Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Ph 2 > Respiratory pharmacology > Flashcards

Respiratory pharmacology Flashcards

1
Q

Airway remodelling in asthma

A

Inflammation stimulates smooth muscle cell proliferation, causing a THICKENING OF THE WALL of the bronchus.

  • Epithelial alterations with the shedding of the epithelium
  • Upregulation of growth factors, cytokines and chemokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Airway remodelling in COPD

A

Inflammation causes accumulation of mucopolysaccharides in the submucosal layer, they act as a glue and thus the wall becomes less elastic.
-> bronchoconstriction is irreversible in these patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Action of glucocorticoids

A

They act on NFkB, negatively regulate IL-4, IL-5, Il-13. Thus, they interfere with inflammation, symptomatic bronchoconstriction and remodelling.

Glucocorticoids

  • bind to the GRE inducing an increased transcription of IkBalpha
  • behave as IkBalpha, direct interaction between NFkB and th glucocorticoid receptor in a monomeric form
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which is the main etiological cause in asthma?

A

Immunological e.g. allergies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which are the 2 main etiological causes in COPD?

A

Smocking and pollution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Phases of asthma attack

A
  • Immediate phase: histamine or leukotrines

- Late phase: inflammation based on cytokines released by T-lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Use of antihistaminic drugs

A

Not useful in asthma or COPD, just in rhinasthma (when allergic rhinitis is present together with asthma). Even with the latter intranasal glucocorticoids is better.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Beta 2 adrenergic agonist: location and mechanism

A

Location: on SMCs and on inflammatory cells
Mechanism: they are GPCR, coupled to Gs, thus stimulating adenylate cyclate which lead to an increase in cAMP. Thus PKA is activated and phosphorylates MLCK and MLCP. The first is inhibited, the latter is activated. So the regulatory chain of myosin is dephosphorylated and muscle relaxation occurs.
-> bronchodilation.

Additional actions

  • activation of mucociliary clearance
  • inhibition of cholinergic transmission
  • decrease plasma exudation
  • increase surfactant levels
  • modulators of the immune response since receptors are also present on inflammatory cells. Even if they undergo a rapid desensitization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Difference in use between short- acting and long- acting beta 2 agonists and explanation

A

Short acting: used in acute attack situations

Long acting: delayed onset, longer lasting action. Used for long-term therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Anticholinergics mechanism

A
  • Antagonists at muscarinic receptors

- Inhibit bronchoconstriction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which is the main neurotransmitter responsible for bronchodilation

A

Adrenaline! Released by the adrenal medulla as rescue mechanism e.g. during exercise

Noradrenaline is mainly used for regulating vessels and secretion, not really for bronchoconstriction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which part of the ANS is responsible for bronchoconstriction? And for bronchodilation?

A

Parasympathetic nervous system -> bronchoconstriction

Sympathetic nervous system -> bronchodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Mechanism of sensitive fibers on SMCs

A

Sensitive fibers are activated by irritants in the bronchus and initiate a reflex which cause the release of Ach. This leads to bronchoconstriction (defence mechanism). Cough is induced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Adverse drug reactions to B2 agonista

A
  • Tachycardia because of B2 receptors in the heart (present until desensitization)
  • Shivering due to the presence of B2 receptors in skeletal muscles
  • Hyperglycemia due to the presence of B2 receptors in skeletal muscles regulating metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Corticosteroids administration for COPD and asthma is local, enteral or parenteral?
Realistic pharmacokinetics

A

Local! Otherwise it would be very dangerous. The drug is deposited in the respiratory airways during inspiration.

90% swallowed -> GI tract -> systemic circulation -> adverse drug reactions but a big portion is inactivated by the liver
10% has a topical effect in the lungs

Oral corticosteroids: no first-pass metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

List of inhaled glucocorticoids

A
  • Fluticasone
  • Budesonide
  • Flunisolide
  • Beclomethasone
  • Monetazione
  • Triamcinolone
17
Q

Why could it be better to treat asthmatic kids with corticosteroids?

A

TNF alpha interferes with growth. Asthmatic kids treated without corticosteroids were shown to grow less.

18
Q

Innervation of the lung

A
  • Sympathetic: for circulation and secretion (especially aqueous). It causes vasodilation only in rescue mechanisms
  • Parasympathetic: vagus nerve -> release of Ach -> activation of muscarinic receptors on SMCs (especially M1 and M3) -> contraction and mucous production
  • NANC fibers (travel with the vagus nerve too): control bronchodilation in the resting state. Release of NO and some peptides (VIP) on SMCs -> activation of guanylyl cyclase -> production of cGMP -> activation of PKG -> inhibition of bronchoconstriction.
19
Q

Why Ca2+ blockers are not used in asthma?

