Antihistamines, Glucocorticoid and DMARDS

Action of H1

Histamine bind to H1 → Gq activation → Increase phospholipase C → IP3/DAG increase → Ca increase → Systemic effect

Systemic effect of H1

Vasodilation, increased vascular permeability, endothelial contraction, bronchial SM contraction

Action of H1RA

INVERSE agonist → stabilizes H1R → Lower H1 signal → lower histamine symptom

What is the difference between first and second gen H1RA

Gen 1 has better CNS penetration → More CNS effect like drowsiness, Gen 2 has lower effect

Why does 2nd gen H1RA have lower CNS effect

Higher polarity, P-Gp efflux of H1RA

Indication of H1RA

Allergy mediated inflammation, nausea, vomiting, motion sickness

Adverse effect of H1RA general

CNS symptom, inhibit CYP2D6 → lower effect of codeine, tramadol and tamoxifen

Contraindication of H1RA

Asthma, promethazine has sulfite that causes tissue injury; caution in Pt with QT prolongation

When is 1st gen H1RA avoided

Kids <6 or older adults should avoid H1RA; H2RA is preferred in children

What is H2

Found stomach → Gs activation → Activate H/K ATPase → Acid secretion

Effect of H2RA

Block H2 → lower gastric acid secretion → gastric pH increase

H2RA indication

Gastric condition: GERD, peptic duodenal ulcer, hypersecretion, heartburn

Why is cimetidine avoided

High CYP450 inhibition, anti-androgen effect (gynecomastia, low libido etc)

H2RA side effect

Mild → headache, drowsiness, fatigue, constipation, diarrhea

CNS in hepatorenal impairment → delirium, confusion, hallucination, slurred speech

When would H2RA be used instead of PPI

Mild infrequent disorders, in pregnancy used antacid + H2RA; other times use PPI

H2RA drug of choice

Famotidine

Types of glucocorticoid ranked by the duration of action

Hydrocortisone (short) < prednisolone, methylprednisolone (intermediate) < dexamethosone (long)

Mechanism of glucocorticoids (genomic)

Diffuse to cell membrane → bind to cytoplasm → HSP protein dissociation → Translocate to nucleus → increase anti-inflam gene transcription + lower pro inflam gene trasncription

What anti-inflammatory gene is increased in glucocorticoid

Annexin A1 → decrease PG and leukotriene production + adhere to EP → Lower inflammation by PG and lower NT migration

Mechanism of glucocorticoids (non-genomic)

Bind to mGR → change immune cell activity → Suppress immune

Glucocorticoid indication

Anti-inflammatory, immunosuppressive, endocrine replacement, allergy disorders

Why is hydrocortisone used instead of dexamethosone in sepsis

Hydrocortisone has water retention effect while dexamethosone does not

What are DMARDS

Slow inflammation used to prevent joint damage

Methotrexate mechanism

MTX → ↑ extracellular adenosine → ↓ inflammatory cytokines/cell activity → ↓ synovial inflammation

Sulfasalazine mechanism of action

Sulfasalazine → sulfapyridine + 5-ASA → anti-inflammatory effect (not well known)

Hydroxychloroquine mechanism of action

Accumulate inside lysosome and endosome → increase pH → Interfere with Ag processing, presentation etc → Lower immune function → Lower inflammation