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SUBSTANE MEDICAMENTOASE CU ACIUNE ANALGEZIC I ANTIPIRETIC
ANALGEZICE - ANTIPIRETICE
Aciunea analgezic (ANA) i antipiretic (ANT) consecina inhibrii sintezei prostaglandinelor la nivel central
Se utilizeaz n tratamentul durerilor minore i moderate
AMINO-FENOLI (ANILIDE)FENACETINA PARACETAMOL
NH
OC2H5
COCH3 NH
OH
COCH3
METABOLISM
NH
OC2H5
COCH3 NH2
OC2H5
NH
OC2H5
OH N
OC2H5
O
METABOLISM LA DOZE TERAPEUTICE
NH
OC2H5
COCH3 NH
OH
COCH3 NH COCH3
glucuronide et sulfate
EXCRETION
METABOLISM LA DOZE TOXICE
NH
OC2H5
COCH3 NH
OH
COCH3
CYP 450
N
O
COCH3
N-ACETYL-p-BENZOQUINONE-IMINE
N
O
COCH3 O
O
liaison covalente aux proteines
SINTEZA
NH2
OH
(CH3CO)2OCH3COOH
NHCOCH3
OH
PARAPROPAMOL PROPACETAMOL
NH
OH
COCH2 CH3 NH
O
COCH3
CO
CH2 N(C2H5)2 HCl
DERIVAI DE PIRAZOL
FENAZONA
Caracter slab bazic
Derivat solubil n ap
PROPIFENAZONA
NN OC6H5
H3C
H3C H
NN OC6H5
H3C
H3C CHCH3
CH3
AMINOFENAZONA NORAMINOFENAZONAMETANSULFONAT SODIC
Risc crescut de agranulocitoz
Retras din terapie
Metamizol sodic
noramidopirina
Aciune ANA, ANT, spasmolitic
NCH3CH3
NN OC6H5
H3C
H3C
NCH3CH2 SO3Na
NN OC6H5
H3C
H3C
ISOPIRINA NIFENAZONA
NH CHCH3
CH3N
N OC6H5
H3C
H3CNH C
O NN
N OC6H5
H3C
H3C
FENAZONA - SINTEZA
CH2 CO
CH3
CO
OC2H5
CH C CH3
CO
OC2H5
OH +
NH NH2
NN OC6H5
H
H3CCH3I
NN OC6H5
H3C
H3C
NORAMIDOPIRINA - SINTEZA
NN OC6H5
H3C
H3CHONO
NN OC6H5
H3C
H3C NOred
NN OC6H5
H3C
H3C NO2
C6H5 CHON
N OC6H5
H3C
H3C N CH C6H5CH3I
NORAMIDOPIRINA - SINTEZA
NN OC6H5
H3C
H3C N CH C6H5
CH3
+I
_ H2ON
N OC6H5
H3C
H3C NH CH3
NN OC6H5
H3C
H3C NCH3
CH2 SO3NaHO CH2 SO3Na
ANTIINFLAMATOARE NESTEROIDIENE(AINS)
AINS inhib biosinteza prostaglandinelor
Clasificare: Acizi aril-carboxilici
Acizi aril-acetici
Acizi 2-aril-propionic
Acizi enoli: derivai de pirazol, oxicami
ACIZI ARIL-CARBOXILICI
ACID ACETILSALICILIC
Aciune analgezic, antipiretic, antiinflamatoare, antiagregant plachetar
COOHOH (CH3CO)2O
H2SO4 conc
COOHOCOCH3
SALICILAMIDA ACETILSALICILAMIDA
CONH2OH
CONH2OCOCH3
ETENZAMIDA BENORILAT
CONH2OC2H5
COOOH
NHCOCH3
ACID ACETILSALICILIC FORME FARMACEUTICE
Aspirina simpl
Aspirina tamponat, aspirina efervescent, aspirina
tamponat i efervescent
Aspirina enteric
Aspirina solubil i injectabil
ACID ACETILSALICILIC - UTILIZARE
Reumatism, artroze, lombalgii
Fracturi, entorse
Dismenoree
Dureri postoperatorii stomatologice i ORL
ACID ACETILSALICILIC CONTRAINDICAII
Alergie la aspirin i la salicilai
Ulcer, gastrit
Pacieni cu risc hemoragic
Tratament cu anticoagulante orale, metotrexat
Sarcin n al treilea trimestru
ACID ACETILSALICILIC - EFECTE ADVERSE
La nivel digestiv: leziuni ale mucoasei, aciditate, ulcer
gastro-duodenal, hemoragie, perforaie
Manifestri alergice: prurit, criz de astm bronic, oc anafilactic
La nivel renal: oligurie, insuficien renal
Tulburri neurologice: cefalee, vertij, insomnie
DERIVAI AI ACIDULUI ANTRANILICACIZI FENAMICI
R DCI
ACIDE MEFENAMIQUE
ACIDE FLUFENAMIQUE
ACIDE CLOFENAMIQUE
COOH
NH R
H3C CH3
CF3
Cl Cl
DERIVAI AI ACIDULUI FENAMIC
R DCI
-H ACIDE NIFLUMIQUE - orale
MORNIFLUMATE - topique
N NH
COORCF3
N OCH2CH2
ACID NIFLUMIC - SINTEZA
N
COOH
Cl+ H2N
CF3N
COOH
NH
CF3
ETOFENAMAT
COONHC2H4 O C2H4 OH
CF3
ACIZI ARILACETICI
DICLOFENAC ALCLOFENAC
FENCLOFENAC
NH
Cl
Cl
CH2 COOH
Cl
CH2
OH2CCHCH2
O
CH2 COOH
Cl
Cl
BUFEXAMAC
CH2 C C2H4O
CONH OHC2H5
DICLOFENAC - SINTEZA
