Asthma & COPD Flashcards

Question

Describe chronic bronchitis histopathology

Answer 1

* **Thickening of smooth muscle** * Collagen deposits under epithelial layer -> **Subepithelial fibrosis** * Goblet cell hyperplasia -> Increased Mucous secretion * Structural remodelling of the airways

Answer 2

Alveolar membranes collapse due to **elastin breakdown** resulting in large holes in which air gets trapped in. * Causes breating problems * Hyperventilation

Answer 3

* Patient adherence * Inhaler technique * Eliminate triggers

Answer 4

* Beclometasone dipropionate * Budesonide * Fluticasone propionate * Mometasone furoate In the case of COPD, they are only ever given IN COMBINATION with LABA or LAMA

Answer 5

Salbutamol,Terbutaline * **Onset**: ~30 mins * **Duration**: 4-6hrs

Answer 6

1. Preventer added immediately - Low dose ICS 2. Add inhaled LABA (Salmeterol 50mcg BD) 3. If no respone to LABA -> Terminate LABA 4. Increase ICS to **medium-dose** OR add LTRA (Montelukast 10m ON) 5. Refer patient for specialist care Check adherence and inhaler technique before stepping up treatment. | Reliever (Salbutamol) is present at all time of the regime (salbutamol)

Answer 7

More than 3 times a week

Answer 8

* Formoterol 12mcg BD|MAX: 24mcg BD * Salmeterol 50mcg BD (COPD max) |MAX: 100mcg BD

Answer 9

Also known as **LABA**. This is a **preventer** therapy * Salmeterol * Formoterol * Bambuterol * Indacaterol^ * Olodaterol^ * Vilanterol^ The last three are only used for **COPD** **Action time**: 12-24 hours No rapid onset of bronchodilation effects with **LABA**s

Answer 10

**Onset**: ~30 minutes **Action time**: 4-6 hours

Answer 11

**SABA**s and **LABA**s can cause any of the following... * Termors * Headaches * Nervous tension * Palpitations (B1 agonistic effects) * Tachycardia (B1 agonistic effects) * Hypokalemia (High-doses of B2 agonists)

Answer 12

Maintenance and reliever therapy. Includes the use of **Formoterol** in combination with a **corticosteroid**. Acts as both a reliever and a preventer as the formoterol has both SHORT acting and LONG acting components.

Answer 13

This is because Qvar has extra fine particles and is therefore twice as potent as *Clenil*. Ergo prescribe by brand even though they are the same Active ingredient (**Beclometasone**)

Answer 14

* Very low dose (children) = 50mcg, 2 puffs BD * Low dose (starting adult dose) = 100mcg, 2 puffs BD * Medium dose = 200mcg, 2 puffs BD * High dose = 250mcg, 2-4 puffs BD

Answer 15

* Medium dose = 80mcg, 2 puffs OD * High dose = 160mcg, 2 puffs OD

Answer 16

* Low dose (starting adult dose) = 50mcg, 2 puffs BD * Medium dose = 100mcg, 2 puffs BD * High dose = 100mcg, 4 puffs BD

Answer 17

* **Very low dose**(children) = 50mcg, 1 puff BD * **Low dose**(starting dose) = 50mcg, 2 puffs BD * **Medium dose** = 125mcg 2 puffs, BD * **High dose** = 250mcg 2 puffs BD

Answer 18

* Hoarseness * Throat irritation * Dysphonia (change of the voice) * Candida

Answer 19

* Reduce exposure to triggers (dust, mites, pollen) * Stop or reduce smoking * Lose weight * Practise breathing exercises * Annual influenza vaccination

Answer 20

* Offer treatment & support to stop smoking * Offer pneumococcal & influenza vaccinations * Offer pulmonary rehabilitation * Treat other comorbidities

Answer 21

1. Considered non-pharmaceutical interventions 2. **SABA** or **SAMA** | **Reliever** 3. Non-asthmatic features -> **LABA**+**LAMA** *(cannot have SAMA so change to SABA for reliever)* 3. Asthmatic features -> **LABA+ICS** 4. **LABA + LAMA + ICS**

Answer 22

Corticosteroid treatment (E.g. Clenil [Beclometasone])

Answer 23

B2 agonist such as Salbutamol or Formoterol

Answer 24

An **autosome recessive condition** inwhich the individual lacks anti-alpha trypsin which are proteins that inhibit neutrophil elastase from breaking down extracellular matrix leading to lung and alveolar damage which eventually leads to **emphysema** COPD

Answer 25

* Mast cells (Histamine, PGD, Leukotrines) * Basophils (IL-4) * CD4+ Th2 lymphocytes (IL-4, IL-5)

Answer 26

* Neutrophils (IL-8, Elastase, ) * Macrophages (MCP1) * CD8+ Th1 cells (IFN-γ, TNF)

Answer 27

Leukotriene B4

Answer 28

1. Cigg smoke or other noxious agents 2. Activate alveolar macrophages & epithelial cells 3. Release of chemokines & cytokines (TNFa, IL-6, MCP1) that recruit CD8+ lymphocyte (Th1) and neutrophils 4. Inflammatory agents + proteases released Causing... * Increase mucous secretion * Breaking down alveolar walls * Activating fibroblast ->Fibrosis

Answer 29

* Use as necessary * Carry with you at all times * Use ahead of exercise * Salbutamol max: 8

Answer 30

There are studies that show monotherapy leads to hospitalisation frequently as receptors and immune cells rapidly desensetize with the frequent use of SABA and therefore has a decreasing therapeutic effect by itself.

