Asthma and COPD Pharmacology

• SABAs are short-acting beta-agonists, while LABAs are long-acting beta-agonists
• Pulmonary pharmacology focuses on how drugs act on the lungs and treat pulmonary diseases, especially airway obstruction in asthma and COPD

Asthma and COPD

• Asthma involves chronic airway inflammation and smooth muscle contraction
• COPD involves respiratory tract inflammation, leading to air trapping, hyperinflation, and alveolar wall destruction

Therapeutic Approaches

• Asthma is managed with bronchodilators to relax airway muscles and anti-inflammatory drugs
• COPD primarily uses bronchodilators, with inflammation addressed if corticosteroids are resistant

Routes of Drug Delivery

• Inhalation is preferred for direct airway action and fewer systemic side effects
• Oral administration requires higher doses, about 20 times that of inhaled dosages, and is for cases when inhalation is not possible
• The intravenous route is reserved for severely ill patients and subcutaneous injections for biologics

Bronchodilators

• Classes include ẞ2 adrenergic agonists, theophylline, and anticholinergic agents ☐ Mechanism: Bronchodilators function by relaxing airway smooth muscle and preventing bronchoconstriction

Therapeutic Challenges

• Asthma poses challenges due to chronic inflammation and structural changes, requiring corticosteroids
• COPD involves progressive airflow obstruction, inflammation, and often comorbidities

Importance of Drug Delivery Devices

• Inhalers, including pressurized metered-dose and dry powder inhalers, and nebulizers offer effective drug delivery
• Spacers are important for ensuring medication reaches the airways

Beta-2 Adrenergic Agonists

• MOA: Act on bronchial smooth muscle relaxation via the Gs-adenylyl cyclase-cAMP-protein kinase A pathway
• Indirectly inhibit release of bronchoconstrictor mediators from inflammatory cells, reducing mucosal edema and ACh release
• Prevent microvascular leakage, reducing bronchial mucosal edema after exposure to mediators like histamine

Additional Beta-2 Agonist Effects

• Prevents mediator release, increases mucus secretion, and reduces neurotransmission in airway cholinergic nerves
• Increases mucus secretion from submucosal glands and ion transport across airway epithelium, enhancing mucociliary clearance
• SABA vs. LABA: SABA is for "rescue," and LABA is for "control"

SABA (Short-Acting Beta-2 Agonists)

• MOA: Inhaled short-acting beta-2 agonists
• Indications include rapid bronchodilation for symptom relief
• Mainstay acute asthma therapy ("rescue therapy")
• SABAs should only be used on demand for symptom control

Commonly Used SABAs

• Albuterol (ProAir, Ventolin, Proventil ®) often has SE of cardiac
• Levalbuterol (Xopenex ®) has less cardiac activity
• Metaproterenol (Alupent ®) is liquid
• Pirbuterol (Maxair ®)

SABA Characteristics

• Rapid-acting (1-5 minutes) with a half-life of 6 hours or less
• Metered Dose Inhaler (MDI) & nebulizer inhalable formulations

LABA (Long-Acting Beta-2 Agonists)

• MOA: Provide prolonged bronchodilation for long-term control, with inhaled corticosteroids (ICSs)
• Combination LABA/corticosteroid inhalers offer convenience, adherence, and synergistic actions
• Provide 12 hours or more of bronchodilation due to their high lipid solubility

Clinical Considerations for LABAs

• Should always be used with an anti-inflammatory corticosteroid to reduce risk of potentially fatal asthma attacks
• Combination with an ICS now recommended as the rescue bronchodilator of choice in asthma
• Tolerance develops after 1 week but recovers after 3 days

Side Effects of Beta-2 Agonists

• Muscle tremor, tachycardia, hypokalemia, restlessness, hypoxemia, and metabolic effects

Histamine Receptors

• Activation of H1 receptors stimulates eNOS, producing nitric oxide (NO) for smooth muscle relaxation
• Stimulation of H1 receptors on smooth muscle causes contraction through Ca2+ mobilization
• H2 activation promotes relaxation via increased cyclic AMP accumulation and PKA activation

Histamine Receptor Distribution

• H1 and H2: Widely distributed in periphery and CNS, causing local or widespread effects when activated
• H3: Mainly in the CNS, influencing sleep, cognition, and neuronal modulation
• Synthesis and Metabolism: Derived from histidine by decarboxylation, stored in mast cells and basophils, released upon stimulation

Histamine Function

• Immediate hypersensitivity and allergic responses, affecting smooth muscle, vessels, leukocyte migration, and gastric acid
• Cardiovascular system: Vasodilation, increased capillary permeability, and leukocyte recruitment modulation
• CNS: Modulates sleep-wake cycles, circadian rhythms, learning, and memory through H3 and H4 receptors

HI Antagonists

• H1 antagonists inhibit histamine effects on smooth muscle, capillaries, and nerve endings, treating allergies, motion sickness, dermatological conditions
• First-generation causes sedation and anticholinergic effects and Second-generation drugs have fewer CNS effects and are preferred in certain populations

Pediatric and Geriatric Considerations

• Second-generation is preferred in the elderly due to reduced sedative and First-generation antihistamines are not recommended for children

HI Receptor Antagonists

• Reduces pruritis, secretions, and stabilizes mast cells (cetirizine, fexofenedine, desloratadine) and CNS effects depend on and has anticholinergic effects

HI Antagonist Indications

• Allergic disease (rhinitis, urticaria, conjunctivitis, limited role in asthma, colds, motion sickness, vertigo, sedation

