Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHYSIOLOGY & PHARMACOLOGY > ANTIINFLAMMATORIES > Flashcards

ANTIINFLAMMATORIES Flashcards

1
Q

What are NSAIDs?

A

Non steroidal anti-inflammatories.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where was aspirin derived and synthesised?

A

Derived from the white willow, a powder called salicylin and then converted to salicylic acid. This had large GI effects and so was converted to acetyl salicylic acid to reduce these effects.
This was the first synthesised drug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the function of NSAIDs?

A

Decrease production of inflammatory mediators.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are some examples of inflammatory mediators?

A

Prostaglandins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the function of prostaglandins?

A 
They works as paracrine mediators ie are synthesised in cells and diffuse out to act up surrounding cells
Mediate constriction of smooth muscle
Vasodilation
Promote platelet aggregation
Increase sensitivity of nociceptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the classes of eicosanoids?

A

Prostaglandins
Thromboxanes
Leukotrienes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the key NSAIDs?

A

Aspirin
Ibuprofen
Paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the three characteristics of NSAIDs?

A

Anti-inflammatory
Analgesic (reduces pain)
Antipyretic (reduces fever)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does aspirin work?

A

Aspirin is a suicide inhibitor. It permanently binds to Ser residue in COX enyzme and so the body has to remake the enzyme.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does Ibuprofen work?

A

It is a competitive inhibitor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How are prostaglandins produced?

A

Phospholipids are converted into arachindonate by phosphlipase.
Arachidonate is converted into cyclic endo-peroxides by cylooxygenase enzymes. Cyclic endo-peroxides give rise to prostaglandins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does NSAIDs target?

A

COX enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the structure of COX?

A

COX is a dimer sitting in the ER.
It has a peroxidase site.
It has a cyclooxygenase site.
Drugs bind in the cyclooxygenase tunnel.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the different forms of COX?

A

COX1 - found in all cells and is always active
COX2 - found in inflammatory cells and is induced
COX3 - a splice variant of COX1 found only in the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Paracetamol is not really anti-inflammatory why?

A

As it mainly occurs at the level of the CNS on COX3.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do NSAIDS lower temperature?

A

Thermostat in hypothalamus is activated via cytokine IL1 induced COX2 production of PGE. This raises the temperature to kill off bacteria.
Since NSAIDs reduce prostaglandin production, this will not happen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the structural difference between COX1 and COX2?

A

Tunnel for entry of arachidonate is restricted by an isoleucine amino acid in COX1. In COX2, the tunnel is wider due to a smaller valine.
We can use this difference for development of specific drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the collective term for the two active sites on COX enzymes?

A

Prostaglandin synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why is COX1 not a good target for drugs?

A

It is found in all cells and so drugs would cause side effects.

20
Q

What was the first truly selective drug to COX2?

A

Vioxx

21
Q

What complications can NSAIDs have?

A

CV complications for those with underlying issues.

22
Q

What is the additional anti-inflammatory property of aspirin?

A

It appears to inhibit expression of NF-kappa B which has a key role in triggering gene expression of infammatory mediators.

23
Q

What are some common side effects of NSAIDS?

A

Prostaglandins homeostatically control acid secretion and protect the mucosa of the stomach, therefore NSAIDs can cause GI damage.
Prostaglandins also maintain renal blood flow and so renal function may be compromised.
Liver damage - paracetamol produces a toxic intermediate.
Bronchospasm attacks
Skin rashes

24
Q

How can side effects of NSAIDs be reduced?

A

Use of COX2 selective drugs.

25
Q

What are the advantages and disadvantages of COX1 inhibition?

A

Gastrotoxicity

Antithrombotic (aspirin)

26
Q

What are the advantages and disadvantages of COX2 inhibition?

A

Increased BP,salt retention

Anti- inflammatory
Analgesic

27
Q

What is rheumatoid arthritis?

