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Home , Adimolol, Sulfinalol

Subject Index

A-64662 497 classification 11-14 AA-861 511 (fig) function 111-114 69,70 hemodynamic effects 110-121 brand names 868 (table) in hypertensive disease 114 dosage 83 (table), 860 (table) mechanism of action 110-121 intrinsic sympathomimetic activity 82 metabolism 108-110 pharmacological profile 83 (table) pharmacodynamics 110-121 see also diuretics 83 pharmacokinetics 108-110 acetazolamide 22, 24 sUbtypes 111,241-246 chemical structure 23 (fig), 24 (table) a2- 246 duration of action 39 (table) classification at central cardiovascular fractional sodium excretion 30 (table) sites 242-244 metabolism 37 definition at peripheral sites onset of action 39 (table) 241-242 peak of action 39 (table) a-adrenoceptor agonists 113 (table) pKa 37 (table) a-adrenoceptor antagonists 15, 105-125 plasma elimination half-life 37 antihypertensive activity 114-119 protein binding 37 (table) chemistry 106-108 renal site/mechanism of action 26, 30 combination with other 123 (table) contraindications 123-124 site of action 29 differential antagonism 242 teratogenesis 800,800-802 dosage 121-123 tubular fluid/plasma-sodium interactions 123 concentrations ratio 30 (fig) effects on: c10nidine 240-241 see also diuretics 240-241 acetylcholine 316 a- 240-241 acetylsalicylic acid 53 hemodynamic profile 119-120 Actinomycetales extracts/compounds side effects 124 728 therapeutic use 121-123 adenosine-3, 5-cyclic monophosphate toxicity 124 (cAMP) 73 ~-adrenoceptor antagonists 66-67, 815 adenosine triphosphate 73,268 a-adrenoceptor stimulating drugs adenyl ate cyclase 73 cerebral application 241 134,135 (table), 196 afzelin 721 chemistry 136 (table) agonist-antagonist interaction curves 73 adolescent children of hypertensive (fig) parents 9 ahpatinins 487 67,75,113 (table), 243 alacepril 418-419 (table) (table), 522 (table) [14C) alacepril 444 non-selective agonist 112 aldehyde 28 489 synapse 111 (fig) aldosterone antagonists 22,24 (table), 25 adrenergic system inhibitors 14-15,751 aldosterone, sodium pump control 28,44 a-adrenoceptor(s) 110-114,815 aldosteronism, primary 32,41,315 brainstem location 112 dopaminergic control of secretion central 239-240 569-570 a 14,117 enzyme secretion 36 902 Subject Index algae extracts/compounds 729 concentration in monkey cardiac alkylpyiidylguanidines (PI 060, PI 075) tissue 436 (fig) 646 (fig) conversion to angiotensin II 429 alkylpyridylthiourea (P950) 646 (fig) blocking 427 71,83 (table) PGI2/PGE2 release from kidney 516 brand names 868 (table) vascular wall 441-442 dosage 83 (table), 860 (table) angiotensin II 32,34,45,400,401-405 alseroxylon (table),431 brand names 868 (table) cardiac effects 437 dosage 866 concentration in monkey cardiac aluminium hydroxide 71 tissue 436 (fig) Amelanchier ovalis 732 faciIitatory action on sympathetic amiloride 25,813 nervous system 426 bioavailabiIity 37 (table) intrarenal actions 432 brand names 868 (table) release from isolated mesenteric arteries clinical structure 23 (fig), 24 (table) 426 dosage 863 (table) vascular wall generation 441,446-447 duration of action 38, 39 (table) unrelated effects 447-449 fractional sodium excretion 30 (table) vasoconstrictor effect 427 -428 intestinal absorption 36 angiotensin III 436 (fig) onset of action 39 (table) angiotensin converting enzyme 381 (fig) oral dose 40 (table) angiotensin converting enzyme inhibitors peak of action 39 (table) 41,43,483,750-751 plasma elimination half-life 37 (table) fetotoxicity 799-800 primary aldosteronism treatment 41 renal changes 789-794 protein binding 36,37 (table) blood urea levels 791-792 renal site/mechanism of action 26 juxtaglomerular apparatus 792-793 side effects 52 renal tubule integrity 790-791 target site 28 renal vasculature 794 tubular fluid/plasma-sodium angiotensinogen mRNA 436 concentration ratios 30 (fig) see also tenin inhibitors see alsQ diuretics aortic chemoreceptors 78 21-amino acid peptide see endothelin 562 (fig), 576-577 amino alcohol 40 489 cardiovascular action 579 (table) 20-amino-3-(3-hydroxy-5-pregnene-(3- spinal site . 577 D-glucoside 720 aprotinin 410 (table), 447 134,135 (table), 178-181 arachidonic acid 35, 507, 508 chemistry 135 (table), 178 antihypertensive drugs effect on hemodynamics 179-180 metabolism 523 metabolism 180 metabolism in kidney 513 mode of action 178-179 metabolites 507-508 pharmacodynamics 139 (table), products, blood pressure control 178-179 512-522 pharmacokinetics 180 renal circulation effects 513-514 side effects 181 Arachis hypogea 732 therapeutic use 180-181 Arctium lappa Iignans 724-725 toxicology 180 arloxyisopropanolamines 134 amrinone, myocardial necrosis 134,135 (table), 139 (table), associated 795 174-178 anatomical-therapeutic-chemical brand names 868 (table) classification system (ATe system) chemistry 135 (table), 174 820 dosage 860 (table) Anemonia sulcata peptides 730 elimination half-life 178 angioneurotic edema 457-458 hemodynamics 176-177 angiotensin, vascular, locally metabolism pathways 510 (fig) generated 441 mode of action 175-176 angiotensin I 400,401-405 (table), pharmacodynamics 175-176 427-429 pharmacokinetics 178 Subject Index 903

therapeutic use 178 renal site/method of action 26 arterial media, cross-sectional area benzothiadiazine-related heterocyclics 25 448 (table) benzthiazide 25 arylethanolamines 133-134 brand names 869 (table) aryloxyacetic acids 22,24 (table) dosage 863 (table) aryltetranaphthalenes 725 benzylhydrochlorthiazide aspartyl proteases 485 brand names 869 (table) aspirin 511 (fig) dosage 863 (table) asthmatics· 79 D-2-benxylsuccinic acid 383 astragalin 721 69,70 brand name 869 (table) fi-blocking action 74 (table) dosage 860 (table) brand names 868 (table) 228 (fig), 294 dosage 83 (table), 860 (table) brand names 869 (table) elimination half-life 72 dosage 865 (table) excretion 71 134,136 (table), 167-174 intestinal absorption 70-71 adrenoceptor blocking activity 139 log partition coefficient 70 (table),168-169 pharmacological profile 83 (table) brand names 869 (table) see also ~-blockers chemistry 136 (table), 167-168 atrial natriuretic factor 570 dosage 860 (table) atrial natriuretic peptide 6712-624 hemodynamics 169-171 chemistry 612-614 metabolism 172 effects: mode of action 168-169 biological 615-616 pharmacodynamics 168-169 blood pressure 617-619 168 hypertension 621-624 pharmacokinetics 171-172 renin secretion 616-617 side effects 174 mechanism of action 620-621 therapeutic use 172-173 receptor 620-621 toxicology 171 release regulation 614-615 B-HT920 113 (table), 230, 243 (table) synthesis regulation 614-615 B-HT933 (azepexole) 113 (table), 230, autoregulatory hypothesis 8-9 243 (table) avian pancreatic polypeptide 606 biofeedback-based behavioral therapy azamethonium 844 brand names 868 (table) dosage 865 (table) brand names 869 (table) azepexole (B-HT933) 113 (table), 230, dosage 860 (table) 243 (table) ~-blockers 66-93, 132-200,748-749 azosemide 25 cardioselectivity 70 dosage 863 (table) chemistry 68-70 brand names 868 (table) combinations 90 teratogenesis 802-803 contraindications 15,91 azotemia, prerenal 51 distribution 71 enantiomers 137 B24n6 196, 198 (table) excretion 71-72 baroreceptorreftex 78,240,314 hepatic metabolism 71 Bartter's syndrome 516 history 66-68 BAY K 8644 307, 309 interactions, pharmacokinetic/ behavioral intervention 778 (fig) pharmacodynamic 6-7 benazepril 386 intrinsic stimulant activity 82-85 bendroftumethiazide (bendroftuazide) 25 intrinsic sympathomimetic activity brand names 868-869 (table) 68-70 dosage 863 (table) isomerism 70 benign essential tremor 79 mechanism of action 72-88 4-(2-benzo(b )furanyl)coumarins 723 baroreftex 78 benzothiadiazine(s) 24 blood pressure lowering 85-88 benzothiadiazine derivatives 22,24-25 catecholamines 77 904 Subject Index