HI Receptor Antagonist Effects on Systems

• Inhibits histamine effects on smooth muscles
• Blocks increased capillary permeability and edema formation
• Suppresses histamine action on nerve endings, like itching
• Doesn't suppress gastric secretion

Immediate Hypersensitivity Reactions and H1 Antangonists

• During reactions, histamine varies with species and tissue
• Edema and itch are suppressed, with less effect on hypotension and little on asthma

Mast Cell-Stabilizing and Anti-Inflammatory Properties

• Second-generation H1 antagonists stabilize mast cells and reduces mediator release
• Properties that are H1 receptor depend

H1 Antihistamines in the CNS

• First-generation can stimulate or depress CNS with restlessness or convulsions
• Second-generation anti-inflammatory properties and effective in allergic conjunctivitis and rhinitis

H1 Feedback and Cardiovascular Effects

• Feedback, histamine effects on blood vessels leads to vasodilation and edema, regulated by histamine receptors themselves Potential Areas of Research involves the role in CNS or better antagonists

Leukotriene Receptor Antagonists (LTRAS)

• Consists of inhibitors of 5-lipoxygenase, and leukotriene receptor antagonists
• Given orally and have been documented to produce beneficial effects in chronic asthma treatment
• They do not have a benefit in treating asthma flare-ups
• 5-lipoxygenase inhibitor: zileuton (Zyflo)
• Receptor Antagonists: Montelukast (Singulair) or Zafirlukast (Accolate)

Leukotrienes Function

• Leukotrienes are inflammatory mediators causing increased production of arachidonic acid and Formation is a variety of leukotrienes, instead of prostanoids & prostaglandins
• Rare cases is hepatic dysfunction and Churg-Strauss syndrome

Selective Leukotrine Inhibitors

• Zileuton is a 5-LOX inhibitor
• Zafirlukast, pranlukast, and montelukast are selective CysLT receptor antagonists
• LTs released from lung tissue are asthmatic patients and induces Contraction is bronchial smooth muscle

Clinical information

• Agent reverses broncho-constrictive effect of LTs and significantly improves asthma
• LTs mediate inflammation to which Efforts of ZILEUTON is is selective: CysLT receptor antagonists
• Prevent bronchoconstriction, mucus secretion, leukocyte chemotaxis, histamine release Less effects than inhaled corticosteroids and May eventually prove use for the Prevention used if long term
• Montelukast binds with high affinity and selectivity to CysLT1 recep

Antimuscarinic Respiratory Agents

• SAMA:lama and governing heart rate, exocrine glands, smooth muscles, and brain function
• The quaternary derivative of atropine and The of muscarinic: Varies for degree amongst patients

SAMA, LAMAS. and Cholinergic Effects Contraindications and Indications.

• SAMA blocks muscarinic receptors to reduce secretions. And are CAUTIOUS in glaucomia
• Tiotroprium Bromide is LAMA brand Spriva long maintaince COPD treament and more the same

Effects and Uses

•

• Muscarin Antagon: ẞ2 with asthma but bronchodilators less, COPD effective reduces and Combo add
• • SAMA and LAMA: Cholinergic are additive as Combo for COPD

Asthma Adverse Effects.

• Effects: well tolerated, occation Dry rare and systemic effects on Developments long term
• LABA or LAMA comb better lung fx

PDE4 (Phosphodiesterase-4) Inhibitors

• Role in severe COPD, consider monitoring • Methylxanthines, Theophylline: THE - DUR

• -Historical use Effectiveness in developing cost - Became with good forms

Chemo Properties

• Methylxanth similar but less than the methyl and a common one - METH

- Action

• Inhib Phosphodiesterase which include 10 release and also decreases of adenosine
• Anti inflam seen less conc., lowers with inflammation, Improves steoroid of the adenosine helps but has more than one

and Pharma and Clinical of Theop and Side Effects

• Large inter clearance and Reserve as add ones for sever cases but with low dose, has beta and improves with

Clinical Usage for Phos-4- inhi

• Side well toler and may be excreted in the urine which is a non sel inhib of long is effective but no sx

Asthma BIO

• Omaliz and others and anti ige receptor treatment.
• Reduct in cells with frequent Attacks at prophylactic for all
• 1200 to 3000 a month
• A skin with only one or

and Anti-Tussives

• For OP or NON, If not productive find with is this? and Don't productively stop
• All those cause related from inhale to not from long

and Antigens and the MoA for Opioids for The action

• Receptors for both medulla and cough, are analgesics and effect

Contraindivations and other action drugs for the action.

• Decrease in the sensitivity of a cough interrupts through some stimulation. They're no and should

HIs and Mech of Action and Contraindicaitons with other actions and Indications and Other actions with different ranges.

• It reduced the that and resets the sensors
• Benzon acts on all and and they and are all

Nasal drugs and steroids and His for nose problems, including allergy.

• Use consistent steroids are ADR and then no steroid and not used in old people with an high chance of falling down

Uses for kinins

• B1 B2, GPCRS, heart is vasodilation, in high cause problems!

Drugs that could block

• Icat etc
• Can alter angine, which is first line therapy for most cases

Differentiatyion and the treat styles and such

• For steroid less effects in, for cases, binds on targets and reduce gene express

Asthma and side effects

• Potent in all. In this one, long term and lower O For acute give only with tappering , increase it to do and watch for levels

Steps

• One is start with steroids to stop it that way