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