Exam 1: Respiratory Drugs Flashcards
SNS versus PSNS effects on bronchioles
- SNS – bronchodilate, want to breathe better if running away
- PSNS – bronchoconstrict
Tell me about airway smooth muscle
o Airway smooth muscle extends as far distal as the terminal bronchioles
o Under the influence of both the PSNS and SNS
SNS innervation
o SNS fibers from the thoracic ganglia pass to the lungs to innervate the smooth muscles of the bronchi and pulmonary blood vessels
o Sympathetic tone – Bronchodilation via beta 2 receptors
- SNS innervate tracheobronchial blood vessels and glands
- Beta -adrenoceptor located in the smooth muscle of the blood vessels, skin muscle mesentary and bronchial smooth muscle
- β2-adrenoceptors, mediate relaxation of smooth muscle in blood vessels, bronchi, the uterus, bladder, and other organs
- β2-adrenoceptors thus cause
- widening of the airways (bronchodilation)
- Increased intracellular cyclic AMP
- Greater sensitivity to EPI vs NE
o Adrenergic β2
- Bronchial smooth muscle RELAXATION
- Relaxation of visceral smooth muscle (leads to?) muscle tremor
- Results in Bronchodilation(B2)
PSNS innervation
o PSNS innervation of these structures is via the VAGUS nerve
o Parasympathetic tone
- Bronchoconstriction via Muscarinic receptors M3 (and musc 1, not so much musc 2)
- Increased secretions
o PSNS reflex mediated
- muscarinic receptor predominated the airway smooth muscle.
- Stimulation of the vagus nerve leads to bronchoconstriction
- M3 receptors are pharmacologically most important
- M3 are found on the
- Bronchial smooth muscle
- Mediate bronchoconstriction via the activation of IP3 (inositol triphosphate) which → increases the intracellular Ca2+ concentrations
- Mediate mucus secretion
o Cholinergic
- Bronchial smooth muscle CONSTRICTION
- Pulmonary Blood Vessels - no dilation -Increased secretion of the bronchial glands
- Results in
- bronchoconstriction
- Increased mucus secretion
tx of laryngospasm vs bronchospams (In-class discussion)
• Laryngospasm
o Can break a laryngospasm with 3-5 mg rocuronium. Defasciculation dose.
• Bronchospasm – meds
o ***Volatiles EXCEPT DES (caustic) – bronchodilation
o Propofol
o O2
asthma (characteristics, causes episodes of, describe the airways)
o Extrinsic vs intrinsic
o Chronic inflammatory disorder of the airways characterized by increase responsiveness of the tracheobronchial tree to a variety of stimuli
o Variable airflow obstruction that is reversible
o This disorder causes recurrent episodes of: Wheezing, Breathlessness, Chest tightness, Cough (night and early a.m.), Tachypnea, Prolonged expiration phase of respiration, Fatigue
o Asthma creates airways that are -Inflamed, edematous airways -Bronchial hypersensitivity/reactivity to irritant stimuli -Difficulty with air outflow
3 characteristics of asthma, and the list of mediators that respond to activation of T2 lymphocytes and cytokines
o Disease is characterized by
• inflammation • hyper-reactivity • Reversible airway obstruction
o Airway hyper-responsiveness and inflammation from allergen in bronchial mucosa → activation of T2 lymphocytes and cytokine release [Degree of airway hyper-responsiveness and bronchoconstriction parallels the extent of inflammation]
o Mediators include: Eosinophils, mast cells, neutrophils, macrophages, basophils, T lymphocytes
(all have been implicated as histologic mediators)
^^ Talking about seeing these in the sputum! And COPD you’ll see more neutrophils and macrophages
o Other probable mediators of acute bronchoconstriction
- **cytokines, **interleukins (3,4,5), -arachidonic acid metabolites leukotrienes and prostaglandins,
- **histamine, adenosine, and platelet activating factor (starred ones were highlighted in ppt)
