Pharma - Basic Toxicology
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(2) !" ! "" ü c # . INSTRUCTIONAL OBJECTIVES c To give a brief overview of Toxicology c To discuss the general concepts that are important in toxicology c To discuss the epidemiology of toxicological cases c To discuss the general approach in the management of poisoning c To cite the PK/PD of common substances involved in poisoning c To give an overview of the various antidotes and their MOA c To define and discuss the different toxidromes which are encountered in practice Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493ʹ1541) a.k.a. PARACELSUS. TOXIN c. 0 c c c c c c c . TOXICANT c c c c c c c c cc RISK c c c c c c cc cc c
(3) c EXPOSURE c c c c c c c
(4) c c c SAFETY c c c c c c c c ccccc Specialized fields in Toxicology. c. c
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(7) cccccc. DESCRIPTIVE TOXICOLOGY
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(9) c c c c c
(10) c c c c
(11) c c c c. c.
(12) c. MECHANISTIC TOXICOLOGY c c c c c c c c c c c c c
(13) c c. TOXICOLOGY c. cc c cc c
(14) ccc c. c. cc c c c c c
(15) c cc. TOXICITYc c. cc c cc c cc c cc. c. cc c. DEFINITION OF TERMS POISON c. c c c c c c c c c c c c c c c c c c c. XENOBIOTIC c. REGULATORY TOXICOLOGY c c c c c
(16) c c c c
(17) c c c c c c c c cc c FORENSIC TOXICOLOGY c c c c c c c c c c c c cc c c CLINICAL TOXICOLOGY c c c c c c c cc cc c ENVIRONMENTAL TOXICOLOGY cc c cc c cc c
(18) cc c c. m c ccc c c c c c. c c.
(19) OCCUPATIONAL TOXICOLOGY c c c
(20) c c c c c c c c c c c c c c c c Toxic Agents may be classified according to: ac ac ac ac ac ac ac ac. c c
(21) c c cc àc c
(22) cc
(23) c m c c c c Oc c c
(24) c c c Ô c c c c c c c c c c. cc c c c c c cc cc c 0c cc c c c c. Subchronic exposure
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(26) c c c c c c c c c c c c"#c c cc cc c Chronic exposure c c c c c c c c c c c c c c c c c c
(27) c c cc c c cc c Exposure Situation: Frequency $ cc c c c c
(28) c c c c c c c c c c c c c c c c c c c Exposure Situation: Route %cc cc
(29) cc c Õc 0 cc Õc % c Õc % cc Õc % c Õc m c Õc % cc Õc & c c' c c O
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(36) . Chemical & Physical Properties wc 0 c m c c c
(37) cc wc m cc c c ccc wc c c c c c
(38) c wc c c c
(39) c c c wc
(40) c c c c c Exposure Situation: Duration Acute Exposure c cc c c ccccc c c c c c !c c c c c c c c c
(41) c c c c c c c c c c c c c !c cc c c !c cc c Subacute exposure
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(43) c c c c c c c c c c c c c c c c c c c c cc cc c c. Exposure Situation: Dosage Dosage (Dose)c c c
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(45) c c c c c c c c c c c c c c c Ô c c cc c Dose-Response (DR) Relationship wc cc ccc c wc Oc c c c c c c c c c c c c c c c c c c
(46) c c c. c c.
(47) wc. Three assumptions: wc c
(48) c c c c c c c wc c
(49) c c c c c c c wc %c c c c c c c c c c c c c
(50) c cc c c. DR curve THRESHOLDc c cc c c c c c %c
(51) c. LD50 Midpoint of the curve wc O c c c c c (#)c c c c c cccc c c wc 0
(52) c c c c c c c c c c c c c c Other Terms wc O'(#c*c cc c c c c c cc(#)cc cc c wc +&OÔc*c+c
(53) c
(54) cc
(55) c wc Ô&OÔc*Ôc
(56) c
(57) cc
(58) c General Classification of Toxic Effects wc c c wc c% c c wc c% c c c c wc c' c c c c wc c
(59) cc wc c%
(60) cc wc cÔ c c wc cm c c c. CHEMICAL INTERACTIONS wc INDEPENDENT EFFECTc c
(61) c c
(62) c c c c cccc c c c wc ADDITIVE EFFECTS cccc c c c c c c c c c c c c c c c c cc c c(3+5=8)c c wc SYNERGISTIC EFFECTS c c c c ccc c
(63) cc c c ccc c c c c cc c c c c c c c
(64) c (3+5=30)c c wc POTENTIATING EFFECTS c c
(65) c
(66) c c c c c c c c c c c c c (0+5=15)c c wc ANTAGONISTIC EFFECTS c c c c c c c ccc ùc c c ( 4+6=8), c c c cc cc cc c c (4+0=2) c c EPIDEMIOLOGY ac In the Philippine settingc +0 c c c##,c ac Total casesc" ccccAdmittedc #-cc ac Telephone referralsc"#!c ac LOCATIONc cc"#)cc c ac ROUTE of EXPOSUREc%cc!")cc c ac TYPE of EXPOSUREc cc-.)cc c ac CIRCUMSTANCES of EXPOSUREc% c c()cc c
(67) c+ c ac AGENT INVOLVEDcm cc c c c(,)cc cc ac AGE CATEGORYcc(#)c0 c c c ac SEX ac cPediatric Age groupc $c/c c cc ac c c c c
(68) c1.4: 1c ac Adult Age Groupc $c/c c c GENERAL APPROACH IN MX OF POISONING CASES c O c c c c
(69) c c O cc cc !c O cc c c (c cc c .c m
(70) c c c
(71) c -c 'c c.
