פרמקולוגיה מצגת מספר 1 (1)

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<p> 1:: -9871. " , " / . : : . - , , - , ...- - " : ( ) - . : , ( ), , ,IV,IM, . : , , , ...., , . : : . : ,ATP . -pH &amp; pKa . ()- IV . - - efficacy . . ( ) ( , ). - . , . , ( ) . : ( )first pass effect .</p> <p> Vd=D/C D C Vd . - : 1 -Phase " ,OH, NH2, SH . 2 -Phase glucuronic acid, sulfuric acid, acetic acid, amino acid - . - , , . :IV s.s . S.S . 5t .S.S , .</p> <p> S.S loading dose" .Loading dose=Vd*C</p> <p> 2: , ( , :Drug- Receptor Interaction ( , ...) , " " " " - . *- " " . : -Regulatory proteins " , . -Enzymes " -Transport proteins Na/K ATPase " . " Structural proteins tubulin . - . -Agonist " ).(allosteric effect - . . </p> <p> -A: , . -G-protein -B , , . . G () G (). . -C - , . ( ) .</p> <p> , " . -Intracellular receptors -D , .DNA DNA . " . . : . )05 -Effective concentration 50% (Ec ( )log %05 . : -Y -X . 05 Ec . :Potency KD ( 05.)Ec -Efficacy . ( efficacy .partial agonist TI :TI %05 )05 (Lc50/LD %05 )05 .(Ec50/ED . warfarin . - " . " . : : , , Emax . : " . . Emax - Emax. : . : . : . , . . . . : . .- .</p> <p> . : , . () . : ,GI , SC /IM . ( ) %08 %56 . . , .: . , GI , , . . CNS .hangover . .orthostatic hypotension( ). : GI . IM . . .: , , , .: . . : - ..., "" . . , . . . :Feedback system () , "" "" . : , . :Down regulation . (" ) "" . :Up regulation. : , , </p> <p> , . " .mixed agonist/antagonist :Resurgence .</p> <p> 3 : ) -(CNS , " .BBB ) -(PNS : - ( ), CNS . . - " : -. . . . . , , CNS : CNS -</p> <p> : 1. - rest &amp; digest . . . . 2. - ,fight or flight . , , " . . . : , - GABA</p> <p> : . ( + ) " . : " ( " ) . A . ( ). " . / / , . . . * . : , , , . . : 5M1,M2,M3,M4,M 1 -M , ,.gastric parietal cells CNS 2 -M , . 3 -M , . 5.CNS -M4+M</p> <p> 4 </p> <p> , . : -N -C, ,G-protein G-protein GTP . :G-protein 1. - ( ) 2. - , .AMP 3 -Gq C 3 IP . 5 -M1, M3, M G-protein Gq . 4 -M2, M G-protein G-inhibitory : ( ) ).(SA node- Ca .</p> <p> : , , . " . . . : . ( ). , , , , , , . " . : , ( ), ( ) . :Bethanechol " . . . :Carbachol , . :Pilocarpine , , , , , .CNS : !, , , . . "-" . . : 1. ... Myasthenia gravis 4-2 ... GI , BBB GI ,miosis . CNS Neostigmine Physostigmine</p> <p> Myasthenia gravis MG</p> <p>6-3 02-01 </p> <p>Pyridostigmine Edrophonium</p> <p>2. : ( ). . : , . " .</p> <p> : , . :Atropine: - GI - - , - . : ( (NN ) (NM , , . : , , . . :Trimethaphan , , . : . : 1. ""- . 2. - , . - . :Non depolarizing agents , . ( ). : , , , , . . , . :Depolarizing agents , ( ) . .</p> <p> 5- : CNS ( )fight or flight : . (.)Varicosities : / . . rate ,limiting step . . , , . " .re uptake ": , " re uptake ,COMT ,symport .Re uptake -MAO-Monoamine Oxidase , : MAO-A . MAO-B . : 2.1,2, 1, 1 : G-protein Gq ( , , , ). ( . 2 : 2 G-protein , , , . 1 : G-protein, , . 2 : , , G-protein, . : up/down regulation :</p> <p> "" . / . G-protein .</p> <p>-</p> <p> : : -: (, ). - - : , , , ,BBB " . : . , - . . " . .: -: 2( ). 1( ) 1( ). . , 1. 2. . : 2. : " . / . : , , , , . : .1 , . . , , , ( ). :Isoproterenol , 2( ) 1( ). : 5 D1-D , 1.D 2 D . . .</p> <p> : 1D ( , )</p> <p> 1( ) 1 </p> <p> .... (CHF ) AV 1 ( ). , " . </p> <p> : : 1 Dobutamine</p> <p> Phenylephrine 2 2 2 Clonidine Terbutaline Albuterol</p> <p> .... , , </p> <p> , MAO CNS Tyramine</p> <p> : :Ephedrine NA, ,, MAO ,COMT , , CNS . : ( ). . .... 2,1 phechromocytoma Phentolamine phenoxybenzamine 4 (42 ) Phenoxybenzamine 2,1 ,TPR ( " 2 ) 1 TPR Prazosin , . , , , . : postal hypotention : , , , , . .... ( ) propranolol 2 . 2,1 ( . , , , , Hyperthyroidism : , , , , ,Timolol 2,1 Timolo Nadolol</p> <p> , , , . , </p> <p>Pindolol 1 ,Labtalol carvedilol</p> <p> : -Reserpine NA ". -Guanethidine NA NA " MAO -Cocaine NA .</p> <p> 6- - : : , , 2,CO 2 CO . . : - , .... - - - . SA node , ( ) . SA node ( AV node , ) (0.5 sec AV node ) (0.1 sec . : , . : -Pacemaker cells . -Automaticity . -Non pacemaker cells . -Over drive suppression - , . over drive suppression SA node , . : , , . - " :</p> <p> 0: ( ) " (05+). 