B.22

Question 1

Antiinflammatory agents inhibiting bronchial inflammatory processes. Antitussive agents and expectorants

Answer 1

1. Corticosteroids: Prednisolone, Methylprednisolon, Fluticazone, Budesonide
2. Leukotriene antagonists: Monteleukast
3. mAb: Omalizumab
4. Expectorants: Acetylcysteine, Bromhexine-ambroxol
5. Antitussive: (Dihydro)-codein, Butamirate, Prenoxdiazine, Dextrometorphan

Question 2

Prednisolone, Methylprednisolone, Fluticazone, Budesonide

Answer 2

MOA: binds and activates glucocorticoid receptors; Therapeutic effect: anti-inflammatory /immunosuppressive effect (vasodilation↓, extravasation and edema↓, neutrophil migration↓, acitvity of WBCs and macrophages↓, pro-inflammatory cytokines↓, iNOS expression↓, IgG production↓, histamine release↓), bronchial hyperreactivity↓, β2-R expression↑;
SEs: at low doses mild - oropharyngeal candidiasis, hoarsness. systemic- infections (oropharyngeal candidiasis), hyperglycemia (diabetes), peptic ulcer (PG↓→defense against H.pylori↓), Cushing’s syndrome, Osteoporosis (avascular necrosis of femoral head), reduced growth, muscle wekness (decreased muscle mass), CNS (seizures, depression, intracranial P↑), GH - LH - TSH secretion↓, glaucoma, hypokalemia, delayed wound healing, thinning of the skin, acute adrenal insufficiency (if chronic treatment stopped suddenly); Relative Contra-IND: cardiovascular diseases, peptic ulcers, glaucoma, diabetes, osteoporosis, psychosis, infections (HSV, TBC);
Kinetics: Budesonide &Fluticazone ROA- inhalation; IND: prevention of attacks in patients with mild-severe asthma or COPD, systemic steroid treatment- in case of severe acute attacks or severe persistent asthma (prednisolone→p.o; Methylprednisolone→i.v)→more SEs in systemic use

Question 3

Montelukast

Answer 3

MOA: CysLT1-R antagonist (Gq-PCR);
Therapeutic effects: Inflammation↓ (LTC4, LTD4, LTE4 →vascular permeability↓, edema↓), bronchodilation (mild→only prophylactic use), some patients are “non-responders”;
IND: Prevention of attacks;
Kinetics: p.o x1-2/day;
SEs: mild(→headache, diarrhea), New FDA warning(→nightmares, agitation, suicide)

Question 4

Omalizumab

Answer 4

MOA: Humanized Ab against Fcε part of IgE (prevents IgE-binding to and activation of mast cells, monocytes and granulocytes), can reduce circulating IgE level up to 90%;
IND: Prevent attacks in severe persistent allergic asthma, treatment of chronic spontaneous urticaria, severe bronchial asthma;
Kinetics: T1/2-26days, adm. every 2-4 weeks (s.c.);
SEs: allergy (local erythema →anaphylactic reactions)

Question 5

(dihydro-)codein

Answer 5

MOA: dihydrocodein is metabolized to dihydromorphine - a highly active metabolite with high affinity for μ-OR (centrally acting anti-tussive);
IND: treatment of moderate-severe pain (including post-operative and dental pain), treat chronic pain, breathlessness and coughing;
Kinetics: hepatic metabolism (CYP2D6), renal excretion

Question 6

Butamirate

Answer 6

MOA: centrally acting anti-tussive (acts through receptors in the brainstem→reduces airway resistance by inhibiting bronchospasm and anti-inflammatory effect);
IND: Cough; Kinetics: rapidly absorbed p.o;
SEs: rare (skin rash, nausea, diarrhea, dizziness)

Question 7

Prenoxdiazine

Answer 7

MOA: acts peripherally by desensitizing the pulmonary stretch receptors (→reduction of cough impulses originating in the lungs);
IND: non-productive Cough; Kinetics: p.o adm.;
SEs: rare (constipation, skin rash, allergies, nausea, dry mouth, dizziness)

Question 8

Dextrometorphan

Answer 8

MOA: NMDA-R blocker;
IND: Dry cough;
Extra: opioid-like molecule

Question 9

Acetylcysteine

Answer 9

MOA: Unknown (may reduce disulfide bonds within mucin →making the mucin less viscous), also has some antioxidant properties (as it participates in the GSH synthsis);
IND: Mucolytic therapy and acetaminophen (paracetamol) overdose (→acetylcystein can directly conjugate NAPQI or provide cystein for GSH production and NAPQI conjugation);
SEs: rare (abdominal pain, nausea, vomiting, constipation, diarrhea, fluching)

Question 10

Bromhexine, ambroxol

Answer 10

MOA: Aids in mucus clearance by reducing the mucus viscosity and activating ciliary epithelium, allowing secretions to be expelled from the respiratory tract (might be working through inhibition of TMPRSS2);
IND: Reduce mucus viscosity and clear mucus in conditions associated with mucus hypersecretion (including common cold, influenza, respiratory tract infections etc);
Kinetics: p.o adm., ↑plasma protein binding,
-Ambroxol (a metabolite of bromhexine might act on ACE-2→ preventing viral entry into alveolar cells, or increases secretion of surfactant →preventing viral entry), excreted in urine

Question 11

NAPQI

Answer 11

the toxic metabolite of acetaminophen metabolism

Question 12

TMPRSS2

Answer 12

transmembrane serine protease 2 receptor