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65 Cards in this Set
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Mild analgesics
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decrease awareness to pain while raising pain threshold.
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Antipyretics
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eg Tylenol
decrease temp in feverish individual |
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Anti-inflammatory
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in animals and humans
Treat, not cure |
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Uses of analgesics
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relief of:
pain if arthritis other skeletal muscle conditions headache other types of visceral pain |
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analgesics
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prototype drug: ASA
NSAIDS Salicylates all are synonymous |
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Group 1: salicylates
Aspirin |
a-acetyl
spirin-an old name for salicylic or spiric acid o-hydroxy benzoic acid!! Know structure :) |
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Structure and SAR of salicylates
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-OH, -COOH ortho to ea other
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Derivatives of salicylates to improve toxicity
1) alternate COOH |
alternate COOH: salts to make eg Mag salicylate; ester eg phenyl salicylate, methyl salicylate; amide
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Derivatives of salicylates to improve toxicity
2) alter the -OH |
*ASA was made this way
also salsate |
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Derivatives of salicylates to improve toxicity
3) alter both OH and COOH |
eg aluminum aspirin
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Derivatives of salicylates to improve toxicity
4) add more gps to phenyl ring |
$$
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Derivatives of salicylates to improve toxicity
5) OH-->NH2 |
"Bioisosteric change"
* (are same size and shape) |
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salts of salicylic acid
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sodium salicylic acid
choline salicylate (arthropan) magnesium salicylate (Doan's pills) Triethanolamine salicylate |
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Sodium salicylate
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less GI irritation :)
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Choline salicylate
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good solubility
(CH3)3N+CH2CH2OH |
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Triethanolamine salicylate
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topical analgesic
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magnesium salicylate (Doan's Pills)
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nothing special
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Esters of salicylic acid
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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 $ |
Others that are not really esters:
Mesalamine (5-aminosalicylic acid) Olsalazine (azo linkage) Diflunisal: 5-(2,4-difluorophnyl) salicylic acid $ |
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External analgesics
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Counterirritants: bind skin receptors
Mech of action: cause mild inflammatory rxn when applied topically |
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Counterirritants:
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allyl isothiocyanate
stronger-ammonia water methyl salicylate turpentine oil menthol camphor capsaicin |
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Phenyl salicylate (salol)
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Intestinal disinfectant in diarrhea
also in combo w/ methenamine and atropine alkaloids as urinary tract antiseptic and analgesic. |
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Acetyl salicylic acid (aspirin)
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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. |
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aspirin toxicity
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mean lethal dose adult: ! 20-30g !
child: 150mg/kg |
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Products to decr GI upset from aspirin:
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effervescent, buffered tab, time release product, EC tab.
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Salsate (salicyl salicylic acid)
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less GI upset
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Mesalamine (5-aminosalicylic acid)
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enema for ulcerative colitis
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Olsalazine
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azo linkage
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Salicylamide
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not a true salicylate--not an ester
more potent with fewer SE's |
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Diflunisal (5-(2,4-difluorophnyl) salicylic acid)
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$ longer acting.
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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.
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Pyrazoline
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from pyrazole to hydrated N at position 2
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Pyrazolidine
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hydrated from pyrazoline
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5-pyrazolone
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oxidized from pyrazoline
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3,5-pyrazolidinedione
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oxidized from 5-pyrazolone
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Pyrazolidinediones
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Phenylbutazone [butazolidin]
Oxyphenyl butazone [tandearil] sulfinpyrazone [anturane] |
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phenylbutazone [butazolidin]
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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 |
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oxyphenyl butazone [tandearil]
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removed b/c HEMATOLOGICAL effects
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sulfinpyrazone [anturane]
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Weak analgesic; potent uricosuric agent; effective in (chronic) gouty arthritis
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5-pyrazolones
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antipyrine: 2,3-dimethyl-1-phenyl-3-pyrazolin-5-one
-for ear infection, but no longer used due to high blood toxicity |
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aminopyrine
2,3-dimethyl-4-dimethylamino-1-phenyl-3-pyrazolin-5-one |
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) |
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Arylacetic acids
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a-methyl arylacetic acid or arylpropionic acid: CHIRAL
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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 |
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Sulindac is a Non-nitrogenous analog of:
Used for: |
Indomethacin
for RA & OA contraindicated w/ ASA active in sulfide form |
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ibuprofen
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for RA
*S(+) isomer is active form of mix chiral with ibuprofen R=CH3 |
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fenoprofen calcium
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highly protein bound
when taking hydrantoins, sulfonamides, & sulfonylureas, USE CAUTION |
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Naproxen
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S+isomer, so more $$
R.A., gout not for lactating/pregnant woman children under 16: AVOID |
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Tolmetin
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R.A.
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Zomepirac sodium
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R.A.
REMOVED from market |
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Suprofen
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for dysmenorrhea
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Ketoprofen [orudis] (+/-)
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causes fluid retention
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Nabumetone [Relafen]
4-(6-methoxy-2-naphyl-2-BUTANONE) |
ketone for RA and OA
Prodrug metabolized to 6-methoxy-2-naphthyl acetic acid |
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Flurbiprofen [ocufen] (+/-) mix
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ophthalmic NSAID for eye surgery
-inhibits miosis |
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Ketorolac [Torado]
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more effective as analgesic than anti-inflammatory
contraindicated w/ ASA or other NSAIDS |
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Diclofenac (Voltasen)
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arylacetic acid AND N-Arylanthranilic acid
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Etodolac [iodine]
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Just another NSAID
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Arylacetic acid conclusions
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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. |
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Group 4 Once per Day:
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Benoxaprofen {oraflex} +/-R&S
Flunoxaprofen (priaxim) S isomer Piroxicam Tenoxicam Oxaprozin Tenidap sodium |
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Benoxaprofen (oraflex)
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R isomer caused hepatotox-->removal
For RA and OA |
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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
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Tenoxicam (Tilcotil)
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Canada & UK
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Oxaprozin (Daypro-Searle)
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For RA
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Tenidap sodium (enablex)
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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) |
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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. |
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Group 5: N-Arylanthranilic Acids
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Use 7 or less days
mefenamic acid [ponste] flufenamic acid [arlef] meclofemanate sodium [meclomen] diclofenac [voltaren] |
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