A

Joint pain and inflammation, auto-immune in nature that can occur on one side of the body. It is characterised by symptoms such as: swelling joints, pain, stiffness in the morning and poor sleep, wight loss and fatigue.
It causes inflammation of the synovium, erosion of cartilage and bone.

28
Q

What are DMARDs?

A

Disease modifying anti-rheumatic drugs.

DMARDs may halt or reverse disease but NSAIDs only treat symptoms.

29
Q

What is the target of DMARDs?

A

It is a mixed group of drugs with different mechanisms of action.

30
Q

Give examples of DMARDs and their targets?

A
  1. Methotrexate - represses cytotoxic adn immune cells such as Th1 cells
  2. Sulfasalazine is thought to be a free radical scavenger buts it mechanism in unknown
  3. Penicillamine-d may decrease generation of Il-1
  4. Gold compounds inhibit induction of Il-1 and TNF-alpha
31
Q

What action do immunosuppressants such as cyclosporin have on rheumatoid arthritis?

A

Cyclophilins control transcription of calineurin which transcribes NFkappaB which promotes transcription of inflammatory cytokines (such as IL2). Cyclosporin prevents this.

32
Q

What is the process of joint damage?

A

T cells activate Th1 cells. Th1 cells activate macrophages that activate IL1 and TNF alpha which release inflammatory cytokine and chemokines.
Activated Th1 cells also cause osteocytes to create enzyme that breakdown cartilage and bone.

33
Q

At what level do glucocorticoids work?

A

At the level of the macrophage.

34
Q

Why are drugs that work at the level of transciption better?

A

They dampen the signalling cascade.

Glucocorticoids and immunnosuppressants do this.

35
Q

What is the advantage of new biological drugs on diseases such as rheumatoid arthritis?

A

They can target pro inflammatory cytokines very specifically.

36
Q

What is an example of a biologic used to treat rheumatoid arthritis?

A

Adalimumab (Humira)

A monoclonal antibody that neuralises TNF

37
Q

How many sufferers of asthma are in the UK?

A

5.4 million

38
Q

What do anti-asthmatic drugs include?

A

Bronchodilators (such as Salbutamol)

Anti-inflammatory agents such as Prednisolone and Omalizumab)

39
Q

Why do some people not respond well to bronchodilators as treatment of asthma?

A

Polymorphisms in the B2 adrenoreceptors reduce efficacy.

40
Q

What are common types of allergens?

A

Inhaled
Injected
Ingested
Contacted

41
Q

What are the phases of allergic reactions?

A

Early phase

Late phase

42
Q

What occurs in the early phase of a reaction?

A

The immediate response: Degranulation of mast cells to release histamine, TNF alpha and prostaglandins which has a number of effects dependent on where in the body the attack is occuring. Mast cells in this phase also recruit other inflammatory mediators.

43
Q

What occurs in the late phase of a reaction?

A

This is the inflammatory response phase where permanent damage is caused that is cumulative over time. Recruitment of inflammatory mediators are now transcribed. These pro inflammatory cytokines cause vascular permeability, mucous secretion, stimulate nerve endings, and recruit eisinophils and immune cells that reside permanently.

44
Q

How do allergies arrise?

A

Through IgE mediated hypersentitivity.

45
Q

What happens when IgE class antibodies are produced against an allergen?

A

When exposed, the allergens bind to IgE antibodies and these antibodies present to the receptors of Mas cells, basophils and eisinophils.
Upon stimulation, mast cells release histamines, prostaglands other inflammatory mediators.

46
Q

What is asthma associated with?

A

Over activity of Th2 cells.
When an allergen is presented, overactivity of Th2 causes production of IgE antibodies as well as induce transcription of IL4/5/13 to produce eisonophils that cause inflammatory side effects and damage.

47
Q

If we know that Th2 cells are overactive, what can we target to decrease this?

A

Th2 cells are activated and induce transcription of IL4/5/13 that produce eisinophils.
Glucocorticoids work at the level of transcription to prevent this and in this way the inflammatory effect is decreased.

PHYSIOLOGY & PHARMACOLOGY (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions