Exam 3 Respiratory Pharmacology

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What is the effect of stimulatory G proteins on ATP in pulmonary smooth muscle when B2 agonists bind to the B2 receptor?

Conversion of ATP to cAMP causing smooth muscle relaxation

What is the primary use of short-acting B2 agonists?

Rapid relief of wheezing, bronchospasm, and airway obstruction

What is a common side effect of B2 agonists?

Tachycardia

What is the mechanism of action of anticholinergic agents in reducing bronchomotor tone?

Inhibition of binding of Ach to muscarinic receptors decreasing release of Ca+ Signup and view all the answers

During exercise, which of the following occurs to increase diffusion capacity?

Recruitment of capillaries, improved V/Q, and increased alveolar ventilation Signup and view all the answers

What is the effect of Ach binding to M1 and M3 receptors in the airway?

Contraction of smooth muscle and increased mucus production Signup and view all the answers

How is diffusion capacity measured?

By having the patient inhale a known amount of CO and measuring the amount of CO exhaled Signup and view all the answers

What is the primary role of the parasympathetic nervous system (PNS) in the airway?

Regulation of bronchomotor tone Signup and view all the answers

What is the normal diffusion capacity for healthy men?

17 mL/min/mmHg Signup and view all the answers

What is the effect of edema and fibrosis on respiratory membranes?

Thicker membranes that make it harder for gases to diffuse Signup and view all the answers

What is the purpose of systemic adrenergic agents in asthma management?

For rescue therapy only Signup and view all the answers

What is the effect of emphysema on the surface area of respiratory membranes?

Decreased surface area for gas exchange Signup and view all the answers

What is the result of a 1/3 to ¼ decrease in surface area of respiratory membranes?

A serious impediment to gas exchange Signup and view all the answers

Which of the following is a common feature of both COPD and asthma?

Inflammation Signup and view all the answers

What is the effect of ketamine on pulmonary vascular resistance?

It has a mixed effect on PVR due to its ability to preserve cardiac stability but has bronchodilutory effects Signup and view all the answers

What is the effect of N2O on pulmonary vascular resistance?

It can cause pulmonary artery vasoconstriction due to catecholamine release - avoid in PHTN Signup and view all the answers

What is the effect of volatile inhalation agents on pulmonary vascular resistance?

They have little to no effect on PVR Signup and view all the answers

What is the effect of fentanyl on the deleterious effects of N2O?

It offsets the deleterious effects of N2O at a dose of 50 mcg/kg... but that's not a great idea Signup and view all the answers

What is a common side effect of Methylxanthines?

Diuresis, seizures, dysrhythmias, and death - these drugs have a narrow therapeutic index Signup and view all the answers

What is a characteristic of intermediate acting NMBers such as rocuronium, cis-atracurium, and vecuronium?

They are known for their cardiac stability and are unlikely to cause histamine release Signup and view all the answers

Which of the following neuromuscular blockers is least likely to cause histamine release?

Cis-atracurium Signup and view all the answers

What is the effect of pancuronium on heart rate?

It increases heart rate through an antagonistic effect on muscarinic receptors Signup and view all the answers

What is the effect of sympathetic activation on pulmonary vascular resistance?

It increases pulmonary vascular resistance Signup and view all the answers

What is the primary mechanism of action of inhaled nitric oxide?

It decreases intrapulmonary shunt because nitric oxide is preferentially delivered to ventilated lung units Signup and view all the answers

What is a potential complication of inhaled nitric oxide therapy?

Methemoglobinemia Signup and view all the answers

What is the primary mechanism of action of phosphodiesterase inhibitors?

They decrease the breakdown of cAMP and cGMP, leading to vasodilation Signup and view all the answers

What is the effect of decreased cardiac output on systemic concentrations of inhaled anesthetics?

Abrupt increase due to slowed blood flow allowing for increased absorption Signup and view all the answers

What is the effect of age on MAC?

MAC is inversely affected by age Signup and view all the answers

What is the effect of pregnancy on MAC?

MAC decreases during pregnancy and returns to baseline in 12-72 hours Signup and view all the answers

What is the effect of red hair coupled with female gender on MAC?

MAC increases in red hair coupled with female gender Signup and view all the answers

What is the effect of opioids on inhaled anesthetic requirements?

Opioids synergistically reduce inhaled anesthetic requirements (i.e. increase potency/lower MAC) Signup and view all the answers

What is the effect of sevoflurane on kidney function?

