Anti-histamines, Corticosteroids, NSAIDs

Question 1

what are the 4 histamine receptors and what type of a receptor is it?

Answer 1

generally GPCR receptors
H1 - allergic reactions
H2 - gastric acid secretion
H3 - CNS disorders (e.g. narcolepsy, ADHD, alzheimers)
H4 - inflammatory conditions and inflammatory pain

Question 2

mechanism of antihistamine drugs

Answer 2

inverse agonists to induce intracellular reactions that reduce inflammation

Question 3

1st generation anti-histamine drugs

Answer 3

[essentially -amines]

chlorpheniramine (common)
diphenhydramine (common)
promethazine (has a lot of sedately side effects)

Question 4

2nd generation anti-histamine drugs

Answer 4

[essentially -dines]
cetirizine (common)
loratadine, deploratidine, fexofenadine (common isomers of each other)

Question 5

clinical uses of 1st generation drugs

Answer 5

used for vertigo, anti-emetic (essentially more CNS, sedately conditions)

Question 6

clinical uses of 2nd generation drugs

Answer 6

used for allergic reactions (e.g. rhinitis, conjunctivitis, urticaria)

Question 7

do we use antihistamines for anaphylaxis?

Answer 7

no we do not, as the onset time is too slow (about 1-2 hours even for 2nd generation) and does not have any dilatory effects. so we only give epinephrine/adrenaline

Question 8

side effects of antihistamine drugs (CNS, CVS, renal/GIT)

Answer 8

more related to 1st gen:

• sedation
• tachycardia
• postural hypotension
• urinary retention / constipation

Question 9

1st generation VS 2nd generation (4 different comparisons)

Answer 9

sedatory effects: 1st gen > 2nd gen
lipophilic: 1st gen > 2nd gen
efflux by p-glycoprotein: 2nd gen > 1st gen
affinity to H1 receptor: 2nd gen > 1st gen

Question 10

pathway of corticosteroid production in the body

Answer 10

hypothalamus produces corticotropin-releasing hormone to stimulate the anterior pituitary to produce adrenocorticotropic hormone which then stimulates adrenal glands to produce 2 hormones - mineralocorticoids (aldosterone) and glucocorticoids (cortisol)

Question 11

function of cortisol in the body

Answer 11

1. increase metabolism - gluconeogenesis, lipolysis etc

2. anti-inflammatory (by mobilising glucose for this active process)

Question 12

examples of corticosteroids

Answer 12

cortisone to hydrocortisone

prednisone to prednisolone

Question 13

clinical uses of corticosteroids

Answer 13

for any inflammatory conditions (e.g. allergic reactions, autoimmune diseases,

Question 14

mechanism of corticosteroids (where it binds to and its function)

Answer 14

binds to: intracellular nuclear receptor with 2 domains (ligand binding and DNA binding) - they differ based on their affinity to their receptors and potency

function: up regulate gene targets that are anti-inflammatory and dilatory but simultaneously down regulates lymphocytes (immunosuppressive)

Question 15

adverse effects of corticosteroids

Answer 15

• Cushing’s syndrome
• suppressed immunity
• hyperglycaemia

Question 16

pathway of inflammatory cytokine production (starting from arachidonic acid)

Answer 16

arachidonic acid forms lipoxins, prostanoids and leukotrienes.

prostanoids include prostacyclin (produced by cox-2), prostaglandin (produced by cox-2) and thromboxane A2 (produced by cox-1)

Question 17

function of prostanoids

Answer 17

prostacyclin - vasoconstriction and inhibit platelet aggregation

prostaglandin - vasoconstriction/vasodilation, vascular permeability and pain

thromboxane A2 - vasodilation and platelet aggregation

Question 18

aspirin - nonselective non steroidal anti-inflammatory drug

what are its functions?

note: generally, aspirin blocks COX 1 more than COX 2 but still blocks both and hence it can have so many functions.

Answer 18

analgesic: prevents stimulation of nociceptors by prostaglandins but has an analgesic ceiling as there are other cytokines such as bradykinin that can still stimulate nociceptors

anti-inflammatory: prevents production of prostaglandins = no vasodilation and vascular permeability and pain

anti-pyretic: knocks out COX enzymes in hypothalamus and hence resets the body’s thermostat

anti-platelet: reduces production of thromboxane A2 in platelets by inhibiting COX-1 and hence reduce aggregation; and since its an irreversible ligand, it will take a 1-2 weeks to remake new platelets and overcome the inhibition + also inhibits COX-2 but endothelial cells can recover quickly and make more enzymes that produce prostacyclins which help to further inhibit platelet aggregation = overall anti-platelet effect

Question 19

what are other kinds of NSAIDs? (2 types and their examples)

Answer 19

COX-2 selective NSAID: coxibs, naproxen

CNS selective NSAID: paracetamol

Question 20

adverse effects of NSAIDs

Answer 20

• GI disturbances
• renal disturbances (cause edema, hypernatremia)
• excessive bleeding
• reye’s syndrome (if you use aspirin in young children)
• bronchospasm (in asthmatics)

Question 21

adverse effects of coxib specially

Answer 21

• renal toxicity (still have even if cox 1 is present as it may be partially blocked)
• contraindicated in pregnant people as it leads to premature closing of arterioles ductus
• increased risk for thrombosis due to shunting to thromboxane A2
• wound healing