Pharma 2: NSAIDs Flashcards by Amnah Ahmad

NSAIDs exhibit 3 actions, these are:

Reduce fever
Reduce inflammation
Reduce pain

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Eicosanoids definition + what are they derived from

Endogenous compounds which consist of oxygenated unsaturated 20-carbon fatty Also, (eg: prostanoids and leukotrienes)
mainly by arachidonic acid. Also, pro inflammatory mediators can be produced by “eicosapentaenoic acid” or “ dihomolinolenic acid”, since they are the precursor of the formation of Arachidonic acid.

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Eicosanoids or pro-inflammatory mediators are mainly derived from …(a)… which is released from cell membrane by …(b)… enzyme

(a): Arachidonic acid
(b): phospholipase A2

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What triggers phospholipase A2?

Once phospholipase A2 is triggered by a stimulus, viruses, bacteria, or any antigen, Arachidonic acid is released.

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arachidonic acid subjected to oxidation whether enzymatically or non enzymatically to give you two parts (mention the pathway and product)

1- “Cyclooxygenase pathway“ —> Prostanoids (Prostaglandins & Thromboxanes).
2- “Lipoxygenase pathway” —> Leukotrienes (mediators in asthma mainly).

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What does the name “eicosanoid” mean?

Eicosa: in latin means 20
noid: 4 conjugated double bonds in their chemical structure

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Eicosanoid (slide)

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Prostaglandins eg: where are they extracted from?
- PGE2 from ?
- PGF2a from?

PGE2 is extracted from Ethanol
PGF2a is extracted from phosphate buffer

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What’s the function of thromboxane?

Aggregate platelets

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Eicosanoids receptors are exitatory? Inhibitory? Both?

Once they are released, they act on their own specific receptors of the cell membrane whether an excitatory or inhibitory action.

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Eicosanoids biosynthesis (slide)

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What’s the difference between COX1 and COX2 in terms of:
1- production
2- action
3- inhibition

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What is the effect of non-selective inhibition of COX?

inhibition of COX-1 is responsible for adverse effects of NSAIDs

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What are the effects of prostaglandins on reproductive system?

PGE2 inhibits motility & tone of non-pregnant uterus, & increase that of pregnant uterus
PGF2a increase the motility & tone of both the non-pregnant & pregnant uterus
induction of abortion & labor (bcz it contracts uterus)

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What are the effects of prostaglandins on CVS?

PGE: increase capillary permeability + decrease systemic atrial pressure & venous pressure + increase coronary & regional arterial blood flow
PGI/PGH: increase systemic arterial & venous pressure + decrease regional arterial blood flow

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What are the effects of prostaglandins on respiratory system?

PGEs: bronchial dilation
TXA2 & PGF2a: bronchial constriction

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What are the effects of prostaglandins on nervous system?

PGEs: pulsating headache + pyrexia + increase ACTH, TSH, LH, FSH,prolactin, GH

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What are the effects of prostaglandins on renal system?

PGE: increase blood flow & induces natriuresis & water diuresis + increase ureter & bladder motility

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What are the effects of prostaglandins on GI system?

PGE: decrease gastric acidity + increase gastric & intestinal motility & may induce vomiting & diarrhea + stimulate mucus secretion

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PGE2 has been used as tablets to treat gastric ulcers by decreasing …….?

gastric acidity

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What are the effects of prostaglandins on haematological system?

PGI2: inhibition of platelet aggregation & adhesives by stimulation of platelet adenyl cycles
TXA2: stimulation of platelet aggregation

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Causes bronchial dilation

PGEs

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Increase motility & tome of both pregnant & non-pregnant uterus

PGF2a

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Effect of PGE on uterus of pregnant vs non-pregnant

Inhibits motility & tone @non-pregnant uterus

Increases motility & tone @pregnant uterus

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What two prostaglandins have opposite actions of haematological system (platelets specifically)

PGI2 and TXA2

What PGs are used in obsterics (induction of labor, termination of pregnancy)?

- PGE2 (dinoprostone) - PGF2a (dinoprost) Note: name not in drug list

What PGs are used in GIT (treat peptic ulcers)?

PGE2

What PGs are used in paediatrics (maintain patency of ductus arteriosus in infants)

PGE1

What PGs are used in inhibiting platelet aggregation and used for pulmonary hypertension?

PGI2 (epoprostenol or Ilprost) Note: name of drug not in drug list

Clinical uses of PGs (slide)

Pharmacological actions of NSAIDs

What are the non-selective cox inhibitors?

- aspirin - paracetamol - indomethacin - ibuprofen - Napraxen - piroxicam (this one is not on drug list)

Selective COX2 inhibitors

- celecoxib - etoricoxib - rofecoxib (not on drug list) - valdecoxib (not on drug list)

From the selective COX2 inhibitors, which drugs drugs have been withdrawn due to their serious side effects?

Rofecoxib, valdecoxib, etoricoxib

has only 2 effects: a good analgesic & antipyretic.

Paracetamol (acetaminophen)

Nowadays, we don’t use ………….. as an anti inflammatory since it has serious side effects. We use it as: - a prophylactic for myocardial infarction - for colon cancer - to reduce hypertension

Aspirin (Acetylsalicylic acid)

T/F: panadol can be used as an anti inflammatory?

False. You can’t use Panadol as an anti inflammatory. You can use it to reduce fever or pain. Note: It’s a weak anti inflammatory bcz it can’t compete during inflammation with mediators like prostaglandins & lysosomal enzymes or peroxidase.

What’s the MOA of aspirin?

Irreversible inhibition of COX1&2. The main action of Aspirin is due to its acetyl group. Acetyl group interacts with cyclooxygenase —> (Cox becomes inactive) therefore prevents synthesis of prostanoids. You need to synthesize a new enzyme to be active that’s why it’s an irreversible inhibition of cyclooxygenase 1 & 2.

What’s the pharmacological action of aspirin?

Analgesic, antipyretic, anti-inflammatory (its effects mediated by inhibition of PGs)

What drug increases alveolar respiration at therapeutic doses?

Aspirin

What can happen in case of high doses of aspirin?

Hyperventilation & respiratory alkalosis

Aspirin (slide)

What are therapeutic uses of aspirin?

What are side effects of mild intoxication Vs. Severe intoxication of salicylates?

Effects of aspirin on: - GIT? - Blood? - respiratory? - two more effects?

Acetaminophen (paracetamol) is metabolized into .…. Or .….. or ……?

* 95% of Acetaminophen is Metabolized to Glucuronoide or sulfate * 5% of Acetaminophen is metabolized to Toxic intermediate.

After metabolism of acetaminophen how is it excreted?

@urine (95% of Acetaminophen is metabolized to glucuronide or sulfate and exerted in urine.)

What detoxifies the toxic intermediate of acetaminophen metabolism at therapeutic doses?

Glutathione (AA contains glycine, cysteine, & glutamic acid) will detoxify the toxic intermediate leading to Mercapturic acid (non toxic).

What happens at toxic doses of acetaminophen?

if there is higher dose (toxic dose) —> depletion of glutathione that can interact with intracellular proteins —> cell death (liver necrosis).

What’s the Paracetamol poisoning antidote?

intravenous acetylcystine or methionine (bcz their action is to produce glutathione in the body).

Metabolism of acetaminophen (slide)

Aspirin (advantages & disadvantages)?

Aspirin: - Advantages: low cost & long history of safety. - Disadvantages: Upper GI disturbances.

Indomethacin disadvantages?

1-Upper GI disturbances. 2- Very potent; should be used only after less toxic agents have proven ineffective. 3- CNS disturbances.

Ibuprofen & Naproxen advantages?

Advantages: lower toxicity and better acceptance in some patients.

Advantages & disadvantages of NSAIDs (slide)

What drug causes respiratory alkalosis at high doses?

Aspirin

Which of the following is a sside effect of aspirin? A. Decrease BT B. Respiratory acidosis C. Fever D. Reye’s syndrome

D. Reye’s syndrome

Used externally as counterritang

Methyl salicylate

Route of administration of salicylic acid to treat corn & calluses

Topical

What is the effect of selective COX2 inhibition on platelets? Why?

No effect on platelets, which lack cox2

Adverse effects of selective COX2 inhibitors?

Which isoform of COX is constitutive & maintain normal function?

COX1

Which isoform of COX is induced during inflammation?

COX2

used as a prophylactic for myocardial infarction?

Aspirin

treat peptic ulcer, induce abortion and labor, & as a powerful vasodilator or bronchodilator?

Prostaglandins (We use pro inflammatory mediators also in medicine such as prostaglandins: we can treat peptic ulcer, induce abortion and labor, & as a powerful vasodilator or bronchodilator).

Why we use Aspirin and not any other NSAIDs as a prophylactic for MI ?

Bcz only aspirin has an irreversible action of cyclooxygenase.

form prostanoids

COX

vasoconstrictors & bronchoconstrictors

Thromboxane

Why aspirin gives vasodilator effect?

What drug is contraindicated in gout patients and why?

Aspirin because it interacts with probenecid (which is used to treat gout) causing decreased urate excretion

Salicylates interact with ….. which reduces rate of aspirin absorption

Antacids

Why aspirin may be contraindicated in patients with heart burn?

For example: if he’s taking antacids (for the heart burn), this will reduce the rate of aspirin absorption (accumulated in his body).

What other drugs interact with salicylates?

I didn’t understand a word from this slide :) مخي قفل