Cough Medications

Case 1: Medications and Mechanisms

• Robitussin (Guaifenesin) loosens and thins mucus by reducing viscosity and adhesiveness
• Robitussin (Guaifenesin) promotes ciliary action to clear mucus and serves as an expectorant to convert dry coughs to productive ones
• Robitussin (Guaifenesin) is commonly used for non-productive and productive coughs and is a first-line treatment for coughs with thick mucus.
• Dextromethorphan suppresses the cough reflex by depressing the cough center in the brain
• Dextromethorphan acts via sigma receptor stimulation and is an antitussive
• Dextromethorphan has no expectorant effect and is a non-opioid medication, serving only to reduce coughing
• Dextromethorphan is an over-the-counter antitussive and a first-line treatment for non-productive, dry coughs.
• Codeine binds to opioid receptors in the central nervous system, inhibiting pain pathways and suppressing coughs by acting on the medulla.
• Codeine functions as an antitussive as well
• Codeine is a CNS depressant that dries the respiratory tract and increases secretion viscosity
• Codeine is a second-line treatment for severe, persistent coughs, often when other antitussives fail
• Antibiotics are a first-line treatment for bacterial infections and are reserved for bacterial causes of cough
• β-lactams (Penicillins, Cephalosporins) inhibit bacterial cell wall synthesis, leading to bacterial cell death
• β-lactams have a broad spectrum and is effective against many bacteria as a first-line treatment for many bacterial infections
• Vancomycin (Non-β-lactam) inhibits bacterial cell wall synthesis by binding to peptidoglycan precursors, killing bacteria for resistant bacterial infections
• Vancomycin is a second-line treatment for resistant Gram-positive infections like MRSA
• Aminoglycosides inhibit protein synthesis by binding to bacterial ribosomes, leading to bacterial death and is effective against aerobic bacteria
• Aminoglycosides are a second-line treatment for serious infections caused by Gram-negative bacteria.
• Isoniazid (INH) inhibits mycolic acid synthesis in the mycobacterial cell wall, disrupting cell wall formation to both kill and stop bacterial growth
• Isoniazid is bactericidal in rapidly dividing organisms and bacteriostatic in slow-growing organisms
• Isoniazid is a first-line medication for treating M. tuberculosis and is a cornerstone of TB treatment
• Rifampin inhibits bacterial RNA synthesis by binding to RNA polymerase, preventing transcription to kill bacteria
• Rifampin is bactericidal and effective against rapidly dividing and slow-dividing mycobacteria, serving as a first-line treatment for M. tuberculosis
• Pyrazinamide converts to pyrazinoic acid inside bacterium lowering pH and inhibiting growth
• Pyrazinamide is bactericidal in early stages of TB treatment and used with rifampin and isoniazid as a first-line treatment for TB
• Ethambutol inhibits cell wall synthesis by interfering with arabinogalactan formation, disrupting mycobacterial cell wall integrity to stop growing
• Ethambutol is primarily bacteriostatic and effective in actively dividing bacilli as first-line treatment for tuberculosis
• Ethambutol used with rifampin, isoniazid, and pyrazinamide in combination therapy

Case 1: Drug Toxicity and Side Effects

• Isoniazid (INH) blocks cell wall synthesis and is metabolized in the liver and excreted by the kidneys in urine, and can cause hepatotoxicity
• Rifampin (RIF) inhibits RNA synthesis, is metabolized in the liver and excreted mostly in bile with some in urine, inducing liver enzymes
• Pyrazinamide (PZA) works in acidic environments (granulomas), is metabolized in the liver and excreted by the kidneys, causing hepatotoxicity and gout
• Ethambutol (EMB) weakens the bacterial cell wall, metabolized in the liver with minimal liver toxicity and excreted primarily by the kidneys, potentially causing optic neuritis

Lung Anatomy

• The upper respiratory tract includes the nasal cavity and assists with filtering, warming, and humidifying air
• In the upper respiratory tract Mucus traps dust, pathogens, and particles and the pharynx is a passage for both air and food
• In the upper respiratory tract The larynx protects the airway during swallowing and includes vocal cords for sound production
• The lower respiratory tract consists of the trachea, bronchi, bronchioles, and lungs
• The trachea is supported by cartilage and lined with mucus to trap debris, while the bronchi branch into smaller airways that expel particles with the help of mucus and cilia.
• Bronchioles control airflow resistance, and the lungs consist of lobes (3 on the right, 2 on the left) that facilitate gas exchange.
• Alveoli are tiny sacs that facilitate gas exchange, maintain a no-mucus environment for free gas diffusion.

