Acetaminophen/ Paracetamol

 N-acetyl-p-aminophenol
 phenacetin acetaminophen
 analgesic, antipyretic
 but weak anti-inflammatory
 S/E: Depletes glutathione which binds to toxic
metabolites of paracetamol
 (N-acetyl – para -benzoquinone) hepatic
necrosis
 Antidote: acetylcysteine glutathion
Anti – inflammatory/analgesics

 NSAIDS
 MOA: COX inhibition
NON – SELECTIVE COX INHIBITORS

 1.ASPIRIN-Irreversibly acetylates COX

 Anti – inflammatory
 Analgesic
 Anti – pyretic – vasodilation
 Anti – platelet aggregation
 ADVERSE EFFECT
 GIT: gastritis
 CNS: low toxic doses( 50 – 80mg/dl)
salicylism( tinnitus, dec hearing, vertigo)
hyperventilation – respiratory alkalosis
 Moderate toxic doses( 80 -110mg/dl)
fever, dehydration,metabolic acidosis
 Severe toxic doses ( 110mg – 160mg/dl)
vasomotor collapse,coma,hypoprothrombinemia
 Lethal toxic doses(> 160mg/dl)
 Reversible decrease in GFR
 Hypersensitivity
 Reyes Syndrome – hepatic failure and
encephalopathy
 Others: diflunisal, Mg choline salicylate, Na
salicylate, salicylsalicylate
 2. PYRAZOLONE DERIVATIVES
 dipyrone, phenylbutazone,
oxyphenbutazone, apazone, sulfinpyrazone
 SE:N/V,GIT disturbance,skin rash, edema,
agranulocytosis, aplastic anemia
 3. INDOLE DERIVATIVES
 Indomethacin – for PDA, gouty, ankylosing
spondylitis
 Sulindac,etodolac
• 4. PYROLE ALKANOIC ACID DERIVATIVES
• Tolmetin
• 5. PHENYLACETIC ACID DERIVATIVES
• Diclofenac(anti-inflam,analgesic,antipyretic),
• sulindac, alclofenac, etodolac,nabumetone
• 6. OXICAM DERIVATIVES
• Piroxicam
• Higher risk for PUD than NSAIDS
 7. FENAMATES
 Mefenamic acid, flufenamic
acid,meclofenamic acid
 GIT disturbance
 8. PROPIONIC ACID
 Ibuprofen,
naproxen,flurbiprofen,ketoprofen,oxaprozin
 Nephrotoxicity, GI irritation
SELECTIVE COX II INHIBITORS

 MELOXICAM
SPECIFIC COX II INHIBITORS

 Celecoxib, etericoxib
AUTOCOIDS

- Local hormones acting on the site of secretion

CLASSIFICATION

AMINES: HISTAMINE, 5HT

SMALL PEPTIDES: KININS
LARGE PEPTIDES: IL
LIPIDS: EICOSANOIDS
AUTOCOIDS

PROSTAGLANDIN
Carboprost
Dinoprost
Dinoprostone
Misoprostol – anti -ulver
Alprostadil - impotence
AUTOCOIDS

PROSTAGLANDIN
Lowering IOP
Latanoprost,
bimatoprost,travoprost,noprostone

epoprostenol
( pulmonary HPN, prevent platelet
aggregation in machines)
HISTAMINE

 Comes from L – histidine

 Located in lungs, skin, GIT, mast cells,
basophils
 Imidazole acetic acid in the urine
 IgE mediated
ACTIONS
H1 receptors
IP3, DAG as 2nd messengers
Increase production of nasal and bronchial
mucus
Bronchial constriction
Vasodilation/ NO
Increase capillary permeability
Intestinal cramps and diarrhea
Itch and pain
H1 ANTIHISTAMINES
1ST GEN/CLASSIC/SEDATING
Ethanolamines
carbinoxamine
dimenhydrinate,
Diphenhydramine
Doxylamine = Most sedating
H1 ANTIHISTAMINES
1ST GEN/CLASSIC/SEDATING

Ethylynediamine
Pyrilamine
tripelenamine
H1 ANTIHISTAMINES
1ST GEN/CLASSIC/SEDATING

Piperazine – anti –motion sickness

Hydroxyzine( iterax)
Cyclizine
meclizine
H1 ANTIHISTAMINES
1ST GEN/CLASSIC/SEDATING

Alkylamines
Brompheniramine
Chlorpheniramine
Components of cold tablets
H1 ANTIHISTAMINES
1ST GEN/CLASSIC/SEDATING

Phenothiazines
Promethazine( phenergan)
Anesthetic adjunct to dec stage II
manifestations
H1 ANTIHISTAMINES
1ST GEN/CLASSIC/SEDATING
Piperidine
Cyproheptadine
Significant serotonin antagonist effect
INDICATIONS

 Allergy
 Motion sickness
 Somnifacients
 2nd GEN/ NON-SEDATING
 Loratidine
 Des – loratidine
 Fexofenadine
Less- sedating
 Cetirizine
 Astemizole - cardiotoxic
 Terfenadine
 Acrivastine
 loracarbustine
H2 RECEPTOR
 Inc HCL

H3 receptor
 Modulation of histaminergic
neurotransmission in the CNS
SEROTONIN RECEPTORS
5- HT1A
Brain
Synaptic inhibition by increasing K
conductance
5- HT1B/1D
Peripheral vascular smooth muscle
5 – HT2A
Smooth muscles
uterus
5- HT3
CTZ

5- HT4
GIT – inc peristalsis
DRUGS ACTING AT 5HT RECEPTORS
5HT1A PARTIAL AGONIST
Buspirone

5HT1B/1D FULL AGONIST

Sumatriptan
naratriptan
DRUGS ACTING AT 5HT
RECEPTORS
5HT2A
Ergotamine, ergonovine – partial
agonist

5HT2A
Methylsergide - antagonist
SEROTONIN ANTAGONIST

 Ketansarin, cyproheptadine – competitive

pharmacologic antagonist
 Phenoxybenzamine – irreversible blocker

5HT3 ANTAGONIST
 Ondansetron,
granisetron,dolasetron,alosetron
 CTZ block
 EICOSANOIDS
 BLOOD VESSELS
 Vasoconstriction - TXA2, PGF2@
 Vasodilation – PGI2,PGE2
 Alprostadil, ( impotence) epoprostenol
 ( pulmonary HPN, prevent platelet
aggregation in machines)
 GIT
 Contraction- PGI2,PGE2,PGF2@
 Relaxation- PGE2
 Cytoprotection – PGE series - misoprostol
 BRONCHI
 Contraction –TXA2, PGF2@, LTC4,LTD4
 Relaxation – PGI2, PGF2@
 PLATELETS
 Aggregation –TXA2
 Inh. Of aggregation – PGE1, PGI2
 UTERUS
 Contraction – PGE1, PGE2, PGF2@
 Dinoprostone,Dinoprost,carboprost
 Dysmenorrhea – PGE2, PGF2@
 EYES
 Lowering IOP – PGE and PGF series
 Latanoprost,
bimatoprost,travoprost,noprostone
SUMMARY

 TXA2
 Vasoconstriction
 Bronchoconstriction
 Platelet aggregation
 PGF2@
 Vasoconstriction
 Bronchoconstriction
 Uterine contraction
 Dysmenorrhea
 Lowering IOP
 PGI2
 Vasodilation
 GIT contraction
 Brochodilation
 Inh. of platelet aggregation
 PGE1
 To maintain PDA
 PGE2
 Vasodilation
 GIT contraction and relaxation
 Uterine contraction
 Dysmenorrhea
 Lowers IOP