B.21

Question 1

Selective β2-stimulants and other bronchodilators

Answer 1

1. SABA: Salbutamol, Terbutaline, Fenoterol
2. LABA: Salmeterol, Formoterol
3. M-antagonists: Ipratropium, Tiotropium
4. Xanthine: Theophyllin

Question 2

Classification of antiasthmatic drugs

Answer 2

1. Basic pharmacological:
   Bronchodilators
   Antiinflammatory drugs
2. Clinical:
   “Relievers”
   “Controllers”
3. Route of administration:
   Local - Inhaled
   Synthetic

Question 3

Bronchodilators

Answer 3

β2-R agonists, Xanthines, Antimuscarinic drugs

Question 4

Antiinflammatory drugs

Answer 4

Glucocorticoids, Leukotrienes antagonists, mAb, Degranulation inhibitors

Question 5

“Relievers”

Answer 5

short acting β2-R agonists(SABA), Xanthines, short acting antimuscarinic drugs (SAMA)

Question 6

“Controllers”

Answer 6

Glucocorticoids, Leukotrienes antagonists, mAb, long acting β2-R agonists (LABA), Xanthines, Long-acting antimuscarinic drugs (LAMA)

Question 7

Local - Inhaled

Answer 7

β2-R agonists, Antimuscarinic drugs, Glucocorticoids, Degranulation inhibitors

Question 8

Synthetic

Answer 8

β2-R agonists, Xanthines, Glucocorticoids, Leukotrienes antagonists, mAb

Question 9

Salbutamol (Albuterol), Terbutaline, Fenoterol

Answer 9

MOA: SABA (short acting β2-R agonist);
Kinetics: onset of action- 5min, max. effect- 1h, DOA- 4-6h. Salbutamol and Fenoterol inhaled, Terbutalin inhaled, s.c., i.v;
IND: relievers (on-demand inhalation);
SEs: (they are acting locally so the risk of SEs is not so big) cardiovascular disturbances (palpitation, tachycardia, angina→direct cardiac effects-β1,2, vasodilation-β2, presynaptic NE release-β2), tremor, hypokalemia, metabolic effects (hyperglycemia, hyperlipidemia), reduced arterial PaO2, mild loss of apetite, disturbed sleep agitation (children - hyperactivity), development of tolerance

Question 10

Salmeterol, Formoterol

Answer 10

MOA: LABA (long acting β2-R agonists),
Salmeterol - partial agonist!;
Kinetics: inhaled (daily), slower onset of action than SABA (>12h), lipophilic (→accumulate in membranes). Formoterol- faster onset of action;
IND: Controllers in patients with moderate/severe asthma and COPD (ALWAYS in combination with GCs since they give synergistic effect→GCs have a permissive effect on β-receptors);
SEs: same as SABA

Question 11

Ipratropium, Tiotropium

Answer 11

MOA: Ipra- non selective M-R antagonist, Tio- M3-R selective antagonist (→bronchodilation, bronchial secretions↓);
Kinetics: Ipra- onset: <15min, DOA: 4-6h, given 3-4X/day. Tio-longer effect, T1/2-11h-6days, X1/day;
SEs: dry mouth, cough (quaternary structure→less systemic effects);
IND: Relievers (ipratrupium) or controllers in asthma and COPD

Question 12

Theophylline

Answer 12

MOA: Bronchodilation (PDE↓→cAMP↑, A1-R↓→blocking bronchoconstriction), release of inflammatory mediators↓ (PDE4↓, A1-R↓, HDAC2↑→to prevent transcription of inflammatory genes), ciliary activity↑; SEs: CNS↑ (→Anxiety, insomnia, tremor, seizures), Cardiovascular events
(-at low doses: mild BP↑,
-at high doses: inodilator effect),
diuretic effect (↑GFR, tubular Na+-reabsorption↓), GI secretions ↑ (gastric acid, digestive enzymes);
Kinetics: good p.o abs., hepatic metabolism (CYP1A2), individual differences in metabolic rate and T1/2, NARROW therapeutic index;
IND: prevention of asthmatic attack (oral, extended release tablets), reliever in acute asthma (i.v)

Question 13

A1-R

Answer 13

Adenosine 1 receptor (regulates diverse functions of the cardiovascular, respiratory, renal, inflammation and CNS);

Question 14

HDAC2

Answer 14

regulator of SERT gene expression in intestinal epithelial cells