Resp Flashcards
What are bronchodilators
Medications which relieve bronchoconstriction caused by conditions that affect air passageways and alveoli.
Alpha and beta adrenoceptors and muscarinic acetylcholine receptors (mAChRs) are…
G-protein coupled receptors
Alpha1 affect
Blood vessels, gut, liver, bladder, sweat glands, iris
Alpha2 affect
Presynaptically on all adrenergic nerve terminals, post-pancreas
Beta1 affect
Heart muscle, gut, juxtaglomerular apparatus
Beta2 affect
Bronchioles, skeletal muscle, pancreas, mast cells, liver, uterus
Beta3 affect
Adipose tissue, heart
Alpha1 receptors activate:
Phospholipase C (PLC) producing inositol trisphosphate (IP3) and diacylglycerol (DAG)
Alpha2 receptors inhibit
Adenylate cyclase thus decreasing cyclic adenosine monophosphate (cAMP)
All subtypes of beta receptors stimulate…
Adenylate cyclase thus increasing cAMP
Alpha1 receptor activation results in
Vasoconstriction, pupil dilation, decreasing peristalsis and decreasing voiding, sweating, hepatic glycogenolysis
Alpha2 receptor activation results in
Autoinhibition of transmitter release (NA and acetylcholine receptor release from autonomic nerves)
Beta1 receptor activation results in
Increased cardiac rate and force, relaxation of GI smooth muscle (decreasing peristalsis), renin release and lipolysis
Beta2 receptor activation results in
Bronchodilation, vasodilation, relaxation of uterine smooth muscle, hepatic glycogenolysis, increased insulin secretion, fine muscle tremor
Beta3 receptor activation results in
Lipolysis
Selective alpha1 agonists
Phenylephrine and oxymetazoline
Selective alpha2 agonists
Clonidine
Selective beta1 agonists
Dobutamine
Selective beta2 agonists
Salbutamol, formoterol, terbutaline and salmeterol used mainly in asthma
The drug class of choice for an immediate phase asthmatic attack and what does it do?
Beta2 adrenoceptor agonist- dilate the bronchi by a direct action on the beta2 adrenoceptors in the bronchial smooth muscle causing relaxation
What do beta2 adrenoceptor agonists inhibit
Inhibit mediator release from mast cells and decrease mucus production
What are the main short-acting drugs in the beta2 adrenoceptor agonist class?
Salbutamol and terbutaline
How are salbutamol and terbutaline administered?
Typically administered by inhalation (aerosol, powder, nebuliser) but can be given by IV in severe attacks
Characteristics of salbutamol and terbutaline:
Rapid onset of action, within a few minutes; effect lasts for 3-5 hours
Common AEs of salbutamol and terbutaline:
Fine muscle tremor, headache, palpitations, hypotension due to peripheral vasodilation, hypokalaemia, increase in BGL
How long do longer acting beta2 agonists (LABA) produce effects for
Up to 12 hours
E.g. of LABA
Salmeterol, formoterol/eformeterol
What are LABA used for
To improve resp function in patients with COPD
What drugs are not recommended for use in asthma and why?
Drugs acting on both beta 1 and 2 (e.g. adrenaline and isoprenaline) are not recommended for use in asthma as they may lead to cardio-acceleration, anginal attack and myocardial infarction (MI)
Beta antagonists (e.g. propranolol) can cause…
Wheezing in asthmatics (no effect on airway function in normal individuals) and can precipitate an acute asthma attack
How many muscarinic receptor subtypes have been identified?
Five
What does M1 act on
Act in the brain on higher cerebral function and peripherally on the parietal cells of the gastric mucosa to increase acid secretion
What does M2 act on
Act in the myocardium and decrease HR and the force of contraction
What does M3 act on
Affect exocrine glands and visceral smooth muscle, pupil constriction, increase gut motility and secretion of digestive juices, promote voiding and defecation as well as secretion from exocrine glands (lacrimation, salivation, sweating)
The physiological roles for which muscarinic receptors are unknown?
M4 and M5
M1, M3 and M5 receptors activate…
Phospholipase C, hence formation of two secondary messengers (IP3 and DAG) eventually leading to an intracellular increase of calcium and excitation
M2 and M4 receptors inhibit
Adenylate cyclase, thereby decreasing the production of the second messenger cAMP leading to inhibition
What are muscarinic receptor antagonists referred to as and why?
Generally referred to as parasympatholytic because they selectively reduce or abolish the effects of the peripheral nervous system (PNS)
What are the parasympatholytic effects muscarinic receptor antagonists have?
Inhibition of secretions- salivary, lacrimal, bronchial and sweat glands.
HR- modest tachycardia.
Eye- pupil dilation, unresponsive to light (blurred vision).
GI tract- reduced GI motility (constipation).
Other smooth muscle- bronchial, biliary, urinary tract smooth muscle dilation (bronchodilation, smooth muscle relaxation, decreased voiding).
CNS- high doses cause agitation and disorientation.
Muscarinic antagonists used specifically as an anti-asthmatic are:
Ipratropium (non-selective) and tiotropium (M3 receptor selective) by inhalation
Ipratropium and tiotropium side effects:
Dry mouth, urinary retention, facial flushing, constipation, pupil dilation
Ipratropium and tiotropium properties:
o Maximum effect is after 30 minutes
o Lasts 3-5 hours
o Can be useful as an adjunct to another therapy (when a beta2 agonist alone is inadequate) to help with bronchodilation and reduce mucus secretion
o Not absorbed well into circulation so there is minimal action on muscarinic receptors in locations other than the bronchi
What do ipratropium and tiotropium do?
These stop the activity of acetylcholine in the smooth muscle preventing contraction and producing relaxation
E.g. of anticholinergics:
Short-acting muscarinic antagonist (SAMA) and long-acting muscarinic antagonist (LAMA)
E.g. of SAMA
Inhaled ipratropium
What does SAMA do
Blocks the action of acetylcholine thereby inhibiting nerve impulses responsible for involuntary muscle movements and various bodily functions
What do LAMA do
Blocks the action of acetylcholine thereby inhibiting nerve impulses responsible for involuntary muscle movements and various bodily functions
E.g. of LAMA
Aclidinium, glycopyrronium (inhaled), tiotropium, umeclidinium
SAMA and LAMA mode of action
Blocks the action of acetylcholine in bronchial smooth muscle
SAMA and LAMA side effects
Dry mouth, throat irritation
E.g. of beta2 agonists
Short-acting beta agonists (SABA) and long-acting beta agonists (LABA)
For what and when are SABA used
To provide quick relief (rescue inhalant) of asthma symptoms, during periods of acute symptoms and exacerbations
E.g. of SABA
Salbutamol and terbutaline
For what and when are LABA used
Taken daily (maintenance inhalant) to relax the muscles lining the airways that carry air to the lungs, used to achieve and maintain prophylactic control of persistent asthma
E.g. of LABA
Formoterol, indacaterol, salmeterol, vilanterol
SABA and LABA mode of action
Both stimulate beta2 adrenergic receptors in the smooth muscle of bronchi and bronchioles. These receptors in turn stimulate the enzyme adenyl cyclase to increase production of cAMP which produces bronchodilation
AEs of SABA and LABA
Dry mouth, throat irritation, tremor, palpitations and headache
What are the three pharmacologically active naturally occurring methylxanthines?
Theophylline (tea, coffee), theobromine (cocoa) and caffeine (coffee, tea)
What are the methylxanthines used in clinical medicine?
Theophylline and aminophylline
What does theophylline do
Produces bronchodilation through enzyme inhibition
Side effects of theophylline
Nausea, vomiting, diarrhoea, gastro-oesophageal reflux, headache, insomnia, irritability, anxiety, tremor, palpitations
What do mucolytics do
Generally lower (alter) the viscosity of mucus and enhance its transport by activating ciliated epithelium (mucociliary clearance)
E.g. of mucolytics
“Bromhexine duro-tuss chest cough liquid”, “acetylcysteine mucomyst” and “dornase alfa pulmozyme”
What is “Bromhexine duro-tuss chest cough liquid” used for
Used to reduce excess mucus associated with colds, flu, other resp tract infections
How is “Bromhexine duro-tuss chest cough liquid” administered
An oral mucolytic agent administered as a liquid or tablet
What does “Bromhexine duro-tuss chest cough liquid” act on
Acts on mucus secreting cells to alter the structure of viscous mucus
AEs of “Bromhexine duro-tuss chest cough liquid”
Nausea, vomiting, diarrhoea, allergy, severe skin reactions
What is “acetylcysteine mucomyst” used for
Used in bronchopulmonary disease (cystic fibrosis), anaesthesia, antidote for paracetamol overdose
What does “acetylcysteine mucomyst” do
Reduces viscosity by interfering directly with the chemical composition of mucus
AEs of “acetylcysteine mucomyst”
Stomatitis, nausea, bronchospasm
What is “dornase alfa pulmozyme” used for
Used to manage resp complications of CF
How does “dornase alfa pulmozyme” work
Works by an enzyme that breaks down the DNA of the decaying neutrophils
Side effects of “dornase alfa pulmozyme”
Voice alteration, pharyngitis, laryngitis and rash
Glucocorticoids are synthesised and released by
The adrenal cortex
Glucocorticoids are regulated by
Hypothalamic corticotropin-releasing factor and pituitary adrenocorticotropic hormone (ACTH)
What are the main actions of corticosteroids
Enteral effects on metabolism, water and electrolyte balance, negative feedback effects (adenohypophysis and hypothalamus) as well as anti-inflammatory and immunosuppressive effects
What can corticosteroids cause when administered early?
