4a078d11da1bad3b2eb3477742985392 jouclimed_a2022v11n4p1004.pdf 8bcef535b5e437d26a3dfe88e57287f5ba664358 jouclimed_a2022v11n4p1004.pdf 72d2bdcb8f0f4c6281a592eb672d84010d7c5b2188d716af0c88ef4d39e31fcb jouclimed_a2022v11n4p1004.pdf Title: Abuse Potential of Cathinones in Humans: A Systematic Review Subject: Introduction and objective: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. Materials and Methods: A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. Results: The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone (n = 5), mephedrone (n = 7), methylone (n = 1), and diethylpropion (n = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. Conclusions: Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health. Keywords: cathinone; mephedrone (4-methylmethcathinone); methylone (3,4-methylenedioxymethcathinone); diethylpropion; abuse potential; new psychoactive substance; pharmacological effects; pharmacokinetics Author: Lourdes Poyatos, Adrián Torres, Esther Papaseit, Clara Pérez-Mañá, Olga Hladun, Melani Núñez-Montero, Georgina de la Rosa, Marta Torrens, Daniel Fuster, Robert Muga and Magí Farré Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 15 10:21:12 2022 CET ModDate: Tue Feb 15 10:43:30 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 783387 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OSMCID+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 FTLBKO+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 VWBHHI+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 OUMVVH+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 SZBXVZ+VnURWPalladioL Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 56 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 59 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 84 0 NHCIKA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 95 0 NHCIKB+PalatinoLinotype CID TrueType Identity-H yes yes yes 98 0 NHCIKC+PalatinoLinotype TrueType WinAnsi yes yes no 104 0 NHCIKE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 107 0 NHCKAN+CambriaMath CID TrueType Identity-H yes yes yes 110 0 NFFZAN+CMSY10 Type 1 Builtin yes yes no 129 0 GIZSCG+EURM7 Type 1 Builtin yes yes no 136 0 NHCIKA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 159 0 NHCIKC+PalatinoLinotype TrueType WinAnsi yes yes no 162 0 NHCIKE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 165 0 NHCIKA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 174 0 NHCIKC+PalatinoLinotype TrueType WinAnsi yes yes no 177 0 NHCIKE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 180 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-15 02:33:05 CET RepresentationInformation: jouclimed_a2022v11n4p1004.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-01 11:43:51 CET Size: 783387 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 458 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Cathinones from Plant to Synthetics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Chemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Mechanism of Action Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Pharmacological Effects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Cathinone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Mephedrone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Methylone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Diethylpropion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Cathinone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Mephedrone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Methylone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Diethylpropion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Limitations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Info: Title: Abuse Potential of Cathinones in Humans: A Systematic Review Author: Lourdes Poyatos, Adrián Torres, Esther Papaseit, Clara Pérez-Mañá, Olga Hladun, Melani Núñez-Montero, Georgina de la Rosa, Marta Torrens, Daniel Fuster, Robert Muga and Magí Farré Subject: Introduction and