Drugs in Respiration - Pharmacology - Ashtma, COPD Flashcards Preview

Pharmacy Year 2 Semester 2 > Drugs in Respiration - Pharmacology - Ashtma, COPD > Flashcards

Flashcards in Drugs in Respiration - Pharmacology - Ashtma, COPD Deck (34)
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1
Q

the CNS goes via the vagus nerve to….

A

Trachea and conducting bronchi

2
Q

The trachea and conducting bronchi branch into what?

A
  • Submucosal gland - M1/M3
  • Blood vessel - M3
  • Airway smooth muscle - M3 - post-ganglionic fibres
3
Q

Innervation of human airway smooth muscle

A

no sympathetic innervation

only of glands and blood vessels

4
Q

Asthma inflammatory cell

A

eosinophils

5
Q

COPD inflammatory cell

A

neutrophils

6
Q

Immediate phase of asthma

A
Trigger: allergen 
↓
mast cells/mononucellar cells 
↓
spasmogens e.g. leukotrienes C4, D4, Histamine, PGD2
↓
Bronchospasm
7
Q

Immediate phase of asthma - mast cell branch

A
mast cells/mononucelear cells
↓
Chemotaxins 
Chemokines
↓
Late phase
8
Q

Late phase of asthma starting at chemotaxins and chemokines

A

chemotaxins
Chemokines

Infiltration of cytokine-released Th2 cells and monocytes; activation of inflammatory cells (especially eosinophils)

-mediators e.g. cysLTs→airway inflammation and airway hyper-reactivity
-eosinophil major basic protein, eosinophil cationic protein→epithelial damage→airway hyper-reactivity

Airway hyper-activity and airway inflammation

bronchospasm, wheezing, coughing

9
Q

Selective B2-receptor agonists
examples
Advanatages
Disavantages

A

Salbuatmol, terbutaline, salmeterol
Advantages: Rapid airway relaxation
Decreased systemic effects

Disadvantages
Receptor desensitization 
Receptor down-regulation 
Refractory bronchoconstriction 
Asthma-related death
10
Q

Pharmacology of B2-receptor agonists

A

Gs-GTP activates adenylyl cyclase and that produces cAMP
This cAMP does 3 things:
1) Increases SERCA
2) Increases PMCA
3) Decreases C2+ entry via channels
These three things decrease the intracellular concentration of Ca2+
Which in turn causes myosin-p to convert to myosin
This causes relaxation
(MLCK causes contraction)

11
Q

What does SERCA stand for

A

Sarcoplasmic/Endoplasmic Reticulum Calcium Atpase

12
Q

What does PMCA stand for

A

Plasma-membrance Ca2+ ATPase

13
Q

Advantages of B2-agonists

A
  • administered via inhalation; mostly well-tolerated, minimises adverse effects
  • rapid onset (minutes), SABAs last 3-6hours
  • Long acting forms last 8-12 hours
14
Q

Disadvantages of B2-agonists

A
  • May stimulate B1 receptors -ADRS in liver, heart and skeletal muscle
  • increased risk of asthma-related death (unusal genotype) - hypoxia
  • even when inhaled, only 10% goes to airways as rest swallowed
  • Tachcardia, ↑release of glucose from liver, tremor, ↑contracility of heart
15
Q

Phosphodiesterase inhibitors

A

inhibits phosphodiesterase, preventing breakdown of phospholipase, increasing cAMP and hence ↑protein kinase A, ↑SERCA, ↑PMCA
all of these increases cause lower intracellular calcium and hence smooth muscle relaxation

16
Q

Methylxanthines

drugs

A

-caffeine, theophylline, theobromine

17
Q

Advantages of methylxanthines

A

↑endogenous cAMP
enhance B2-agonist effects
↑cAMP can inhibit some inflammatory processes
Antagonists at adenosine receptors
Cheap, may work in COPD and severe, unresponsive asthma

