Med Chem Analgesics

Front 1

Mild analgesics

Back 1

decrease awareness to pain while raising pain threshold.

Front 2

Antipyretics

Back 2

eg Tylenol
decrease temp in feverish individual

Front 3

Anti-inflammatory

Back 3

in animals and humans
Treat, not cure

Front 4

Uses of analgesics

Back 4

relief of:
pain if arthritis
other skeletal muscle conditions
headache
other types of visceral pain

Front 5

analgesics

Back 5

prototype drug: ASA
NSAIDS
Salicylates
all are synonymous

Front 6

Group 1: salicylates
Aspirin

Back 6

a-acetyl
spirin-an old name for salicylic or spiric acid
o-hydroxy benzoic acid!!
Know structure :)

Front 7

Structure and SAR of salicylates

Back 7

-OH, -COOH ortho to ea other

Front 8

Derivatives of salicylates to improve toxicity
1) alternate COOH

Back 8

alternate COOH: salts to make eg Mag salicylate; ester eg phenyl salicylate, methyl salicylate; amide

Front 9

Derivatives of salicylates to improve toxicity
2) alter the -OH

Back 9

*ASA was made this way
also salsate

Front 10

Derivatives of salicylates to improve toxicity
3) alter both OH and COOH

Back 10

eg aluminum aspirin

Front 11

Derivatives of salicylates to improve toxicity
4) add more gps to phenyl ring

Back 11

$$

Front 12

Derivatives of salicylates to improve toxicity
5) OH-->NH2

Back 12

"Bioisosteric change"
* (are same size and shape)

Front 13

salts of salicylic acid

Back 13

sodium salicylic acid
choline salicylate (arthropan)
magnesium salicylate (Doan's pills)
Triethanolamine salicylate

Front 14

Sodium salicylate

Back 14

less GI irritation :)

Front 15

Choline salicylate

Back 15

good solubility
(CH3)3N+CH2CH2OH

Front 16

Triethanolamine salicylate

Back 16

topical analgesic

Front 17

magnesium salicylate (Doan's Pills)

Back 17

nothing special

Front 18

Esters of salicylic acid

Back 18

via carboxylic acid or hydroxy group
Phenyl salicylate (Salol): intestinal disinfectant in diarrhea; also in combo w/ methenamine and atropine alkaloids as urinary tract antiseptic and analgesic.
Methyl Salicylate: external analgesic; Counterirritant
Acetyl Salicylic acid! ("dirty drug")
Salsate (salicyl salicylic acid)
Salicylamide (not true salicylate)
Mesalamine (5-aminosalicylic acid)
Olsalazine (azo linkage)
Diflunisal: 5-(2,4-difluorophnyl) salicylic acid $

Hint 18

Others that are not really esters:
Mesalamine (5-aminosalicylic acid)
Olsalazine (azo linkage)
Diflunisal: 5-(2,4-difluorophnyl) salicylic acid $

Front 19

External analgesics

Back 19

Counterirritants: bind skin receptors
Mech of action: cause mild inflammatory rxn when applied topically

Front 20

Counterirritants:

Back 20

allyl isothiocyanate
stronger-ammonia water
methyl salicylate
turpentine oil
menthol
camphor
capsaicin

Front 21

Phenyl salicylate (salol)

Back 21

Intestinal disinfectant in diarrhea
also in combo w/ methenamine and atropine alkaloids as urinary tract antiseptic and analgesic.

Front 22

Acetyl salicylic acid (aspirin)

Back 22

325-650 mg/4hr
<4g/24hr
975mg=max dose
HYDROLYSIS
Inhibits prostaglandins --> COX enzymes 1 & mainly 2 (irreversible)
Cox1-->SE's of the stomach
1) lengthen bleeding time; 1 wk prior to surgery
2) gum ulceration after local application
3) avoid in hypoprothrombinemic, VitK deficiency, peptic ulcer, GI bleeding.
4) ! GI irritation and bleeding !
5) 0.3% have aspirin hypersensitivity..asthma-like symptoms, skin rxn, rash, hives.

Front 23

aspirin toxicity

Back 23

mean lethal dose adult: ! 20-30g !
child: 150mg/kg

Front 24

Products to decr GI upset from aspirin:

Back 24

effervescent, buffered tab, time release product, EC tab.

Front 25

Salsate (salicyl salicylic acid)

Back 25

less GI upset

Front 26

Mesalamine (5-aminosalicylic acid)

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enema for ulcerative colitis

Front 27

Olsalazine

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azo linkage

Front 28

Salicylamide

Back 28

not a true salicylate--not an ester
more potent with fewer SE's

Front 29

Diflunisal (5-(2,4-difluorophnyl) salicylic acid)

Back 29

$ longer acting.

Front 30

Pyrazole derivatives: nomenclature

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the simple doubly unsaturated compound containing 2 N and 3 C atoms in the ring and with the N atoms neighboring is known as pyrazole.

