what are nsaids

8/11/2019 What Are NSAIDs

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What are NSAIDs?

Non-steroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen) are widely used as antithrombotic

agents.

These drugs affect prostaglandin synthesis. There are several kinds of prostaglandins which have

both beneficiary and harmful affects.

NS!"s block prostaglandin synthase or cycloo#ygenase ($%&' and $%&). This down

regulates *! and T& (increases aggregation).

Define the mode of action of aspirin in anti-clotting.

spirin inactivates both $%&' and $%& by covalently acetylating serene residues of the active

sites of both en+ymes. This blocks proper substrate access and orientation at the active site.

spirin in actives the en+yme in both platelets and endothelial cells, but endothelial cells canrecover $%& activity by synthesi+ing the en+yme. latelets cannot recover (no nucleus no new

synthesis)

New platelets must replace the inhibited platelets to recover T& reproduction. (takes - days)

%ver that time period, anticlotting is favored because *! is still being dumped into circulation.

What can drugs be targeted towards?

any of these factors. (if you know the function, you know the effect of a drug)


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What are the function group targets for drugs?

anti activation (inhibitors of signaling, ie. " receptor antagonists, thrombo#ane inhibitors,-' antagonists), anti adhesion (von willebrand factor inhibitors), or antiaggregation (nti-

*!!b!!!a (alpha!!/beta0) of platelets.

favor pro clotting or favor anticlotting coagulation (this can also be done by dietary manipulation

and lifestyle changes)

Define the mode of action for vitamin K antagonists warfarin and dicoumarol!

for prothrombin.

!nhibit epo#ide reductase and vitamin 1 reductase. $an2t make vitamin 1 hydro3uinone.

What are the categories of anti-clotting factor drugs?

basically 4ust direct and indirect. there are drugs for nearly every pathway.


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What do the coumarin warfarin and dicoumarol! drugs do?

'. !nhibit coagulation by inhibiting the vitamin 1-dependent carbo#ylase responsible for gamma-carbo#ylation reactions necessary for thrombin (factor !!), factors 5!!a, !&a, and &a, &!a and

&!!a.

. lso inhibit vitamin 1-dependent anti-coagulating proteins6 protein $ and protein S.0. /ecause of the mode of action of coumarin drugs, it takes several days for their ma#imum

effect to be reali+ed. These drugs have side effects.

What is the effect of a fish oil diet?

7ish oil (diet) has high content of eicosapentanoic acid (8) (a 9-carbon fatty acid with double bonds, an omega-0 fatty acid, relative to arachidonic acid (: double bonds).

eople who eat lot of fish have high 8 in their membrane and when eicosanoid synthesis isinitiated, they will produce *!0 and T&0 instead of *!.

*!0 has the same anti-platelet- aggregating activity as *! but T&0 has much weaker

platelet aggregating activity than T&. Thus people who eat lot of fish have less tendency toaggregate platelets and less risk of heart attacks.


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"ow do warfarin and dabigatran affect coagulation?

ll anticoagulant agents work by inhibiting the activity of thrombin. Thrombin enables theconversion of fibrinogen into fibrin during the coagulation cascade, therefore its inhibition

prevents the development of thrombus.

The anticoagulatory effect of warfarin is due to inhibition of several components of the

coagulation pathway including vitamin 1-dependent factors !!, 5!!, !& and &, and proteins $and S, therefore indirectly inhibiting thrombin. "abigatran, in contrast, selectively and directly

inhibits thrombin (7igure ').

/y inhibiting thrombin, dabigatran prevents a number of processes in the coagulation pathwayincluding6;

The conversion of fibrinogen into fibrin

ositive feedback amplification of coagulation activation

$ross-linking of fibrin monomers

Thrombin-induced platelet activation

The inhibition of fibrinolysis

Figure 1. Coagulation cascade showing site of action of anticoagulants warfarin and

dabigatran


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Shaken-Baby Syndrome

Shaken-baby syndrome is an intracranial hemorrhage with no apparent external

injuries that is caused by vigorous shaking of an infant.

!"#

$t is characteri%ed by thetriad of severe intracranial injury" retinal hemorrhages" and minimal or no external


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signs of trauma.!"&he injury mechanism is from the shearing of intracranial

bridging veins and incompletely myelinated nerves by acceleration-deceleration

forces from the shaking. &here may be a slam component as the infant is thrown

against a bed" creating a force from the sudden deceleration of the baby's head.

&he infant's relatively large head and weak neck muscles predispose to injury from

the head slamming forward and backward. &hese acceleration and deceleration

forces disrupt intracranial blood vessels and disturb the integrity of the brain

parenchyma leading to multiple areas of hemorrhage and edema.

&he presentation is fre(uently nonspeci)c and vague. &he diagnosis of shaken-baby

syndrome is missed about one-third of the time.!*$nitial misdiagnoses include

gastroenteritis" colic" apparent life-threatening events" sepsis" febrile or new-onset

sei%ures" and accidental head injury.!*""+&he physical examination typically reveals

no external signs of trauma. ,owever" small bruises on the chest or upper arms

where the child was held while being shaken or retinal hemorrhages on funduscopic

examination may be present. etinal hemorrhages occur in +/-0/ of shaken

infants but are not mandatory for the diagnosis of shaken-baby syndrome."+-+1

what are nsaids

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