18
Q

How Bronchodilator M3 receptor antagonists work

A

2 mechanisms: things it blocks

  • Rhok inhibits MLCPP which means contraction is blocked
  • PLC→IP3→increase in intracellular ca2+ to activate MLCK which increases phosphorlyation of myosin, causing contraction
19
Q

advantages of antimuscarinic bronchodilators

A
  • reduces mucus secretion
  • may be useful as add-on in life-threatening acute asthma
  • may alleviate acute asthma unresponsive to standard therapy
20
Q

disadvantaages of antimuscarinic bronchodilators

A

numerous adverse effects
constipation, dry mouth, nausea, cough, headache, dizziness
Less common side effects:
vomiting, palpitation, tachycardia, urinary retention, throat irritation,
blurred vision, mydriasis, raised intra-ocular pressure, angle-closure glaucoma

21
Q

Contraindiciations of antimuscarinic bronchodilators

A

benign prostatic hyperplasia, bladder outflow obstruction, narrow angle glaucoma

22
Q

Allergic asthma - role of T lymphocytes

Corticosteroid action

A

Glucocorticoids inhibit transcription of genes for interleukins
-drug binds to intracellular protein (receptor) and then they both enter the nucleus
Binds to DNA and changes gene expression
Inhibits transcription of genes for COX2, iNOS, cytokies,interleukins and cell adhesion molecules
-stimulate synthesis and release of annexin-1

23
Q

Corticosteroids indication

A

effective in asthma and possibly in COPD
reduces airway inflammation
reduce oedema by increasing membrane permeability
-reduce mucous secretion

24
Q

Corticosteroids

A

Beclometasone dipropionate 100-400ug
Fluticasone propionate 50-200ug

Each twice daily

25
Q

Other drugs used for asthma

A

-Omalizumab (monoclonal antibody - binds to IgE and prevents it from attaching to mast cells) - side effect is analphalactic shock
-mast cell stabilisers - mechanism unclear
sodium cromoglicate, nedocromil - more effective in 6-12 year olds

26
Q

COPD mechanism

A

epithelial cells/macrophages→TGF-B→fibrosis and remodelling of airways

smoke, irritants cause secretion of chemotactic factors - attract monocytes (become macrophages) and neutrophils

proteases e.g.:
-metalloproteinase 9 - breaks down basement membrane and causes mucous hypersecretion, acts in alveolar wall too
-elastase
Both proteases cause alveolar wall destruction (emphysema)
Reduces surface area for gas exchange

27
Q

MMPs

A

-matrix melloproteinases (neutrophil-derived proteases)
destroy elastin fibres in the lung parenchyma
Cause proteolytic degradation of extracellular matrix (ECM)
PDE4 inhibitors help reduce MMP production

28
Q

Roflumilast

A

PDE4 inhibitor used in conjunction with SABA
Main PDE in macrophages, eosinophils, neutrophils
Roflumilast enhancese SABA/LABA effects and improves FEV1

29
Q

Roflumilast side effects

A
Diarrhoea 
Nausea 
Abdominal pain 
Headache 
Unexplained weight loss
30
Q

Analeptics

A

respiratory stimulants

Doxapram

31
Q

Doxapram action pharmacology

A

1-Carotid chemoreceptors→Inhibition of Task1/Task 3 K+ leak channels
2-Brainstem respiratory control centres→respiratory motor neurones→increase frequency and depth of breathing by acting on diaphragm
3-Aortic chemoreceptors→inhibition of Task1/Task3 K+ leak channels

32
Q

Doxapram action

A

stimulates medullary respiratory centres

  • transiently ↑volume and rate of respiration
  • requires IV administration- short duration of 8-10min
33
Q

Doxapram indications

A
  • post operative respiratory depression
  • complication of opioid analgesic therapy
  • overdose of CNS depressant drugs
  • ventilatory failure in COPD
  • reduces frequency of apnoea in premature neonates but caffeien preferred alternative
34
Q

Doxapram safety

A

narrow margin of safety

May cause convulsions (mechanical ventilation preferred)