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Respiratory > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Postganglionic cholinergic fibres stimulation causes (3)

A

Bronchial smooth muscle contraction on airway smooth muscle cells
Increased mucus secretion on goblet cells
Mediated by M3 muscarinic ACh receptors

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2
Q

Postganglionic noncholinergic fibres stimulation causes

A

Bronchial smooth muscle relaxation mediated by nitric oxide (NO) and vasoactive intestinal peptide (VIP)

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3
Q

Sympathetic division stimulation causes (4)

A

Bronchial smooth muscle relaxation via β2-adrenoceptors
Decreased mucus secretion mediated by β2-adrenoceptors
Increased mucociliary clearance mediated by β2-adrenoceptors
Vascular smooth muscle contraction, mediated by α1-adrenoceptors

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4
Q

Smooth muscle contraction results from

A

Phosphorylation of regulatory myosin light chain (MLC) in presence of elevated intracellular Ca2+ and ATP

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5
Q

Smooth muscle relaxation results from

A

Dephosphorylation of MLC by myosin phosphatase

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6
Q

Activities of myosin light chain kinase (MLCK) and myosin phosphatase oppose/for each other

A

Oppose

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7
Q

The presence of elevated Ca2+ (2)

A

The rate of phosphorylation exceeds the rate of dephosphorylation
Relaxation thus requires return of intracellular Ca2+ concentration to basal level achieved by primary and secondary active transport

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8
Q

Chronic Asthma Pathological changes (5)

A

Increased smooth muscle mass
Accumulation of interstitial fluid (oedema)
Increased secretion of mucus
Epithelial damage (exposing sensory nerve endings)
Sub-epithelial fibrosis

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9
Q

Epithelial damage (exposing sensory nerve endings) causes

A

Increased sensitivity of the airways to bronchoconstrictor influences
Based on hypersensitivity and hyper-reactivity

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10
Q

How to detect hyper-responsiveness

A

Provocation tests with histamine and methacholine

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11
Q

Drugs in Asthma Treatment Categories (6)

A

Short acting β2-adrenoceptor agonists (SABAs)
Long acting β2-adrenoceptor agonists (LABAs)
CysLT1 receptor antagonists
Glucocorticoids
Cromoglicate
Humanised monoclonal IgE antibodies

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12
Q

Aerosol Therapy for Asthma (9)

A 
Slow absorption from lung surface
Rapid systemic clearance
Low dose delivered rapidly to target
Low systemic drug concentration
Low adverse effects
Distribution reduced in airway diseases
Good with bronchodilators but not anti-inflammatory drugs
Difficult for children and infirm people
Only good in mild to moderate disease
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13
Q

Oral therapy in Asthma (8)

A 
Good oral absorption
Slow systemic clearance
High systemic dose needed to achieve drug concentration in lung
High systemic concentration
High adverse effects
Distribution unaffected by airway disease
Good compliance and administration ease
Good even in severe disease
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14
Q

SABAs and LABAs are

A

β2-Adrenoceptor Agonists

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15
Q

SABAs (6)

A

Example is salbutamol
First line treatment for mild asthma
Administrated by inhalation, oral or IV
Acts rapidly in 5 minutes
Relaxes smooth muscle, increases mucus clearance and decrease mediator release from mast cells and monocytes
Few adverse effects - Fine tremor, tachycardia, hypokalaemia

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16
Q

LABAs (3)

A

Example is Salmeterol,Formoterol
Not for acute relief but useful in nocturnal asthma
Must always be co-administered with a glucocorticoid

17
Q

Cysteinyl leukotriene (CysLT1) receptor antagonists (6)

A

Example is Montelukast
Blocks CysLT1 receptor preventing CysLT release from mast cells and inflammatory cells
Causes bronchial smooth muscle relaxation
Administered orally
Not for acute severe asthma relief
Few adverse effects - Headache, GI upset

18
Q

Methylxanthines (7)

A

Theophylline, Aminophylline
Inhibits phosphodiesterase PDE3 inactivating cAMP and cGMP
Causes smooth muscle relaxation, anti-inflammatory effect and increases mucus clearance
Improves lung ventilation by causing diaphragmatic contractility reducing fatigue
Administrated orally
Very narrow therapeutic window
Many adverse effects - nausea, vomiting, headache, seizures, hypotension, dysrhythmia

19
Q

Glucocorticoids (6)

A

Beclometasome (mild) and predinisolone (severe)
Prevents and resolves inflammation by decreasing number of inflammatory cells, cytokine mediators, mucus secretion, and endothelial cell leak
No acute bronchodilator action but acts as long term or prophylaxis in mild/moderate asthma
Delivered via inhalation to minimize adverse effects like dysphonia (hoarse, weak voice) and thrush
In severe asthma glucocorticoids are taken orally with inhaled steroid to minimize systemic effects
Must be taken regularly to avoid disease progression which is irreversible

