NSAIDs Flashcards

Question

what happens when injured - specifics

Answer 1

Releases various prostaglandins More cells come in from blood and cope with injury Immediate release prostaglandins And other things = bradykinin = stimulate free nerve endings If prolonged = stimulate nerve endings and impulse goes here = Synapse in spinal cord Inflammation to any injury - not mild Activate macrophages and mast cells Release all kinds of mediators = Histamine, prostaglandin, E2, bradykinin, interleukins = Act on receptors Instantaneous Nocioceptors = prostaglandins sensitive to other mediators More serious injury = platelets and thrombosis

Answer 2

some activity in spinal cord If noxious problem persists = changes take place in spinal cord Nsaids can act here

Answer 3

4 classical signs = Heat redness = Vasodilation Swelling = Leakage of vessels pain Also may be loss of function Ex = break bone

Answer 4

Usually occurs acutely but if have arthritis = happens in multiple joints Nsaids useful for relieving pain with an acute injury in one place but ALSO relieving pain from chronic issues

Answer 5

reaction of living tissues to injury Additional cells and mediators from circulation Pull in mast cells, macrophages, neutrophils Peripheral nociceptor Prostaglandin E2 very important here in periphery Receptors on nerve ending End result = impulse that travels into spinal cord and goes up into it

Answer 6

If long problem or significant inflammation = get changes in the spinal cord and further synthesis of prostaglandin E = increased receptors for prostaglandins on postsynaptic side and on neighbouring internours and on primary afferent fibres Complicated Usually action in tissue but also spinal cord to dampen sensation of pain

Answer 7

Relief of mild to moderate somatic pain including headache, toothache, myalgia (muscle pain), arthralgia (joint pain) Relief in inflammatory disorders including rheumatoid arthritis (autoimmune problem), osteoarthritis (pretty common, in people who use particular joints more), gout (except acetaminophen) Reduce fever Prophylaxis (prevention) of myocardial infarction and stroke (aspirin only)= Major use of aspirin worldwide

Answer 8

Cardiovascular diseases= Atherosclerosis, cerebrovascular diseases, heart failure, cardiomyopathy, stroke Chronic inflammatory diseases = IBD, COPD, RA, psoriasis, chronic pancreatitis, CIDP, CICTD Bone muscular and skeletal diseases = Osteoporosis, osteoarthritis, DDD, muscular dystrophy Decrease incidence of some types of cancer = Lung cancer, kidney cancer, gastric cancer, colon cancer, pancreatic cancer, lymphoma

Answer 9

or joint pain Rheumatoid arthritis and osteoarthritis Osteoarthritis = Tends to be focused on certain joints Can impair walking Hip replacements can be done Milder problems solved by taking nsaids

Answer 10

Also used in horses For horse races Dogs Hip arthritis in dogs Relieve pain and inflammation Has to be tested tho For species TOXIC TO CATS

Answer 11

Temperature regulating center in the hypothalamus Can be altered by exogenous pyrogens = bacteria and viruses, can cause infection and release pyrogens

Answer 12

elevates body temperature and act in hypothalamus

Answer 13

Also macrophages, monocytes and t cells can release endogenous pyrogens Move into hypothalamus and trigger increase in temp

Answer 14

Increase in production of prostaglandin E2 and raises set point Impulses sent to periphery = person starts to vasoconstrict and sweating = lose less heat With The shivering and muscle contraction = generate more heat = Increase body temp

Answer 15

Hypothalamic set point = have prostaglandin E2 increases in terms of synthesis Drugs interfere and control fever

Answer 16

stomach Dyspepsia = gastric discomfort Erosions = Of musical lining, Can cause bleeding Anemia - GI bleeding = Not normal number of circulating blood cells Ulcers - bleeds/perforations

Answer 17

Renal dysfunction Renal failure - acute/chronic Blood pressure Heart failure - If significance problems

Answer 18

= contributes to blood loss If too much = bad

Answer 19

More issues if chronic use or high doses Ex = rheumatoid arthritis Taking high dose Lining of stomach = secrete HCL, lining of music, protecting stomach Nsaids can = Interfere with production of prostaglandins and mucus and bicarbonate = Decreases protective features, Protection from HCL Nsaids get access to these exposed ells Does not affect everyone Biological variability Can get ulcers

Answer 20

Tea from willow leaf 1800s = salicin Felix hoffmann Aspirin = generic name Easy to manufacture and cheap Most commonly used drug in the world Close to 3 billion worth of aspirin sold every year

Answer 21

400 BC: Greece, Hippocrates gives willow leaf tea to relieve pain 1828: In Italy, active ingredient is extracted from willow and named salicin 1897: In Germany, Bayer’s Felix Hoffmann develops and patents a process for synthesizing aspirin. 6 First clinical trials begin because back then, people just swallowed the drug. 1899: Aspirin was launched for the first time 1930s: Bayer’s patent runs out; aspirin generic

Answer 22

Analgesic, anti inflammatory, antipyretic, antithrombotic Used in other parts of the world for pain and inflammation and fever In canada = mainly for preventing heart disease

Answer 23

homodimer Attached to cell membrane Arachidonic acid comes in and then acted on by enzyme Aspirin acetylates enzyme = leaves acetyl group Inactivates cyclooxygenase = permanent inhibition Sine acetyl group stays there and doesn't come off Inactivated enzyme Have to synthesize more of enzyme Irreversible effect Salicylic acid bound = serine acetylated

Answer 24

Aspirin = small molecule so can block both cox1 and cox2 Variety of effects Anti pain anti inflammatory Vascular effect = block thromboxane and prostacyclin