objective: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. Materials and Methods: A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. Results: The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone (n = 5), mephedrone (n = 7), methylone (n = 1), and diethylpropion (n = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. Conclusions: Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health. Keywords: cathinone; mephedrone (4-methylmethcathinone); methylone (3,4-methylenedioxymethcathinone); diethylpropion; abuse potential; new psychoactive substance; pharmacological effects; pharmacokinetics Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 15 10:21:12 CET 2022 ModDate: Tue Feb 15 10:43:30 CET 2022 ID: 0x98e1ddc78ffe35acb1ef76230b685dae, 0x98e1ddc78ffe35acb1ef76230b685dae Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: NFFZAN+CMSY10 FontSubset: true FirstChar: 1 LastChar: 6 FontDescriptor: FontName: NFFZAN+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: VWBHHI+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: VWBHHI+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QDCWHF+EURM10 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: QDCWHF+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: OUMVVH+URWPalladioL-Ital FontSubset: true FirstChar: 40 LastChar: 151 FontDescriptor: FontName: OUMVVH+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GIZSCG+EURM7 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: GIZSCG+EURM7 Flags: Symbolic FontBBox: -5, -243, 1229, 720 FontFile: true Font: BaseFont: OSMCID+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 243 FontDescriptor: FontName: OSMCID+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: SZBXVZ+VnURWPalladioL FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: SZBXVZ+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FTLBKO+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 FontDescriptor: FontName: FTLBKO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 115, 347, 152, 356 Annotation: Subtype: Link Rect: 34, 335, 128, 344 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 757, 176, 793 Annotation: Subtype: Link Rect: 515, 757, 560, 793 Annotation: Subtype: Link Rect: 130, 680, 141, 693 Annotation: Subtype: Link Rect: 428, 680, 439, 693 Annotation: Subtype: Link Rect: 348, 667, 359, 681 Annotation: Subtype: Link Rect: 437, 667, 449, 681 Annotation: Subtype: Link Rect: 525, 667, 536, 681 Annotation: Subtype: Link Rect: 131, 654, 142, 668 Annotation: Subtype: Link Rect: 130, 17, 267, 28 Annotation: Subtype: Link Rect: 424, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 432, 86, 451 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 476, 736, 483, 744 ActionDest: 192 Annotation: Subtype: Link Rect: 360, 547, 367, 556 ActionDest: 192 Annotation: Subtype: Link Rect: 198, 409, 205, 418 ActionDest: 192 Annotation: Subtype: Link Rect: 352, 258, 359, 267 ActionDest: 192 Annotation: Subtype: Link Rect: 362, 258, 369, 267 ActionDest: 192 Annotation: Subtype: Link Rect: 325, 221, 332, 229 ActionDest: 192 Annotation: Subtype: Link Rect: 333, 220, 340, 229 ActionDest: 192 Annotation: Subtype: Link Rect: 198, 195, 205, 204 ActionDest: 192 Annotation: Subtype: Link Rect: 271, 183, 283, 192 ActionDest: 192 Annotation: Subtype: Link Rect: 201, 158, 213, 167 ActionDest: 192 Annotation: Subtype: Link Rect: 213, 158, 225, 167 ActionDest: 192 Annotation: Subtype: Link Rect: 457, 145, 464, 154 ActionDest: 192 Annotation: Subtype: Link Rect: 193, 107, 200, 117 ActionDest: 192 Annotation: Subtype: Link Rect: 201, 107, 213, 117 ActionDest: 192 Annotation: Subtype: Link Rect: 279, 82, 286, 91 ActionDest: 192 Annotation: Subtype: Link Rect: 286, 82, 293, 91 ActionDest: 192 Annotation: Subtype: Link Rect: 294, 82, 306, 91 ActionDest: 192 Annotation: Subtype: Link Rect: 331, 70, 338, 79 ActionDest: 192 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 194, 685, 206, 694 ActionDest: 192 Annotation: Subtype: Link Rect: 354, 673, 366, 682 ActionDest: 192 Annotation: Subtype: Link Rect: 367, 673, 379, 682 ActionDest: 192 Annotation: Subtype: Link Rect: 231, 635, 242, 644 ActionDest: 192 Annotation: Subtype: Link Rect: 439, 572, 451, 581 ActionDest: 192 Annotation: Subtype: Link Rect: 341, 519, 348, 531 ActionDest: 81 Annotation: Subtype: Link Rect: 281, 497, 288, 506 ActionDest: 192 Annotation: Subtype: Link Rect: 288, 497, 300, 506 ActionDest: 192 Annotation: Subtype: Link Rect: 363, 276, 375, 285 ActionDest: 192 Annotation: Subtype: Link Rect: 544, 213, 556, 222 ActionDest: 192 Annotation: Subtype: Link Rect: 399, 188, 411, 196 ActionDest: 192 Annotation: Subtype: Link Rect: 414, 187, 426, 196 ActionDest: 192 Annotation: Subtype: Link Rect: 247, 162, 259, 171 ActionDest: 192 Annotation: Subtype: Link Rect: 262, 162, 274, 171 ActionDest: 195 Annotation: Subtype: Link Rect: 206, 137, 218, 146 ActionDest: 192 Annotation: Subtype: Link Rect: 219, 137, 231, 146 ActionDest: 195 Annotation: Subtype: Link Rect: 231, 137, 243, 146 ActionDest: 195 Annotation: Subtype: Link Rect: 209, 112, 221, 121 ActionDest: 195 Annotation: Subtype: Link Rect: 198, 62, 210, 71 ActionDest: 195 Annotation: Subtype: Link Rect: 210, 62, 222, 71 ActionDest: 195 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 386, 735, 398, 744 ActionDest: 195 Annotation: Subtype: Link Rect: 348, 723, 360, 732 ActionDest: 195 Annotation: Subtype: Link Rect: 458, 672, 465, 681 ActionDest: 192 Annotation: Subtype: Link Rect: 466, 672, 478, 681 ActionDest: 195 Annotation: Subtype: Link Rect: 421, 635, 428, 644 ActionDest: 192 Annotation: Subtype: Link Rect: 429, 635, 436, 644 ActionDest: 192 Annotation: Subtype: Link Rect: 436, 635, 448, 644 ActionDest: 195 Annotation: Subtype: Link Rect: 484, 610, 496, 619 ActionDest: 195 Annotation: Subtype: Link Rect: 217, 572, 229, 581 ActionDest: 195 Annotation: Subtype: Link Rect: 232, 572, 244, 581 ActionDest: 195 Annotation: Subtype: Link Rect: 526, 534, 538, 543 ActionDest: 195 Annotation: Subtype: Link Rect: 354, 509, 366, 518 ActionDest: 195 Annotation: Subtype: Link Rect: 363, 471, 375, 481 ActionDest: 195 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 424, 519, 431, 531 ActionDest: 153 Annotation: Subtype: Link Rect: 472, 519, 479, 531 ActionDest: 133 Annotation: Subtype: Link Rect: 482, 519, 489, 531 ActionDest: 149 Annotation: Subtype: Link Rect: 256, 396, 268, 405 ActionDest: 195 Annotation: Subtype: Link Rect: 347, 396, 359, 405 ActionDest: 195 Annotation: Subtype: Link Rect: 448, 396, 459, 405 ActionDest: 195 Annotation: Subtype: Link Rect: 460, 396, 472, 405 ActionDest: 195 Annotation: Subtype: Link Rect: 394, 371, 401, 380 ActionDest: 192 Annotation: Subtype: Link Rect: 401, 371, 413, 380 ActionDest: 195 Annotation: Subtype: Link Rect: 500, 371, 512, 380 ActionDest: 195 Annotation: Subtype: Link Rect: 515, 371, 527, 380 ActionDest: 195 Annotation: Subtype: Link Rect: 276, 268, 283, 280 ActionDest: 133 Annotation: Subtype: Link Rect: 291, 270, 298, 279 ActionDest: 192 Annotation: Subtype: Link Rect: 298, 270, 305, 279 ActionDest: 192 Annotation: Subtype: Link Rect: 306, 270, 317, 279 ActionDest: 192 Annotation: Subtype: Link Rect: 318, 270, 330, 279 ActionDest: 195 Annotation: Subtype: Link Rect: 330, 270, 342, 279 ActionDest: 195 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 118, 388, 123, 395 ActionDest: 192 Annotation: Subtype: Link Rect: 121, 276, 130, 283 ActionDest: 195 Annotation: Subtype: Link Rect: 116, 180, 122, 186 ActionDest: 192 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 120, 359, 129, 366 ActionDest: 192 Annotation: Subtype: Link Rect: 129, 359, 138, 366 ActionDest: 195 Annotation: Subtype: Link Rect: 238, 252, 244, 259 ActionDest: 192 Annotation: Subtype: Link Rect: 117, 148, 126, 155 ActionDest: 198 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 117, 420, 126, 427 ActionDest: 198 Annotation: Subtype: Link Rect: 118, 308, 127, 315 ActionDest: 198 Annotation: Subtype: Link Rect: 117, 300, 126, 307 ActionDest: 198 Annotation: Subtype: Link Rect: 117, 160, 126, 166 ActionDest: 198 Annotation: Subtype: Link Rect: 126, 160, 135, 166 ActionDest: 198 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 117, 412, 126, 419 ActionDest: 198 Annotation: Subtype: Link Rect: 116, 268, 125, 275 ActionDest: 198 Annotation: Subtype: Link Rect: 116, 128, 125, 135 ActionDest: 198 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 116, 412, 125, 419 ActionDest: 198 Annotation: Subtype: Link Rect: 116, 308, 125, 315 ActionDest: 198 Annotation: Subtype: Link Rect: 118, 211, 127, 218 ActionDest: 198 Annotation: Subtype: Link Rect: 116, 143, 125, 150 ActionDest: 198 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 116, 412, 125, 419 ActionDest: 198 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 463, 306, 470, 318 ActionDest: 143 Annotation: Subtype: Link Rect: 477, 308, 489, 318 ActionDest: 198 Annotation: Subtype: Link Rect: 492, 308, 504, 318 ActionDest: 198 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 199, 710, 206, 722 ActionDest: 168 Annotation: Subtype: Link Rect: 238, 461, 246, 473 ActionDest: 143 Annotation: Subtype: Link Rect: 253, 464, 265, 473 ActionDest: 198 Annotation: Subtype: Link Rect: 516, 336, 523, 347 ActionDest: 149 Annotation: Subtype: Link Rect: 530, 338, 541, 347 ActionDest: 198 Annotation: Subtype: Link Rect: 544, 338, 556, 347 ActionDest: 198 Annotation: Subtype: Link Rect: 184, 313, 196, 322 ActionDest: 198 Annotation: Subtype: Link Rect: 380, 313, 392, 322 ActionDest: 198 Annotation: Subtype: Link Rect: 522, 313, 534, 322 ActionDest: 198 Annotation: Subtype: Link Rect: 377, 300, 389, 309 ActionDest: 198 Annotation: Subtype: Link Rect: 274, 74, 286, 83 ActionDest: 198 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 347, 725, 359, 734 ActionDest: 198 Annotation: Subtype: Link Rect: 303, 675, 310, 684 ActionDest: 192 Annotation: Subtype: Link Rect: 473, 486, 480, 495 ActionDest: 192 Annotation: Subtype: Link Rect: 544, 473, 556, 483 ActionDest: 192 Annotation: Subtype: Link Rect: 330, 411, 342, 420 ActionDest: 198 Annotation: Subtype: Link Rect: 267, 386, 279, 395 ActionDest: 195 Annotation: Subtype: Link Rect: 280, 386, 292, 395 ActionDest: 198 Annotation: Subtype: Link Rect: 465, 272, 477, 281 ActionDest: 198 Annotation: Subtype: Link Rect: 531, 159, 543, 168 ActionDest: 198 Annotation: Subtype: Link Rect: 544, 159, 556, 168 ActionDest: 198 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 366, 712, 378, 721 ActionDest: 195 Annotation: Subtype: Link Rect: 378, 712, 390, 721 ActionDest: 195 Annotation: Subtype: Link Rect: 391, 712, 403, 721 ActionDest: 198 Annotation: Subtype: Link Rect: 313, 687, 325, 696 ActionDest: 195 Annotation: Subtype: Link Rect: 440, 675, 452, 684 ActionDest: 198 Annotation: Subtype: Link Rect: 298, 624, 310, 633 ActionDest: 198 Annotation: Subtype: Link Rect: 450, 574, 462, 583 ActionDest: 198 Annotation: Subtype: Link Rect: 287, 473, 299, 483 ActionDest: 198 Annotation: Subtype: Link Rect: 300, 473, 312, 483 ActionDest: 198 Annotation: Subtype: Link Rect: 214, 348, 226, 357 ActionDest: 195 Annotation: Subtype: Link Rect: 226, 348, 238, 357 ActionDest: 198 Annotation: Subtype: Link Rect: 239, 348, 251, 357 ActionDest: 198 Annotation: Subtype: Link Rect: 533, 310, 544, 319 ActionDest: 198 Annotation: Subtype: Link Rect: 545, 310, 556, 319 ActionDest: 198 Annotation: Subtype: Link Rect: 269, 297, 281, 307 ActionDest: 198 Annotation: Subtype: Link Rect: 488, 247, 500, 256 ActionDest: 198 Annotation: Subtype: Link Rect: 337, 210, 349, 219 ActionDest: 198 Annotation: Subtype: Link Rect: 350, 210, 362, 219 ActionDest: 198 Annotation: Subtype: Link Rect: 502, 197, 514, 206 ActionDest: 198 Annotation: Subtype: Link Rect: 481, 160, 493, 168 ActionDest: 195 Annotation: Subtype: Link Rect: 288, 71, 300, 81 ActionDest: 198 Annotation: Subtype: Link Rect: 300, 71, 312, 81 ActionDest: 198 Annotation: Subtype: Link Rect: 312, 71, 324, 81 ActionDest: 198 Page: Sequence: 16 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 291, 611, 329, 622 Annotation: Subtype: Link Rect: 216, 589, 254, 599 Annotation: Subtype: Link Rect: 519, 577, 557, 588 Annotation: Subtype: Link Rect: 59, 555, 96, 565 Annotation: Subtype: Link