When sevoflurane is exposed to CO2 absorbents, it can produce compound A which is nephrotoxic Signup and view all the answers

What is the effect of halothane on the heart?

Halothane sensitizes the heart to the arrhythmogenic effects of catecholamines Signup and view all the answers

What is the effect of isoflurane, desflurane, and sevoflurane on mean arterial pressure?

They decrease mean arterial pressure due to decreases in systemic vascular resistance Signup and view all the answers

What happens to the concentration of inhaled gas in the systemic circulation when cardiac output is elevated?

It decreases, resulting in delayed induction Signup and view all the answers

What is the effect of a high cardiac output on the delivery of parenterally (IV) administered anesthetic agents to the systemic circulation?

It speeds up their delivery. Signup and view all the answers

Which of the following anesthetics reduce bronchomotor tone?

Ketamine, propofol, and midazolam Signup and view all the answers

When were ether and nitrous oxide broadly used as anesthetics?

Initially in the mid-19th century and broadly used in the World Wars Signup and view all the answers

When was halothane first used as an anesthetic?

1955 Signup and view all the answers

When were enflurane and sevoflurane first used as anesthetics?

1970s and 1980s Signup and view all the answers

What agents are typically used as a first-line treatment in the management of asthma?

Long acting Beta2 agonists and corticosteroids Signup and view all the answers

What agents are typically used as a first-line treatment in the management of COPD?

Anticholinergics and steroids Signup and view all the answers

What is the primary difference in White Blood Cells (WBCs) present in asthma and COPD?

Eosinophils are more prevalent in asthma, while neutrophils are more prevalent in COPD Signup and view all the answers

What drug class is methylxanthine?

Non-selective phosphodiesterase inhibitor Signup and view all the answers

What is the mechanism of action of non-selective phosphodiesterase inhibitors?

Increase in cAMP, inhibits release of histamines/leukotrienes, and inhibits phosphodiesterase leading to bronchodilation Signup and view all the answers

What is the mechanism of action for mast cell stabilizers?

Inhibition of histamine release from mast cells Signup and view all the answers

Mast cell stabilizers are used for asthma, not COPD

True Signup and view all the answers

In what stage of COPD are inhaled corticosteroids used in combination with long-acting beta2 agonists to synergistically reduce inflammation?

Severe to very severe COPD Signup and view all the answers

What is the mechanism of action of corticosteroids?

Corticosteroid binds to glucocorticoid receptor and reducing expression of inflammatory gene products Signup and view all the answers

What is the primary effect of leukotrienes in the lung?

Bronchoconstriction and increased permeability Signup and view all the answers

What is the main difference between leukotriene inhibitors and leukotriene antagonists?

Leukotriene inhibitors prevent the synthesis of leukotrienes, while leukotriene antagonists block the action of leukotrienes at the receptor. Signup and view all the answers

Leukotriene modifiers are used in long term asthma therapy

True Signup and view all the answers

What is true about Ipratropium in COPD?

It is a short-acting medication used for maintenance therapy. Signup and view all the answers

What is ipatropium typically used for?

Rescue therapy in COPD and asthma exacerbations Signup and view all the answers

What is true about tiotropium?

It is a long-acting medication used for COPD maintenance therapy Signup and view all the answers

What are the effects of increases in cAMP on vasculature?

Vasodilation and decreased blood pressure Signup and view all the answers

What is the regulatory effect of cAMP and Ca(2+) on vascular smooth muscle tone?

Rising levels of Ca(2+) lead to vasoconstriction, whereas an increase of cAMP induces vasodilatation Signup and view all the answers

How does cyclic GMP activate protein kinase G in relation to bronchodilator pathways?

By linking to the cAMP pathway Signup and view all the answers

What is a risk of prolonged use of beta2 agonists?

Tachyphylaxis due to downregulation and desensitization Signup and view all the answers

Autonomic NS and Non-adrenergic non-cholinergic (NANC) system influence bronchomotor tone

True Signup and view all the answers

What drugs are commonly used for emergency or acute exacerbations of COPD and asthma?

All of the above Signup and view all the answers

What is the pulmonary first pass effect?

The metabolism of a drug within the lungs before reaching systemic circulation Signup and view all the answers

What is the primary site of uptake for fentanyl and lidocaine?

Pulmonary uptake (90% fentanyl and 50% lidocaine) Signup and view all the answers

What is the role of ACE in maintaining blood pressure?

ACE increases blood pressure by converting angiotensin I to angiotensin II which stimulates vasoconstriction Signup and view all the answers

Where is most angiotensin-converting enzyme concentrated in the human body?