Histology and Cells

• Mucus is secreted by goblet cells and submucosal glands, trapping pathogens, particles, and debris that are moved upward by cilia.
• The upper respiratory tract includes ciliated pseudostratified columnar epithelium to move mucus out of the airway, and goblet cells to produce mucus
• The trachea and bronchi are made of ciliated columnar cells to propel mucus upward and basal cells for regenerating airway epithelium after injury
• The trachea and bronchi also contain submucosal glands to secrete mucus and serous fluid for airway defense
• Bronchioles have simple cuboidal epithelium for smooth airflow and Clara (Club) cells to secrete surfactant-like proteins that detoxify toxins.
• Alveoli consist of Type I pneumocytes for efficient gas exchange, Type II pneumocytes to produce surfactant
• Alveolar macrophages in the alveoli engulf and digest debris and pathogens

Cough Mechanism

• Sensory receptors in the larynx, trachea, or bronchi triggered by irritants (e.g., mucus, dust).
• Impulses sent from nerves to the medulla (cough center) and diaphragm and intercostal muscles contract to increasing lung volume
• Glottis closes during compression and Abdominal muscles then increase thoracic pressure
• Glottis opens during expulsion to expel mucus and irritants.

Sputum - Production and Indication

• Sputum mechanisms include production by goblet cells and submucosal glands in response to irritation or infection to facilitate removal via coughing
• Sputum appearance indicates clear for normal/viral infections, yellow/green, Red/Bloody for trauma, TB, or lung cancer and Brown/Black for smoking

Lung Infections

• Common colds occur in the nasal cavity as viruses cause inflammation, increasing mucus and causing nasal congestion
• Sinusitis occurs in the sinuses due to viruses or bacteria and blocked drainage causes pressure, pain, and mucus build-up
• Pneumonia occurs in the alveoli as bacteria, viruses, or fungi cause inflammation, filling alveoli fluid which impairs gas exchange
• Bronchitis occurs in the bronchi due to viruses or bacteria, with inflammation causing excess mucus to obstruct airflow
• Tuberculosis (TB) occurs in the alveoli and macrophages caused by Mycobacterium tuberculosis: Bacteria infect macrophages → granuloma formation
• Bronchiolitis occurs in the bronchioles caused by the Respiratory Syncytial Virus (RSV), and swelling/mucus obstructs the airway, causing wheezing.

Tuberculosis (TB) Structure

• TB is caused by the bacterium Mycobacterium tuberculosis, which is rod-shaped, aerobic, acid-fast, non-motile, and non-spore forming
• TB can not grow rapidly
• The cell wall is thick, hydrophobic, and resists desiccation, antibiotics, and host defenses due to mycolic acid

TB Mechanism of Pathogenesis

• First, infection occurs through airborne droplets
• The lung's alveolar macrophages engulf the bacteria, however mycobacteria can prevent phagosome fusion allowing survival and replication to recruit immune cells
• Macrophages and T-cells surround infected macrophages to form granulomas that encapsulate the infectious agent

TB Bacteria

• The bacteria enter the lungs and immune cells (macrophages) engulf them, forming an inflammatory response known as the Ghon focus
• An immune cells surround the Ghon focus, forming a granuloma preventing spread of infection
• If spreads to nearby lymph nodes often forms the Ghon complex
• Ghon complex is the Gohn focus and lymph node
• If TB infection is controlled, the Ghon complex can calcify/harden with calcium

TB Symptoms

• Symptoms manifest as chronic blood coughed up, fever, losing weight, sweating at night, weariness, and pain in the chest

TB: Stages, Pathology, and Chest X-Rays

• TB's latent stage includes bacteria in the lungs, with no presentation of infection
• TB's active stage includes Granulomas break down, releasing bacteria
• During TB's active stage symptoms increase
• TB's primary infection occurs in the children/immunocompromised and is an initial infection which is usually mild

Pathology

• Primary TB presents granulomas in the middle/lower lobes
• Primary TB includes the formation of granulomas but can progress to Miliary TB (spread out)
• Secondary TB presents Cavitation and extensive tissue destruction
• Upper lobes are affected by high oxygen levels in secondary TB

TB Chest X-Ray

• Ghon focus is calcified in the lungs during a primary infection
• Ghon complex occurs, which creates hilar lymphadenopathy and lung granulomas in primary infections
• Secondary infections manifest as cavitary lesions and nodules along the upper lobes
• Miliary TB shows nodules

Diagnosing TB

• Skin and blood tests are conducted
• A skin test (PPD) induces a hypersensitivity reaction
• Positive PPD requires an induration of 10mm (≥5 mm if immunocompromised)
• Interferon release is measured by the blood test (IGRA)

TB Sputum Tests

• Tests run include detection of acid fast bacilli (AFB) smear, culture growth, and NAAT presence
• AFB smears have a low sensitivity for mycobacteria and retain acid-fast characteristics
• TB cultures confirm the diagnosis and DNA confirms rapidly

TB Treatment

• First-line drugs kill bacteria (Isoniazid, Pyrazinamide) but can be static (Ethambutol)
• Drug regimens begin initial phases of 4 drugs across 2 months
• If there is a positive response, drug combination can be reduced across 4 to 7 months