20
Q

Cromoglicate (Cromones) (6)

A

Sodium Cromoglicate
Delivered via inhalation
More effective in children than older adults
No effect on bronchial smooth muscle
Stabilises mast cells that forms a weak anti-inflammatory effect
Reduces short and late term asthma attack but efficacy requires several days to block late phase reaction so requires frequent dosing

21
Q

Monoclonal antibodies directed against IgE (3)

A

Example is Omalizumab
Suppresses mast cell response to allergens
Administered via IV
Con is very expensive

22
Q

Muscarinic ACh Receptors in Airways (2)

A

Decreasing parasympathetic neuroeffector transmission with muscarinic receptor antagonists is a vital COPD treatment
Muscarinic receptor antagonists act as antagonists of bronchoconstriction caused by smooth muscle M3 receptor activation in response to ACh released from postganglionic parasympathetic fibres

23
Q

M1 location and function

A

Ganglia

Facilitate fast neurotransmission mediated by ACh acting on nicotinic receptors

24
Q

M2 location and function

A

Postganglionic neurone terminals

Act as inhibitory autoreceptors reducing release of ACh

25
Q

M3 location and function

A

Airway smooth muscle and goblet cells

Mediate contraction and mucus secretion to ACh

26
Q

Short acting muscarinic antagonist (SAMA) (6)

A

Ipratropium
Administered via inhalation
Quaternary ammonium group decreases absorption and systemic exposure causing few adverse effects
Non-selective blocker of M1, M2 and M3 receptors
Decreases bronchospasm and mucus secretion
Only in asthma

27
Q

Long acting muscarinic antagonists (LAMAs) (6)

A

Tiotropium, Glycopyrronium, Aclidinium, Umeclidinium
Administered via inhalation
Quaternary ammonium group decreases absorption and systemic exposure causing few adverse effects
Decreases bronchospasm and mucus secretion
Only in asthma
LABA/LAMA combinations are scientifically logical
and are likely to be most effective when both drugs are deposited in the same location in the airways

28
Q

Ultra LABAs (3)

A

Indaceterol, olodaterol
Not for acute bronchospasm relive
Once daily dosing is effective

29
Q

Phosphodiesterase-4 (PDE4) inhibitor (4)

A

Rofumilast
Suppresses inflammation and emphysema
Taken orally in severe COPD
Few adverse effects (GI tract)

30
Q

Glucocorticosteroids (3)

A

Affect in combination with β -adrenoceptor agonists and/or muscarinic receptor antagonists in COPD patients is debatable
Benefits patients who develop frequent and severe exacerbations when given with LABAs
Glucocorticoid unresponsiveness in COPD patients may be due to oxidative/nitrative stress

31
Q

Rhinitis and Rhinorrhoea Treatments (6)

A 
Glucocorticoids
H1 Receptor Antagonists (Anti-Histamines)
Muscarinic Receptor Antagonists
Sodium Cromoglicate (Cromones)
CysLT1 receptor antagonists
Vasoconstrictors
32
Q

Glucocorticoids in Rhinitis (7)

A

Beclometasome, Predinisolone, Fluticasone
Reduce vascular permeability, recruitment and activity of inflammatory cells and the release of cytokines and mediators
Applied topically as spray to nasal mucosa
Effective as monotherapy
Can be combined with anti-histamine in moderate/severe rhinitis
Given orally (short term) in very severe cases
Effective in SAR, PAR, NARES and vasomotor rhinitis

33
Q

H1 Receptor Antagonists (Anti-Histamines) (6)

A 
Cetirizine, Ioratidine, Fexofenadine
Causes vasodilation, increased capillary permeability, sensory nerve activation, mucus secretion
Effective in allergic rhinitis only
Less effect on congestion
Taken orally or spray
Effective as monotherapy
34
Q

Muscarinic Receptor Antagonists in Rhinitis (4)

A

Ipratropium
Reduces rhinorrhoea in PAR and SAR only
Administered intranasally
Minor adverse effects (dryness of nasal membrane)

35
Q

Sodium Cromoglicate in Rhinitis (3)

A

Stabilizes mast cells
Administered nasally
Maintenance treatment with onset action of 4 to 7 days but full effect takes weeks

36
Q

CysLT1 receptor antagonists in Rhinitis (3)

A

Montelukast
Taken orally
Effective in PAR and SAR

37
Q

Vasoconstrictors in Rhinitis (5)

A

Oxymetazoline
Mimics effect of noradrenaline by activating α1-adrenoreceptors to decrease swelling in vascular mucosa
Taken intranasally
Short term effectiveness in reducing congestion
Taking more than a few days causes a rebound upon discontinuation

38
Q

Mucolytics (2)

A

Oral carbocisteine , erdosteine

Reduces sputum viscosity and aide sputum expectoration in COPD

Respiratory (8 decks)

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