cellular processes 72-74 peak of action 39 (table) central nervous effects 79 pKa 37 (table) cheDloreftexes 78 plasDla eliDlination half-life 37 (table) glucose DletabolisDl 80 protein binding 37 (table) heart 75 relative natriuretic potency 31 (table) intra-orbital pressure reduction 85 renal heDlodynaDlics 31 intrinsic sYDlpathoDliDletic activity renal site/DlechanisDl of action, 26,30 81-85 (table) lipid DletabolisDl 80-81 tubular ftuid/plasDla-sodiuDl nerve activity 77-78 concentrations 30 (fig) peripheral autonoDlic nerves 72 see also diuretics peripheral blood vessels 75-76 plasDla renin activity 77 brand naDles 869 (table) platelet agregation inhibition 85 dosage 866 (table) renal effect 76 respiratory effects 79-80 brand naDles 870 (table) seruDl potassiuDl 81 dosage 860 (table) tear reduction 85 throDlboxane production reduction brand naDles 870 (table) 85 dosage 860 (table) thyroid 81 butanolides 724-725 treDlor 79 buthiazide (butizide) overdosage 92 brand naDles 870 (table) pharDlacokinetics 70-72 dosage 863 (table) side effects 91-92 BW 855C 511 (fig) stereospecificity 134-137 BW A575C 134,136 (table), 194-195 therapeutic use 88-89 cheDlistry 136 (table), 194 toxicity 92 pharDlacology 195 blood pressure, persistence of norDlal, after withdrawal of drug therapy cadralazine 755-761 brand naDles 870 (table) blood vessels dosage 866 (table) eicosanoids generation 519-520 calcitonin, Dlessenger RNA encoding 601 endothelial cell role in hypertension calcitonin gene related peptide 601-605 520 aDlino acid sequence 602 (fig) bODletolol 196,198 (table) anatoDlical distribution 601-603 cheDlistry 601 brand naDle 869 (table) functions 603-604 dosage 860 (table) DlechanisDl of action 604-605 bradykinin 379,438-439,516 calciuDl 324 brain converting enzyDle 452-454 altered intake effect on blood pressure Brazil 840-843 697-699 bretyliuDl 288 (fig), 292, 294 blood pressure effect 692-693 broDlocriptine 582 overload 322 134,136 (table), 196 seruDl concentration, diuretic effect 48 cheDlistry 136 (table) calciuDl antagonists 15-16,301-350, 133-134,135 (table), 196 749-750 bUDletanide 25 binding sites 306-308 bioavailability 37 in hypertension 308 brand naDles 869 (table) cODlparisons with: cheDlical structure 23 (fig), 24 (fig) croDlakaliDl 665 distribution coefficient, ether/water nicorandil 665 31 (table) pinacidil 665 dosage 863 (table) contraindications 346-347 duration of action 39 (table) doses 333-335 excretion 37 drug interactions 346-347 onset of action 38, 39 (table) effects: oral dose 40 (table) blood pressure 310-312 Subject Index 905

cardiac hypertrophy 320-322 mercapto group induced 458 hemodynamic 312-314 neutropenia 456-457 isolated cardiac preparations 308 renal 457 renal 315-320 structure 384 (fig) smooth muscle migration 324 synthesis 381-386 vascular integrity 322-324 see also converting enzyme inhibitors' vascular smooth muscle 308-310 p4C)-captopril 444 mechanisms of action 304-306 metabolism 324-332 brand name 870 (table) pharmacodynamics 304-305 dosage 860 (table) pharmacokinetics 324-332 carbachol 239 side effects 347-350 ~-carboline-derived alkaloids 715~716 therapeutic use 333-335 carbonic anhydrase inhibitors 23 toxicity 347-350 target site 28 (fig) calpurnine 718 teratogenesis 800-802, 803 cancrenoate carboxypeptidase A 381 brand names 870 (table) carcinogenicity testing 786 dosage 863 (table) cardiovascular hemodynamics 7-8 canrenone 26, 37 bioavailability 37 (table) brand names 870 (table) chemical structure 23 (fig) dosage 860 (table) excretion 37 134,136 (table), 184-190 plasma elimination half-life 37 (table) chemistry 136 (table), 184 protein binding 37 (table) hemodynamics 186-188 see also diuretics metabolism 188-189 capsaicin 603 mode of action 184-186 captopril 385 (table), 386, 392-304, 517, pharmacodynamics 139 (table), 184- 750-751 186 absorption 392-393 pharmacokinetics 188-189 binding hypothetical model 383 (fig) side effects 190 brand names 870 (table) therapeutic use 189-190 continental Europe use 818 toxicology 188 distribution 393 catechin 720 dosage 860 (table) catecholamines 77 effect on: influence 146 angiotensin II in essential catechol-o-methyl transferase 581 hypertension 515 Cecropia obtusifolia 732 endogenous kin ins 410-419 (table) 134,136 (table), 162-167 isolated rat kidneys 428-429 bioavailability 164 isolated vessel preparations 427-428 brand names 870 (table) prostaglandins 410-419 (table) chemistry 136 (table), 162 vascular resistance 424-425 dosage 860 (table) elimination 393-394 elimination 164 fetotoxicity 799-800 elimination half-life 164 first-dose hypotension avoidance 462 hemodynamics 164 hypertensive patients 423-434 in: inhibition constants 396 (table) bronchoconstriction 166 metabolism 393 peripheral obliterative disease 167 pharmacodynamic properties 388-390 renal impairment 165 (table) metabolism 164 postsynaptic inhibition of noradrenaline pharmacodynamics 139 (table), 162- pressor action 427 163 protein binding 393 pharmacokinetics 164 side effects 385,456-459 side effects 167 angioneurotic edema 457 -458 therapeutic use 165-167 fetal abnormalities/deaths 458 toxicology 164 incidence in post marketing studies cell-cell interactions 520-522 458-459 centhaquin 542 (fig), 544 906 Subject Index central blood volume expansion 33 red blood cell binding 36 centrally acting drugs 227 - 252 protein binding 36 chemistry 229-230 site of action 30 combinations with other drugs see also diuretics 249-250 cholesterol, serum 6 drug interactions 250 cholestyramine 53 side effects 250-253 cilazapril 388-390 (table), 446 cerebellar tremor 79 cimetidine 90 Cervus elaphas L. var. xanthophygus 730 cinchophylline 718 CGP 38560A 497 113 (table) CGS 13945 387 (fig) C1906 387 (fig) CGS 14824A 387 (fig) C1907 (indolapril) 387 (fig) chemoreftexes 78 C1242,817 384 (fig) children 8 clinical trials 796-775 China 848-852 marginal effects 774-776 chinoin-l03 196,199 (table) measures of prognosis 772-773 chlorobenzamides 25; see also diuretics mild hypertension 769-772 6-chloro-N-methyl-2,3,4,5-tetrahydro- rationale 769 I-H-benzazepine (SKF clofibrate 53 86466) 108,113 (table) 14,113 (table), 228-252, 813 chlorothiazide 22, 24, 28 absorption 230 biliary excretion 38 u-adrenoceptor-blocking drugs effects bioavailability 37 (table) 240-241 brand names 870-871 (table) uI/uz-adrenoceptor selectivity 243 chemical structure 23 (fig), 24 (table) (table) dosage 863 (table) bioavailability 230 dose-effect curve in nonedematous bradycardia induced by 112 subjects 31 (table) brand names 871 (table) duration of action 39 (table) chemistry 229-230 ether/water distribution coefficient combination with other drugs 249-250 31 (table) discontinuation syndrome (withdrawal intestinal absorption 36 syndromes; rebound metabolism 37 syndrome) 251 onset of action 39 (table) dosage 249,862 (table) oral dose 40 (table) drug interactions 250 peak of action 39 (table) hemodynamics 233-234 pKa 37 half-life 230 plasma elimination half-life 37 intracisternal injection 245 protein binding 36,37 (table) metabolism 231 relative natriuretic potency 31 (table) mode of action 237-238, 242-247 see also diuretics pharmacodynamics 236-237 90,563 (fig) pharmacokinetics 230-231 chlorprotixene 562 (fig) post/presynaptic u-adrenoceptor chlorthalidone 25 potency 243 (table) bioavailability 37 (table) side effects 14-15,250-251 brand names 871 (table) site of action 238-239 chemical structure 23 (fig), 24 (table) therapeutic use 247 - 249 dosage 863 (table) toxicity 250-251 duration of action 39 (table) clonidine-displacing substance 247 excretion 37 clonidine-like drugs 229 (table) hypokalemia incidence 47 (table) clopamide 25 intestinal absorption 36 brand names 871 (table) onset ofaction 39 (table) dosage 863 (table) oral dose 40 (table) cloranol peak of action 39 (table) brand name 871 (table) pKa 37 (table) dosage 861 (table) plasma elimination half-life 37 (table) clorexolone protein binding 37 (table) brand name 871 (table) Subject Index 907

