Woman presents in ER with paroxysmal noctural dyspnea, dyspnea on while exercising, and pink frothy sputum with mild traces of blood. What could be causing these symptoms?
Mitral stenosis and left ventricular failure.
What drugs can cause hemoptysis?
Anticoagulants, aspirin, cocaine, penicillamine.
AIDS patient + fungus = What type of hemoptsys?
aspergillosis
Gold standard for diagnosis of COPD?
Chest X-ray and Spirometry.
CXR: lung hyperinflation, flattened diaphragms, barrel chest w/ increased AP diameter
Spirometry: Irreversible FEV1/FVC ratio distinguishes COPD from Asthma
How does your differential diagnosis change when a patient has an inspiration vs an expiration problem doctor?
Inspiration problem means restrictive pulmonary disease: Fibrosis, chest wall issue, amyloidosis
Expiration problem means obstructive pulmonary disease: bronchiectasis, chronic bronchitis, emphysema, asthma
How will lung volume changes differ in restrictive vs obstructive lung disease?
Restrictive:
Decreased FVC
Decreased TLC
(Obstruction in air entering lungs causes reduced volumes)
Obstructive: Increased RV (resid vol) Increased TLC Increased FRC (functional reserve) Decreased FVC
Explain the V/Q mismatch seen in COPD. What results from the mismatch?
Increase in physiological dead space results in a decrease in ventilation. Creating a lower VQ ratio.
Result: Increase in Alveolar-arterial gradient (A-a gradient) AND decreased PaO2
(CO2 excretion is also impaired, but you never see increased PaCO2 because it very quickly leads to respiratory stimulation to blow it off)
Where would you see a high VQ ratio?
Typically this would be seen in a pulmonary embolus. You have high ventilation, but the ventilation is wasted because the circulation is impaired by an embolus and the blood does not get oxygenated.
How will a patient’s chronic alcoholism influence drug and treatment choices for pneumonia?
Liver Cirrhosis - Avoid macrolides (erythromycin) and vancomycin
Cough Syrup: contains alcohol
2 main categories of medications used to treat COPD?
Bronchodilators
(beta agonists, antocholinergics, theophylline)
AND
Glucocorticoids
Name 2 short-acting beta-agonists and 3 long-acting beta agonists used for COPD:
Short acting:
Albuterol
Levalbuterol
Pirbuterol
Long Acting:
Salmeterol, Formoterol, Arfomoterol, Indacaterol
Explain the mechanism of theophylline:
Theophylline is a long-acting bronchodilator.
Inhibits phosphodiesterase to increase cAMP and increase bronchodilation
(Also is an adenosine receptor antagonist, which causes cardiac stimulation)
Let’s talk about anticholinergic medication for COPD. What are the short-acting and long-acting forms? What is their mechanism?
Short: Ipatropium(atrovent)
Competitively inhibits muscarinic ACh receptors in smooth muscle of bronchi
Long: Tiotropium(Spiriva), Alidinium (Tudorza)
M3 muscarinic ACh receptor antagonist
What distinguishes adrenocorticoids from mineralcorticoids?
Objective probs should be asking Glucocorticoids vs Mineralcorticoids…
The adrenal cortex releases many steroids into circulation. 3 main categories:
1 - Glucocorticoids are important for immune function and metabolism
2 - Mineralcorticoids are important for salt retention
3- Androgenic/estrogenic hormones
Major glucocorticoid is cortisol.
Major mineralcorticoid is aldosterone.
(Synthetic mineralcorticoid = fludrocortisone)
What receptors does albuterol interact with?
Why is it better or bronchodilation than propanolol, ephedrine, or epinephrine?
Albuterol (same is salbutamol)
is a beta-2 selective, fast-acting, agonist that relaxes bronchial and tracheal smooth muscle
OTHERS
Epinephrine has greater system effects, as it binds to alpha 1,2 and beta 1,2 recptors (tachycardias, arrythmias)
Ephedrine is a sympathomimetic and also acts on alpha/beta receptors
Propanolol is a general beta-blocker and would thus decrease HR and contractility though beta-1 receptors and cause bronchoconstriction through beta-2 blockage
Please compare usefulness of Ipatropium vs Beta-agonists in tx of COPD:
In COPD:
Ipatropium has shown to be superior to beta-agonists in both short and long-term therapy.
Studies show better symptom improvement and lower side effects. (Side effects low in beta-agonists low, but can sometimes produce a troublesome tremor)
Doc, why is it better for me to be on inhaled glucocorticoid drugs? It would be way easier for me to remember to just give myself an injection or throw another pill in my pill box.
Long-term glucocorticoid use, even in low doses is a significant independent predictor of serious adverse effects.
Hyperglycemia, infection, wound healing problems, bone density, cataracts, skin changes, some psychiatric effects
Non-systemic administration just puts the meds right where you want them without effecting a lot of other systems.
Can still see things like thrush in the mouth
What is the mechanism of action of the beta-2 agonists for COPD?
Acting on the beta-2 GPCR, they increase adenylate cyclase, increasing cAMP and activating pka. This leads to decreased intracellular Ca and relaxation of bronchial and tracheal smooth muscle
Local infection caused by inhaled beta-2 drugs?
Thrush
What about the distribution of salmeterol and formoterol make them long-acting agents?
They have high lipid solubility
What is the major toxicity limiting the use of theophylline?
It has a similar structure to caffeine and causes CNS stimulation. For some this makes it intolerable for chronic use.
(Seizures, anorexia, nausea, vomiting, headache, anxiety)
Also adenosine receptor antagonist can stimulate the heart causing tachyarrythmias
Mechanism of glucocorticoids?
Bind glucocorticoid receptor, preventing translocation of transcription factors, inactivating NF-kappa-B which is responsible for TNF-alpha and other inflammatory agents (eosinophils, mast cells, lymphocytes)
What are the long-acting, medium-acting, and short-acting systemic glucocorticoids we should know?
Long: Betamethasone, Dexamethasone
Medium: Triamcinolone
Short: Prednisone, Prednisolone, Methylprednisolone
What are the main inhaled glucocorticoids you should know?
Fluticasone, beclomethasone (1st line for chronic asthma), bedesonide, flunisolide
Give an example of an endogenous and a synthetic mineralocorticoid. What is their mechanism of action?
Aldosterone: endogenous
Fludrocortisone: Synthetic
Act by binding to mineralocorticoid receptor in the cytoplasm of target cells.
Expression of Na/K ATPase and epithelial Na channels is increased to retain more salt from the distal convoluted tubule!
Is it worthwhile to combine muscarinic antagonists like ipatropium and tiotropium with beta agonists like albuterol or methylxanthines like theophylline?
Yes, combinations of these drugs will increase the dilation effect on the bronchi.
What are the main toxicities of anticholinergic drugs like ipatropium and tiotropium?
Contraindicated in narrow-angle glaucoma, GI/urinary tract obstructions
Minimal side effects: dry mouth, sedation, flushing, tachycardia, nausea, angioedema