Respiratory Medications: SABAs and LABAs

Respiratory Medications

• Short-Acting Beta-Agonists (SABAs) are inhaled beta-2 agonists that quickly and effectively dilate airways, providing rapid relief from asthma symptoms.
• SABAs are primarily used as needed as rescue therapy for acute asthma exacerbations.
• SABAs are typically delivered via metered-dose inhalers (MDIs) or nebulizers.
• SABAs begin working within 1-5 minutes and have a half-life of 6 hours or less.
• Example SABAs are albuterol (ProAir, Ventolin, Proventil), levalbuterol (Xopenex), metaproterenol (Alupent), and pirbuterol (Maxair).
• SABAs should be used on demand for symptom control only; frequent use suggests the need to step up therapy.

Long-Acting Beta-Agonists (LABAs)

• LABAs provide extended bronchodilation for long-term control of asthma.
• LABAs are typically prescribed in combination with inhaled corticosteroids (ICSs).
• Combination inhalers offer convenience, improved adherence, and synergistic effects.
• LABAs have a duration of action of 12 hours or more due to their high lipid solubility.
• BB WARNING: LABAs should never be prescribed by itself but must be in COMBO for asthma patients!
• LABAs have no anti-inflammatory properties; always combine with an anti-inflammatory corticosteroid to reduce the risk of potentially fatal asthma attacks.
• Black Box Warning: LABA monotherapy is associated with an increased risk of asthma-related death.
• LABAs should be used as additional therapy for patients inadequately controlled by low to medium doses of inhaled corticosteroids only.
• Tolerance to LABAs may develop after 1 week of use but can recover after 3 days of non-use.
• Formoterol combined with an ICS is now the preferred rescue bronchodilator; this combination is more effective and avoids potential overuse of SABAs.
• Example single med inhalers are Formoterol (Peroromist) & Arformoterol (Brovana).
• Example ICS and LABA combinations are Symbicort (Budesonide + Formoterol) & Advair (Fluticasone + Salmeterol).
• LABAs improve COPD symptoms and exercise tolerance by reducing air trapping and exacerbations.
• Desensitization of receptors can occur with long-term use.

SABAs and LABAs Side Effects

• Side effects are dose-related.
• Muscle tremor
• Tachycardia
• Hypokalemia
• Ventilation-perfusion mismatch.
• Tolerance may develop to bronchoprotective effects, but not usually to bronchodilator effects.
• Continuous use of corticosteroids prevents tolerance development in airway smooth muscle.

First and Second Generation H1 Receptor Antagonists

• First-generation H1 antagonists include doxepin, diphenhydramine, chlorpheniramine, and cyproheptadine.
• H1 antagonists inhibit histamine's effects on smooth muscle, capillary permeability, and nerve endings.
• They treat allergic reactions, motion sickness, and certain dermatological conditions.
• First-generation H1 antagonists can cause sedation and anticholinergic effects.
• Second-generation drugs have fewer central nervous system effects and are preferred in certain populations.
• Second-generation antihistamines are preferred in the elderly due to reduced sedative effects. - risk for falls
• First-generation antihistamines are not recommended for children due to potential learning and cognitive impairments.
• H1 receptors modulate sleep-wake cycles, circadian rhythms, learning, and memory via H3 & H4 receptors.
• H1 & H2 receptors cause vasodilation and increased capillary permeability, contributing to edema.

H1 Receptor Antagonist Effects on Physiological Systems

• H1 antagonists reduce pruritus and secretions; second-generation H1 antagonists may have mast cell stabilizing effects.
• CNS effects may be stimulating or suppressing depending on the generation.
• Anticholinergic effects, such as a reduction in secretions, are more common with first-generation drugs.
• H1 antagonists are indicated for allergic diseases with caution in the elderly due to the increased risk of falls.

H1 Receptor Antagonist Effects on Smooth Muscle and Capillary Permeability

• H1 antagonists inhibit histamine's effects on smooth muscle, especially respiratory smooth muscle constriction.
• They inhibit rapid vasodilator effects mediated by H1 receptors on endothelial cells.
• H1 antagonists strongly block increased capillary permeability and formation of edema and wheal caused by histamine.
• H1 antagonists suppress histamine action on nerve endings, reducing flare and itch.
• H1 antagonists do not suppress gastric secretion, but antimuscarinic properties may reduce secretions in cholinergically innervated glands.