dosage 864 (table) hypertension with disturbed renal co-dergocrinmesilat 711 function 434-435 Continental Europe 811-818 primary hypertension 433-434 a-adrenoceptor antagonists 815 renovascular hypertension 433 ~-adrenoceptor antagonists 815-816 normotensive individuals 432-433 calcium antagonists 816 renal salt excretion 433 converting enzyme inhibitors 817-818 side effects 455-462 diuretics 812-813 sulfur containing 384 (fig) ganglionic blocking drugs 813 systemically administered, effects on Rauwolfia drugs 811-812 brain converting enzyme sympatholytica with central action 452-454 813-814 vascular resistance effects 424-426 vasodilators 814-815 humans 425-426 converting enzyme 379-380 hypertensive animals 424-425 converting enzyme inhibitors 16, 379- vascular wall 441: see also vascular 462,817-818 converting enzyme antihypertensive action 397-409,444- coronary disease 50 446 coronary risk estimates 767,768 (fig) endogenous kinins role 409 113 (table) renin-angiotensin system 400-409 cost of antihypertensive treatment 16-17 antihypertensive treatment in diabetic Crataegus sp. 730-731 nephropathy 435-436 cromakalin 656-666 blood· pressure effects 409-424 adverse effects 666 hypertensive animals 420-422 chemistry 656-658 hypertensive patients 423-424 clinical studies 665-666 normotensive animals/humans comparisons with: 409-420 calcium antagonists 665 captopril-related 384-385 nicorandil 665 cardiac actions 436-437 pinacidil 665 cardiac hypertrophy effect 440 distribution 658 congestive heart failure effect 441 effects on: functional 426,437-438 agonist-induced contractions 660 sympathetic transmission 440 agonist-induced pressor responses centrally mediated antihypertensive 659 actions 449-453 basal blood pressure 658 development 380-392 bladder 662 first-dose hypotension avoidance 462 cardiac muscle 661-662 inhibitory mechanism 396 central nervous system 663 interference with neurogenic gastrointestinal tract 662 /autonomic heart rate 658 reflexes 426-432 42K efflux 660-661 humans 430-432 membrane potential 660 intact animals 430 86Rb efflux 660-661 isolated rat kidneys 428-429 regional blood flow 658-659 isolated vessel preparations 427-428 reproductive tract 662 pithed rats 429-430 spontaneous mechanical activity 659 intracerebroventricularly administered trachea 662 450-451 K channel modulation 664-665 large arteries 446 mechanism of action 663-664 local administration effects 449-450 metabolism 658 nonpro-drug/nonsulfhydryl 387-392 pharmacodynamics 658-663 non-sulfur/non-sulfhydryl moieties pharmacokinetics 658 containing 387 (fig) stereospecificity of in vitro effects 660 phosphorus containing 391 stereospecificity of in vivo effects 659 prodrug, synthesis of 385-386 coumarins 722-723 prostaglandins effect 410-420 (table) cyclooxygenase 510-512,513 renal effects 432-436 .inhibitors 510,511 (fig) in: pathway 509 (fig) 908 Subject Index cyclopenthiazide 25 dosage 344-345,862 (table) brand name 871 (table) drug interactions 332-346 dosage 864 (table) effect dose-effect in nonedematous subjects blood pressure 300 31 (fig) cardiac 309 distribution coefficient, ether/water cardiac hypertrophy prevention 322 31 (table) hemodynamic 313 relative natriuretic potency 31 (table) negative chronotropic 314 see also diuretics renal 317 cyclothiazide 25 smooth muscle cell proliferation brand names 871 ( table) inhibition 324 dosage 864 (table) excretion 332 see also diuretics hydrochloride salt 303 cytochrome P-450 monooxygenase 513, metabolism 331 (fig) 514 pKa 303 pathway 509 (fig) receptor site 306 Czechoslovakia 821 side effects 349 therapeutic use 344-345 toxicity 349-~50 Dahl salt-sensitive rat 8 see also calcium antagonists 288 (fig), 294 diuretics 13-14,21-36,746-748 brand names 871 (table) antihypertensive action 32-36 dosage 865 (table) biliary excretion 38,41 defined daily dose (DOD) 820,821 bioavailability 36,37 (table) Denmark see Scandinavia biotransformation 37 chemical structure 22-25 brand name 871 (table) combined with other antihypertensives dosage 866 (table) 42-43 diabetes mellitus 6,91,435 contraindications 52-53 diabetic nephropathy, converting enzyme dosage 39-40 inhibitors effect 435-436 drug interactions 53-55 diazepam 90 duration of action 38-39 diazoxide 315-316,667,814 early phase of treatment 34, 35 (table) brand names 871 (table) elimination 38 dosage 866-867 (table) European use 812-813 myocardial necrosis associated 795 fluid/electrolyte reabsorption 26-28, water/sodium retention 315-316 29 (fig) 66-67,81,82 intestinal absorption 36 chemical structure 67 lipid solubility/distribution 36,37 see also ~-blockers (table) dichlorphenamide 800 long-term administration effect 34 dihydralazine loop 25,26 brand names 871 (table) elimination 38 dosage 867 (table) hemodynamic effects 32 1,4-dihydropyridine 306 onset of action 38 dilevalol 134,135 (table), 181-184 patients with normal renal function chemistry 135 (table), 181 41 (table) hemodynamics 182-183 prostaglandin metabolism stimulation mode of action 181-182 36-37 pharmacodynamics 139 (table), 181- receptor 27 182 renal blood flow rise 32 side effects 183-184 mechanisms of action 26-36 therapeutics 183-184 metabolism 37 diltiazem 302-303,331-332, 749-750 natriuretic potency 28-31 absorption 331 onset of action 38-39 bioavailability 331-332 patients with impaired renal function brand names 871-872 (table) 41-42 chemical structure 302 (fig) patients with normal renal function contraindications 346 40-41 Subject Index 909

