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OD2 (S1&2) > PHARM - Anti-Inflammatory Drugs I: The Arachidonic Acid Pathway and NSAIDS - Week 5 > Flashcards

PHARM - Anti-Inflammatory Drugs I: The Arachidonic Acid Pathway and NSAIDS - Week 5 Flashcards

1
Q

Describe two means of chemical signalling between cells and give examples for each (5).

A

Release of molecules by other cells
-neurotransmitters
-hormones
-local mediators
-exosomes
Membrane-bound molecules
-immune system

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2
Q

What are exosomes?

A

Extracellular vesicles

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3
Q

Name 5 kinds of important local mediators and their composition.

A

Histamines - small amine
Prostaglandins - lipid-derived
Leukotrienes - lipid-derived
Bradykinin - a peptide
Nitric oxide - a gas

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4
Q

In what two cells are histamines largely stored in and released from? Where are these cells found?

A

Mast cells
-found in tissue, particularly mucosal surfaces/skin
Basophils
-blood

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5
Q

What relation do enterochromaffin-like cells have with histamines?

A

They regulate stomach acid secretion using histamine

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6
Q

Describe the triple response of Lewis and what each one occurs due to.

A

Occurs due to the release of histamine
Reddening - due to capillary dilation
Flare - redness in the surrounding area due to arteriolar dilation
Wheal - due to exudation of fluid from capillaries and venules

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7
Q

List 7 biological effects of histamine.

A

Vasodilation - hypotension
Increased vascular leak - hypovolaemia
Bronchospasm
Pain/itch - sensory nerve activation
Mucus secretion
Increased wakefulness
Gastric acid secretion

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8
Q

How does histamine induce pain/itch?

A

Sensory nerve activation

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9
Q

List the four major histamine receptors.

A

H1, H2, H3, H4

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10
Q

What is the major histamine receptor for allergic inflammation? What drug class targets this receptor and in what way?

A

H1 receptor
Anti-histamines are antagonists to this receptor.

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11
Q

Name four conditions that anti-histamines are useful in treating.

A

Hayfever - allergic rhinitis
Urticaria
Anaphylaxis
Angioedema

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12
Q

Can anti-histamines be useful in treating colds or athsma?

A

No

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13
Q

Are H1 receptor antagonists reversible or irreversible?
List the three classes of this drug.

A

Sedative
Non-sedative
Newer non-sedative

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14
Q

Which class of anti-histamines lacks anti-muscarinic activity and what is a consequence of this?

A

Non-sedative - lacks GIT effects but can cause sudden ventricular arrhythmia (rare)

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15
Q

What can be said of the newer non-sedative class of anti-histamines?

A

Reduced risk of unwanted cardiac effects

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16
Q

What is the active constituent of aspirin? What is it derived from?

A

Salicylate - derived from willow bark.

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17
Q

Name three effects of salicylate.

A

Anti-pyretic (fever)
Analgaesic
Anti-inflammatory

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18
Q

How did prostaglandins get their name?

A

The active components were thought to be from the prostate gland and was first derived and isolated from semen ( ͡° ͜ʖ ͡°)

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19
Q

What do prostaglandins have structural similarity to?

A

Arachidonic acid

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20
Q

What defines an eicosanoid?

A

20 carbon containing compounds

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21
Q

What umbrella term do prostaglandins and thromboxanes fall under?

A

Prostanoids

22
Q

Are eicosanoids stored? Explain.

A

No, they are produced on demand

23
Q

Which cells produce prostaglandins?

A

Most of them

24
Q

Briefly describe the generation of eicosanoids and name two stimuli that can induce this process.

A

A cytokine/inflammatory mediator acts on its receptor to begin the process. Mechanical trauma may also induce it.
This increases Ca2+ levels, which activates phospholipase A2, which liberates arachidonic acid from the cellular membrane.

25
Q

Where is arachidonic acid liberated from, and what is the rate-limiting step?

A

From the cell membrane - the action of phospholipase A2 is the rate-limiting step.

26
Q

Are levels of free phospholipase A2 high or low in resting cells?

A

Very low

27
Q

How does phospholipase A2 act?

A

It cleaves a phospholipid at its second carbon atom to result in the release of arachidonic acid

28
Q

Name three derivatives of arachidonic acid (4) and two enzymes responsible for its conversion.

A

Cyclo-oxygenase to form prostanoids
-prostaglandins
-thromboxanes
Lipoxygenase to form leukotrienes

29
Q

How many major cyclo-oxygenase enzymes are there and which of the two do most cells have? Which one do inflammatory cells have?

A

2 enzymes, COX1 and COX2
Most cells have COX1
Inflammatory cells have COX2

30
Q

Which cells mainly use lipoxygenase?

A

Inflammatory cells

31
Q

How do eicosanoids produce their effects?

A

Selective G-protein coupled receptors and subsequent second messengers.

32
Q

What effect do prostaglandins have on vascular smooth muscle?

A

Vasodilation

33
Q

What effect do thromboxanes have on vascular smooth muscle?

A

Vasoconstriction

34
Q

What effect do leukotrienes have on bronchial smooth muscle?

A

Constriction

35
Q

What effect do prostaglandins have on uterine smooth muscle?

A

Contraction

36
Q

What effect do prostaglandins have on gastrointestinal smooth muscle?

A

Contraction

37
Q

What effect do prostaglandins and thromboxanes have on platelet aggregation?

A

Prostaglandins - anti-aggregatory
Thromboxanes - pro-aggregatory

38
Q

What effect do leukotrienes have on leukocytes?

A

Chemoattractant

39
Q

Haemostasis is the balance between what two hormones?

A

PGI2 (prostaglandin) and TXA2 (thromboxane)
PGI2 is a vasodilator and anti-thrombotic
TXA2 is a vasoconstrictor and pro-thrombotic

40
Q

What effect do prostaglandins have on gastric secretion?

A

Inhibits gastric acid secretion

41
Q

What effect do prostaglandins have on the kidney (3)?

A

Increases renal blood flow and increases excretion of water and sodium.

42
Q

List three therapeutic uses for eicosanoids.

A

Glaucoma (latanoprost)
Gastric ulceration
Uterine contraction

43
Q

Do leukotrienes induce vasodilation?

A

No

44
Q

Which of the following induce chemotaxis (2):
Histamine
Bradykinin
Prostanoid
Leukotriene

A

Histamine
Bradykinin

45
Q

Which of the following induce pain:
Histamine
Bradykinin
Prostanoid
Leukotriene

A

Bradykinin

46
Q

Which of the following most induce vascular permeability (2):
Histamine
Bradykinin
Prostanoid
Leukotriene

A

Histamine
Leukotriene

47
Q

Which of the following acts synergistically with other mediators:
Histamine
Bradykinin
Prostanoid
Leukotriene

A

Prostanoid

48
Q

Describe what is meant by hyperalgaesic and give two hormones that fall under this term.

A

Increases sensitivity of receptors to painful stimuli
PGE2 and PGI2 (prostaglandins)

49
Q

Briefly describe how fever occurs in 5 steps.

A

Inflammation
Neutrophil activation
Cytokine release
PGE2 release in the hypothalamus
Temperature raised

50
Q

What do NSAIDs target?

A

COX enzyme

51
Q

What three effects do NSAIDs have?

A

Anti-pyretic
Analgaesic
Anti-inflammatory

OD2 (S1&2) (174 decks)

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