PHARM REVISION QUIZ PART 3

Question 1

give one example of a synthetic glucocorticoid with significant mineralocorticoid activity and one without.

Answer 1

Prednisolone (w); dexamethasone (w/o)

Question 2

Glucocorticoids and mineralocorticoids are both…

Answer 2

corticosteroids

Question 3

what is the role of glucocorticoids and mineralocorticoids

Answer 3

Locally synthesized glucocorticoids regulate activation of immune cells, while locally synthesized mineralocorticoids regulate blood volume and pressure (its release increases BP).

Question 4

name an endogenous corticosteroid with glucocorticoid properties.

Answer 4

cortisol

Question 5

what is the pathway of release of cortisol

Answer 5

Stress causes the hypothalamus to release CRH which acts on the pituitary to release ACTH. ACTH acts on the adrenal gland which releases cortisol.

CRH is corticotrophin releasing hormone
ACTH is adreno cortico trophic hormone

Question 6

where are corticosteroid released from

Answer 6

adrenal gland on the kidney

Question 7

what are the metabolic, cardiovascular system, CNS and hormonal regulatory roles of glucocrticoids

Answer 7

m- increased break down of fats and proteins. increased gluconeogenesis and decreased glucose usage which causes hypergylcemia.

c- hypertension, decrease in permeability and vasodilation in microvascular

cns- mood changes, linked with changes in memory/stress

h- - Negative feedback on both hypothalamus & pituitary gland

Question 8

what are the anti-inflammatory effects of Glucocorticoids

Answer 8

Decreased microvascular fluid exudation
- Reduces influx of cells to areas of inflammation

Decreased inflammatory mediators and cytokines

- Decrease expression of COX-2
- Reduced levels of eicosanoids

Decreased function of inflammatory effector cells
-reduction in chronic inflammatory events

Question 9

why are gluticosteroids effective for asthma

Answer 9

Corticosteroids can be used for asthma because the increased effect of B2 receptors increases bronchodilation due to the air way smooth muscle relaxation. Also, the decrease in mucus secretion is helpful for asthma.
also reduces inflammation

Question 10

Glucocorticoids can get into the cell really easily because they are lipophilic so use …… as a method of transport

Answer 10

passive diffusion

Question 11

How do glucocorticoids switch genes on and off? and how does this work with cortisol.

Answer 11

1. ) Interaction of steroid/receptor with promoter regions.
2. ) Steroid/receptor complexes prevent gene activation by other transcription factors.
3. ) 3)Induction of IkB-a (inhibitor of NF-κB), which keeps NF-κB in cytosol and thus represses NF-κB (which normally has an important role in inflammation)

Leading to:
Increased expression of anti-inflammatory proteins: increased Beta 2-adrenergic receptors; increases lipocortin which decreases AA/ eicosanoids
- Levels of some anti-inflammatory cytokines go up: IL-10, IL-12, Decreased expression of pro-inflammatory proteins
-decreases cytokine production

Question 12

give two examples of therapeutic uses pf glucocorticoids

Answer 12

• Adrenal Insufficiency or failure (aka Addison’s disease) because remember glucocorticoids are made in the adrenal glands
• Treatment of inflammation
• Immunosuppression

examples of glucocorticoids:
-hydrocortisone, predisolone, betamethasoe, beclomethasone.

Question 13

compare the effects of NSAIDs and Glucocorticoids on Eisconoid biosynthesis

Answer 13

Remember eicosanoids are prostaglandins, thromboxane’s and leukotrienes which are synthesised from AA.

Glucocorticoids act very early on even before AA is made + causes decreased expression of COX-2
Whereas NSAIDS inhibits the expression of all of COXs

Question 14

what is an example of an endogenous mineralcortidcoids

Answer 14

aldosterone.
Basically, mineralocorticoids work to increase blood pressure/ volume. If BP is low the renin-angiotensin system will cause it to be released but when there is high blood pressure this inhibits its release.