peak ofaction 38-39 pharmacokinetics 109 potassium-sparing 42 DP-5,6-ADTN 522 (fig) pro-drugs 25-27 DP-6,7-ADTN 562 (fig) prot~in binding 36,37 (table) dramedilol 196,198 (table) red blood cell sodium reduction 34 renal hemodynamics, effect on 31-31 eicosanoids 508-512 renal sites 26-27 blood vessels wall generation tubular Z6-31 519-520 resistance to 42 kallikrein-kinin system 517-518 second (late) phase of treatment metabolism 508-512 35 (table) renal effects 513-514 side effects 43-52 renin-angiotensin system effects glucose metabolism 50 514-517 hypokalemia 44-48 synthesis 508 hyponatremia 48-49 elderly patients 51 magnesium loss 48,49 (table) electrolyte intake 687 - 701 metabolic 49-50 enalapril (MK421) 385-386,387 (fig), hyperuricemia 49 394-396,750-751 lipid metabolism 50 absorption 394 nephrolithiasis 52 brand ilames 871-872 (table) orthostatic hypotension 51 continental Europe 818 ototoxi<;ity 51-52 conversion to enalaprilat 395-396 prerenal azotemia 51 converting enzyme (CE)-inhibitory serum calcium concentration 48 action 443 teratogenesis 800 death rate 460-461 thiazide see thiazides distribution 395 domperidone 562 (fig) dosage 860 (table) 559-583 effect on: aldosterone secretion control 569 endogenous kinins 412 (table) atrial natriuretic factor and 570 prostaglandins 412 (table) cardiovascular actions 560 vascular resistance 425-426 central cardiovascular actions 575-580 elimination 395 central pathways/cell groups 573-575 in chronic renal failure 396 central systems role in hypertension fetotoxicity 800 580-581 first-dose hypotension avoidance 462 chemical formula 562 (fig) hypertensive patients 423-424 clinical use 581-583 inhibition of aortic enzyme 443 dopaminergic neurons distribution metabolism 395 573-575 pharmacodynamic properties 388-390 ligands 560-566 (table) metabolism 561 (fig) side effects 449-456,461 (table) neurotransmitter in small intensively see also converting enzyme inhibitors fluorescent cells 571 enalaprilat 385,395 receptors 560-566 absorption 394 distribution in CNS 575 binding hypothetical model 383 (fig) postsynaptic Dat 565 elimination 395-396 presynaptic Da2 565-566 in chronic renal failure 396 renal effects 566-569 inhibition constants 396 (table) sources 570-571 see also converting enzyme inhibitors synthesis 560,561 (fig) endothelial-derived relaxant factors dopamine-Jl-hydroxylase 269 (EDRF) 604-605 dopaminergic nerves 571-573 endothelin (21-amino acid peptide) 307, 106,113 (table), 118,751 624-630 brand name 871 (table) . amino acid sequences 625 (fig) chemical structure 107 (fig) cardiovascular effects 626-628 combination with other drugs 123 mechanism of action 628-629 dosage 866 (table) structure 625-626 hemodynamic profile 120 (table) endotheliapepsin 492 910 Subject Index endralazine felodipine 302 brand name 872 (table) brand names 872 (table) dosage 876 (table) chemical structure 303 (fig) enkephalins 599 dosage 862 (table) enoximone 795 effects: E-olefin 489 kaliuresis with negative potassium 69,70, 197 (table) balance 317 j3-blocking action 74 renal 317-320 chemistry 197 (table) sodium excretion 318-320 daily dose 83 (table) vascular selectivity 309 intrinsic sympathomimetic activity see also calcium antagonists 82-83 fenoldopam (SKF 82526) 526 (fig), 562, pharmacological profile 83 (table) 571 see also j3-blockers antihypertensive action 581-582 ephedra dines 712 cardiovascular action 579 (table), 581 epoxyeicosatrienoic acids (EETs) 516 fenquizone ergot alkaloids 563,711 brand name 872 (table) Ericaceous diterpenoids 727 dosage 864 (table) ethacrynic acid 25 Finland see Scandinavia biliary excretion 38 fixed ratio combination 137 brand names 872 (table) flavan-3,4-diol 720 chemical structure 23 (fig), 24 (table) flavanon 720 (fig) dosage 864 (table) flavanonol 720 (fig) dose-effect curve in nonedematous flavon 720 (fig) subjects 31 (fig) flavonoids 720-722 duration of action 39 (table) flavonol 720 (fig) excretion 37 flesinoxan 541,542 (fig), 543, 544 (fig), onset of action 38,39 (table) 545 (fig), 547 oral dose 40 (table) side effects 547 peak of action 39 (table) flupenthixol 562 (fig) pKa 37 (table) 562 (fig) protein binding 37 (table) foroxymithine 728 receptor 27 forskolin 727 - 728 renal hemodynamics 31 fosenopril (SQ 28555) 391 renal site/mechanism of action 26 fungi extracts 729 resistance 42 furosemide (frusemide) 14,25 side effects 52 arachidonic acid release 35 tubular fluid/plasma-sodium bioavailability 37 (table) concentrations ratio 30 (fig) brand names 872-873 (table) see also diuretics chemical structure 23 (fig), 24 (table) ethambutol 326 distribution coefficient, ether/water ethoxzolamide 800 31 (table) etozolin 25 dosage 864 (table) bioavailability 37 (table) dose-effect curve in nonedematous brand name 872 (table) subjects 31 (fig) chemical structure 23 (fig), 24 (table) drug interactions 54, 55 dosage 864 (table) elimination 38 duration of action 39 (table) fractional sodium excretion 30 (table) metabolism 37 hypokalemia incidence 47 (table) onset of action 39 (table) intestinal absorption 36 oral dose 40 (table) kallikrein excretion 35 peak of action 39 (table) 9-keto-reductase inhibition 35 pKa 37 (table) metabolism 37 plasma elimination half-life 37 (table) 15-0H-PG-dehydrogenase inhibition protein binding 36,37 (table) 35 renal site/mechanism of action 26, 30 onset of action 38.39 (table) (table) oral dose 40 (table) see also diuretics patients with impaired renal function 41 Subject Index 911

peak of action 39 (table) bioavailability 231 pKa 37 (table) brand names 873 (table) plasma elimination half-life 37 (table) combination with other drugs protein binding 36,37 (table) 249-250 receptor 27 discontinuation syndrome (withdrawal relative natriuretic potency 31 (table) syndrome; rebound syndrome) . renal excretion of PGE2 34 251 renal hemodynamics 31 dosage 249,863 (table) renal site/mechanism of action 26, 30 drug interactions 250 side effects 52 hemodynamic effects 235 sodium loss 44 half-life 231 teratogenesis 800, 802-803 metabolism 231 tubular fluid/plasma-sodium mode of action 237-238,246-247 concentrations 30 (fig) pharmacodynamics 236-237 tubulo-glomerular feedback mechanism pharmacokinetics 231 inhibition 32 side effects 250-251 urinary calcium excretion 48 site of action 238-239 see also diuretics therapeutic use 247 - 249 furosemide test 845-846 toxicity 250-252 guanisoquin 288 (fig) GABA 239 288 (fig) gallopamil brand name 873 (table) brand name 873 (table) dosage 865 (table) dosage 862 (table) 288 (fig) ganglionic blocking drugs 813 brand names 873 (table) garlic 731 dosage 865 (table) glucose metabolism, diuretics effect 50 Guyton's hypothesis 690 gout 49 288 (fig) H-77 compound 4&6 brand name 873 (table) H-142 compound 486 dosage 863 (table) 562 (fig), 563 guanacline 288 (fig) heart 865 (table) congestive failure 441 brand name 873 (table) hypertrophy 440 dosage 865 (table) sympathetic transmission in 440 287 - 294 Hedychium coronarium 732 absorption 293 heliosupine 718 bioavailability 293 hemanthamine 715 brand names 873 (table) 813 chemical structure 288 (fig) HOE498 see ramipril clinical effects 291-292 hydralazine 90,814 . antiarrhythmic 292 brand names 873-874 (table) atherogenesis 292 dosage 867 (table) glaucoma 292 myocardial necrosis associated 795 hemodynamic 291-292 renin secretion stimulation 315 sympathetic dystrophies 292 water/sodium retention 315-316 dosage 865 (table) hydrochlorothiazide 24 drug interaction 293 biliary excretion 38 elimination 294 bioavailability 37 (table) metabolism 293 (fig), 294 brand names 874-875 (table) mode of action 289-291 chemical structure 23 (fig), 24 (table) l3-adrenoreceptor increase 291 dosage 864 (table) neuropeptide Y . 290-291 dose-effect curve in nonedematous postsynaptic responsiveness 291 subjects 31 (fig) side effects 292-293 duration of action 39 (table) guanfacine 113 (table), 231, 235-236 ether/water distribution coefficient a-adrenoceptor-blocking drugs effects 31 (table) 240-241 hypokalemia incidence 47 (table) 912 Subject Index