Lungs Signup and view all the answers

What drugs are contraindicated for use in pulmonary hypertension?

Nitrous oxide and catecholamines Signup and view all the answers

What drug types are pulmonary vasodilators?

All of the above Signup and view all the answers

What drives movement of air during ventilation?

Pressure gradient Signup and view all the answers

What difference drives gas exchange at the alveolar level during respiration?

Concentration gradient Signup and view all the answers

What does Henry's Law state about the partial pressure of an anesthetic?

The partial pressure of an anesthetic in blood is proportional to the partial pressure of the anesthetic in alveoli Signup and view all the answers

What is the source of energy for diffusion in the respiratory system?

Molecular kinetic energy Signup and view all the answers

What factors determine the diffusion coefficient of a substance according to Graham's Law?

Solubility and molecular weight Signup and view all the answers

What does the diffusion coefficient represent?

The relative rates at which different gases at the same partial pressure levels will diffuse Signup and view all the answers

What factors influence the movement of gas once it's at the alveolus?

All of the above Signup and view all the answers

According to the partial pressure gradient, which direction will oxygen diffuse in the alveoli?

From higher partial pressure in the the gas phase in alveoli to the lower pressure areas in the blood Signup and view all the answers

Why does CO2 diffuse from the blood into the alveoli?

The partial pressure of CO2 is higher in the blood than in the alveoli Signup and view all the answers

What is the relationship between alveolar PCO2 and alveolar ventilation?

They vary inversely Signup and view all the answers

Oxygen concentration in the alveoli and partial pressure is a function of which of the following? (Select 2)

Rate of absorption into the blood Signup and view all the answers

What is unique about the weight of oxygen as compared to the weight of CO2?

CO2 is heavier than oxygen so it moves slower Signup and view all the answers

Which of the following statements about gases of respiratory importance is FALSE?

Gases of respiratory importance are not highly soluble in lipids Signup and view all the answers

What is the limiting factor in the diffusion of gases in tissues?

The rate in which the gas diffuses through water Signup and view all the answers

Air (i.e. N+O+CO2) is almost totally humidified before reaching the alveoli

True Signup and view all the answers

How does water vapor affect the partial pressures of gases in air?

It dilutes all gases, driving their partial pressures down Signup and view all the answers

If oxygen has a diffusion coefficient of 1, what would be the diffusion coefficient of CO2?

20 Signup and view all the answers

What is unique about the concentrations of oxygen and CO2 of alveolar air as compared to expired air?

Alveolar air has a lower oxygen concentration and a higher CO2 concentration compared to expired air. Signup and view all the answers

Why does expired air have more oxygen than alveolar air?

Expired is partially comprised of air that has never made it deep enough in the lungs for the oxygen to be absorbed into the blood Signup and view all the answers

What is a characteristic of alveolar air?

It is only partially replaced by atmospheric air with each breath Signup and view all the answers

What is the importance of slow replacement of alveolar air?

It prevents sudden changes to gas concentrations in blood Signup and view all the answers

Multiple breaths are required to exchange alveolar air due to the difference between FRC (2300mL) and alveolar volume (350mL)

True Signup and view all the answers

Expired air = dead space air + alveolar air

True Signup and view all the answers

Why does expired air have the gas concentrations that it does?

Due to the combination of dead space air and alveolar air, putting concentrations in the areas between the two Signup and view all the answers

Dead space air = anatomic dead space air + alveolar dead space air

True Signup and view all the answers

What is dead space air in the respiratory system?

Air that does not participate in gas exchange and does not come into contact with the alveoli Signup and view all the answers

What is alveolar dead space air?

Air in alveoli that are ventilated but not perfused Signup and view all the answers

When alveoli are ventilated but not perfused, the V/Q = infinity

True Signup and view all the answers

When alveoli are perfused but not ventilated, the V/Q = 0

True Signup and view all the answers

When alveoli are ventilated but not perfused, what does the alveolar air equilibrate to?

inspired air Signup and view all the answers

When alveoli are perfused but not ventilated, what does the alveolar air equilibrate to?

Mixed venous blood Signup and view all the answers

What are the partial pressures of O2 and CO2 when ventilation and perfusion are matched?

O2: 104 mmHg, CO2: 40 mmHg Signup and view all the answers

What are the partial pressures of O2 and CO2 when V/Q=0?