Hypersensitivity Reactions and CNS Effects

• H1 antagonists can partially protect against edema formation and itch during hypersensitivity reactions, but are ineffective in blocking bronchoconstriction due to asthma.
• Many second-generation H1 antagonists also exhibit mast cell-stabilizing and anti-inflammatory properties, reducing mediator release and eosinophil infiltration.
• First-generation H1 antagonists can both stimulate and depress the CNS.
• Central depression leading to diminished alertness, slowed reaction times, and somnolence is common at therapeutic doses.
• 2nd generation H1 receptor antagonists include Olopatadine, Acrivastine, Cetirizine, Loratadine.

Leukotriene Receptor Antagonists (LTRAs) or Leukotriene Modifiers

• LTRAs: Montelukast (singulair) or Zafirlukast (Accolate)
• Consist of both inhibitors of 5-lipoxygenase, and leukotriene receptor antagonists.
• Both classes of drugs are typically given orally.
• There is documented evidence that these medications produce beneficial effects in the chronic treatment of asthma.
• They do not have a recognized benefit in treating asthma flare-ups and are used as control medications, not rescue medications
• Zileuton (Zyflo) - 5-lipoxygentase inhibitor

Leukotrienes Info

• Leukotrienes are inflammatory mediators produced by activated leukocytes via increased phospholipase A2 activity
• Leukotrienes are released from lung tissue of asthmatic patients and purified human lung-mast cells by antigens
• Leukotrienes directly induce the contraction of bronchial smooth muscle.
• The use of antileukotriene (anti-LT) agents, like LT-receptor antagonists (LTRAs), reverse the bronchoconstrictive effect of LTs by significantly improving asthma symptoms.
• Selective INhibitors Zileuton - inhibitor of 5-LOX; selective CysLT receptor antagonists zafırlukast, pranlukast, and montelukast.
• A common polymorphism in the gene for LTC4 synthase, correlating with increased LTC4 generation, may be associated with higher asthma risk.

LTRA functions

• LTRA's prevent Bronchoconstriction, Increased secretion of mucus, and Leukocyte chemotaxis - Prescribed after when there is IgE symptoms
• LTRA's are less effective than corticosteroids (inhaled form)
• LTRA's may become useful in cardiovascular disease prevention (long term)

Muscarinic Cholinergic Antagonists

• Anticholinergics work on either nicotinic or muscarinic receptors (high dose).
• Muscarinic ACh receptors affect heart rate, exocrine glands, smooth muscles, and brain function.
• Competitive inhibitors that result in bronchodilation as acetylcholine is blocked.
• Less effective than SABA/LABA in asthmatics, only add on therapy due to a bronchial cholinergic hyper-reactivity
• Muscarinic Cholinergic Antagonists are less effect than b2 in asthmatics
• Ipratropium bromide (Atrovent): antimuscarinic bronchodilator
• quaternatry derivative of atropine
• less side effects, but less broncholdilation

Mechanisms of Action and Indications of Muscarinic Cholinergic Antagonists

• Quaternary derivative of atropine that results in broncholdilation
• The degree of muscarinic involvement in bronchomotor responses varies amongst patients.
• Administered by itself or w/ other bronchodilators, especially beta adrenergics
• Bronchodilator for maintenance treatment of chronic bronchospasm and obstructive pulmonayr disease

Muscarinic Cholinergic Antagonists Side effects and considerations

• Narrow-angle glaucome and prostatic hypertrophy
• Caution for those w/ narrow-angle glaucoma, prostatic hypertrophy
• Adr: dry mouth, urinary retention
• Long Acting Muscarinic Antagonists (LAMAs)-
• Tiotropium Bromide (Spiriva and Spiriva Respimat)
• antimuscarinic bronchodilatior- same action
• approved for the treatment of bronchospasm associated w/ chronic obstructive pulmonary disease
• Long Term use effective in improving lung function, reducing exacerbations and mortality, but does not reverse the lung disease

Muscarinic Cholinergic Antagonists cont.

• Low dose from Tiotropium approved by FDA 2016 for for asthma in ADULTS
• Used to treat more sever forms of asthma
• once a day dosing Less Effective in Asthma than B2 Agonists and is used as additional rescue therapy when needed. Reduces Air Trapping by being Effective in COPD and Improves Exercise Tolerance.