intestinal absorption 36 classification 2-3 metabolism 37 consequences 11-12 onset of action 39 (table) definition 2 oral dose 40 (table) essential 33 peak of action 39 (table) genes 11 pKa 37 (table) hereditary aspects 10-11 plasma elimination half-life 37 (table) hyperreactivity to pressor stimuli 114 protein binding 36,37 (table) mild 3-5 relative natriuretic potency 31 (table) management 4-5 renal excretion of PGE2 34 prevention 6-7 tubular fluid/plasma-sodium natural history 765-767 concentration ratios 30 (fig) neurogenic hypothesis 9-10 see also diuretics non-drug measures 5-6 hydroflumethiazide 25 orthostatic 15 brand names 875 (table) pathophysiology 7-8 dosage 864 (table) prognosis 767 see also diuretics assessment in clinical trials 769-775 hydrogenated ergot alkaloids 105 made worse by treatment of mild hydroperoxyeicosatetraenoic acids hypertension? 776-777 (HPETEs) 512,513,514 stepwise treatment see stepwise hydrothiazides 23 treatment 6-hydroxydopamine 243,245,607 stopping antihypertensive therapy hydroxyeicosatetraenoic acids (HETEs) 754-761 508,509 (fig), 512, 513, 514 therapeutic attitudes 777-778 hydroxymethylene isoteres (and related treatment guidelines 778 (fig) inhibitors) 487-489,490-491 volume-dependent 14,32,33 (fig) (table) whenlhow to treat 12-13 4-hydroxypropranolol 71 hypertensive animals 420-422 p-hydroxytrianterene 42 genetic hypertension 421-422 5-hydroxytryptamine (serotonin) 533-4 non-renin-dependent 420-421 agonists 547 renin-dependent models 420 antagonists see hypochloremia 44 arterial blood pressure effects 536-547 hypokalemia long-lasting depressor effect cardiac arrhythmias 47, 48 539-546 diuretic-induced 44-48 endothelium-derived relaxant factor, risk factor in hypertension 47 related 546 sudden death 47, 48 receptors 534-536,537 (table), hypomagnesemia 48 538 (table) hyponatremia, diuretic-induced 48-49 activation of vascular smooth cells 546-547 5-hydroxytryptamine agonists 547 ibuprofen 511 5-hydroxytryptamine antagonists see icariin 721 ketanserin Iceland see Scandinavia 5-hydroxytryptaminel-like agonists lei 89406 196,198 (table) 540-544 lei 89963 196,198 (table) hyperaldosteronism, primary 813 lei 141292 196 hyperglycemia 50 lei 118551 69,80 hypertensionogenic factor 33-34 108,113 (table) hypertension 1-18 /lex pubescens 732 asymptomatic, ~-blockers for 15 imidazole analogue 34 489 atrial natriuretic peptide involvement immunotoxic effects 788 621-624 indacrinone 800,802-803 autoregulatory hypothesis 8-9 indapamide 25,850 blood vessel endothelial cell role 520 bioavailability 37 (table) borderline 2, 3 brand names 875 (table) cell-cell interaction role 529-522 chemical structure 23 (fig), central dopamine systems role 24 (table) 580-581 dosage 864 (table) Subject Index 913

duration of action 39 (table) al-adrenoceptor blockade 549 metabolism 37 blockade of 5-HT2 receptor-mediated onset of action 39 (table) vasoconstriction 548-49 oral dose 40 (table) brand names 875 (table) peak of action 39 (table) central vasomotor loci inhibition pKa 37 549-550 plasma elimination half-life 37 (table) chemical structures 107 (table) protein binding 36,37 (table) clinical effects 550-551 site of action 30 (table) combined blockade al-adrenoceptorsl see also diuretics 5-HT2 receptor-mediated indolapril (Cl907; SCH31846), 386, 387 amplification of noradrenaline (fig),387 response 550 see also converting enzyme inhibitors "direct" vasodilatation 550 indomethacin 53,54,418 (table), 428, dosage 867 (table) 511 (fig) side effects 551 effects on renin 515 6-keto-prostaglandin-F 1« 32 in essential hypertension 515 9-ketoreductase 35.517-518 105-106,115 KF-577 196 brand names 875 (table) KF-4317 196.199 (table) dosage 866 (table) kidney indorenate 542 (fig), 544 defect in hypertension 8, 9 intrinsic stimulant activity (ISA) 82-85, diuretic effects on hemodynamics 88,92 31-32 isoniazid 326 dopamine effects 566-569 67, 78 hypertension effects 12 N-isoprophyl-1-methylenpyrrolizidinium pain effect 33 bromide 719 parenchymal disease, reduced nephron isoquinolone alkaloids 713-715 population 32 isoteres 485 potassium balance maintenance 44 reduced peptide 486 stress effect 33 isradipine 302 kinins 35 chemical structure 303 (fig) endogenous 409 effect on blood pressure 310 converting enzyme inhibitors effects see also calcium antagonists on 410-419 (table) kukoamine A 713 kuwanon G 721 Japan 854-857 kuwanon M 721 antihypertensive therapy 855-857 hypertensive disease 854-855 jatamansone (valeranone) 727 labetalol 133,134.137-162,816 jikoppi 713 absorption 146-147 Juniperus communis 732 acute blood pressure response 144.146 animals 144 kaempferol 721 humans 144-146 kaempferol-3-O(2" ,6" -O-di-p-cumaryl)-~­ adverse reactions 157-162 D-glactopyranoside 721 adrenoceptor blockade induced kallikrein 35 159-160 kallikrein-kinin-prostaglandin system after i.v. administration 151 380 (fig), 512, 517-518 non-specific 161-162 K-channels, open smooth muscle bioavailability 147 643-668 a-/~-blockade activity 138-142 causal relationship between K channel in vitro 138 opening in vitro and hypotensive in vivo 140-142 effects in vivo 653-654 brand names 875 (table) evidence for role 653.663-664 catecholamines influenced by 146 type modulated by cromakalin chemistry 107 (table), 135 (table), 137 664-665 daily dose 83 (table) type modulated by pinacidil 654-655 distribution 147 ketanserin· 108.547-551.751 dosage 861 (table) 914 Subject Index

elimination 148 luteinizing hormone releasing hormone hemodynamics 144-146 379 animals 144 lysophosphatidyl choline 730 humans 144-146 in: magnesium 41 chronic liver disease 149 altered intake effect on blood pressure clonidine withdrawal 156 699 controlled hypotensive anesthesia effects on eclampsia/pre-eclampsia 699 156-157 loss-diuretic-induced 48 impaired renal function 155 blood pressure effect 693-4 myocardial infarction 157 magnoflorine 715 pheochromocytoma 156 majarol 714 pregnancy 148-149, 155 market for antihypertensive treatment renal disease 149 16-17 renal function impairment 155 renal hypertension 155 brand names 875 (table) tetanus 156 dosage 865 (table) long term oral treatment 145 meclofenomate 53 melanin pigment of eye binding 147 135 (table), 196 metabolism 150 mefruside 25 metabolites 150 brand names 875 (table) pharmacological profile 83 (table) dosage 864 (table) plasma concentration-blood pressure 8-MeO-CIEPAT 542 (fig), 543 effects relation 149-150 receptor binding 138 brand names 875-876 (table) renin-angiotensin-aldosterone system dosage 861 (table) influenced by 146 mercapto group 458 steady state kinetics 148 D-3-mercapto-2-methylpropanoyl-l- therapeutic use 150-157 proline 383 acute 150-152 mercaptotolactum 384 (fig) black patients 154-155 messenger RNA encoding calcitonin 601 chronic 152-155 metabolic acidosis 44 other drugs compared 153-154 metergoline 545 toxicology 146-147 methiothepin 545 vasodilatory action 142-144 see also ~-blockers brand names 876 (table) lanthanum 306 dosage 866 (table) leukotrienes 508 113 (table), 243 (table) peptidolipid 512 3-methoxy-a-methyldopa 233 levomoprol 3-methoxy-a-methyldopamine 233 brand names 875 (table) methylclothiazide 25 dosage 861 (table) brand names 876 (table) lignans 724-725 dosage 864 (table) lignocaine 90 a-methyldopa 14,228-229,232-234, lipid metabolism, diuretics effect 50 813 Iipoxygenase 510, 513 absorption 232 inhibitors 510,511 (fig) a-adrenoceptor-blocking drugs effects pathway 509 (fig) 240-241 Iisinopril (MK-521) 387 (fig), 388-390 bioavailability 232 (table),391 brand names 876 (table) brand names 875 (table) combination with other drugs 249-250 dosage 860 (table) contraindications 252 563 (fig) discontinuation syndrome (withdrawal lithium 53 syndrome; rebound clearance 318 syndrome) 251 dosage 249,863 (table) brand names 875 (table) drug interactions 250-251 dosage 863 (table) metabolism 232-233 Subject Index 915

