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10
CONTENT
Foreword to 1st Edition ......................................................................................................17
Foreword to 2nd Edition .....................................................................................................19
1. GENERAL PHARMACOLOGY. INTRODUCTION................................................21
1.1. Subdivisions of Pharmacology..............................................................................21
1.1.1. Main Subdivisions ..........................................................................................21
1.1.2. Other Developing Subdivisions ......................................................................22
1.2. Border Sciences......................................................................................................23
1.3. The Practical Usefulness of Pharmacology..........................................................23
1.4. Phases of Drug Evolution in the Body, from Administration until Time
of Therapeutic Effect ............................................................................................24
1.4.1. Biopharmaceutic Phase ...................................................................................24
1.4.2. Pharmacokinetic Phase ...................................................................................24
1.4.3. Pharmacodynamic Phase.................................................................................26
2. INTRODUCTION IN GENERAL BIOPHARMACY ................................................27
1.1. Drug Bioavailability ..............................................................................................27
2.1.1. General Aspects ..............................................................................................27
2.1.2. Types of Bioavailability and Ways of Determining........................................29
2.2. Factors Influencing Bioavailability ......................................................................38
2.2.1. General Aspects ..............................................................................................38
2.2.2. Physicochemical Factors Influencing Dissolution and Bioavailability...........40
2.2.3. Organism-Related Factors Influencing Absorption and Bioavailability .........44
2.2.4. Changes in per os Absorption and Bioavailability..........................................49
3. GENERAL PHARMACOKINETICS..........................................................................58
3.1. Drug Transport Across Biological Membranes (Biotransport).........................58
3.1.1. General Aspects ..............................................................................................58
3.1.2. Types of Biotransport......................................................................................61
3.2. Drug Absorption ....................................................................................................67
3.2.1. General Aspects ..............................................................................................67
3.2.2. Absorption in Enteral and Other Natural Routes ............................................72
3.3.3. Absorption in Parenteral Routes .....................................................................89
3.3. Drug Distribution ..................................................................................................95
3.3.1. Drug Transport into the Blood Stream............................................................96
3.3.2. Drug Diffusion into the Tissues ....................................................................103
3.3.3. Drug Distribution into the Tissues ................................................................109
3.3.4. Drug Tissue Binding .....................................................................................114
3.4. Drug Elimination .................................................................................................117
3.4.1. Clearance.......................................................................................................117
3.4.2. Drug Biotransformation (Drug Metabolism) ................................................119
3.4.3. Drug Excretion..............................................................................................156
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12
13
14
15
16
140
204
299
Agentul
Mecanism
Reacii imediate
IgE reactiv reacia antigen-IgE, la nivelul mastocitelor sau
al bazofilelor, cu eliberare de histamin i de
alte substane tisular-active
IgG, IgM
reacia ntre IgG i celulele sanguine purttoare
de antigen, cu efect citotoxic
IgG, IgM
complexele circulante antigen-IgG, depuse n
vasele mici, mediaz inflamaia
Reacii ntrziate
Limfocite T limfocitele T sensibilizate elibereaz limfokine,
sensibilizate ce mediaz infiltrate monocelulare perivenulare
Medicamentele alergizante produc diferite tipuri de RA, cu diferite manifestri clinice alergice. Medicamentele cu potenial mare alergizant pot declana
mai multe tipuri de RA alergice (tabelele 5.11 5.14) [37].
Tabelul 5.11
Medicamente ce declaneaz RA alergice de tip I anafilactic
Manifestri clinice
x
Medicamente alergizante
Peniciline (penicilina G inj.x, ampicilina etc.),
cefalosporine, dextrani, substane iodate
radiografice de contrast, anestezice locale i.v.,
acid acetilsalicilic, metamizol, procain,
antihipertensive IEC
Tabelul 5.12
312
Medicamente alergizante
Peniciline, sulfonamide, rifampicina, PAS,
izoniazida, fenacetina, chinidina
Peniciline, sulfonamide, fenilbutazona, metamizol,
izoniazida, sulfoniluree hipoglicemiante, tiouracili
Sulfonamide, rifampicina, tiouracili, chinina,
chinidina, tiazide diuretice, izoniazida
Exemple
n cazul morfinomimeticelor se instaleaz sensibilizarea receptorilor
adrenergici (up-regulation), sistemul adrenergic fiind modulat de ctre sistemul
opioid endogen, la nivelul cruia acioneaz morfinomimeticele, n sensul
diminurii eliberrii de neuromediator adrenergic;
n cazul barbituricelor (fenobarbital) se sensibilizeaz receptorii glutamatergici, deoarece eliberarea neuromediatorului specific acidul glutamic este
inhibat de un tratament ndelungat cu barbiturice, prin stimularea activitii
transmisiei inhibitoare GABA-ergice.