Muscarinic Cholinergic Antagonists Classifications

• Short-acting (SAMAs): ipatropium: for rescue therapy to reduce mucus production and open airway
• Long Acting(LAMAs) tiotropium: for maintainable maintenance for symptoms, prevent exacerbations
• Additive Effects seen when anticholinergic and B2-agonists are used in combination w/ fixed does of COPD drugs

Muscarinic Cholinergic Antagonists Adverse Effects and future development

• They are generally well-tolerated, with occasional dry mouth and urinary retention
• Due to limited systemic absorption systemic side effects are uncommon Future combination development includes:
• LABA/LAMA combination inhibitors
• Triple Inhalers as preferred treatments

Inhaled Corticosteroids for comparison with the LTRAs

• ICS: primary medications for asthma pt's d/t reduces inflmation of airways and reduces inflam resp, this is an Acute Attack Med -COPD: ICS Less effective Reserved for severe COPD cases and/or increased numbers of blood eosinophils Mech: ICS inhibits proinflammatory transcription factors like NF-kB-lead to anti inflam effects and also reduces risk of fatal exacerbat from loss of breath.
• ICS Interactions: potentiates effects of Beta Agonists receptors on brachial smooth muscle
• ICS: as 1st therapy for persistent asthma+ dosing depends on how the severe it is.
• ICS: may need higher steroid level due to potential adrenal suppression
• ICS: can be used in COPD with severe effects

H1 Receptor Agonist

• Reduces Pruritus and Secretions; Mast Cell Effects with 2nd Generation Reductions that lead Less mucous production
• CNS Effects are can be Stimulated or Suppressed is related to what Generation of antihistamine you Think benadryl vs claritin
• Anticholinergic Effects are Reduced
• Indications: to treat Allergic disease; rhinitis, conjucntivits. limit role in Asthma, Colds, Motion Sick, Vertigo and for sedation and Caution
• Adverse Effects: elderly has anti cholinergic Side effects increase the Risk of Falls

Phosphodiesterase Inhibitors-overview

• Reduce inflamm cells to control sevre COPD w chrontic bronchitis
• Relaxes smooth muslce and inhibi inflammatory cells for cellular and its sequelae.
• Reduces Exacerrbations in Severe COPD
• Oral nonselecitve PDE4 Inhibitor
• PDE4 predominant in inflammatory Cells as mast cells-suggest the PDE4 inhibitors control as antiinflammatory both in Astham and COPD

Monoclonal Antibody therapy: Omalizumab (Xolair) for IgE mediated Asthma

• Anti-IgE receptor therapy/Prophylactic Asthma med for pts over 12 y.o that need to be more controlled by inhaled corticosteroids
• Antibodies (Monoclonal) treat patients allergic asthma that will otherwise only need ics . Treat lymphocytic, eosinophilic, bronchial inflammation w/sub-Q 2-4 weeks. Reduces frequnecy and severity of asthma attack. Side Effect of Omalizumab
• The ADE anaphylaxis has was can occur at anytime during treatment.
• Given @ Dr's Office cause anaphylaxis Risk
• Xolair is approved for patient that symptoms not controlled or has a skin test reaction
• Extremely Expensive. Dosing dependent & frequency of dosing for the patient

Antitussive Medication

• Antitussive for both Central and Peripheral use- Cough suppress due Secretions are all cleared
• The Underling CAuse should identified then Treat for the cough- not treat the Symptoms just treat for the Relief instead
• Astham- responds to to Corticosteroids Inhalers
• Camphorand Menthol has soothing effect that can inactivate receptors on the pharynx
• Codeine (Opioid) is mainly mediated in relation through the Opioid present in the Medulla or Drowsdiness Side Effect
• Dextromethorphan Non Opioid) a Opioid derivative (Delsym) causes less constriipation compare to Codeine due to interrupt transmission and decreasing the sensitization of opioid receptors

Antitussives Cont.