(72) Emergency Stabilization ac c cA c ac O c cB
(73) c ac c cC c ac c
(74) c c cD c ac c c c E c c c ac c c c Complete Clinical Evaluation ac üc c c ac c c c c O
(75) c c c c O cc c c c c 0c c c c c c c Ôcc 0c c c c c c c 'c cc c c ac c c cc ac Ô c c c Information to be Elicited During History Taking ac cc c ac cc c ac % cc c c ac c ccc ac c c ac 0 c c c ac c c c c c Elimination of the Poison ac O c' c ac O c c c c Oc c ü c
(76) cc ac Ôcü%c c c
(77) c c c ' c c c 111Demulcent at homecc c c Effectc c#ccc cccccccccccccc cc cü%c Childc c! .cc c c Adultc, cc c c c External Decontamination ac mc c c c ac c c c ac
(78) c c c c c ac c c cc0 c ac c c ac ' c c. ac +c c ac & c c c+mmc c Gastric Lavage ac Contraindications:c à c c c c c &'c O c 0 c ac Complications: c Aspirationcc c0 c c Kinked Orogastric Tubec c 0 c c O c m c c Ô c O c Great Discomfortc ac âShould Not Be Routinely Used͟cc ac +cO
(79) cc%
(80) c& c ac m c c& c c ac IndicationcÔc c&'c2c 3c.#c c0%cc c c.#c c0%ccm c%c2c% c 0 cc4àc$c c c c c c c c c c c c c c c c c c c. Activated Charcoal ac O c cc&
(81) ccc ac Contraindicationsc à c c +c cc c c ac Indicationsc 3c c c c 0 cc c2c cc ac Dosec cü4càcc(#cüc ac c10:1c c c
(82) c c c cc. c !c.
(83) Substances Not Adsorbed by Activated Charcoal ac c ac c ac % c ac Ô c ac 0 c c c cccccccccccccccccccccc cc cc ccc cccccccccccccccccccccccccccc c Multiple Dose Activated Charcoal ac âIn conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of
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(87) c c
(88) cc c Current role of Syrup of Ipecac ac +&c c c ac 0c c should not be routinely usedc ac Rationale for changec c c c c c c c c c c &'c c
(89) c c c c c c % c c
(90) c c c c ccc c Enhancement of Elimination of Absorbed Substances ac 11 c c( urine pH 7-8)c c m c c ac 11 c 1c(urine pH 5-6)c c c c ac ' c c cc ac cc
(91) c c c. ññ Principle usedc%c c c Indications for Dialysis ac c cc ac c c c ac
(92) c cc c c ac
(93) c c c cc ac c c Indications for Dialysis (Dependent on Patient͛s Condition) cc c c cc c cc c c c cc c c. c cc 0 cc O
(94) cc c $ c %cc c % cc ccc Ô c 0 cc c 0 c m cc c m cc 5 cc c cc 5 c c Indications for Hemoperfusion ac c c c c c ac ' cc ac ü cc ac cc ac 0 c ac m cc ac cc c Use of Antidotes ac Seldom necessary in poisoning c c c c c c 'c c c c c c c c ac MECHANISMS OF ACTION c % cc c c c c c c c
(95) c c c c c c
(96) c c c c c c c ccc cc c c c ccc c Inert Complex Formation ac Chelating agents c $ c c c c c c c c cc c c c c c ac Heavy metal poisoning c Ô c c c c cc c c c c c ac Specific chelating agents c DMSA (succimer)c *c c c c c c c cc c c c c. c (c.
(97) c. c c. c c. DMPSc *c c c cc c c cc Penicillamine c Ô c c EDTAc*c c cc c c c Ô c BALc*c c Ôc c c NAPAc*c c cc c cc. c Accelerated Detoxification ac O c c c c c c c c c ac Na thiosulfatec c cc c 0 c c c c c c c c c c c c Reduction in Conversion to More Toxic Compounds ac % c cc c c c cc c c c c ac O c c c c c c c ac O c c c c c c c c c c c cc cc c Competitive Inhibition at Receptor Sites ac c c c c c c c c c c c c c c c ac + c ccc c cc cc c+mc ac c c c c cc c c c c c c c c c c c c Bypassing the Effect of the Poison ac % c c ccc cc ac & c c cc c m c c c c
(98) c c c c c c cc ac 0 c c%+ cc c 0 c c c c c c c c c üc c c cc%+ cc c. Antibody Interacting with Poison ac c c c c c c
(99) c ac ' c c c 'c c cc c c c c c cc ac c
(100) c c c
(101) cc + c c
(102) c Supportive Therapy ac O c c c c c c cc ac 0 c c c c c c c c ' c c c % c
(103) c c % c c c c 0 cc c c % c c $ c c c c c c c %
(104) c c c c c c $ c c c c c c c c c c c 0
(105) cc c c 0
(106) cc c c c c c c c c c c c cc
(107) cc c cc c c c Disposition ac &
(108) c c c c c c c!c c cc c ac $ c
(109) c ac 0 c
(110) c c c c c c c ac c c
(111) c c c c c cc ac $ c c c c ac 0 c c cc ac 'c
(112) c c Toxidromes ac mc c c c c c
(113) c c c c c c ac c c c c c
(114) c c c c c cc. c .c.
(115) ac Seizures + coma + metabolic acidosisc/c%+ c % c c ANTICHOLINERGIC/ANTIDEPRESSANT SYNDROME ac ac ac ac ac. c c ' c c c $ cc c ' c c c c. 6 c c 7c 6 c c c7c 6 c c7c 6c c 7c 6 c c c 7c. Cholinergic Toxidrome ac D c c ac U c ac Mc c cc ac B c cc ac Ec ac L cc ac S
(116) c Sympathomimetic Toxidrome ac M cc ac T c ac H c ac H c ac S c Narcotic/Opiate Toxidrome ac cc ac cc ac c ac
(117) c ac c Over-All Top Ten Poisoning cases 2008 (N= 3,931) ñNPMCC UPCM-PGH 1. Caustics - 442. Acid ʹ 91, Alkali ʹ 337, Unk - 14. 2. Hydrocarbons - 249. 3. Alcohol - 243. Household ʹ 100 ; Beverage - 143. 4. Silver Jewelry Cleaner ʹ 226. 8. Salicylates - 67. 9. Elemental Hg ʹ 54. 10 Mefenamic Acid 42. CAUSTICS ac MOTc ' c
(118) c c c c c c c c c c ac Sources of exposure c c c c c c ac Treatmentcm
(119) cm c HEAVY METALS Mercury ac MOTc c c c c c c c c c c c c c c c c ac Sources of exposurec c c c 2c c c c c
(120) c c
(121)
(122) c ac Health Effectsc c $c c c c c c c c c cc ac Treatmentc c cc c. Lead ac MOT:
(123) c c c c c c c c c c c c c c c c c c c8c c c$c ac Sources of exposurec c c c c c c ac Health Effectsc c c ü%c +mc c cc ac Treatmentc c cc c. 5. Paracetamol -211. 6. Pesticides ʹ 209. 7. Iron - 82. Pyrethroids ʹ 112; Carbamates ʹ 14 Organophos ʹ 46 ; Unknown - 37. Arsenic ac MOT:c cc c c
(124) cc c c
(125) c c ccc c ac Sources of exposure:c% c c c c c ac Health Effects:c ü%c mc +mc c mc c c cc cc ac Treatment:c c cc. c -c.
(126) Paracetamol ac Mechanism of toxicity: c
(127) c 0O c0 c c 0 c c c c 0 c cc c c c c c üm c c c c c c c cc c V ! V
(128) " #c c £ $ c cc ac Antidote:c+ c+c c INH (Isoniazid) ac MOT:c c
(129) c c c c c c c
(130) c c c ( c c c c üc cc c+mc ac Health Effects: c
(131) c +mc cc ac Antidote: 0 c c.c IRON ac MOT: c c
(132) c c c c ü%c c O
(133) c c c c c c c c c c c
(134) c c c c ac Health Effects:c ü%c c c c c c+mc ac Antidote:c' c c Silver Jewelry Cleaner (Cyanide poisoning) ac MOT: c c c ccc c c cc c cc ac Health Effects:ü%c m+mc c'O c ac Sources of Exposure:% cc c c c c c . ac Antidote: & c+ c+ c c+ c . Alcohol ac MOT:c+mc c cc cc ac Health effects:c+mc c mc c c c ac Antidote:c cc c c c c 999999999cOcc c9999999999c 6
(135) c c c 0 c c c %c üc c c c cc c c c c c c c c Occ c c6c c 4c c$% ::cc. Salicylates ac MOT:c c cc c c c cc c c
(136) c c c c c c c c ac Health Effects:c c+mc mcü%c ac Antidote/ Tx:c+cc c cc c c ccc
(137) c c c cc. c ,c.
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