NSAIDs, Opioids and Steroidal drugs Flashcards
What are NSAIDs and what are they used for
Synthetic non-steroidal anti-inflammatory drugs
Used for treatment of
inflammation
pain
fever
Mechanism of action not fully understood but is known to disruption prostanoid biosynthesis by inhibition of cyclo-oxygenase (COX) enzymes
What are cyclooxygenase
Enzymes of prostanoid biosynthetic pathways
Consist of two identical protein monomers
Has hydrophobic entry
heme cofactor
Two key amino acids
- tyrosine and arginine
What are the types of COX
COX 1
- constitutive isoform
Biosynthesis is constant within body
Inhibition of COX 1 = decreased gastric mucosa production
COX 2
- inducible form
Biosynthesis is stimulated by cytokines
Inhibition of COX 2 = anti-inflammatory, anti-pyretic and analgesic effects
What are salicylates
Most are acidic due to COOH group
- ionic bonding to Arg 120
Weakly acidic phenol
All are reversible and competitive binding
Salicylates
Reversible inhibition
Target mainly COX 1
Anilides
Paracetamol
Activated of cannainoid receptors
Profen
More potent due to high lipid solubility and COX binding
Target mainly COX 1
Reversible competitive inhibition of COX
Fenamates
Anthranilic acid derivatives
Target mainly COX 1
Rarely used
Aromatic acetic acids
Can contain aromatic or heteroaromatic structure
Target mainly COX 1
More lipophilic = more potent
Etodolac
NSAIDs - COX 1
Aromatic acetic acid
Diclofenac
NSAID
Selectivity 2:1
Phenylpyrazolones
NSAID
contains acidic pyrazololone proton
Oxicams
Acidic enol
quite active on COX 2
Coxibs
Non-acidic
Act only on COX 2
Cardiotoxic side effects with increased potency
What are the different types of opioid receptors
Mu
Endomorphin 1 and 2
Causes analgesia, respiratory depression, decreased GIT motility and emesis
Kappa
Dynorphins
Beta-endorphins
Causes analgesia, diuresis, sedation, constipation and dysphoria
Delta
Enkephalins
Beta-endorphins
Causes analgesia, diuresis, sedation, constipation, convulsions and dysphoria
Morphine
Five fused rings with five chiral centres
Mainly protonated at physiological pH
Explain the structure-activity relationship of morphines
N essential
Must be a tertiary amine - lipophilic = BBB penetration
N-methyl - agonist activity
3C = antagonist
4C = agonist
3-hydroxy subs
Phenolic characteristic
3-methoxy = codeine
6-hydroxyl subs
not required for activity
if lipophilic = better penetration of BBB
Morphinans
Morphine analogue
No epoxy bridge = loss of ring D
-ve isomers = analgesics
+ve isomers = antitussives
Benzomorphans
Morphine analogues
without rings C and D
Kappa agonist
Dysphoric effects
4-phenylpiperidines
Morphine analoge
Without ring B, C and D
Anikkidopiperidines
Morphine analogue
Structural modification of 4-phenylpiperidine
Analgesics at lower dose
Buprenorphine
Morphine analogue
Contains tricylic structure
Agonist
Naloxone and naltrexone
Mu antagonist
contains 3-OH, N-allyl, N-cyclopropylmethyl or N-cyclobutylmethyl sub
Steran skeleton
19 carbons
4 ring structures
Makes up sex hormone structure
Contains 4 cyclic structures, one is penta
3-C=O and 4-enone
Testosterone analogue
Addition of ester at C17
Increases lipophilicity
Testosterone analogue
Addition of methyl at C17
Blocks metabolism of C17 OH
Testosterone analogue
Addition of C11 hydroxyl group or C9a fluorine
Improve anabolic/ androgenic ratio
Testosterone analogue
Removal of C19 methyl group
Increase potency
Testosterone analogue
Addition of unsaturated group at C2/3
Prevent ring A metabolism
Estradiol
Based on estrogen
Contains two hydroxyl groups 14.5 apart
Estradiol analogue
Increases oral bioavailability
Estradiol analogue
Increases orally availability
Estradiol analogue
Addition of ethynyl alkyne on C17
Increases oral activity
As per testosterone skeleton
Contains acetyl on C17
Progesterone analogue
Addition of C6 alkyl group
Decreases metabolic reduction of ring A
Preventing metabolic hydroxylation at C6
Increasing lipid solubility
Progesterone analogue
Addition of acetyl and ester on C17
Adrenocortical drugs
Cortisone
C-O on C11
Hydrocortisone
C-OH on C11
Aldosterone
no OH on C17
C11 bridge
Cortisone analogue
Contains enone at C1/2
Cortisone analogue
Based on prednisolone
Methyl at C6
Reduce metabolic hydrolysis = more potent
Cortisone analogue
Addition of F atom at C9
Prevent oxidation of C11-OH
Cortisone analogue
Addition of methyl at C16
Hinder metabolic attack at C17
Cortisone analogue
Addition of OH on C16
Increases metabolic activity of C17 side chain