1: , . 2: . 3: ( ). 4: , " " , . .. :SA node 4 , . SA node, AV node (06-) ( 06-) (09-) SA node , . SA node , 09- ( 08- %08 06- %5 ) SA node , , . 4,3,0 : / :Na/K ATPase , ( )ER RYR 2 . SERCA (ER ( ER ER ) .</p> <p> 4 ( 2). 4 , . NCX Na/K ATPase . ( Phospholamban 71) SERCA" " ATP .ADP : adrenergic " , G-protein ,cAMP ) PKA (phosphatase kinase , . PKA ( SERCA ) . ER , . cAMP" ( cAMP), cAMP cAMP . %07 cardiac output cardiac output %04. ""- , , , , . " , , 2 : 1. , , . 2. . , - . . , . 4 ( 4 ) . , .</p> <p> , , , , . . cardiac output , , ": .Remodeling , afterload , preload :Afterload , . :Preload ( ) ( 4), . preload . preload , preload preload cardiac output. preload afterload , cardiac output. preload : : cardiac output , preload. : cardiac output .preload ( : )shock cardiac output ,preload preload ?cardiac output :Afterload ( )A afterload cardiac output cardiac output . ( )C ,afterload () Cardiac output ( )B afterload cardiac output. </p> <p> : :Inotropic agents : Cardiac glycosides Sympathomimetic amines -Phosphodiesterase inhibitors cAMP PKA , . :Afterload reduction ( .)afterload : ACE inhibitors adrenoceptors antagonists vasodilators -preload reduction preload : ( diuretics ) .Venodilators ( 82) Na/K ATPase . - , , . :Na/K ATPase 4 . , , , , . - , . , .Na/K ATPase "- " .Na/K ATPase "" . . , , , , -AV node ,AV node ( 4) . , , . , , , . - . -Digitoxin , ( 7 - t). : , . AV node .</p> <p> :cardiac output -A . -B : cardiac output A B cardiac output , , preload cardiac output .C -C cardiac output C ,D , -E E cardiac output preload, , "" .preload : ,cardiac output ( , ). :Dobutamine 1 , , . :PDEinhibitors ,cAM , 3PDE :Amrinone; Milrinone / , (+) ,preload &amp; afterload .ion-dilators :Renin , , . :Tubuloglomerular feedback . , 1 "" 4 1 " " 2 " 2 2. 2 , ,collecting duck , , ( preload ). 2 .afterload : - - . (- , - tension / .) : , . " 2 . 2 " ACE , ACE : 2. ( ) . 2: 1 :AT = ,G-protein .- 2AT</p> <p> -ACE inhibitors : --&gt; . .CHF . . . : Postural hypotention hyperkalemia . :ACE inhibitors :Captopril . :Enalapril Ramipril , . :Lisinopril " , ( ). : :Losartan &amp; Valsartan . : adrenergic antagonists / cardiac output . "" , , cardiac output . , afterload .preload -Metoprolol 1. -Labetalol 1. _Carvedilol 1 . . -Bisoprolol 1 : () , . - , , , %001 , %4.0 ( ) (-6 ), Na/K ATPase . ( ) , , . ,CAII , . :Acetazolamide CAII .</p> <p> ,Mannitol , . , . :Loop diuretics , , - - ,Na/K ATPase . . , . : distal convoluted tubule ,Thiazides . ,, . . %5-1 , . collecting duct ( / ) ( DNA ), , . : 1. - spironolactone " . 2. -ENaC .Amiloride ; Triamterene , . - ( , ) . :Vesodilators/Venodilators afterload " , preload" . , , . : -Minoxidil , , ( </p> <p> 7- - :- , , " . , . -: 1. ) : (resting m h -06. 2. ) -(active m h, - %05 0, , -06 -04 3. ) -(inactive m h -04 -06. . - m </p> <p> ( )rest . " %52 .rest -Altered Automaticity : 4 . - : " , , 4 4 . , ( 07 011 ) - " - " . ( -07 06 .)</p> <p> : 1. -Fast response 2. -slow response , 0 " ( Vmax) , " . -ERP , . ( -%52 )rest : : ( ) ( ) - - . : :Altered impulse formation ( 4) ( SA node ) SA node . , : :AV block SA node .AV node :Bundle branch block . :Early afterdepolarization . :delayed afterdepolarization . :Re entry , . " , . . ( B ) . B</p> <p> ( A ), ,re-entry , .Cardiac output : - , . - 0 . - . . : , ( , ), " .AV node . : , " .supera ventricular " , , . ,SA node . , , , . , , ( ) - , , . : , . , ,rest . " - " . . 1. : -A . -B " -C Umax . 2. , " , 1 2,M G-protein inhibitory , 4, . 3. , .</p> <p>4. AV node" . , . , , . . ( ) , ( ). : -Quinidine , . " - , AV node -lidoocaine Ventricular arrhythmias IV , - (" 2) : .CNS -Aminodarone , , .</p> <p> 8- : - : , , . : 1. -Chronic stable angina , . " , . 2. -Un stable angina , . 3. -Variant angina , . : . ( ) , ( ). ATII . ATII ATI - " ATII " G-protein 1 Q . 2 G-protein , . - ) .Myosin-LC-Kinase (MLCK ( ). ' . - 1 , .</p> <p> , :NO NO , , ( .)Guanylyl cyclase GTP cGMP - -' ,...</p>