TB Vaccine

• Vaccines only provide protection in the form of miliary TB and can cause false positive skin tests

TB Patient Notes

• If sputum is present, patients are contagious
• Transmission is caused by coughing blood out of the lungs
• Fever, weight loss and coughs all lead to inflammation
• A history of previous reactions to TB (Delayed hypersensitivity) assists in detecting previous TB exposure
• Vaccines are not readily available to treat previous infections
• TB attacks the immune system which causes inflammation and cavitation
• Bacteria walls prevent environmental stresses and makes TB difficult to identify

TB: Immunity, Granulomas, and Transmission

• Immune cells attempt to isolate the disease making blood transmission rare
• Granulomas form in the lung initially, but can spread to other organs
• TB is transmitted through coughing and airborne particles that are inhaled

Other TB Factors

• Alveoli assist in removing C02 from the body using the respiratory and circulatory systems to transport gasses in the bloodstream
• Diaphragms pull air into the alveoli where gas exchange occurs and carbon dioxide exits

TB Medication Summary

• Stopping mycolic production is how TB is dealt with
• Livers that are used to clear blood can be affected by TB
• Prevention includes treatment and screening along w masks

Case 2: Acid-Base Balance

• Acids release H+ ions, while bases accept H+ ions
• Normal blood pH is between 7.35 and 7.45
• Carbonic acid (H2CO3) is the most important body acid
• The body makes more acid than base because of metabolism
• Lungs remove CO2 quickly whereas kidneys regulate HCO3- at a slow pace
• Acidosis occurs in cases with high levels of acid and low pH and Alkalosis occurs in cases with low acidity and high pH

Acid-Base Disorders

• Respiratory Acidosis: Caused by hypoventilation
• Respiratory Acidosis: Kidneys excrete H+ and retain HCO3-
• Respiratory Alkalosis: hyperventilation
• Respiratory Alkalosis: Kidneys retain H+ & excrete HCO3-
• Metabolic Acidosis: diarrhea, kidney failure
• Metabolic Acidosis: Lungs hyperventilate (blow off CO2
• Metabolic Alkalosis: vomiting, excess antacids
• Metabolic Alkalosis: Lungs hypoventilate (retain CO2)

Pancreas and Digestion

• The exocrine pancreas is responsible for producing bicarbonate and digestive enzymes
• Digestive enzymes produced are amylase
• Insulin lowers blood glucose and is released by beta cells
• Glucagon raises blood glucose and is released by alpha cells
• Somatostatin inhibits both glucagon and insulin and is released by delta cells

Insulin & Glucose Metabolism

• Glucose is stored in the liver through insulin and fat
• Fasting uses stored glucose to prevent low blood sugar

Diabetes

• Body stops the release of insulin
• Cells are resistant to insulin
• Leads to increased hunger, peeing, and thirst

Diabetes Complications

• Can lead to no release of insulin through type DM
• Can lead to insulin assistance
• Regular symptoms include high thirst and excessive eating

Diabetes Medications

• Type 1 can have severe reactions
• Can cause short term damages
• Can lead to hypoglycemia

Energy Production

• Glycosis can lead to the breakdown of ATP
• It occurs in cytoplasm
• TCA cycles make acetyle
• Acetyl occurs in Mitochondria
• Liver muscles and cells can be accessed too

Keynotes about Energy Production

• Fatty acids are the primary energy source for cell growth and can lead to cancer if not carefully maintained
• Low levels of glucose lead to ketogenesis in the kidney which causes ketones and uncontrolled glucose intake
• Too much glucose leads to ketoacidosis

Kidney Function

• The kidney removes and regulates the balance of electrolytes
• Production of hormones and PH balance prevent acidic bodies and reabsorption of hco3

IV Fluid and its Functions

• Fluid aids in assisting and correcting the loss of fluids in the body
• Normal saline can assist with dehydration
• Dextrose is great for patients with diabetes and low levels of insulin

Syncope

• Can cause low blood flow to the brain
• Can cause heart problems and strokes

Blood Vessels

• Supply blood to digestive system

Case 2 Conclusions

• The imbalance of the process leads to issues with ketones and acidosis
• Fast acid regulation occurs in lungs with Kidneys acting as a long term treatment
• High glucose intake can cause diabetes

Diabetes Type 1 vs 2

• Type 1 has very low release of insulin where as type 2 shows to prevent insulin resistance
• Type 2 has a small amount of release where type 1 needs to be life long
• Type 2 is common as aging occurs
• Type 1 can have high fat content

Key Differences

• Low blood sugar vs high blood sugar
• High level of sugar damages retina in the body
• SGLT2 reduces sugar

Treatment

• Use of insulin
• Reduces glucose intake

Insulin Treatment

• Insulin pumps are used to control the glucose production
• Metformin inhibits the liver process

DKA vs HHS

• Very low treatment where fluids are pushed

Conjuagted Key Differences

Too high

Conjuagted

Outflow can not be facilitated