STUDENT INDEX NUMBER eh . UNIVERSITY OF CAPE COAST S COLLEGE OF HEALTH AND ALLIED SCIENCES SCHOOL OF ALLIED HEALTH SCIENCES EPARTMENT OF MEDICAL LABORATORY SCIENCE (BSc. Medi al Laboratory Science). End of Second Semester Examination, 2019/2020 MLS 310: DRUG METABOLISM & TOXICOLOGY EXAMINATION DURATION: TWO HOURS GENERAL INSTRUCTION Answer all questions in section ‘A’ in the spaces provided on the question sheets. Answer TREE (3) questions from section ‘B’ in the answer booklets provided. Answer ALL questions on the question paper. Provide concise and specific answers or explanations in the blank spaces provided. 1. State TWO (2) ligands that interact (bind) with each of the following plasma proteins: (@). ay-albumin... [2 Marks] (b). az-albumin... [2 Marks] (©). By-albumin...... eesoeesa2 Marks] (@). B-albumin, [2 Marks] (©). Albumin. [2 Marks] 2. Mention FIVE (8) xenobiotic exposure sites. ; [5 Marks] 3. Mention THREE (3) outcomes of interaction between an ultimate toxicant and a target molecule. [3 Marks}STUDENT INDEX NUMBEI 4, State FOUR (4) react molecule. [4 Marks} 5. Humans who accidentally get bitten by venomous snakes normally de instantly How. ever ‘when the same venom from these snakes are exposed to humans orally, the venome fail t é 10 cause death or become completely harmless. Explain. [3 Marks} 6. Provide ONE (1) named example of each of the following enzyme-substrate interactions: (@). A single CYP450 enzyme catalysing a two-way metabolism of a single xenobiotic, seeeseee(2 Marks] (b). Two CYP450 enzymes catalysing metabolism of a single xenobiotic, 2 Marks} (©). Three CYP450 enzymes additively catalysing metabolism of a single xenobiotic. [2 Marks} 7. Itis often generalized that hydrophobicity and lipophobicity respectively favours absorption and elimination of xenobiotics. Mention ONE (1) exception to this generalization,STUDENT INDEX NUMBER...... 8, Toxicity from methanol and ethylene glycol is treated by using ethanol. Explain the detoxication mechanism of ethanol. [3 Marks] 9. Bach of the following drugs was withdrawn from the market (i.e., banned from public use). To each of these drugs provide the adverse event that led to their withdrawal. (@). Thalidomide (b). Terfenidine 10. Complete the table below: ‘Xenobioticdrug | Toxie metabolite ‘Cyclophosphamide | Acrolein ‘Acetaminophen Paraquat Alcohol Carbon tetrachloride Trifluoroacetic acid [5 Marks]STUDENT INDEX NUMBER I. The following are ligand-receptors that xenobioties may interact with to produce a wide spectrum of toxic reactions. For each receptor state the full name and mention ONE a xenobiotic that interacts with it: (@). ER. --[2 Marks] (b). PPAR«..... ---[2 Marks} (©). AHR. s-{2 Marks} OC [2 Marks} OP seo Marks] '2. Identify the toxicological phenomenon demonstrated in the table below and how it accounts for toxicity of many xenobiotics, Concentration of DDT in a Lake Michigan Food Chain DDT (ppm) Water 0.000002 Bottom mud 0.014 Fairy shrimp 0.410 Coho salmon, lake trout 3-6 Herring gull 99 soURCE: Harrison ef al. (1970). .-[3 Marks]STUDENT INDEX NUMBER SECTION ‘B’ “Answer question TWELVE (12) and any other TWO (2) questions in the answer booklet vovided. At the end of the examination, ensure that section ‘A’ is securely fastened (0 the a ‘answer booklet provided 12. (@). Hypoglycemic coma and kernicterus respectively may affect diabetics and children respectively as a result of drug-plasme protein interactions. By using a named example, explain how drug-plasma protein interactions specifically lead to adverse effects (i.e. hypoglycemic coma and kernicterus). [8 Marks] (b). Occupational risk assessment was conducted in a medical laboratory. Chemical X was identified as a potential chemical hazard, Follow-up investigations by a descriptive toxicologist led to the following details on chemical X: LDso = 12.5 mg, LDjo, SDso= 10.5 mg, SDioo = 12 img, Estimate the margin of safety and protective index of chemical X. [4 Marks} (©). The table below describes the metabolism of Griseofulvin. Use the information in the table to: Urinary and Biliary Excretion of Griseofulvin and/or Metabolites in Rats and Rabbits RATS* RABBITS* URINE BILE URINE BILE Total 12 77 78 ll Phase I metabolites NDt 23 70 3 Phase II metabolites ND 54 8 8 *Expressed as percent of dose ‘ND, not determined. SOURCE: Modified from Symchowicz et al. (1967), with permission. (i. comment on excretion of Griseofulvin. [4 Marks} (ii). estimate the concentrations of Griseofulvin metabolites (metabolic intermediates) in urine and bile for the two experimental animals, assuming a total dose of 200 mg of Griseofulvin was administered in each case. (4 Marks}STUDENT INDEX NUMBER. (4). Use the information in the table to answer the sub-questions below: Effect of Urine Alkalinization on Renal Clearance and Plasma Half-Life of 2,4-D URINE pH RENAL CLEARANCE (mL/min) HALF-LIFE (h) 5.10-6.5 0.28 219 6.55-1.5 1.14 42 7.55-8.8 9.60 47 source: Park ef al., (1977). (@. what is the relationship between urine pH and renal clearance of 2, 4-D? [3 Marks] ). what is the relationship between urine pH, renal clearance and plasma t'2 [3 Marks} relate the Henderson-Hasselbalch equation to the relationship and explain how you will use this relationship to enhance renal excretion of toxicants. [4 Marks} 13. (@). State the United States Environmental Protection Agency (USEPA)’s definition of RD and provide TWO (2) methods used in the estimation of R{D. [7 Marks} (©). A pump station attendant is exposed to a petroleum fraction at both inhalational and dermal exposure sites. According to the USEPA, RfD of the petroleum fraction is 1.08*10° mg/kg. Assuming daily inhalational and dermal exposures of the petroleum fraction to the pump attendant is 1.71*10 mg/kg/day and 1.91*10° mg/kg/day respectively: (). estimate the hazard quotient (HQ) of the petroleum fraction with respect to the two exposure sites. (3 Marks] i). calculate the hazard index (HI) for the petroleum fraction. [3 Marks} iii). comment on the implications of the calculated. [4 Marks] 14. Explain the following: (2). Risk assessment [S Marks] (b). Hazard identification (5 Marks] (©) Risk communication [5 Marks}STUDENT INDEX NUMBER 15. Define the following: (a). Target organ dose [3 Marks] (b). Internal dose [3 Marks} (c). Latent toxicity (3 Marks] (6). Entero-hepatic recirculation [3 Marks} (@). Co-carcinogen [3 Marks] 16, (a). What is food-drug interaction? [5 Marks) (). Describe phase | and phase 2 biotransformation reactions. [10 Marks]