COOH
Cl
+ H2N
Cl
Cl
COOH
NH
Cl
Cl
CH2OH
NH
Cl
Cl
CH2
NH
Cl
Cl
COOH
ACIZI INDOLACETICI I ANALOGIINDOMETACIN SULINDAC
H3CO
N
CH2
CH3C
O
Cl
COOH
C
CH2
CH3CH
S
COOH
H3CO
F
INDOMETACIN
Indicaii i contraindicaii generale ale AINS
Utilizare: reumatism, spondilartrit, poliartrit, gut
Contraindicaii: ulcer gastro-duodenal evolutiv, ulcer n antecedente
Interaciuni medicamentoase: asocieri cu alte AINS, anticoagulante orale, sulfamide
ACEMETACIN OXAMETACIN
N
CH2
CH3C
O
Cl
COO CH2 COOHH3CO
N
C
CH3C
O
Cl
O
NH OHH3CO
TOLMETIN FENTIAZAC
CO
H3C NCH3
CH2 COOH
N
S CH2 COOH
Cl
LONAZOLAC ACID METIAZINIC
ClN
N
CH2COO
C6H5
_)2 Ca S
NCH3
CH2 COOH
BENZIDAMINA
Antiinflamator
Antalgic
Local n faringite si vaginite
NNCH2
O (CH2)3 N(CH3)2
IBUPROFEN - DERIVAT AL ACIDULUI 2-ARIL-PROPIONIC
Indicaii i contraindicaii generale pentru AINS
Utilizare: antalgic, antiinflamator
H9C4 CHCH3
COOH
R DCI
FENPROFENE
FLURBIPROFENE
KETOPROFENE
SUPROFEN
NAPROXENE
ACIDE TIAPROFENIQUE
R CH COOHCH3
O
F
CO
SCO
H3CO
CO
S
KETOROLAC TRIMETILOL-AMIN
CO
NCOOH H2N C(CH2OH)3
ACIZI ENOLIDERIVAI DE PIRAZOLIDIN
R1 R2 DCI
-H -C4H9 PHENYBUTAZONE
-C4H9 SUXIBUZONE
-C4H9 PIPEBUZONE
-H KEBUZONE - prodrogue
NN
R1R2
O
C6H5
C6H5O
HOOC C2H4 COO CH2
N NH3C CH2
CH3 CO C2H4
FENILBUTAZON
4-n-butil-1,2-difenil-pirazolidin-3,5-dion
Forme enolice:
NN
H9C4H
O
C6H5
C6H5O
NN
H9C4H
C6H5
C6H5O
OH
NN
H9C4 O
C6H5
C6H5
HO
FENILBUTAZON - SINTEZ
H9C4 CH COOC2H5COOC2H5
+HN
PhNHPh EtONa NN
H9C4H
O
C6H5
C6H5O
OXICAMI
R DCI
PIROXICAM
SUDOXICAM
MELOXICAM
ISOXICAM
NS CH3
CO NH R
O O
OH
N
N
S
N
S CH3
NO CH3
TENOXICAM LORNOXICAM
S
NS
OHCO
CH3
NHN
S
O O
S
O O
S
NS
OHCO
CH3
NHN
Cl
PIROXICAM - SINTEZA
NHS
O
O O
+ Br CH2 COOCH3 NS
O
O O
CH2 COOCH3base
C2H5O-
transp. GabrielColman
2NH
SO O
OCO
OCH3 (CH2OH)2/H+
NHS
O O
CO
OCH3
O OCH2 CH2
1)+ CH3I2)+ H+
NS
O O
CO
OCH3
O
CH3
NH2N
NS
O O
CO
NH
O
CH3
N
NS
O O
CO
NHCH3
NOH
CONSIDERAII TERAPEUTICE
Tratamentul poliartritei reumatoide i a afeciunilor caracterizate prin fenomene inflamatorii ale articulaiilor, se realizeaz cu
ajutorul urmtoarelor clase de medicamente:
AINS terapie de prim intenie
Glucocorticoizi
AI de fond: clorochin, sruri de aur, penicilamin
Citostatice
SUBSTANE MEDICAMENTOASE CU ACIUNE ANALGEZIC I ANTIPIRETICANALGEZICE - ANTIPIRETICEAmino-fenoli (anilide)fenacetina paracetamolmetabolismMetabolism la doze terapeuticeMetabolism la doze toxicesintezaParapropamol propacetamolDerivai de pirazolAMINOFENAZONA NORAMINOFENAZONA metansulfonat sodicIsopirina nifenazonafenazona - sintezaNoramidopirina - sintezaNoramidopirina - sintezaAntiinflamatoare nesteroidiene(AINS)Acizi aril-carboxiliciSalicilamida acetilsalicilamidaEtenzamida benorilatAcid acetilsalicilic forme farmaceuticeAcid acetilsalicilic - utilizareAcid acetilsalicilic contraindicaiiAcid acetilsalicilic - efecte adverseDERIVAI AI ACIDULUI ANTRANILICACIZI FENAMICIDERIVAI AI ACIDULUI FENAMICACID NIFLUMIC - SINTEZAETOFENAMATACIZI ARILACETICIBUFEXAMACDICLOFENAC - SINTEZAACIZI INDOLACETICI I ANALOGIINDOMETACIN SULINDACINDOMETACIN Acemetacin oxametacinTolmetin fentiazacLonazolac acid metiazinicbenzidaminaIbuprofen - derivat al acidului 2-aril-propionicSlide Number 37Ketorolac trimetilol-aminAcizi enoliderivai de pirazolidinfenilbutazonFenilbutazon - sintezoxicamiTenoxicam LornoxicamPiroxicam - sintezaConsideraii terapeutice