Non-Sterodial Anti Inflammatory Drugs Flashcards
What does the term NSAIDS refer to and what do they do?
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS! Purpose to reduce pain, fever and decrease inflammation.
What is the relationship between the enzymes ‘cyclo-oxygenase’ and ‘lipo-oxygenase’?
CYCLO-OXYGENASE FACILITATES THE PROCESS BY WHICH ARACHIDONIC ACID FORMS PROSTAGLANDINS, PROSTACYCLIN & THROMBOXANE A2.
LIPO-OXYGENASE FACILITATES THE PROCESS BY WHICH ARACHIDONIC ACID FORMS LEUKOTRIENES
Name the enzyme required to convert phospholipids to arachidonic acid?
PHOSPHOLIPASE A2
Explain the function of the inflammatory process?
2 stages of acute inflammatory response
1) Vascular response: Begins immediately after injury, initiated by vasoconstriction of small vessels followed by arteriole and venules leading to congestion, redness and warmth. Capillary permeability increases (fluid leaks into tissues, leads to swelling) which causes pain and impaired function, chemical mediators also involved.
2) Cellular blood cell response: Marked by movement of leukocytes (white cells) into injured area - stages include margination of leukocytes, emigration, chemotaxis, phagocytosis (engulf). All symptoms and signs are produced by inflammatory mediators.
What do Prostoglandins do? They are involved in the healing process, causing reactions related to pain, fever and inflammation.
Any medication that reduces prostaglandin synthesis is going to help with reducing vasodilation, pain and fever!!! Phospholipids are converted by the enzyme phospholipase A2 to arachadonic acid. One pathway Arachadonic acid can go down is to be converted by the the enzyme lipo-oxygenase into leukotrienes. Another pathway is that arachidonic acid can be converted by the enzyme cycle-oxygenase (COX1 and COX2) to make prostaglandins, thromboxane A2 and prostacyclin (this is what happens in an acute inflammatory response). The COX1 enzyme helps convert arachadonic acid to prostaglandin I2 (stomach), prostaglandin E2 (kidneys) and Thromboxane A2 (platelets). The COX2 enzyme helps convert arachidonic acid to prostaglandin E2 (kidneys) and to pro-inflammatory prostaglandins. Ok so their are first and second generation NSAID’s. First generation NSAID’s (drugs) inhibit COX1 and COX2 enzymes equally. Second generation NSAID’s predominantly inhibit COX2 but only have a minimal effect on COX1. So any drug inhibiting COX2 will have minimal effect on prostaglandins for the stomach, kidneys and platelets. So second generation NSAIDS’s COX2 drug inhibit more specifically, whereas a drug that inhibits COX1 and 2 you inhibit the formation of all of those
Role of prostaglandins? INCREASE VASCULAR PERMEABILITY, PAIN, FEVER
Prostaglandins control several processes in the body, especially as it relates to the healing process. When tissue is damaged or infected, this group of hormones will create the reactions that cause pain, fever and inflammation, which sparks the healing process. Prostaglandins also stimulate the formation of a blood clot and the contraction of the blood vessel wall when your body is bleeding. Once blood clots are no longer needed and the injury begins to heal, another prostaglandin will stimulate the changes that allow the clots to dissipate and the blood vessel wall to relax. So prostaglandins act as signals to control several different processes depending on the part of the body in which they are made. Prostaglandins are made at sites of tissue damage or infection, where they cause inflammation, pain and fever as part of the healing process. When a blood vessel is injured, a prostaglandin called thromboxane stimulates the formation of a blood clot to try to heal the damage; it also causes the muscle in the blood vessel wall to contract (causing the blood vessel to narrow) to try to prevent blood loss. Another prostaglandin called prostacyclin has the opposite effect to thromboxane, reducing blood clotting and removing any clots that are no longer needed; it also causes the muscle in the blood vessel wall to relax, so that the vessel dilates. The opposing effects that thromboxane and prostacyclin have on the width of blood vessels can control the amount of blood flow and regulate response to injury and inflammation.
How are protoglandins controlled?
The chemical reaction that makes the prostaglandins involves several steps; the first step is carried out by an enzyme called cyclooxygenase. There are two main types of this enzyme: cyclooxygenase-1 and cyclooxygenase-2. When the body is functioning normally, baseline levels of prostaglandins are produced by the action of cyclooxygenase-1. When the body is injured (or inflammation occurs in any area of the body), cyclooxygenase-2 is activated and produces extra prostaglandins, which helps the body to respond to the injury.
Prostaglandins carry out their actions by acting on specific receptors; at least eight different prostaglandin receptors have been discovered. The presence of these receptors in different organs throughout the body allows the different actions of each prostaglandin to be carried out, depending on which receptor they interact with.
Prostaglandins are very short-lived and are broken down quickly by the body. They only carry out their actions in the immediate vicinity of where they are produced; this helps to regulate and limit their actions.
What happens if I have too much prostaglandins?
High levels of prostaglandins are produced in response to injury or infection and cause inflammation, which is associated with the symptoms of redness, swelling, pain and fever. This is an important part of the body’s normal healing process.
However, this natural response can sometimes lead to excess and chronic production of prostaglandins, which may contribute to several diseases by causing unwanted inflammation. This means that drugs, which specifically block cyclooxygenase-2, can be used to treat conditions such as arthritis, heavy menstrual bleeding and painful menstrual cramps and certain types of cancer, including colon and breast cancer. New discoveries are being made about cyclooxygenases which suggest that cyclooxygenase-2 is not just responsible for disease but has other functions.
Anti-inflammatory drugs, such as aspirin and ibuprofen, work by blocking the action of the cyclooxygenase enzymes and so reduce prostaglandin levels. This is how these drugs work to relieve the symptoms of inflammation. Aspirin also blocks the production of thromboxane and so can be used to prevent unwanted blood clotting in patients with heart disease.
At what stage of the inflammatory process do NSAIDS exert their action?
AT THE POINT WHERE PROSTAGLANDINS ARE PRODUCED
Why don’t NSAIDS completely eradicate the inflammatory process?
OTHER INFLAMMATORY MEDIATORS WHICH ARE NOT RELATED TO COX ARE STILL PRESENT EG LEUKOTRIENES
If the inflammatory process is so beneficial for our survival, why do we even need anti- inflammatory drugs?
ASSOCIATED SWELLING CAN BE ASSOCIATED WITH MORBIDITY AND MORTALITY
Apart from NSAIDS, which is the other group of drugs frequently prescribed as anti- inflammatories?
Steroids
Name the 2 main sub-groups of NSAIDS. Describe in one sentence the fundamental difference between these 2 types, in terms of its mechanism of action.
1ST GENERATION and 2ND GENERATION. 1ST GEN INHIBITS BOTH COX 1 and COX 2 2ND GEN INHIBITS ONLY COX 2
What does COX stand for? What are the differences between COX-1 and COX-2?
CYCLO-OXYGENASE
COX 1 WORKS ON ARACHIDONIC ACID THAT HAS BEEN PRODUCED FROM A PHYSIOLOGICAL STIMULUS
COX 2 WORKS ON ARACHIDONIC ACID THAT HAS BEEN PRODUCED FROM AN INFLAMMATORY STIMULUS AND HAS NO AFFECT ON STOMACH & PLATELETS (UNLIKE COX1)
Complete table
Substance - Produced by COX-1 or COX-2 pathway? PGI2 - COX 1 PGE2 - BOTH TXA2 - COX 1 Pro-inflammatory PG - COX 2