• The effectiveness of medication can be impacted by the receptors activity in the passafes
• The anesthiziation can occur cause of chest tightness
• Benzonattate - Mechanism is that it Anethetizes which can make you feel the feeling reduced

General Points For Intranasal Corticisterioids and Anti Histamines

• Must be used on a continual basis due to reduce of inflammation of release or suppression; must angle the tip laterally in you nose for it to work
• Second generation Antihistamine promotes promotion and improving cognitive function.
• impact in the central nurvous system
• Potential can treat
• H4 for pain due treatment or improve Schizophrenia
• Example of other types in development due to Parkinson's

ESA and granulocyte and what its used for

• Treatment: Erythopeotin used to help with low RBS, and Cancer Chemotherapy, kidney functions, and AIDS/perioperative settings with cancer. Red production
• Adverse Reactions: bone pain and skin reactions/splenomegaly and cell changes
• EPO Reommendation/ Caution Black Bow : HCt above g/dl =cardio higher risks Contraindications: Uncontrolled HTN or albumin derivatives or albumins
• Folic- <4 is low
• B12 <200 is low
• Serun Iron &TBIC is a marker of irons depletion -iron storage

Platelet Acting Factors

• Eicosanoids Act of platelet to the system such as
• Kidney
• Gl Muosal-Protection

ESA Mech action and other treatments

Eicosanoids Are important for Innate immunity and Inflmation.

• Prostaglandin and leukotriene are the Prim recepor they help to exert the effects which is the Distinct Physio Roles. And sig pathways for their act
• Anti Inflam: glucorticods like is PLA/COX -to manage Inflamatio or pain

NSAID use and restriction

• Nonselective COX inhibitor
• NSAID:s used to inhibit prostaglandin
• Uses: Symptomatic relief from pain Fever from lowering for body to temperature Cautions For Nsaid
• Adverse Affect GI: is from inhibit cox 1 in physiology and or function such is GI Tracy,cardio, Reno
• Adverse Afffect pt is lab for Routine labs .CB/UC/serum-1- 3months during after therapist and then every 3-6 motsh after monitoring
• Analgesic and Anti pyretic
• Adverse Affexts cardio/ Reno for symptoms

ASPirin and its Mechanism

• ASpirin uses to be the only IRreversible inhibit during Clinical. Other than reversible and acts direct on the acids active site.
• Low Does is used selectively is for Plate activing drug

Aspirin Contra and Side effects

• Contraindications:

NSAIDS/bleeding, Pregnancy or children before dr. consults consults

• PK

Hydrolyzed primarily the liver, with salicylate excreted in the urine

• SE:

Trigger symptoms is Athsma/Therpupetic Doses/Vomting tinnitus Progressively Higher, P edema and Cardio collapse from Death due to CN failure. Mech -blocks the enzymes, interferes w/ the kallikrein system

• Low doses produce mild bleeding Therpeutics Kawaski helps Microglots from Infect Kids or help strokes as in Males due fibrogen

Cyclooxygenase (COX2) Contraditions and its effects

• Selective: Blocks Cox - 2 then Reduces pain, renal /hepatic, preg
• ADR/C/I pregnancy

CV increase to the heart

Acetominophen,

• anal gesic is reduced enzymes and then has little impact, liver failure

NSAID Indomathicin,

• has great potency but many issues. greater then effects over time due side effects
• High risk for over dose

Other nonselective NSAID for IBS/RA

• propionic acid derivares Mefenmic and oxicams piroxicam are used for short term pain in tissues and short term

Gout and Treatments

• Gout can treated and for long time but also you control attack. Aim is to relieve symptoms and risk for the recurrent Methotrexate preg and brest feeding High cause with effects and most effects for all Blood pressure and weight check w/ oral dose Anti inflammatory help gout first then go to the main cause Colchicine treats with first 24 hours, prevent in 36 hrs. for most problems and gout. But use caution because severe: myelosuppression. Also many interations

Gout Treatments cont.

Allopurinol/ Febuxostat

Allopurinol decreases the ynthesis . Skin rxns Feb is the drug. Starts dose at w increments weekly and and if patients have allpur use feb Uricosuc Increase ecretion from and Inhibits the absorption

Immune response modulatants

Monoclonal- used antibodies more than other -and block with the function. Adverse of Immunosupressio is risk to infextions.

Monclonal Mech

• The mech is targeting or affecting on protein b or lym surface.

More Information on Immunosuppressive Agents

• Anti - IL2-receptors like: daclizumab and basiliximab are transplanted
• Alemtuzmab- target the cell and is used in transplantations

More information on certain deficiencies

• Iron -take iron replacement on empty stomach , and can take supplements too in a combo
• B12-Essential replication if cell repl,deficiency in the ineffivess.
• folliacid/ folvite/ B is essential cofactor for protein synthesis