mode ofaction 237-238,247 dosage 340-341,862 (table) pharmacodynamics 236-237 drug interactions 346-347 side-effects 14-15,250-251 hydrochloride salt 303 therapeutic use 246-249 metabolism 329 a-methyldopamine 233 renal effects 317 methylenethio group 489 side effects 348-349 a-methylnoradrenaline 229,233,236 therapeutic use 340-341 a-methyl-p- 245 toxicity 348-349 methyseride 545 see also calcium antagonists meticrane nicorandil 668 brand name 876 (table) comparisons with: dosage 864 (table) calcium antagonists 665 cromakalim 665 brand names 876 (table) pinacidil 665 dosage 861 (table) nicotine 239 metolazone 25,42 nifedipine 302,326-328,749-750,816 brand names 876 (table) absorption 326-327 dosage 864 (table) bioavailability 327 69,70 brand names 877 (table) brand names 876 (table) chemical structures 302 (fig) dosage 83(table), 861 (table) co-administration of other drugs 328 hepatic metabolism 71 contraindications 346-347 intestinal absorption 71 dosage 336-240,862 (table) nerve activity effects 78 drug interactions 346-347 pharmacological profile 83 (table) effects see also j3-blockers aldosterone secretion inhibition 315 milrinone 795 blood pressure 310 mini press see cardiac 308 minoxidil 90,667,814 cardiac hypertrophy prevention 320 brand names 876 (table) cholesteryl ester decrease 324 dosage 867 (table) hemodynamic 314 myocardial necrosis associated 795 natriuretic 316 renin secretion stimulation 315 preservation of vascular integrity side effects 795, 814 323 treatment of hypertensive rats renal 316,317,318-319 321 (figs) serum potassium decrease 317 water/sodium retention 315-316 smooth muscle cell proliferation see also calcium antagonists inhibition 324 mistletoe, European 731 metabolism 327 (fig), 328 MK-421 see enalapril pharmacokinetics 328 MK-761 134,136 (table), 196 side effects 348 chemistry 137 (table) therapeutic use 336-340 monoamine oxidase 581 toxicity 348 morphine 715 treatment of hypertensive rats 319 mortality, blood pressure-related 766 (figs), 321 (figs) (table) see also calcium antagonists mulberrofuran C 721 nifedipine-oxidising microsomal enzymes 328 nimodipine 795 brand names 877 (table) 134, 136 (table), 190-194 New Guinea, absence of hypertension chemistry 136 (table), 190 688 hemodynamics 192-193 nicardipine 302,328-329 metabolism 193-194 absorption 328-329 mode of action 191-192 bioavailability 329 pharmacodynamics 139 (table), brand names 877 (table) 191-192 chemical structure 320 (fig) pharmacokinetics 193-194 contraindications 346-347 therapeutic use 194 916 Subject Index

toxicology 193 8-0H-DPAT 541,542 (fig), 543, 545 (fig) nisoldipine 302 15-0H-PG dehydrogenase 35 chemical structure 303 (fig) Olax gambecola 732 effects Olea europa 726 cardiac hypertrophy prevention 320 oleuropein 726 vascular selectivity 308 orthostatic hypotension 51 myocardial necrosis associated 795 osthole 723 see also calcium antagonists ototoxicity 51 nitramarine 716 69 nitrendipine 302,329-331 brand names 877 (table) absorption 330 dosage 83 (table), 861 (table) bioavailability 330 intrinsic sympathomimetic activity 82 brand names 877 (table) pharmacological profile 83 (table) chemical structure 302 (fig) see also j3-blockers co-administration of other drugs 245 330-331 oxypropanolamines 69 contraindications 346-347 ozolinone 25,32 dosage 341-343,862 (table) bioavailability 37 (table) drug interactions 347 chemical structure 23 (fig), 24 (table) effects pKa 37 (table) atrial natriuretic peptides 320 plasma elimination half-life 37 (table) blood pressure 310-311 protein binding 37 (table) cardiac hypertrophy prevention 320 receptor 27 presentation of vascular integrity see also diuretics, loop 323 renal 317 pacrinolol 196, 197 (table) vascular selectivity 309 pancreatic polypeptide 605 myocardial necrosis associated 795 avian 606 pharmacokinetics 330 papaverine 316 side effects 349 therapeutic use 341-343 brand names 877 (table) see also calcium antagonists dosage 865 (table) nitroglycerin 309 Parkinson's disease 79,582 nitroprusside Pasteurella multocida lipopolysaccharide brand names 877 (table) 728 dosage 867 (table) pempidine nondrug measures 5-6 brand names 877 (table) nonedematous subjects, diuretics dose• dosage 865 (table) effect curves 31 (fig) nonselective agonists 112 brand names 877 (table) nonsteroidal antiinflammatory drugs 53, dosage 83 (table), 861 (table) 55 lipid solubility 70 noradrenaline 34,67,75,111 (fig), 243 pharmacological profile 83 (table) (table), 427,522 (table), 613 (table) see also j3-blockers (J.-m- 243 (table) penicillopepsin 492 nonselective agonist 112 pentobarbitone sodium 239 ramiprilat influence on 431 (fig) 813 release from presynaptic sites 112 brand names 878 (table) normotensin 2, 3 dosage 865 (table) Northern Ireland 821, 825 pepsin 492 norverapamil 325 pepstatin A 484,486-487 Norway see Scandinavia peptides 597-630 nucleus reticularis lateralis 239 peptide YY 605-606 nucleus tractus solitarii 239 562 (fig), 579 (table) perindopril 386,388-390 (table) obamegine 714 peripheral neuronal inhibitors 14 oblongate medulla 239 phase-I-metabolite p-hydroxytriamterene obtusoside 723 42 Subject Index 917 phenethylphosphonamide 391 (fig) reproductive tract 652 phenhydantoin 53 spontaneous mechanical activity 649 phenobarbitone 90 trachea 652 phenoxyacetic acid derivatives 22 evidence for role of K channels 653 105, 106, 81S mechanisms of action 653-655 absorption 108 metabolism 647 brand names 878 (table) myocardial necrosis associated 795 chemical structure 107 (fig) pharmacodynamics 648-652 dosage 866 (table) pharmacokinetics 647 duration of action 109 stereospecificity of cardiovascular dosage 121 actions 649 nonselective compound 112 stereospecificity of in vitro effects 650 therapeutic use 121 tissue distribution 647 phenocyethylamine 134 pinacidil-N-oxide 646 (fig), 651,652 (regitine) 105,109,112, 69,74,84 113 (table), 241, 815 brand names 878 (table) brand names 878 (table) dosage 83 (table), 861 (table) dosage 121,866 (table) intrinsic sympathomimetic activity 82 therapeutic use 121 isomers 70 vasodilatation due to 115 pharmacological profile 83 (table) phenylbutazone 511 (fig) see also ~-blockers 113 (table), 243 (table) pinoresinol diglucoside 724 1-phenyl-3-methyl-propylamine 134 piperoxam 240, 242 pheochromocytoma 32, 108, 156, 180, piretanide 25 293 bioavailability 37 (table) neuropeptide Y overproduction 606 brand names 878 (table) prazocin preoperatively 122 chemical structure 23 (fig), 24 (table) phospholipidase A2 508 dosage 864 (table) N-phosphoryl-ala-pro 391 (fig) duration of action 39 (table) photosensitisation 788 onset of action 38,39 (table) phototoxicity 788 oral dose 40 (table) phthalimidines 25 peak of action 39 (table) physostigmine 239 pKa 37 (table) Picrasma quassioides derivative 717 plasma elimination half-life 37 (table) pinacidil 645-656 protein binding 37 (table) adverse reactions 656 renal site/mechanism of action 26, 30 chemistry 645-7 (table) clinical effects 655-656 tubular fluid/plasma-sodium comparisons with: concentrations ratio 30 (table) calcium antagonists 665 see also diuretics cromakalim 665 piroprost 511 (fig) nicorandil 665 pivalopril (RHC3639) 384 (fig), 385 effects on: plant extracts 730-732 agonist-induced contractions platelet calcium levels 312 649-650 platelet-activating factor (PAF-acether) agonist-induced pressor responses 516 649 poly thiazide 25 basal blood pressure 648 brand names 878 (table) bladder 652 dosage 864 (table) cardiac muscle 651-652 potassium 690-692 electrical/mechanical activity"in rat altered intake effect on blood pressure" portal vein 651 (fig) 696,697 (table) gastrointestinal tract 652 balance, diuretic effects, healthy heart rate 648 subjects!hypertensive patients 42K efflux 650 47 (table) membrane potential 650 effects on blood pressure 43-44 86Rb efflux 650 blood pressure lowering effect 46 regional blood flow 648, 649 diuretic induced depletion 46 (fig) 918 Subject Index

urinary 44 Fza 513,515 69, 70 G2 513 ~-blocking action 74 (table) H2 513 intrinsic sympathomimetic activity 12 513 82-83 converting enzyme inhibitors effects side effects 92 410-419 (table) see also ~-blockers decreased degradation 35 prazosin 15,106,113 (table), 751 metabolism stimulation by loop diuretics absorption 109 34-35 animal reactions 115 renal excretion effects 518 brand names 878 (table) synthesis/release abnormalities in chemical structure 107 (fig) essential hypertension 521 (table) chemistry 106 prostenon 846 combination with other drugs 123 protein kinase 73 dosage 121,866 (table) Prunus spinosa 732 hemodynamic profile 119 psychorelaxation therapy 844 metabolism 109 pteridine derivatives 22,24 (table), 25 phosphodiesterase inhibition 117 pyrazine derivatives 22 side-effects 15, 124 pyrimidine derivatives 22 therapeutic use 121-122 pyrrolizidines 719 venous dilatation due to 117 prerenal azotemia 51 quinapril 386 prevented events rate (PER) 772,774 quinazolinones 25 primitive societies 688 quinethazone 25 prizidilol 134, 136 (table), 196 brand names 879 (table) probenecid 53 dosage 864 (table) prodrugs 25-27 quinolizidine alkaloids 718-719 progressive muscular relaxation 844 quinpirole 562 (fig), 571 proline 383 prolylhydroxylase, aortic 447 racemic hybrids 137 67; see also ~-blockers ramipiril (HOE498) 386,387 (fig), 388- 69,815,878 (table) 390 (table), 414 (table) adrenoceptor blocking activity brand name 879 (table) 138-139 (table) different doses effect on regional blood baroreflex effect 78 flow/vascular resistance 434 (fig) bioavailability 71,90 dosage 860 (table) brand names 878-879 (table) effect on prostaglandins 410 central nervous effects 79 inhibition of aortic enzyme 443 chemical structure 67 pretreatment effect on angiotensin II chemoreflexes effect 78 concentration in rat heart 436 (fig) dosage 83 (table), 861 see also converting enzyme inhibitors interaction with serotonin ramprilat 383 (fig) receptors 73-74 effect on: intestinal absorption 71 noradrenaline 431 (fig) lipid solubility 70 prostaglandins 410 log partition coefficient 70 sympathetic nerve stimulation 439 nerve activity effects 77 - 78 (fig) peripheral autonomic nerves effect 88 inhibition constants 396 (table) peripheral blood vessels effect 76 see also converting enzyme inhibitors pharmacokinetic interactions 90 rats, spontaneously hypertensive 319 pharmacological profile 83 (table) (figs), 321 (figs), 322, 323 (table) renal effect 76 Rauwolfia alkaloids 811-812 see also ~-blockers see also prosegment peptides 489-491 Rauwolfia whole root prostacyclin 32, 34 brand names 881 (table) prostaglandins 32-33,506-525 dosage 866 (table) E J 508 108,113,243 (table) Ez 34,55,316,508,513,518,519 ~-receptors 72-73,74 Subject Index 919

reflex tachycardia 90 dopamine depletion 267 - 268 lack 115-116 dopamine-j3-hydroxylase affected by regitine (phentolamine) 105,109,112, 269 113 (table) dosage 866 (table) relaxant factor, endothelium-derived, 5- European use 811-812 hydroxytryptamine related 546 hemodynamic effect 272-273 renal artery stenosis 32 5-hydroxytryptamine depletion renal kinin system 35 267-268 renal nerves terminals 572 menbrane Ca channels affected 272 renin 436,441 metabolism 264 (fig), 275 renin-angiotensin system 11 , 379, 380 mode of action 265-272 (fig),4oo-409 neuronal/extraneuronal uptake eicosanoids effects 514-517 265-266 local, in heart 436-437 neuropeptide Y depletion 268 labetalol influence 146 noradrenaline depletion 266-267 synthesis/release model 442 (fig) other uses 264-265 renin antibodies 484 postsynaptic sensitivity 270-271 renin inhibitors 483-498 receptor sensitivity response 269 administration in humans 497 receptor transport with neurons affected chemistry 484-494 272 hydroxymethylene isoteres (and serotonin receptor modification related inhibitors) 478-479, 271-272 490-491 (table) side effects 273-274 molecular modelling 491-492 sympathetic responses 269-270 prosegment peptides 489-491 increase 269 reduced peptide isoteres 486 retroinverso analogue 32 489 renin antibodies 484 retronamides 719 statine-/modified statines containing REV6000-A 387 (table) inhibitors 486-487,488 (table) rhomotoxin 849 substrate analogues 484-485 rhynchophylla 849 transition state analogues 485 196,197 (table) hemodynamic effects 493-497 rifampicin 90,326 intravenous application 494-495 R0160A 196,199 (table) mechanism of action 493-497 R031-2848 387 (table) metabolism 493 RP 49356 666-667 oral application 495-497 pharmacodynamics 493-497 S-9490-3 391 (fig) pharmacological studies 494 SA-446 384-385,453 pharmacokinetics 493 salt-sensitive hypertensive subjects 34, 35 reproductive toxicology 787-788,798- Sambucus ebuLus 732 803 sanggenon 721 angiotensin-converting enzyme sarafotoxins 626 inhibitors 799-800 saralasin 400,413 (table), 427, 429 carbonic anhydrase inhibitors Scandinavia 820-826 800-802, 803 death rate from cardiovascular disease diuretics 800 825 loop 802-803 drug sales 821 (fig), 822 (fig), 823 (fig), 824 (figs) brand names 879 (table) expenses for hypotensive drugs 826 dosage 866 (table) SCH-2330 565 reserpine 14,245,263-275,607 SCH-23390 562 (fig) adenosine triphosphate depletion scoparone 722-723 268-269 scopoletin 723 adrenaline depletion 267-268 sea anemone polypeptides 730 adrenoceptor modification 271 selective compounds 112 binding sites 266 serotonin see 5-hydroxytryptamine brand names 879 serromechanism, biological 516 distribution 274-279 sesquiterpenes 727 920 Subject Index