Front 31

Pyrazoline

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from pyrazole to hydrated N at position 2

Front 32

Pyrazolidine

Back 32

hydrated from pyrazoline

Front 33

5-pyrazolone

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oxidized from pyrazoline

Front 34

3,5-pyrazolidinedione

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oxidized from 5-pyrazolone

Front 35

Pyrazolidinediones

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Phenylbutazone [butazolidin]
Oxyphenyl butazone [tandearil]
sulfinpyrazone [anturane]

Front 36

phenylbutazone [butazolidin]

Back 36

SE's: blood dyscrasias makes it for short term use, sore throat, mouth lesions, BM suppression: short term use.
For gout--uricosuric effect
Arthritis use

Front 37

oxyphenyl butazone [tandearil]

Back 37

removed b/c HEMATOLOGICAL effects

Front 38

sulfinpyrazone [anturane]

Back 38

Weak analgesic; potent uricosuric agent; effective in (chronic) gouty arthritis

Front 39

5-pyrazolones

Back 39

antipyrine: 2,3-dimethyl-1-phenyl-3-pyrazolin-5-one
-for ear infection, but no longer used due to high blood toxicity

Front 40

aminopyrine
2,3-dimethyl-4-dimethylamino-1-phenyl-3-pyrazolin-5-one

Back 40

has been employed as an antipyretic & analgesic as is antipyrine but is somewhat slower in action. more powerful and its effects last longer.
!Can cause fatal agranulocytosis! (not often used)

Front 41

Arylacetic acids

Back 41

a-methyl arylacetic acid or arylpropionic acid: CHIRAL

Front 42

Indomethacin

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Not for children
For those who cannot tolerate ASA, in place of phenyl butazone (in long-term therapy).
Drug of choice for acute gouty arthritis

Front 43

Sulindac is a Non-nitrogenous analog of:
Used for:

Back 43

Indomethacin
for RA & OA
contraindicated w/ ASA
active in sulfide form

Front 44

ibuprofen

Back 44

for RA
*S(+) isomer is active form of mix
chiral with ibuprofen R=CH3

Front 45

fenoprofen calcium

Back 45

highly protein bound
when taking hydrantoins, sulfonamides, & sulfonylureas, USE CAUTION

Front 46

Naproxen

Back 46

S+isomer, so more $$
R.A., gout
not for lactating/pregnant woman
children under 16: AVOID

Front 47

Tolmetin

Back 47

R.A.

Front 48

Zomepirac sodium

Back 48

R.A.
REMOVED from market

Front 49

Suprofen

Back 49

for dysmenorrhea

Front 50

Ketoprofen [orudis] (+/-)

Back 50

causes fluid retention

Front 51

Nabumetone [Relafen]
4-(6-methoxy-2-naphyl-2-BUTANONE)

Back 51

ketone for RA and OA
Prodrug metabolized to 6-methoxy-2-naphthyl acetic acid

Front 52

Flurbiprofen [ocufen] (+/-) mix

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ophthalmic NSAID for eye surgery
-inhibits miosis

Front 53

Ketorolac [Torado]

Back 53

more effective as analgesic than anti-inflammatory
contraindicated w/ ASA or other NSAIDS

Front 54

Diclofenac (Voltasen)

Back 54

arylacetic acid AND N-Arylanthranilic acid

Front 55

Etodolac [iodine]

Back 55

Just another NSAID

Front 56

Arylacetic acid conclusions

Back 56

particular value in patients who can not tolerate aspirin: ASA is 1st choice
Appear to have fewer SE's than usually anti-inflamm dose of ASA
If one agent not effective for a particular agent try another.

Front 57

Group 4 Once per Day:

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Benoxaprofen {oraflex} +/-R&S
Flunoxaprofen (priaxim) S isomer
Piroxicam
Tenoxicam
Oxaprozin
Tenidap sodium

Front 58

Benoxaprofen (oraflex)

Back 58

R isomer caused hepatotox-->removal
For RA and OA

Front 59

Flunoxaprofen (priaxim) S isomer

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For RA and OA
Once a day
modified benoxaprofen

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Piroxicam

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OA + RA

Front 61

Tenoxicam (Tilcotil)

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Canada & UK

Front 62

Oxaprozin (Daypro-Searle)

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For RA

Front 63

Tenidap sodium (enablex)

Back 63

has disease modifying profile
also provides symptomatic relief
For RA & OA.
Inhibits COX, interferes w/ 5-lipoxygenase, inhibits production of IL-1, inhibits cytokines.
(long-term use effects led to not be US approved)

Front 64

Chirality and NSAIDs

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Racemates: chiral drugs that exist 2 or more mirror-image forms (enantiomers) are frequently offered as half-and-half enantiomer mixes (racemates)
-single enantiomer agents-one enantiomer.

Front 65

Group 5: N-Arylanthranilic Acids

Back 65

Use 7 or less days
mefenamic acid [ponste]
flufenamic acid [arlef]
meclofemanate sodium [meclomen]
diclofenac [voltaren]