o Some asthmatics are atopic (produced by allergen) and have IgE synthesis and are considered to have atopic or extrinsic asthma
o Medications are aimed at flattening the response to mediators
“L-M(acrophages)-N(eutrophils)-O-COPD”
“Mast = m-asthma” + eosinophils, cytokines, T lymphocytes, interleukins, histamine
Look at this picture
risk factors for COPD
- Genes
- Smoking
- Age/gender
- Lung growth/devt
- Exposure to particles
- Cigarette smoke
- Occupational dusts and fumes
- Indoor air pollution (biomass fuels)
- SES
- Types of occupations
- Housing areas
- Work
- Health literacy
- Asthma/bronchial hyperreactivity
- Chronic bronchitis
- Infections
COPD/Emphysema/Bronchitis
- Obstruction is either not reversible or incompletely reversible by bronchodilators
- Cell death and destruction of the alveoli is due to impaired lung parenchyma, degraded matrix, and toxic actions of inflammatory cells (specifically macrophages and neutrophils)
- Results in enlargement of air spaces (barrel chest), fibrosis, and increased mucus production
- Steroids have limited effect on inflammation process in COPD
- Inhaled corticosteroids help in reducing frequency of exacerbations and
- Bronchodilators have modest role in air outflow with patient suffering from chronic breathlessness “worsened by exertion”
- Thickened PCM/ACP (pulm capillary membrane/alv…) ineffective gas exchange
tx of airway outflow disorders
- Step 1-Short-acting bronchodilators
- Step 2-Regular inhaled corticosteroid
- Step 3-Long-acting bronchodilators ** mainstay of asthma therapy
- Step 4-
- Phosphodiesterase Inhibitors
- Methylxanthines
- Leukotriene inhibitor
- Step 5-Oral corticosteroid
- Other-Cromolyns
list the 3 types of bronchodilators
- Beta-Adrenergic Agonists
- Anticholinergics
- Methylxanthines
B-adrenergic AGONISTS (we want to activate B2ARs)
name 3 of them, and say which receptors they target
describe which are short vs long-acting
MOA
- Variable receptor selectivity b2, b1
- Epinephrine - b2, b1, a
- Isoproterenol - b2, b1
- Metaproterenol - b2, b1
- Receptor selectivity b2
- Bind to b2 200-400 times more strongly than b1
- Short-acting
- Terbutaline, **Albuterol, Levalbuterol (isomer of albuterol, more b2 specific) - b2, Salbutamol
- Long acting
- Salmeterol
- MOA:
- Beta adrenergic receptors are coupled to stimulatory G proteins
- Activate adenylyl cyclase which increases the production of cAMP (adenosine monophosphate) → bronchodilation (by inhibiting release of Ca++)
- reduced intracellular Calcium release and alters membrane conductance
- Primary effect is to dilate the bronchi by a direct action on the B2 Adrenoceptors l
- Results in smooth muscle relaxation and bronchodilation l Inhibits mediator release from the mast cells l Increase mucus clearance by action on the cilia
“It’s B2 RELAX”
B2 agonist →
- ↓ Ca++
- ↑ cAMP (bc of ↑ adenylyl cyclase)
“It’s B2 use EPI > NE” (more sensitive to EPI)
NANC nerves
-
Non adrenergic Non-cholinergic nerves (NANC)
- Influences inflammation and smooth muscle tone.
- excitatory: release Substance P & neurokinin → neurogenic inflammation/bronchoconstriction
- inhibitory: releases NO & VIP (vasoactive intestinal peptide) → relaxation/bronchodilation
- “Substance P excites me! Neuro-kinda excited!” = bronchoconstriction
- “Inhibitory = NO! VIPs only.” = bronchodilation
B-Adrenergic AGONIST:
onset, duration
SEs
- Rapid onset of action - within minutes
- Short duration of action – 4-6 hours
- Good for use as Rescue inhaler
- Given via
- inhalation or aerosol
- Powder or Nebulized
- Orally or injected (SC)
- Short or long acting – usually just have pts take a couple puffs of their short-acting inhaler just before surgery
- Side Effects
- Minimized by inhalation delivery
- Tremor
- Increased heart rate
- Vasodilation
- Metabolic changes - Hyperglycemia, hypokalemia, and hypomagnesemia