Tipuri de toxicomanii
n funcie de numrul drogurilor, exist:
monotoxicomanii
politoxicomanii.
n funcie de drog, sunt:
toxicomanii minore (de ex.: la barbituricele hipnotice, tranchilizante, alcool);
toxicomanii majore (de ex.: la morfin, heroin, canabis, LSD).
Substane capabile s produc farmacodependena
Sunt:
deprimante SNC (alcool, hipnotice precum barbituricele, sedative,
tranchilizante, ca diazepamul i meprobamatul);
morfinomimetice (tip morfin i heroin);
stimulente SNC (tip amfetamin, tip cocain i tip khat);
halucinogene (tip indol, precum dietilamida acidului lisergic LSD , i
tip mescalin);
cannabis (marijuana, hai, tetrahidrocanabinol);
solveni organici volatili (aceton, tetraclorur de carbon, toluen);
323
Tabelul 6.8
Subtipuri de R colinergici
R
Agonist definitoriu
Nicotinici (N)
N1N2
Muscarinici (M)
M1M5
nicotin
(alcaloid din Nicotiana tabacum)
muscarina
(alcaloid din Amanita muscaria)
Receptorii nicotinici:
sunt mprii n dou tipuri: N1 (neuronali = NSNC; i ganglionari = NN) i
N2 = NM (jonciune neuromuscular);
sunt receptori ionotropici, pentameri, alctuii din 17 subuniti (subunitile 2-7 i 2-4 au fost identificate la om, restul au fost identificate la
galinacee i obolani); subunitile au fost mprite n 4 subfamilii (I-IV); familia
III a fost mprit n 3 triburi (vezi tabelul 6.9) [142].
Tabelul 6.9
Subunitile, subfamiliile i triburile receptorilor nicotinici
Familia I
9, 10
Familia II
7, 8
N1 (neuronal)
Familia III
Tribul 1
Tribul 2
2, 3, 4, 6
2, 4
N2 (muscular)
Familia IV
Tribul 3
3, 5
1, 1, , /
386
Localizare
2
jonciune
neuromuscular
ganglioni
vegetativi
Efect
3
potenial excitator
postsinaptic,
crete
permeabilitatea
pentru K+ i Na+
potenial excitator
postsinaptic,
crete
permeabilitatea
pentru K+ i Na+
Agoniti
Antagoniti
4
Acetilcolina
Carbacol
Suxametoniu
5
-bungarotoxina
-conotoxina
Tubocurarina
Pancuronium
Acetilcolina
Carbacol
Nicotina
Epibatina
Vareniclina
-bungarotoxina
Hexametoniu
Bupropion
Dextrometorfan
6.9.11.1. Neuromediatorii
Sunt cunoscute urmtoarele endocannabinoide:
arahidonoyletanolamida (AEA), denumit anandamid;
2- arahidonoylglicerol (2- AG);
2-arachidonoylglicerol eter (noladin eter).
453
10
FARMACOLOGIE INFORMAIONAL
SAU
FARMACOINFORMATOLOGIE (FI)
Farmacologia informaional sau farmacoinformatologia* este o ramur a
farmacologiei, care studiaz natura informaional a medicamentului i a proceselor
farmacologice. n forma actual, prezentat n carte, farmacologia informaional
este fundamentat pe baza unui concept de farmacologie cibernetic - informaional,
elaborat i dezvoltat teoretic i experimental (Cristea, A., 1985 1998).
Avnd n vedere noutatea i dificultatea de abordare a farmacologiei cibernetice-informaionale, din punct de vedere didactic, capitolul 10 este mprit n
dou mari pri:
10.1. Sinteze de farmacologie informaional;
10.2. Analize de farmacologie informaional.
536
Energie
FOR
CMP
CALORIE
Informaie
ORDINE
ORGANIZARE
BIT
Mrimea informaiei (I) pe care o aduce un eveniment, n cazul n care fenomenele sunt echiprobabile, este dat de urmtoarea ecuaie (dup Hartley R. V.,
1928) [35]:
I = log2n,
unde:
538