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Integrated Physiology and Pharmacology > Anti-inflammatory drugs > Flashcards

Anti-inflammatory drugs Flashcards

1
Q

Where is asparin derived from naturally?

A

Willow tree

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2
Q

Who isolated the parent compound for asparin?

A

Henry La Roux

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3
Q

What is the parent compound for asparin?

A

Salicylic acid

Asparin is acetlysalicylic acid

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4
Q

How many types of NSAIDs are there?

A

50

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5
Q

NSAIDs work to reduce the production of what?

A

prostaglandins and thromboxane

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6
Q

What is PG12?

A

Prostacyclin which causes endothelial vasodilation

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7
Q

What is TxA2?

A

Causes endothelial vosoconstriction

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8
Q

What is PGE2?

A

Causes inflammation, bronchorestriction and vasodilation

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9
Q

What is PGF2?

A

Causes uterus contraction

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10
Q

What is the action of NSAIDs?

A

Normally prostaglandin production is caused by the following pathway: Phospholipase A causes lipids to breakdown in the membrane, Arachadonic is produced which is acted on by COX to cause the production of prostaglandins
NSAIDs inhibit COX enzmes

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11
Q

What is the role of prostaglandins E?

A

It is a vasodilator and hypoallgesic

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12
Q

How does prostaglandins E cause heightened pain?

A

Nococeptors have receptors for prostaglandins E - these nococeptors are G protein coupled receptors
This binding causes an increase in excitability of nococeptors in response to other sources of pain eg touching the area

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13
Q

What is the role of prostaglandins D2?

A

Platelet aggregation

Asparin can reduce the risk of stroke by reducing aggregation

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14
Q

What does Thromboxane A favour?

A

Blood clotting

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15
Q

How do NSAIDs modify the inflammatory reaction?

A

They decrease vasodilation and therefore decrease oedema
They are ineffective against mediators that contribute to tissue damage associated with chronic inflammatory conditions
They work on COX enzymes outside of the CNS

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16
Q

Why is paracetomol a poor anti-inflammatory drug?

A

It exerts its effect mostly in the CNS

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17
Q

What is an analgesic?

A

A drug which reduces pain

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18
Q

How do NSAIDs reduce pain?

A

They decrease the production of prostaglandins which sensitises nociceptors to inflammatory mediators

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19
Q

What is an antipyretic?

A

A drug which lowers a raised temperature

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20
Q

What are the three types of cyclooxygenases and where are they found?

A

COX1 - all cell types
COX2 - only produced under inflamed conditions ie they are induced
COX3 - spliced variant of COX1 which is limited to the CNS and kidneys

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21
Q

Which type of COX is paracetamol a good inhibitor of?

A

COX3

22
Q

Which types of COX is asparin a good inhibitor of?

A

COX1 and 2

23
Q

Where are COX enzymes found inside the cell?

A

They are docked into the endoplasmic reticulum membrane

24
Q

What is meant by ‘asparin is a suicide inhibitor’?

A

It makes the COX enzyme permanently inactived as it forms makes a covalent bond in the enzyme ( forms an ester bond with serine from asparin’s acetyl group)

25
Q

How long does it take for asparin to be cleared and why?

A

It takes 4 hours as this is how long it takes for COX enzymes to be resynthesised

26
Q

How quickly is asparin absorbed?

A

10 to 20 minutes

27
Q

What are the differences in structure between COX1 and COX2?

A

COX1 has an isoleucine lining the channel
COX2 has valine lining the channel which is a smalle amino acid
The channel of COX1 is narrower than COX2

28
Q

Drugs that treat back pain work better if they are selective for which COX enzyme?

A

COX2

29
Q

What are the side effects of NSAIDs in the gut?

A

dyspespsia, diarrhoea, nausea, vomitting, gastric bleeding and ulceration
This is because prostaglandins work to inhibit acid secretion and protect mucosa

30
Q

What are the side effects of NSAIDs in the kidney?

A

May cause renal failure

Prostaglandins maintain renal blood flow

31
Q

What are the side effects of NSAIDs in the liver?

A

Usually side effects are more of a result to use of paracetomol. This is because in its first phase metabolism it produces a toxic intermediate compound which can cause death in very large amounts eg overdose

32
Q

Why can NSAIDs cause asthma attacks?

A

Prostaglandins are bronchodilators so if they are inhibited they could cause astha attacks

33
Q

What is rofecoxib?

A

It is a very potent COX2 inhibitor which is toxic

34
Q

Using asparin is associated with reducing the risk of what?

A

Colonic and rectal cancer, alzheimer’s

35
Q

What is the hepatoxic compound formed from paracetomol called?

A

N-acetly-p-benzoquinone

36
Q

How are headaches caused and how does NSAIDs treat the pain caused?

A

Headaches are caused by the vasodilation of vessels in the brain which press on pain sensory fibres and nociceptors in the skull
Use of NSAIDs reduces vasodilation so reduces activation of pain fibres

37
Q

What is rheumatoid arthritis?

A

Where the synovium of the joint becomes inflamed causing pain, stiffness and poor sleep
It is an example of an autoimmune disease

38
Q

What is the onset of rheumatoid arthritis?

A

40 to 60 years of age usually but can also be juvenile

39
Q

What is mehotrexate and what does it do?

A

Helps suppress immune activity and interacts with folic acid
It is used in the induction stage of RA
It inhibits the action of T helper cells so they dont form Th1 cells
It also inhibits the proliferatio if Th1 which limits the production of cytokines (IL-1 and TNF- alpha)

40
Q

What is sulfasalazine?

A

A drug used for chronic inflammatory bowel disease and RA
Bacteria in the colon can produce 5-aminosalicylic acis which may act as a free radical scavenger to decrease damage produced by neutrophils

41
Q

What are glucocorticoids?

A

Steroidal drugs

They act at the level of transcription to inhibit the production of pro-inflammatory cytokines

42
Q

What are DMARDs?

A

Disease modifying anti rheumatic drugs
Work to reduce symptoms by a diverse mechanism of action
Different targets used
Not well understood

43
Q

What is cyclosporine?

A

Used to control the rejection of implants
Works to supress the action of cytokines
Large complicated molecule
Inhibits the induction phase of RA

44
Q

What happens inside a T cell once it has been activated?

A

Intracellular calcium rises
Enzyme called calcaneum is activates which is a phosphatase
This enzyme targets NFKappaB which is a transcription factor which enters the nucleus to control transcription

45
Q

What two categories of drugs have been developed to treat arthritis?

A

Antibodies

Mimic Small Molecule Receptors

46
Q

How do mimic small molecule receptors work?

A

They mop up free cytokines so it can’t interact with the receptors on cells

47
Q

List some anti-asthmatic drugs

A

Bronchodilators eg salbutamol
Anti-inflammatory agents eg prednisolone and omalizumab
Glucocortoids eg zolaire

48
Q

How can different materials cause allergies?

A 
They can be:
Inhaled
Injected
Ingested
Contacted
49
Q

What is the emergency treatment for allergies?

A

Epinephrine (adrenaline)

50
Q

Where can allergies occur and what are the effects of the allergy?

A

Cardiovascular system - Causes cardiovascular collapse
Respiratory system - Bronchospasm, Laryngeal Oedema
Skin - Erythma (redness), Angiodema (swelling), Urticaria (rash/hives)
GI tract - vomitting, diarrhoea

51
Q

Where are mast cells found?

A

Everywhere in the body where there is an opening to the body

52
Q

Where are basophils found?

A

In the blood

Integrated Physiology and Pharmacology (17 decks)

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