Respiratory Pharmacology Flashcards
Drug groups in respiratory system
Upper airways
- Allergy
Lower Airways
- Asthma
- COPD
Respiratory infection
- Bronchitis
- Pneumonia
- Atypical infection
Interstitial lung disease
Novel CF gene drugs
Ventilatory failure
Airway drugs
Bronchodilators
- Adrenergic Agonists
- Beta-2 agonists (Salbutamol, Salmeterol)
- Anticholinergics (Tiotropium Iptratropium)
- Methylxanthines (Aminophylline)
Anti-inflammatory
- Steroids (Prednisolone, Beclomethasone)
- Leukotriene Inhibitors (Monteleukast)
Mucokinetic agents
- Carbocysteine
- Hypertonic saline
- Dnase
Inhaled Drug Devices
Metered Dose Inhalers (MDIs)
- Deep exhale /Inhale and puff/Hold breath for slow ten count/Exhale slowly/Wait one minute before second puff
- Use spacer
Dry-Powder Inhalers
- Usually one inhalation, not a puff
Nebulisers
Multitude of new devices
Salbutamol
Duration - Short acting (begin immediately, 3-5 hour duration)
Routes - Inhaled/IV/Oral
Mechanism of action
Binding to beta(2)-receptors in the lungs results in relaxation of bronchial smooth muscles. It is believed that salbutamol increases cAMP production by activating adenylate cyclase, and the actions of salbutamol are mediated by cAMP
Use - Asthma and COPD
Serevent - Salmeterol
Duration - Long acting (begin 2-30 min, 10-12 hour dur)
Routes - Inhaled
Mechanism of action - Long-acting beta-adrenoceptor agonist
Use
- Asthma: in patients requiring long-term regular bronchodilator therapy on ICS
- NOT PRN
- COPD: persistent symptoms despite therapy
(ICS/LABA combination FEV1 < 50%)
eg seretide
Tiotropium
Duration - Long acting (24 hour)
Routes - Inhaled (Dry powder Handihaler/Mist resimat)
Mechanism of action
Tiotropium is a long-acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation
Indication:
- Stable COPD: Symptoms despite SABA (any severity)
- Asthma: new indication step 3
Ipratropium
Short acting antimuscarinic agent
Onset 30 minutes; lasts 6 hours
MDI, Nebulised
Nebulised for acute presentations of COPD (and sometimes asthma
Theophylline
Duration: Half life around 5 hours healthy adults
Routes: IV/PO
Mechanism of action - Phosphodiesterase inhibitor
Indication:
- PO: COPD and asthma –persistent symptoms
- IV COPD and asthma medical emergencies
Adverse Events - Bronchodilators
Tachycardia Nervousness, Irritability, Tremor Inhaled preparations: less common Oral preparations: More common Tachyarrhythmias/Angina Usually dose related
Glucocorticoids - systemic
IV or oral
Stronger effects
Action unaffected by lung restriction
More side effects, esp with long term therapy
Eg Prednisolone
Glucocorticoids - inhaled
Localized action
Fewer side effects: some absorption occurs
Disease may prevent penetration of drug to affected areas
Eg Beclometasone
Glucocorticoids - airway effects
Decrease release of inflammatory mediator
Decrease infiltration and action of WBCs
Decrease airway oedema
Decrease airway mucus production
Increase number and sensitivity of beta-2 receptors
Adverse events
Inhaled: gargle and use spacer
- Oral candidiasis
- Dysphonia
General
- Adrenal suppression
- Bone loss: exercise, Vit D, calcium
- Slow growth in children, but not ultimate height
- Increase risk of cataracts and glaucoma
- Increased risk of infection
- Gastric ulceration
- Hypertension
- Diabetes
- Mood disturbance
Allergic Rhinitis Medications
Antihistamines
Intranasal Glucocorticoids
Montelukast (Singulair)
Sympathomimetics (Decongestants)
Antihistamines
Cetirizine, Chlorpheniramine
H1 antagonists
Side effects: Drowsiness, Dry Mouth, Dry Eyes, Confusion
Intranasal Glucocorticoids
Beclometasone (Beconase)
Montelukast (Singulair)
Inhibit leukotriene receptors
↓inflammation, bronchoconstriction, oedema, mucus, recruitment of eosinophils
Sympathomimetics (Decongestants)
Pseudoephedrine (alpha agonist) Problems with abuse and MAOI
Asthma treatment ladder
There is an asthma treatment ladder - 5 steps
You move up and down the ladder depending on symptoms and success of current drugs
Side effects
It is as important to move down the ladder as to move up
Patients are left often on too much steroids
Oxygen
Indications
Oxygen is a drug –must be prescribed (target sats)
SIDE EFFECTS ARE LIFE THREATENING
(over oxygenation in type 2 respiratory failure)
Oxygen delivery Nasal Hudson mask Venturi Reservoir
Respiratory infection
Bronchitis- (COPD and asthma)
Community acquired pneumonia (CAP) - Severity scoring
Hospital acquired pneumonia HAP (early and late)
Ventilator acquired pneumonia (VAP)
Aspiration
Bronchitis ≠ Pneumonia
Different treatments!
Antibiotics used to cover respiratory infection
Penicillins
Amoxicillin
- Moderate-spectrum, bacteriolytic, B lactam antibiotic
- Routes - IV/Oral
- Use – CAP/COPD exabaerbations/bronchitis
- Active against gram negative and gram positive bacteria
Comamoxiclav
Amoxicillin is susceptible to degradation by B lactamase -producing bacteria so can be combined with clavulinic acid – a b lactamase inhibitor
Tazobactum – hospital acquired infections & gram neg bacteria
extended spectrum b lactam antibiotic
Tetracyclines (Doxycycline)
Tetracycline inhibits protein synthesis
Broad spectrum action Gram positive and negative
Useful for ‘atypical infections’ eg mycoplasma
Oral route only
Side effects - GI Upset/staining teeth/lupus/allergy/photosensitivity
Quinolones
Eg Ciprofloxacin/moxifloxacin
Mechanism of action - DNA fragmentation
Gram negative and positive coverage (And Pseudomonas)
Route - IV/Oral/Inhaled (CF)
Side effects – GI upset/ C difficile/ Tendonitis/Liver upset/Prolonged QTc and arrthymia
Marcolides
Eg clarithromycin
Commonly used in respiratory infection
Mechanism of action - Protein synthesis inhibitors
Route- IV/PO
Gram positive /limited gram negative cover
Side effects- GI/allergy/liver abnormality/prolonged QTc and interactions
TB therapy
Standard treatment for TB is a minimum of 6 months:
- 2 months (initial phase) of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. Known as standard quadruple therapy.
Followed by:
- 4 months (continuation phase) of Isoniazid and Rifampicin. Known as standard dual therapy
N.B. If there is central nervous system involvement the continuation phase of treatment is extended to 10 months making a 12 month full treatment plan.
TB treatment is taken all together on an empty stomach 1 hour before breakfast; compliance is essential for cure.
DOT
Directly observed treatment is known as DOT.
Each DOT case is assessed by the TB specialist team regarding the patient’s ability to adhere to the six-month treatment regimen.
DOT is initiated for those at risk of being unable to adhere to treatment.
A professional case worker, person trained to be a DOT observer, or a trusted family member or friend will watch the patient take their TB treatment.
Primary care providers, such as GP practices
or pharmacists, may be asked to provide DOT
TB therapy
Isoniazid (H/I)
Rifampicin (R)
Pyrazinamide (Z/P)
Ethambutol (E)
General side effects: Hepatotoxcity, nausea and skin rashes, Allergy
Isoniazid (H/I)
Bactericidal and bacteriostatic – inhibits cell wall growth
Cytochrome P450 inhibitor – interactions!!
fever, peripheral neuropathy and optic neuritis
Rifampicin (R)
inhibits bacterial DNA-dependent RNA synthesis
Cytochrome P450 inducer – interactions!!
reddish colour to the urine
Pyrazinamide (Z/P)
Causes accumulation pf pyrazinoic acid
use with caution in patients with gout
Ethambutol (E)
Bacteriostatic obstructs development of cell wall
Peripheral neuropathy, optic neuropathy , gout, AKI
CF Novel therapies
Most common lethal inherited disorder of Caucasian people
70,000 cases worldwide
Gene codes for the cystic fibrosis transmembrane conductance regulator (CFTR)
About 2000 mutations have been identified in the CFTR gene since its discovery in 1989
- 242 different disease causing mutations
- CFTR2 project
Pulmonary Fibrosis
ILD MDT important for therapeutic decision making
Some idiopathic interstitial pneumonias -Prednisolone/Azathiprine/MMF
Sarcoid - prednisolone
Idiopathic pulmonary fibrosis
Perfenidone
Anti inflammatory/ Anti Fibrotic
Reduces fibroblast proliferation, reduces collagen production