Answer 25

Thromboxane A2 made in platelets = causes vasoconstriction, thrombosis can block with aspirin Platelets have No nuclei Blockade for life of platelet = 8-12 days Decreases risk of blood clot in coronary or cerebral artery

Answer 26

Little doses of aspirin Decreases potential of platelets to clump and cause thrombus Decrease chance of thrombus forming in vasculature Will not block all since low dose

Answer 27

Platelet activated Thromboxane A2 Platelets clump and thrombus forms Activates glycoprotein receptor Aspirin interferes with thromboxane a2 = agonist ADP, thrombin, epinephrine, etc Useful in preventing strokes and heart attack = small doses

Answer 28

Also discovered by chance = long term aspirin use lowers colon cancer risk Led to discovery that inflammation is a part of carcinogenesis

Answer 29

Low dose = first order kinetics Switch to zero order at high dose = longer to get rid of it

Answer 30

Aspirin converted back to salicylic acid and a significant amount is just excreted in urine , Other parts of it = type 2 reaction converted something we can easily excreted from kidney = add glucuronide Salicylic acid can be reabsorbed from kidney If urine changed to alkaline conditions = resorption is less and it will remain in lumen More excreted Alkaline urine more excreted

Answer 31

aspirin toxicity = if chronic use, or kids swallow

Answer 32

Headache, tinnitus, dizziness, hearing impairment, dim vision = Cns effects, Tinnitus = if hear ringing in ears = must cut down since getting to toxic dose Condusion, drowsiness Sweating and hyperventilation Nausea, vomiting Marked acid base disturbance = issue Hyperexia Dehydration Cardiovascular and respiratory collapse, coma convulsions and death If overdose can be fatal Easy ways to monitor concentration in blood

Answer 33

Do not give aspirin to kids REYE’s syndrome So rare, only occurs in some people Hard to study Other nsaids can be given to children instead of this one

Answer 34

Many drugs Blocks cox1 and 2 Depends on drug

Answer 35

Iso-butyl-propanoic-phenolic acid C12H18O2 MANY different names Should not take aspirin before ibuprofen

Answer 36

Ex = low dose aspirin for cardiovascular effects then if need something for pain = do not take ibuprofen Since aspirin permanently acetylated enzyme When take ibuprofen - before or after = they block each other If take ibuprofen first = aspirin cannot access Other way around too

Answer 37

Liver deals with it P450 conjugation = now water soluble and can be excreted by kidney Inactivated then made water soluble - kidney gets rid of tem

Answer 38

COX2 inhibitors Some nsaids designed specifically for this Cox2 - mainly activated during tissue injury and inflammation Maybe if can block= give fewer side effects Thromboxanes platelets, And prostaglandins = endothelial cell

Answer 39

Low dose aspirin = less platelet aggregation and inhibit coagulation and cause vasodilation = More blood flow and less clotting If cox2 inhibitor= Still have cox1 so bigger chance of platelet aggregation = risk

Answer 40

Some developed specific for cox2 BUT Problems tho Non selective cox inhibitors = effect both Selective cox 2= only effect on Pain fever and inflammation But also has some functions in body generally = Renal electrolyte homeostasis and renal blood flow maintenance Knock out this role = bad if inhibit Channel wider in cox2 in enzyme

Answer 41

selective cox2 inhibitor Vs aspirin Aspirin can get into both Celecoxib = designed so can get into the bigger one but not the smaller one- wont block cox1

Answer 42

1 year long study Adverse cardiovascular effects increases a bit with using only cox2 inhibitor Small difference Rofecoxib taken off market after this experiment Taken off by company that made it Beneficial effects must be greater than potential side effects

Answer 43

Name by chemical structure = Para acetylaminophenol = Acetaminophen Para acetylaminophenol = Tylenol, Trade name Sales gone up beyond aspirin and ibuprofen- Aspirin no longer given to kids Combined with many things Many different names

Answer 44

Analgesic, antipyretic, NOT anti inflammatory Brings down fever Helps with pain

Answer 45

Specific cyclooxygenase? Do not KNOW Acetaminophen only acts in some tissues = endothelial cells, not platelets or inflammatory cells

Answer 46

t1/2 = 2-3 hours - Not long 1500mg/dose Can be converted to toxic metabolite that damages liver

Answer 47

Hepatotoxic metabolites If have overdose = serious liver damage Can be metabolized many ways = Glucuronide conjugate, sulfate conjugate, cysteine conjugate Can also be converted to toxic metabolite by p450s Injures liver Can kill you Gradually

Answer 48

High fatal poisoning cases Sometimes kids get into it Sometimes people take it on purpose Stages of poisoning

Answer 49

The effects don’t show up immediately: 0-24 hours: anorexia, nausea, vomiting => if treated on the first day, the rest can be avoided 24-72 hours: abdominal pain, right upper region, elevated serum enzymes indicating liver injury. 72-96 hours: vomiting and symptoms of liver failure, sometimes renal failure, and pancreatitis. > 5 days: the resolution of hepatotoxicity or progression to multiple organ failure – sometimes fatal => if ignored for over 5 days, can cause many organ failures and thus death.

Answer 50

Metabolite - Can be conjugated with glutathione = now harmless With poisoning = exceeded capacity of glutathione Antidote = glutathione precursor N acetylcysteine

Answer 51

Ethanol acetaminophen interaction Chronic ethanol - at risk of acetaminophen hepatotoxicity ETOH induced p450 enzymes (1AA2, 2E1, 3A4) that convert acetaminophen into toxic metabolites that cause liver injury ETOH depletes glutathione stores, slowing removal of metabolites Increased possibility of liver injury