Answer 31

* β₂ receptor repeated stimulation * GPCR phosphorylated * Becomes a substrate for other protein binding * Internalisation * **Receptor downregulation** {Increase in receptor lysosomal degradation and a decrease in β2 receptor mRNA}

Answer 32

* Decrease mediator release in mast cells * Reduce plasma exudation = Reduce oedema * Reduce cholinergic neurotransmission thereby reducing parasympathetic effects in the lungs

Answer 33

1. Bind to β2 receptor coupled with Ga_s 2. Ga_s dissociates from GPCR complex and stimulates adenylyl cyclase 3. ATP converted to cAMP 4. cAMP inhibit MLCK * Inhibits Ca2+ release from intracellular stores * Reduces Ca2+ entry into cells * Induces Ca2+ sequestration into ER Decrease in Calcium causes airway smooth muscle relaxation.

Answer 34

Ephedrine stimulates other β receptors causing unwanted systemic effects ∴ not as effective

Answer 35

* Not everyone reacts well with LABA * It is started on a low dose * Monitored and trialled for 6 weeks * Removed if no significant improvement or worsening of symptoms occurs

Answer 36

* Use regularly- has no effect if missing doses * Brush teeth after taking in morning (reduces likelyness of candida) * Do not suddenly stop taking it

Answer 37

* **Reduce IL-2 transcription** preventing clonal expansion of Th cells and subsequently **decreasing the amount of cytokines** that promote eosinophils. * Less IgE antibody production * Upregulate β2 receptors (good for combination therapy) * Inhibit leukotriene production * Inhibit prostaglandins ∴ reducing vasodilation and subsequent oedema

Answer 38

**Ipratropium bromide** (Atrovent) * Non-selective antagonist * Onset: 30 mins * Duration: 3-6hrs (taken 3-4 times/day) * Poorly absorbed ∴ few systemic side effects * Available as MDI and nebuliser (nebuliser only for severe acute asthma)

Answer 39

* **Tiotropium** OD (Asthma & COPD) -> Spiriva * **Glycopyrronium** OD (COPD)-> Seebri Breezhaler * **Umeclidinium** OD (COPD) -> Incruse Elipta * **Aclidinium bromide** BD (COPD)-> Eklira Genuar

Answer 40

**Side effects**: * Dry mouth * Cough * Constipation * Headache

Answer 41

It blocks the **CysLt1** receptor thereby inhibiting leukotrienes and.. * **Relaxing airway smooth muscle** * **Reducing eosinophil** and **oedema**

Answer 42

* **GI disturbances** {Diarrhoea, Vomitting, GI discomfort} * **Nausea**

Answer 43

LTRA has the potential to induce **neurophychiatric reactions** such as: * Depression * Obsessive compulsive symptoms * Speech impairment (starting as a stutter) **Churg-strauss syndrome** * Inflammation of blood vessels * Associated with patients who have been on oral steroids Report any of the above symptoms immediately

Answer 44

**Aminophylline** which is given only intravenously for severy acute exacerbation of COPD and severe acute Asthma. **Theophylline** is given orally as an MDR drug and for long-term asthma treatment | Not very useful in exacerbations as it is not fast acting

Answer 45

* Xanthines have a very narrow therapeutic index **10-20 mg/L** and GI disturbances can still be experienced when in the index range. A blood sample should be taken 4-6 hours after administration and concentration should be measure 5 days after. * Smokers require a high dose

Answer 46

* CNS stimulation * Palpitations * Tachycardia * Vasodilation * Nausea/vomitting * Diarrhoea

Answer 47

* Airway smooth muscle relaxation * Reduce endothelial leaks = less migration and less oedema. * Reduction of mast cells and eosinophils * Reduction in neutrophils * Less pro-inflammatory chemokines

Answer 48

* Aclidinium + Formoterol * Tiotropium + Olodaterol * Glycoyrronium + Indacaterol * Umeclidinium + Vilanterol

Answer 49

* Fluticasone + Umeclidinium + Vilanterol * Beclometasone + Glycopyrronium + Formoterol

Answer 50

* **Increase side chain length** at amine + **steric bulk** = Increases β2 activity + DoA * **Including an ether at the long side chain** = Increases DoA * **Adding a carbon at the upper hydroxyl of the catechol** = Slows COMT metabolism = Increases DoA * Inclusion of an **R enantiomer at hydroxyl** = Increases β2 activity

Answer 51

* **TM5**: Hydrogen bonding (catechol hydroxyls - *serine* residues) * **TM3**: Ionic interaction (Protonated amine - *Aspartic acid* carboxylic group) * **TM6**: Hydrogen bonding (Hydroxyl group - *Phenylalanine* amide) * **TM6**: π-π stacking (*Catechol* benzene - *Asparagine* benzene)

Answer 52

Beclometasone (ICS) + Formoterol (LABA) | A MART therapy

Answer 53

Budesonide + Formoterol | A MART therapy

Answer 54

Beclometasone + Formoterol

Answer 55

Budesonide + Formoterol