulfs the substance by forming a vesicle to hold the have to possess drug. to be absorbed through ENDOCYTOSIS 12. If we have a drug made from a weak acid where do we want it to be absorbed and why. If we have a drug made from a weaker acid we want it to be absorbed by the proximal duodenum (stomach) as the environment is more acidic here. By increasing the amount of H+ the equilibrium shifts left to increase the amount of HA which is much better absorbed into the bloodstream. HA -> H+ + A- 13. HA is non polar is it easy to absorbed? HA is more easily absorbed across the phospholipid bilayer and into the bloodstream. 14. If we have a If we have a drug made from a weaker base we want drug made from a eqilllibrium to shift to the right side increading B which is weak base where 2/7 do we want it to non polar making it more alkaline therefore decreasing the be absorbed and H+ conectration by it being absorbed in the distal ileum. how is this done? 15. How does blood flow affect the rate of absorption? If patient is in a state of decreased blood flow (i.e. shock) there will be less absorption to the GI tract therefore less drug absorbed into the bloodstream. Generally why when a patients in shock drug is administered through IV. 16. Hoe does total If the patient has dioraea there is less contact time with the surface area and cells of the GI tract. But if they have constipation contact contact time af- time is significantly increased. fect the absorption of a drug? 17. What is the neg- P-glycoprotein (P-gp) is a protein found in cell membranes ative effect of P that pumps drugs out of cells, affecting their absorption. If glycoproteins? a drug is a substrate for P-gp, it may be pumped out of the intestinal cells, reducing its absorption into the bloodstream and therapeutic efficacy. 18. Define bioavailability. The fraction of drug that can enter the bloodstream and becomes available to have an active effect on the body. 19. What equation is F = AUC ORAL/ AUC IV used to calculate AUC= area under the curve bioavailability of a drug? 20. What are the 3 Solubility factors that affect Instability bioavailability? First pass effect 21. How does solubility affect bioavailability. If a drug is small hydrophobic it will easily pass through membranes into the blood therefore increase in F. If a drug is large and hydrophilic absorption is very small therefore a decrease in F. 22. 3/7 How does instability affect bioavailability? 23. How does the FIRST PASS MECHONISM EFFECT F? Some drugs will be broken down by the stomach acid of some enzymes that will break down the drug therefore decreasing F. The portal system is the movement of the drug from the GIT into the blood to the liver. From the liver a little less makes it to the systemic circulation as the liver will metabolise some of it. 24. If a patient has an Intravenous overdoes what's the most desirable route of administration for the antidote? 25. What 5 factors af- Blood flow fect the distribu- Capillary permeability tion of a drug? Protein binding Solubility Volume of distribution Vd 26. How does blood The liver kidneys and brain= More BF therefore a inflow affect the creased theoretical drug distribution rate of distribution? VICE VERCA like the ogans with a low BF would be the skin 27. How does capil- Fenestrated capillaries have holes in the endothelial cells lary permeability which allow for drugs to leak out into the blood flow and affect drug distri- reach tissues faster. bution? 28. How does protein binding affect drug distribution? Protein binding refers to the attachment of drugs to proteins in the bloodstream, primarily to albumin and globulins. When a drug is bound to proteins, it becomes temporarily inactive and unable to exert its pharmacological effects. However, protein-bound drugs also serve as a reservoir, prolonging their presence in the bloodstream. 4/7 If we have a decreased amount of protein-bound plasma there is an increase in the amount of free drug 29. What is the equa- Vd = F X DOSE/ C tion to calculate F= bioavailability VOLUME OF DIS- C= concentration mg/L TRIBUTION? 30. When a drug Toxic leaves the liver Active prodrug it can come out Inactive- excreted from the body into feces or urine in three different forms what are they? 31. What is phase one called in the metabolism of a drug and what happens here? Biotransformation: The drug will attach to the enzyme in the hepatocyte (liver cell) as a lipid soluble non polar drug and will undergo either an oxidation reaction a reduction reaction or hydrolysis leading to the drug being water soluble and polar therefore making it easier to secrete. 32. What does the second phase of biotransformation do. It INCREASES POLARITY AND WATER SOLUBILITY. Transfer enzymes will add groups : Methyl Acetyl Sulfur This will increase drug polarity 33. What does drug Turn toxic drugs into non- toxic drugs and active drugs into metabolism do? inactive drugs. 34. What are the 4 Kidneys= Urine ways we excrete Liver= Bile a drug? The lungs= Exhale Via the GI tract not absorbing and releasing thru the kidneys. 35. Why does filtration affect rate If a patient has kidney problems less filtration means ab increased blood concentration of the drug. 5/7 of excretion of a drug? 36. How do proteins When there is lots of drug binding proteins in the blood affect the rate of like ALBUMIN there will be less drug filtered from the excretion? glomerulus into the Bowens capsule therefore an increase concentration of drug in the blood leading to an increased risk of toxicity and potency. 37. What drugs are small hydrophobic ones buy once sent to the liver phase easy to reabsorb 1 and 2 they become polar and water soluble making it easier to excrete. 38. What are the 2 1) Rate of elimination of the drug/ Plasma conc of drug equations related to drug clear- 2) Volume of distribution X 0.7/ T1/2 ance? 39. what happens if a Clearance will decrease person has either liver of=r kidney damage? 40. Define half life The half-life of a drug is the time it takes for the concentration of the drug in the bloodstream ( to decrease by half. It is a measure of the rate at which a drug is removed from the body. 41. What properties Half-life is typically determined by the drug's pharmacois a drugs half life kinetic properties, including its absorption, distribution, determined by? metabolism, and excretion. 42. Why is knowing a Knowing a drug's half-life is important for determining drugs half life im- dosing intervals and achieving therapeutic concentrations portant when de- within the body. veloping a drug? 43. What does a de- Decrease clearance time crease in half life lead to. 6/7 44. what does an in- increase clearance time more risk of toxicity in the blood. crease in half life lead to 45. In the first order graph of elimination of a drug what are its main factors. Exponential curve = First order which is most drugs [T1/2] is Constant Increase drug concentration is directly proportional to increase rate of elimination. 46. Define steady state of drug elimination Amount your taking is the amount your eliminating. This takes around 4-5 half life to reach a steady state. 47. In terms of the ZERO order graph what are they key main points Linear is 0 order Rate of elimination is constant [DRUGS] not directly proportional to the rate of elimination. If I increase the conc of drug this doesn't increase the rate of elimination therefore they are independent of one another. 7/7