Sideritis mugronensis 732 741-761 SKF 3'3393 562 (fig) a-adrenergic blockers 751 SKF 82526 see fenoldopam ~-adrenergic blockers 748-749 SKF 86466 113 (table) angiotensin-converting enzyme SKF94120 795 inhibitors 750-751 small intensively fluorescent cells 571 calcium antagonists 749-750 smoking 6 diuretics 746-748 snake venoms 730 down-stepping 753-754 sodium 688-690 individualized therapy coexisting altered effect on blood pressure 751-753 694-696 liberal stepped-care program 752 sodium nitroprusside 311,814 side-stepping 753-754 sodium pump 26 traditional programs 743-745, sodium transport defect 10 746 (fig) Solomon Islanders, absence of up-stepping 753-754 hypertension 688 steroid alkaloids 720 stopping antihypetensive therapy brand names 879 (table) 754-761 dosage 83 (table), 861 (table) stroke survivors, hypertension elimination half-life 72 treatment 775 excretion 71 substance P 379 intestinal absorption 71 substance III 384 (fig) pharmacological profile 83 (table) substance-20 387 (fig) see also ~-blockers substrate analogues 484-485 Southern Californians, incidence of succinylproline 383 stroke 691 sulfamoylbenzoates 25 specific central antihypertensives 228 sulindac 511 (fig) spermidine alkaloids 712-713 135 (table), 196 spironolactone 25,26, 813 chemistry 135 (table) bioavailability 37 (table) sulfonamide( s) brand names 879-880 (table) benzene 25 chemical structure 23 (fig), 24 (table) thiazide-like 23 dosage 864 (table) onset of action 38 duration of action 39 (table) patients with impaired renal function excretion 37 42 fractional sodium excretion patients with normal renal function 30 (table) 41 inhibition of aldosterone action 28 renal hemodynamics 31 intestinal absorption 36 side effects 52 kallikrein release suppression 35-36 sulfonamide derivatives 22-24 on~et of origin 39 (table) chemical structure 23 (fig) oral dose 40 (table) chloruretic 23 metabolism 37 renal site/mechanism of action 26 peak of origin 39 (table) sulpiride 562 (fig) plasma elimination half-life 37 (table) Sweden see Scandinavia protein binding 37 (table) sympathetic systems, overactive 9 primary aldosteronism treatment 41 sympatholytica with central action renal excretion of PGEz 34 813-814 renal site/mechanism of action 26, 29-30 brand names 880 (table) side effects 52 dosage 866 (table) see also diuretics spiroperidol 563 tabernulosine 716 542 (fig) tali nolo I SQ 28555 (fosenopril) 391 brand name 880 (table) statine/modified statines, inhibitors dosage 861 (table) containing 486-487,488 (table) tannins 726 statine analogue 41 489 TE-176 199 (table) stepwise treatment of hypertension teoprolol 196,199 (table) Subject Index 921

teprotide 381,383,427 hepatic metabolism 71 106,113 (table), 118 pharmacological profile 83 (table) absorption 109 see also f3-blockers brand names 880 196,197 (table) combination with other drugs 123 105,107 (fig), 113 (table) dosage 122,866 (table) torasemide 25 hemodynamic profile 120 toxicity testing of antihypertensive drugs metabolism 109-110 783-804 plasma-elimination half-life 110 acute (single dose) 788 side effects 124 carcinogenicity 786 therapeutic use 122 immunotoxic effects 788 see also a-adrenoceptor agonists multidose general toxicity 784-6 terpenoids 726~ 728 " mutagenicity 786-787 phototoxicity/photosensitisation tests brand name 880 (table) 788 dosage 862 (table) predictivity 788-789 tetandrine 849 reproductive toxicology see reproductive tetraethylrutoside 722 toxicology tetrahydrofurans 725 skin irritancy/sensitisation 788 bis-tetrahydrofurans 725 trachelogenin 725 tetrahydroisoquinoline alkaloids trandolapril 443 713-715 transition state analogues 485 tetramethylpyrazine 719-720 treatment guidelines 778 (fig) thalystyline 714 triamterene 25,26,813 therapeutic attitudes 777 - 779 bioavailability 37 (table) therapeutic quotient (TQ) 772-773 brand names 880 (table) thermolysin 381 (fig) chemical structure 23 (fig), 24 (table) thiazide(s) 23,813 dosage 864 (table) cholesterol changes 50 duration of action 39 (table) elderly patients with normal renal excretion 37 function 40-41 fractional sodium excretion 30 (table) fractional sodium excretion metabolism 37 30 (table) onset of action 39 (table) negative influence on glucose/lipid oral dose 40 (table) metabolism 435 patients with impaired renal function onset of action 38 42 patients with impaired renal function peak of action 39 (table) 42 plasma elimination half~life 37 (table) patients with normal renal function primary aldosteronism treatment 41 40-41 protein binding 36,37 (table) renal hemodynamics effect 31 renal site/mechanism of action 26, 30 side effects 52 (table) sodium excretion 29 side effects 52 see also diuretics target site 28 thiazide analogues 23, 24, 25 see also diuretics thiazolidine derivatives 22,24 (table); trichlormethiazide 25 see also etozolin brand names 880-881 (table) thrombocytes, ionized calcium in 312 dose-effect in nonedematous subjects thrombpxane A2 513, 515 31 (fig) thromboxane B2 515 distribution coefficient, ether/water thyrotoxicosis 81 31 (table) dosage 864 (table) brand name 880 (table) relative natriuretic potency 31 (table) dosage 863 (table) see also diuretics tiapamil 310 trichotomine" 717 tilirosid 721 triethylrutoside 722 69 trifluotoketone analogues 39 489 brand names 880 (table) 106,113 (table), 117-118 dosage 83 (table), 862 (table) bioavailability 109 922 Subject Index

chemical structure 107 (fig) absorption 325 combination with other drugs 123 bioavailability 325 dosage 122 tuberculostatic therapy effect 326 hemodynamic profile 120 brand names 881 (table) side effects 124 chemical structure 302 (fig) therapeutic use 122 contraindications 346 trimethaphan 813 digoxin/digitoxin co-administration brand name 881 (table) 326 dosage 865 (table) distribution 325 tripamide dosage 333-336,862 (table) brand name 881 (table) drug interactions 346 dosage 864 (table) effects troxerutin 722 blood pressure 310,311 tubulo-glomerular feedback mechanism hemodynamic 313 32 intracellular cholesteryl esters 324 tyrosine hydroxylase 269 intracellular phospholipids 324 intracellular triglycerides 324 UK-14,304 113 (table) isolated cardiac preparations 308 Union of Soviet Socialist Republics negative chronotropic 314 844-847 reflex tachycardia 313 United Kingdom 827-831 smooth muscle cell proliferation United States of America 833-838 inhibition 324 antihypertensive combinations available excretion 325 881-883 (table) hydrochloride salt 303 urapadil 108,118-119,542 (fig), 544, 751 liver disease patients 326 bioavailability 110 metabolism 325 (fig) brand names 881 (table) pharmacokinetics 324-326 chemical structure 107 (table) pKa 303 dosage 123,866 (table) receptor site 306 hemodynamic profile 120-121 side effects 347 p-hydroxylated 110 therapeutic use 333-336 plasma elimination half-life 110 toxicity 347-348 side effects 124 see also calcium antagonists therapeutic use 120-121 Veratum alkaloids 711 see also a-adrenoceptor antagonists vincamine 717 uric acid clearance 318 viscotoxin 731 Urtica dioica 732 vitexin 721 warfarin 53 valeranone Uatamansone) 727 WY-44,221 384 (fig), 358 vas afferens 316 vasopressin 516 84 vascular converting enzyme 441 xipamide 25 inhibition 443-444 brand names 881 (table) antihypertensive action 444-446 dosage 864 (table) functional aspects 446-447 243 ( table) specificity 442-443 vascular hypertrophy 449 108, 113 (table), 240, 241, 242 vasodilators 16 chemical structure 107 (table) side effects 16 YS980 384 (fig), 410 (table) vasopressin 34 verapamil 301-302, 749-750, 816 zofenopril (SQ26,991) 384 (fig)