A reduction in the acute inflammatory response by inhibiting mast cell degranulation, decrease in inflammatory mediators, cause vasoconstriction, reduced exudation, decrease in number and activity of leucocytes and macrophages
What can corticosteroids cause when administered later?
Can decrease number and activity of mononuclear cells and fibroblasts, decrease angiogenesis and chronic inflammation but also decrease healing
How can corticosteroids be administered
Orally, topically or parentally
How are corticosteroids used therapeutically
Therapeutically useful for anti-inflammatory therapy and immunosuppression but can have unwanted metabolic actions
What can prolonged use of corticosteroids cause
Prolonged use can cause suppression of response to infection and endogenous glucocorticoid synthesis as well as osteoporosis and iatrogenic Cushing’s syndrome
Corticosteroids aren’t useful in asthma because
They aren’t bronchodilators and are not useful in acute asthma. Clinical effects take days to develop.
How is corticosteroid useful in asthma
They have an important role in reducing airway inflammation (oedema, mucus production, bronchoconstriction) in prophylaxis if taken continuously
How can corticosteroids be administered in asthma
Inhaled, given orally, IV
E.g. of corticosteroids that can be inhaled
Beclomethasone, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate
E.g. of corticosteroids that can be taken orally
Prednisolone, dexamethasone
E.g. of corticosteroids that can be given via IV
Dexamethasone, hydrocortisone
What do corticosteroids do in asthma
Inhibit activation of macrophages and mediator release from eosinophils, reduce the formation of various inflammatory mediators
AEs of corticosteroids in asthma
o infection of candida albicans in the pharynx (thrush) due to immunosuppression of the pharyngeal mucosa o dysphonia o bruising o sodium and water retention o oedema o hypertension o hypokalaemia o hyperglycaemia o diabetes o dyslipidaemia o osteoporosis o psychiatric effects
What is the aim in pharmacological treatment of asthma
Eliminating the causative agent and based on the severity of the asthma
Acute asthma treatment goals
Reverse bronchoconstriction and relieve inflammation (if required, oral corticosteroids can also be administered early as part of treatment)
Best treatment of chronic asthma
Prevent and avoid known allergens/triggers
Chronic asthma meds are
Usually inhaled anti-inflammatory agents like corticosteroids
E.g. of chronic asthma meds
LABA and ipratropium used to control persistent bronchospasm and leukotriene receptor antagonists (montelukast and zafirlukast)
What are the leukotrienes inflammatory mediators (LTC4, LTD4, LTE3) associated with?
Asthma causing mucus secretion, airway wall oedema and bronchospasm
Meds for mild asthma
Use beta2-agonist (salbutamol) as a reusable inhalant.
A short course of inhaled corticosteroids may be appropriate
Meds for moderate asthma
Salbutamol (5-10mg; 8 puffs every 15 mins for 3 doses) used initially with corticosteroids (50mg oral prednisolone, 250mg hydrocortisone) and then reviewed an hour after last dose (O2 therapy may be required)
Meds for severe asthma
- Oxygen required to maintain SpO2 at >92%
- Continuous beta2-agonists administered intravenously and corticosteroids/ipratropium
- In cases of status asthmatics, where asthma attacks follow one another without pause, intubation is typically required
Meds for chronic bronchitis
Consists of bronchodilators and mucolytics, long acting inhaled beta2-agonists ipratropium, oral theophylline and corticosteroids in the later stages
Meds for acute exacerbations of emphysema
Bronchodilators (inhaled) and oral corticosteroids, oxygen therapy
Meds for emphysema management
Inhaled anti-cholinergic medications and beta2-agonists
When should a pneumonia pt’s IV antibiotic therapy be switched to oral therapy?
As soon as the pt is:
o hemodynamically stable
o improving clinically
o able to ingest oral medication and has a normally functioning gastrointestinal (GI) tract.
What med for an outpatient who was previously healthy and had no recent antibiotic therapy in the past 3 months and no risk for medication-resistant staph pneumoniae (DRSP)
A doxycycline or macrolide class of antibiotic should be prescribed
What med for an outpatient who has comorbidities (e.g. COPD; diabetes; chronic liver, heart, lung of renal disease; malignancy; use of antibiotics in past 3 months)
Resp and antimicrobial meds or fluoroquinolone (restricted PBS scheme) OR penicillin plus doxycycline or a macrolide
What med for an outpatient who has regions with over 25% macrolide-resistant S.pneumoniae
Doxycycline or a macrolide
What med for an inpatient in the medical unit
Doxycycline or a macrolide
What med for an inpatient in ICU
Doxycycline or a macrolide
What med for a pt with a Pseudomonas infection
Antipneumococcal, antipseudomonal beta lactam plus either ciprofllaxin or levofloxacin OR antipneumococcal, antipseudomonal beta lactam plus aminoglycoside and azithromycin OR antipneumococcal, antipseudomonal beta lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone (restricted PBS scheme)
What med for a pt with a Pseudomonas infection but pt has a penicillin allergy
Substitute aztreonam for the beta lactam
What med for a pt with a community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
Add vancomycin or linezolid
E.g. of antipneumoccoal, antipseudomonal beta lactams
Imipenem/cilastatin, meropenem (PBS restricted use), cefepime, piperacillin/tazobactam
What are the antibiotics used in typical pneumonia
(Broad spectrum)- beta lactams (penicillins and cephalosporins), macrolides (erythromycin), fluoroquinolones
How quickly would a pneumonia pt respond to the antibiotics
In 48-72 hours in uncomplicated cases
What are the vaccines used to prevent typical pneumonia
Hib vaccine, flu vaccine, pneumococcal vaccine
Who is Hib vaccine usually used by
Mainly kids for Haemophilus influenzae type B
Who is flu vaccine usually used by
Older people, smokers and people with chronic illness and weakened immune system
Who is flu vaccine usually used by
Chronic illness, asplenic (no normal spleen function) patients, transplant recipient
What is the treatment for atypical pneumonia
Supportive therapy oxygen therapy, hydration (IV fluids), fever management (antipyretic therapy) and possibly macrolides
Antiviral agents may be prescribed in severe infections and immunocompromised patients (famciclovir)
What kind of antibiotics for community acquired pneumonia?
Broad spectrum antibiotics
How long should the total treatment time for community acquired pneumonia be?
Minimum 5 days, pt should be afebrile for 48-72 hours before stopping treatment, but treatment could be longer if there are complications or the initial therapy was not active against the identified pathogen
Meds for opportunistic pneumonia
Treatment consists of a course of trimethoprim/sulfamethoxazole (Bactrim), either IV or orally depending on the severity of disease and the patient’s response
Meds for CMV, a herpesvirus, that can cause viral pneumonia?
Antiviral medications and high-dose immunoglobulins are used for treatment.
Pulmonary oedema treatment depends on
The cause
Cardiogenic pulmonary oedema meds are and for:
Pharmacological agents (e.g. diuretics, vasodilators, drugs that improve heart contractions (reverse cause of decreased contractility and increase systolic function))
E.g. of cardiogenic pulmonary oedema meds
Dopamine, dobutamine, adrenaline
Cardiogenic pulmonary oedema management:
Supportive measures like mechanical ventilation, hemodynamic and CV monitoring with pharmacological agents may be required
E.g. of meds for pulmonary oedema
Spironolactone, frusemide, vasodilators and sympathomimetics, dopamine and dobutamine (sympathomimetics)
What is spironolactone
Aldosterone antagonist and potassium sparing diuretic
What does spironolactone do
Decrease reticulation volume by diuresis by inhibiting sodium absorption in the distal tubule by blocking sodium channels and aldosterone. This causes an increase in sodium excretion and thus fluid.
AEs of spironolactone
Hyperkalaemia
What is frusemide and what does it do
The most common diuretic, short acting and rapidly reduces fluid volume. Causes diuresis by reabsorption of sodium and chloride in the ascending limb
AEs of frusemide (dose related)
Electrolyte disturbances (hyponatraemia, hypokalaemia, syncope, dehydration, orthostatic hypotension)
E.g. of vasodilators
Glyceryl nitrate
How can vasodilators and sympathomimetics be administered
Sublingual or IV
What do vasodilators and sympathomimetics do?
Dilates vessels addressing the workload on the heart
AEs of vasodilators and sympathomimetics
Tachycardia, hypotension, flushing, headache
What do dopamine and dobutamine do
Increase CO
Dopamine and dobutamine are both
Vasodilators but dopamine is a vasoconstrictor at higher doses and can cause tachycardia and ventricular ectopic beats
How is respiratory distress syndrome treated and why
With corticosteroids to accelerate formation of surfactant or a post-natal surfactant (e.g. beractant) into the trachea
What can’t be used to treat viral croup?
Antibiotics, mucolytics or bronchodilators
What could help in some cases of viral croup?
Corticosteroids
How is viral croup treated?
Primarily with supportive measures including oxygen, antipyretics and increased fluid intake with careful monitoring
