5.1 Pulmonology Pharmacology – Comprehensive Study Notes

Main jobs:
- Get $O_2$ (oxygen) to all body parts.
- Clear out $CO_2$ (carbon dioxide) made by cells.

Parts inside the chest: windpipe (trachea), branching airways (bronchial tree), lungs.
Where gas exchange happens:
- $\text{Alveoli}$ = tiny air sacs in the lungs where oxygen moves into the blood, and carbon dioxide moves out into the lungs to be exhaled.

Asthma: Airways get narrow temporarily and repeatedly.
Chronic Obstructive Pulmonary Disease (COPD): Includes emphysema and chronic bronchitis, both are long-lasting and get worse over time.
What they all have in common: Airflow gets blocked, making it hard to exchange gases (oxygen in, carbon dioxide out).

When there's inflammation or an allergic reaction, certain cells (mast cells & white blood cells) release “chemical messengers.”
- A key messenger, called leukotrienes, is a target for medicines.
- Leukotrienes cause airways to constrict strongly and for a long time, and also cause swelling and mucus buildup.
Ways airways get narrow (especially in asthma):
1. Bronchospasm: Muscles around airways tighten.
2. Mucosal inflammation & edema: Airway lining gets swollen and inflamed.
3. Hypersecretion of mucus: Too much mucus is produced.

Types: Allergic (triggered by outside things) vs. intrinsic (no clear outside cause).
Triggers: Allergens (like pollen), colds or infections, stress, cold air, exercise.

Long-term exposure to irritants (like cigarette smoke, pollution) causes ongoing inflammation in airways.
Leads to thick, excessive mucus, which blocks airways and makes infections common.
Typical signs: long-lasting cough with mucus, shortness of breath from activity.

Used to just focus on opening airways.
Now, it's best to use a mix of airway openers and anti-inflammatory/antiallergy medicines.
Main types of drugs:
1. Beta-2 adrenergic agonists (rescue and long-acting).
2. Anticholinergics (short and long-acting).
3. Xanthine derivatives (like theophylline).
4. Inhaled corticosteroids (ICS).
5. Leukotriene inhibitors.

Where they act: $\beta<em>1$ receptors are mostly in the heart, $\beta</em>2$ receptors are mostly in the lung's airway muscles.
How they work:
- Stimulating $\beta_2$ receptors turns on a process that increases $cAMP$ , which relaxes smooth muscle and opens up airways.
Types & examples:
- SABA (Short-Acting Beta Agonist — for quick relief): albuterol, levalbuterol.
- LABA (Long-Acting Beta Agonist — for ongoing control): salmeterol, formoterol (NEVER for sudden attacks).
When to use them:
- SABA: For immediate relief of airway tightening; can use before exercise to prevent problems.
- LABA: For daily maintenance in asthma/COPD (used with ICS in asthma).
Side effects (usually mild because they are inhaled):
- Muscle tremors, fast heartbeat, or palpitations.

How they work:
- They block a chemical called acetylcholine in the airways, which reduces airway tightening and mucus production.
Medicines:
- Short-acting: ipratropium (Atrovent).
- Long-acting: tiotropium (Spiriva).
When to use them:
- First choice for daily help in COPD.
- Can be added to asthma treatment if more bronchodilation is needed or if beta agonists can't be used.
Side effects:
- Local: Dry mouth, throat irritation; rarely cause body-wide effects because they aren't absorbed much.

Natural chemicals in tea/coffee/cocoa: caffeine, theobromine, theophylline.
Medicine used: theophylline (taken by mouth; sometimes by IV).
How they work:
- They stop an enzyme (PDE) from breaking down $cAMP$ , which leads to more $cAMP$ . This opens airways and gives a mild energy boost.
- Also reduces the release of histamine and other inflammatory chemicals.
When to use them:
- For COPD & asthma prevention when other daily medicines aren't enough.
Drawbacks:
- Have a narrow safety window (can easily become toxic); interact with many other drugs.
- Not for quick relief because they work slowly.
Side effects:
- Stomach issues: Nausea, vomiting, loss of appetite.
- Heart issues: Fast heartbeat, palpitations, irregular heartbeat.
- Other: Increased urination, high blood sugar.

Examples: fluticasone, budesonide, beclomethasone, triamcinolone, mometasone.
How they work (many ways):
1. Make cell membranes (like mast cells, eosinophils) more stable, which reduces the release of bad chemicals.
2. Stop a pathway that produces prostaglandins and leukotrienes.
3. Improve how well $\beta_2$ receptors work (team up with LABA).
When to use them:
- For ongoing asthma (main treatment).
- For moderate-to-severe COPD to reduce flare-ups.
- Stronger steroids (oral/IV) are only for very severe asthma attacks or COPD flare-ups.
Side effects:
- Inhaled: Oral yeast infection (thrush), hoarse voice; can be prevented by rinsing mouth/using a spacer device.
- Body-wide (with long-term pills/IV): Fluid retention, muscle weakening, high blood sugar, weakened immune system, bone thinning.

Two main ways they work:
1. Blocking synthesis: zileuton (Zyflo) stops the making of leukotrienes.
2. Blocking receptors: montelukast (Singulair), zafirlukast (Accolate) stop leukotrienes from attaching to their receptors.
Overall effect: Less airway constriction, less mucus, less airway swelling.
When to use them:
- Long-term prevention and daily control of ongoing asthma; easy to take by mouth (good for kids, exercise-induced asthma).
Side effects:
- Zileuton: Headache, nausea, dizziness, trouble sleeping; liver function needs to be checked.
- Montelukast/Zafirlukast: Headache, nausea, diarrhea; rarely, psychiatric issues (has a serious warning).

Asthma management steps: Start with SABA as needed, add low-dose ICS, then combine ICS/LABA, then add LAMA (tiotropium), leukotriene modifiers, or body-wide steroids if needed.
COPD guidelines: LAMA or LABA are first choice; ICS is added for people who have many flare-ups.
Patient education is super important:
- How to use inhalers correctly.
- Knowing the difference between “rescue” (quick relief) and “controller” (daily maintenance) medicines.
- Rinsing mouth after ICS; using spacer devices helps medicine get to lungs better.
Lifestyle/ethics:
- Quitting smoking is the single best thing for slowing down COPD.
- Dealing with exposure to pollutants or allergens in the environment/at work.
What to monitor:
- Peak-flow meters for asthma self-checks.
- Theophylline blood levels (aim for $5–15\,\text{µg/mL}$ ) to avoid toxicity.
- Liver function with zileuton; bone density for long-term body-wide steroid use.

Immunology: How steroids weaken immune responses and affect body chemicals.
Cardiology: How selective $\beta_2$ drugs are made to avoid affecting the heart—shows how drugs can target specific body parts.
Biochemistry: How theophylline works to block an enzyme, similar to how Viagra works (different enzymes, but same idea).
Public health: How high rates of COPD tie into worldwide tobacco use; public policies to prevent smoking directly help lung health.