• Low Na+ plasma levels increase aldosterone by directly activating adrenal gland and stimulating RAA system to produce Ang II
• Increases Na+ retention in distal tubules of kidney
• It causes H2O retention, and loss of K+ and H+

Question 15

what are two examples therapeutic uses of mineralocorticoids

Answer 15

adrenal insufficiency,

orthostatic hypotension/postural hypotension- when a persons bp drops when significantly when they stand or lie down. due to failure of baroreceptor.

Electrolyte disorders- cerebral salt wasting

e.g Fludrocortisone

Question 16

what are the side effects of corticosteroids

Answer 16

• Cushing’s syndrome (buffalo hump, euphoria, increased abdominal fat, moon face, thin arms and legs, muscle wasting, poor wound healing, easy bruising)
• Opportunistic infection
• Osteoporosis
• Gastric ulceration
• Growth suppression
• Behavioural or reproductive problems
• Prolonged HPA suppression after cessation of therapy
• Diabetes
• Hypertension
• Cataracts, etc.

Question 17

What are the 3 main roles of NSAIDS

Answer 17

Analgesic (pain prevention)
Anti-pyretic (lowering fevers)
Anti-inflammatory (decrease on immune response)

Question 18

How do NSAIDS work?

Answer 18

Main therapeutic action is by inhibition of COX:

• COX converts AA to PGs and TXs

Question 19

what is the role of COX 1 vs COX 2

Answer 19

Both COX-1 and COX-2 produce the prostaglandins that contribute to pain, fever, and inflammation,

COX-1’s primary role is to protect the stomach and intestines and contribute to blood clotting.

Both enzymes produce prostaglandins that promote inflammation, pain, and fever; however, only COX-1 produces prostaglandins that activate platelets and protect the stomach and intestinal lining. NSAIDs block the COX enzymes and reduce production of prostaglandins.

Question 20

why is paracetamol not considered an NSAID

Answer 20

• Little inhibition of COX-1 or COX-2 in peripheral tissue (which is to do with inflammation)

Question 21

explain the antipyretic mechanisms of NSAIDs

Answer 21

• Bacterial endotoxins stimulate macrophages to release interleukin-1 (IL-1)
• IL-1β acts on the hypothalamus to cause PGE2 release (via COX-2)…..
– ↑PGE2 depresses temperature sensitive neurons
• PGE2 elevates set point temperature - onset of fever
• NSAIDs block PGE2 production, so fever dissipates

• NSAIDS have no effect on normal body temperature

Question 22

explain the analgesic mechanisms of NSAIDs

Answer 22

• PGs sensitise and stimulate nociceptors
• Oedema produced by inflammation also directly activates nociceptive nerve fibres
• PGs interact synergistically with other pain producing substances (e.g. 5-HT, histamine) to produce hyperalgesia (↑ sensitivity to pain)
• Blockade of PG production breaks this cycle and leads to pain relief
• Useful for pain associated with production of inflammatory agents (PGs/TXs), e.g. arthritis, toothache, headache (as NSAIDs inhibit PGs-mediated vasodilatation)

Question 23

explain the anti inflammatory mechanisms of NSAIDshttps://www.brainscape.com/

Answer 23

• PGE2 and PGI2 have powerful acute inflammatory effects
– Arteriolar dilatation (increases blood flow)
– Increase permeability in post-capillary venules
– Both processes increase influx of inflammatory mediators into interstitial space
• Aspirin inhibits the activation of NF-kB (very important signalling molecule which can switch on certain inflammatory genes)
• Inhibition of their formation reduces redness and swelling
• NSAIDs provide only ‘symptomatic relief’
- they do not cure the underlying cause of inflammation
- e.g. help, but do not cure arthritis
• ↓ COX-2-generated PGs; effects develop gradually

Question 24

what is the role of NFkb and why is it a target anti- inflammatory drugs

Answer 24

very important signalling molecule which can switch on certain inflammatory genes on. it is pro-inflammatory.