A

Ca2+ channels are expressed much more on SMCs of vessels but not on the SMCs of the bronchi.

20
Q

Role of M2 muscarinic receptors

A

Auto receptors regulating the release of Ach. Present at preterminal level. Inhibit further release of Ach by causing an increase in K+ currents in the nerve (the terminal is hyperpolarized) -> calcium channels don’t open and neurotransmitters are not released

21
Q

Antimuscarinic drugs

A

SMCs relaxation + inhibition of mucus production
Because of the localization of muscarinic receptors, these drugs are indicated more in COPD than in asthma.

In asthma a combination of B2 agonists and glucocorticoids is sufficient.

22
Q

Ipratroprium and tiotropium

A

Antimuscarinic non - specific drugs. They block everything also M2 receptors
→ inhibit bronchoconstriction
→ inhibit mucous secretion

23
Q

B2 agonists on immune cells

A

Dampening of the immune response.
Negative correlation between cAMP levels in immune cells and the degree of immune response.
Rapid desensitization

24
Q

Apremilast

A

Specific blockage of PDE4 which is on inflammatory cells. PDE4 normally degrades cAMP thus once inhibited, levels of cAMP increases leading to a dampening of the immune response.

  • PKA phosphorylates NFkB decreasing it’s activity
  • phosphorylation of corticosteroid receptors, increasing their activity
  • Stimulates CREB
25
Q

Advantage of PDE inhibitors compared to B2 agonists

A

B2 agonists undergo desensitization

26
Q

3 examples of B2 agonists

A
  • Salbutamol (Albuterol in USA): rapid onset (5 minutes), short acting (6 hours), full agonist
  • Salmeterol: delayed onset (30 minutes), long-acting ( 12-14 hours), partial agonists (less desensitization and down regulation of B2 receptors)
    Similar structure to salbutamol but with the presence of an aliphatic chain that links to the exposure on the receptors leading to a stable intensity of relaxation over time. The binding to the exosite further decrease desensitization.
    It is less lipophilic, so it has a delayed onset of action.
  • Formeterol: rapid onset, long acting, full agonist (cause desensitization). It is always administered together with steroids which Inhibit the transporter oct3 (influx transporter that would take up and lead to metabolization of the drug). Formeterol is very lipophilic and arrives really fast to the SMCs -> rapid acting.
27
Q

NANC pathway

A

Action potential –> opening of calcium channels -> vesicles containing peptides + nNOS activation (calcium dependent enzyme) -> NO diffuses to the SMCs -> activate guanylate cyclase -> production of cGMP -> activation of PKG -> it blocks Ca concentration :

  • inhibits PLC
  • inactivate IP3 receptor
  • activate CaATPase on PM
  • stimulate MLCP

—> bronchodilation

28
Q

PDE 4 inhibitors

A

Apremilast, cilomiblast, roflublast
PDE 4 Is present on inflammatory cells (not in SMCs)
PDE degrades cAMP
These drugs don’t interferes with bronchodilation but with inflammation.
But they are not so specific => many adverse drug reactions.
Apremilast is new but still not indicated in asthma.

29
Q

Pharmacodynamics of corticosteroids

A
  • transactivation of certain genes: IkBalpha, annexin 1
  • cis repression of other genes (negative GRE): ACTH (via the POMC gene)
  • trans repression: inhibition of NFkB direct and through CBP (CREB protein).
30
Q

Smokers response to corticosteroids

A

50% of response. They have a large amount of peroxynitrite which binds to HDAC causing it’s degradation. Thus they have a reduced number of HADC2.

31
Q

Leukotrine mechanism and possible counteraction

A

Leukotrines are released by inflammatory cells as macrophages and mast cells.
They derive from arachidonic acid via the lipo-oxygenase pathway. They act on
- GPCR on leucocytes -> inflammation
- Receptors on SMCs of the airways -> contractions.

Manipulation:

  • receptor antagonist e.g. Montelukast, Zafirlukast
  • block of synthesis by interfering with 5 LO. E.g. Zileuton, withdrawn for asthma because of its hepatotoxicity.
32
Q

Omalizumab

A

Antibody directed againat the Fc portion of IgE. Effective within a certain range of IgE. Specificity of IgE doesn’t matter.

Ph 2 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions