CPTP 3.14 15 16 Drugs Inflammation Allergy Repair 1 2 3

Question 1

Describe the effects of histamine in the inflammatory process

Answer 1

Lungs - bronchoconstriction

Vascular smooth muscle dilation - erythema

Vascular endothelium contraction and separation - edema, wheal response

Peripheral nerves - sensitation - itch and pain

Heart - increased heart rate (minor)

Question 2

What does histamine receptor stimulation lead to?

Answer 2

Increased expression of endothelial adhesion molecules

Release inflammatory cytokines and eicosanoids

Activation of NFkB

Question 3

Mechanism of action of antihistamines

Answer 3

Negative modulation of receptor activity, tipping it towards inactivation compared to the basal level where there is slight activity.

Question 4

Pharmacokinetics of antihistamines

Answer 4

Most are oral administration
Well absorbed
2-3 hours peak plasma
Liver metabolism, some have cyp450 interaction

Question 5

Major side effects of antihistamines

Answer 5

1st gen - antimuscarinic SE, drowsiness, dry mouth

2nd gen - less sedation, does not cross BBB

3rd gen - less cardiotoxicity and muscarininc activity

Question 6

What are the eicosanoids

Answer 6

Prostanoids such as prostacyclin and thromboxane

Leukotrienes

Question 7

Two pathways used to target inflammation

Answer 7

5-lipooxygenase
And COX (better)

Question 8

How does ibuprofen work?

Answer 8

Competitive inhibitor of COX enzymes against arachidonic acid

Question 9

How does aspirin work?

Answer 9

Irreversible acetylisation of COX enzyme

Question 10

Effects of aspirin

Answer 10

Inhibits COX
Anti-platelet activity
Risk of GI bleeding/irritation

Question 11

Explain why NSAIDs cause GI bleeding

Answer 11

COX1 is a “house keeper” enzyme in the GIT, inhibition causes perforation and ulceration risk.

Question 12

Describe how celecoxib works

Answer 12

Specific COX 2 inhibitor, fewer GI side effects

Increased cardiovascular risks

Question 13

Describe how a serotonin agonist can be used to treat migraines

Answer 13

E.g. Sumatriptan

Sumatriptan inhibits a specific subtype receptor for 5-ht that is present in the cranial vessels.

It is a vasoconstrictor, by constricting large blood vessels, reduces the vascular inflammatory effects of a migraine.
5-ht also decreases activity of the trigeminal nerve

Question 14

What are the interactions of sumatriptan

Answer 14

Medications of anxiety, OCD, SSRIs, MAOIs, St. Johns wort.

Question 15

What are some prophylactic treatments for migraines

Answer 15

Antihistamines
Beta agonists
Serotonin antagonists (pizotifin)
TCAs

Question 16

How does pizotifin work?

Answer 16

Similar to TCAs, use for prophylaxis for migraines.

Question 17

Side effects of pizotifin

Answer 17

Antimiuscarinic effects
Weight gain
Increased appetite

Question 18

What are the 3 types of hormones made by the adrenal gland?

Answer 18

Glucocorticoids, mineralcorticoids and sex hormones

Question 19

What do the three zones in the adrenal cortex each do?

Answer 19

Zona reticularis -> precursor sex hormones
Zona fasciculata -> glucocorticoids e.g. Cortisol & corticosterone
Zona glomerulosa -> mineralcorticoids e.g. Aldosterone

Question 20

What do mineralcorticoids do?

Answer 20

Regulate electrolyte levels through RAAS cascade

Question 21

How do glucocorticoids do?

Answer 21

Manage stress, pain, metabolism and inflammatory response.

Question 22

What is the hypothalamus-pituitary-adrenal axis?

Answer 22

Hypothalamus secrets CRH which stimulates pituitary gland to make ACTH which tells the adrenal glands to make cortisol.

There is a negative feedback effect of cortisol on the hypothalamus to reduce production of cortisol

Question 23

3 biological effects of glucocorticoids

Answer 23

Modulate metabolism - lipid, glucose and protein

Stress resistance - control nutrient availability, stress coping

Immuno-modulators - control release of inflammatory and antiinflammatory cytokines

Question 24

How do glucocorticoids affect the immune reaction?

Answer 24

It is an anti-inflammatory molecule. It inhibits production of inflammatory cytokines made by cells. It does so by binding to the glucocorticoid receptor which downregulates proinflammatory protein expression and upregulates antiinflammatory proteins.

Question 25

What enzymatic effects do glucocorticoids have?

Answer 25

Activated Annexin I which inhibits phospholipase A2, thereby inhibiting conversion of arachidonic acid into eicosanoids.

Question 26

Why do glucocorticoids lead to osteoporosis after prolonged used?

Answer 26

It down regulates the gene for bone regulation, leading to osteoporosis.

Question 27

What are some uses of glucocorticoid drugs?

Answer 27

Antiinflammation
Chemotherapy
Replacement therapy

Question 28

Common GCC drugs given

Answer 28

Hydrocortisone
Prednisolone
Betamethasone

Question 29

Why is hydrocortisone used for?

Answer 29

Oral or topical, used for GCC replacement or for inflammation

Question 30

How is prednisolone used?

Answer 30

Orally for asthma and severe inflammatory conditions

Question 31

How is betamethasone different from prednisolone and hydrocortisone?

Answer 31

It has a very long half life.

It is given for inflammatory and autoimmune conditions

Question 32

What are some side effects of long term GCC usage?

Answer 32

Osteoporosis
Thinning of the skin
Cushing-like symptoms e.g. Moon face, nuchal buffalo hump, purple striae on umbilicus

Muscle wasting, hyperglycaemia