Rect: 95, 520, 133, 530 Annotation: Subtype: Link Rect: 59, 497, 96, 507 Annotation: Subtype: Link Rect: 422, 473, 459, 484 Annotation: Subtype: Link Rect: 216, 462, 504, 473 Annotation: Subtype: Link Rect: 338, 427, 375, 438 Annotation: Subtype: Link Rect: 187, 405, 225, 415 Annotation: Subtype: Link Rect: 458, 347, 496, 358 Annotation: Subtype: Link Rect: 302, 324, 339, 335 Annotation: Subtype: Link Rect: 312, 255, 349, 266 Annotation: Subtype: Link Rect: 113, 233, 150, 243 Annotation: Subtype: Link Rect: 420, 209, 457, 220 Annotation: Subtype: Link Rect: 268, 174, 305, 185 Annotation: Subtype: Link Rect: 474, 151, 511, 162 Annotation: Subtype: Link Rect: 518, 151, 554, 162 Annotation: Subtype: Link Rect: 398, 128, 436, 139 Annotation: Subtype: Link Rect: 442, 128, 478, 139 Annotation: Subtype: Link Rect: 294, 105, 332, 116 Annotation: Subtype: Link Rect: 215, 82, 253, 93 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 122, 713, 159, 723 Annotation: Subtype: Link Rect: 431, 689, 468, 700 Annotation: Subtype: Link Rect: 475, 689, 511, 700 Annotation: Subtype: Link Rect: 59, 667, 96, 677 Annotation: Subtype: Link Rect: 102, 667, 138, 677 Annotation: Subtype: Link Rect: 260, 644, 298, 654 Annotation: Subtype: Link Rect: 397, 620, 435, 631 Annotation: Subtype: Link Rect: 441, 620, 477, 631 Annotation: Subtype: Link Rect: 59, 598, 96, 608 Annotation: Subtype: Link Rect: 102, 598, 138, 608 Annotation: Subtype: Link Rect: 153, 552, 191, 562 Annotation: Subtype: Link Rect: 197, 552, 233, 562 Annotation: Subtype: Link Rect: 282, 516, 319, 527 Annotation: Subtype: Link Rect: 196, 493, 233, 504 Annotation: Subtype: Link Rect: 427, 482, 465, 493 Annotation: Subtype: Link Rect: 206, 448, 244, 458 Annotation: Subtype: Link Rect: 59, 414, 96, 424 Annotation: Subtype: Link Rect: 102, 414, 138, 424 Annotation: Subtype: Link Rect: 378, 390, 416, 401 Annotation: Subtype: Link Rect: 422, 390, 458, 401 Annotation: Subtype: Link Rect: 479, 367, 515, 378 Annotation: Subtype: Link Rect: 521, 367, 557, 378 Annotation: Subtype: Link Rect: 469, 355, 506, 366 Annotation: Subtype: Link Rect: 203, 332, 240, 343 Annotation: Subtype: Link Rect: 388, 298, 426, 309 Annotation: Subtype: Link Rect: 59, 264, 96, 274 Annotation: Subtype: Link Rect: 131, 230, 168, 240 Annotation: Subtype: Link Rect: 329, 206, 367, 217 Annotation: Subtype: Link Rect: 113, 184, 150, 194 Annotation: Subtype: Link Rect: 251, 160, 288, 171 Annotation: Subtype: Link Rect: 295, 160, 331, 171 Annotation: Subtype: Link Rect: 131, 126, 168, 136 Annotation: Subtype: Link Rect: 175, 126, 211, 136 Annotation: Subtype: Link Rect: 59, 92, 96, 102 Annotation: Subtype: Link Rect: 102, 92, 138, 102 Annotation: Subtype: Link Rect: 187, 69, 224, 79 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 425, 724, 462, 735 Annotation: Subtype: Link Rect: 477, 701, 514, 712 Annotation: Subtype: Link Rect: 216, 666, 253, 677 Annotation: Subtype: Link Rect: 519, 643, 557, 654 Annotation: Subtype: Link Rect: 328, 620, 365, 631 Annotation: Subtype: Link Rect: 341, 586, 379, 596 Annotation: Subtype: Link Rect: 59, 552, 96, 562 Annotation: Subtype: Link Rect: 102, 552, 138, 562 Annotation: Subtype: Link Rect: 312, 516, 349, 527 Annotation: Subtype: Link Rect: 356, 516, 392, 527 Annotation: Subtype: Link Rect: 216, 471, 254, 481 Annotation: Subtype: Link Rect: 260, 471, 296, 481 Annotation: Subtype: Link Rect: 521, 436, 557, 447 Annotation: Subtype: Link Rect: 275, 413, 312, 424 Annotation: Subtype: Link Rect: 269, 390, 306, 401 Annotation: Subtype: Link Rect: 497, 367, 534, 378 Annotation: Subtype: Link Rect: 290, 345, 327, 355 Annotation: Subtype: Link Rect: 108, 322, 146, 332 Annotation: Subtype: Link Rect: 243, 286, 281, 297 Annotation: Subtype: Link Rect: 477, 263, 515, 274 Annotation: Subtype: Link Rect: 521, 263, 557, 274 Annotation: Subtype: Link Rect: 449, 240, 487, 251 Annotation: Subtype: Link Rect: 493, 240, 529, 251 Checksum: fd218d0c Type: CRC32 Checksum: 4a078d11da1bad3b2eb3477742985392 Type: MD5 Checksum: 8bcef535b5e437d26a3dfe88e57287f5ba664358 Type: SHA-1