P O2 = 40 mmHg, P CO2 = 45 mmHg Signup and view all the answers

What are the partial pressures of O2 and CO2 when V/Q = infinity?

PO2 = 149mmHg, PCO2 = 0 mmHg Signup and view all the answers

Dead space air has no CO2.

True Signup and view all the answers

What is a shunt in the context of respiratory physiology?

Blood passing through the pulmonary vasculature and not oxygenated, resulting in underventilated alveoli Signup and view all the answers

What is the V/Q ratio in a shunt?

V/Q below normal because perfusion exceeds ventilation Signup and view all the answers

In dead space ventilation, what is the outcome of the work of ventilation?

It never makes it to the blood, therefore "wasting" alveolar ventilation Signup and view all the answers

In which type of ventilation does ventilation exceed perfusion (VQ is greater than normal)?

Dead space ventilation Signup and view all the answers

What comprises physiologic dead space?

Anatomical dead space and alveolar dead space Signup and view all the answers

What respiratory consequence can result from smoking?

Increased shunt and dead space ventilation secondary to obstruction Signup and view all the answers

What is unique about the MAC when combining two inhaled agents?

The MAC is additive Signup and view all the answers

What determines the concentrations and partial pressures of O2 and CO2 in the alveoli?

Rate of absorption and excretion of O2 and CO2, and amount of alveolar ventilation Signup and view all the answers

What are the factors that determine the rate of diffusion through the respiratory membrane?

Thickness of membrane, surface areas of membrane, diffusion coefficient, and partial pressure difference Signup and view all the answers

When was desflurane first used?

1992 Signup and view all the answers

Study Notes

Diffusion Capacity

Diffusion capacity is the volume of gas that will diffuse through the membrane per minute per 1 mmHg partial pressure difference
Increased during exercise due to recruitment of capillaries, improved V/Q, and increased alveolar ventilation
Can be estimated using diffusion capacity for CO (DLCO)
DLCO in healthy men = 17 mL/min/mmHg

Factors Affecting Diffusion Rate

Thickness of membrane: thicker membranes (edema, fibrosis) make it harder for gases to diffuse
Surface area of membrane: decreased surface area (emphysema) impedes gas exchange
Diffusion coefficient and partial pressure difference also affect diffusion rate

Respiratory Pharmacology

Inhaled Beta-2 Agonists

Bind to beta-2 receptor in pulmonary smooth muscle, leading to smooth muscle relaxation and bronchodilation
Short-acting (albuterol, levabuterol, metaproterenol, pirbuterol) for rapid relief of wheezing, bronchospasm, and airway obstruction
Long-acting (salmeterol, formoterol, aformoterol) for maintenance therapy
Side effects: tremors, tachycardia, temporary decrease in PaO2, tolerance due to downregulation and desensitization

Anticholinergic Agents

Not used for asthma maintenance
Act on M1 and M3 receptors in airway to reduce tone
Inhibit binding of Ach to muscarinic receptors, reducing smooth muscle tone and mucus production
M1 and M3 receptors produce bronchoconstriction and mucus production when bound by Ach

COPD and Asthma

Shared feature: inflammation
Asthma: mast cells, COPD: neutrophils
COPD has a more pronounced inflammatory response

Pulmonary Artery Pressure

NMDA receptor antagonists (e.g. ketamine): stimulate release and inhibit uptake of catecholamines, causing cardiostimulatory and bronchodilatory effects
Volatile inhalation agents and N2O: little to no effect on pulmonary vascular resistance, but decrease bronchomotor tone
Neuromuscular blocking agents: unlikely to cause histamine release, but can increase HR
Vasopressors and inotropes: sympathetic activation increases PVR
Nitric oxide (NO): preferentially delivered to ventilated lung units, decreasing intrapulmonary shunt
Phosphodiesterase inhibitors: decrease metabolism and breakdown of cAMP and cGMP, causing vasodilation and enhancing NO effects

Volatile Inhalation Agents and N2O

Relative potency (MAC): lower the MAC, the higher the potency
Immobility is how potency is measured
Blood gas coefficient: lower the BGC, the faster the onset and emergence
Determinants of alveolar partial pressures: cardiac output, co-existing disease, and co-administration of other pharmacologic agents
Factors influencing MAC: age, pregnancy, red hair, and opioids
MAC values for inhaled anesthetics are additive

Complications of Inhalation Agent Administration

Cardiac dysrhythmia: halothane has a risk of cardiac depression and VT
Hepatic disease: halothane has a risk of postoperative hepatic dysfunction
Kidney injury: enflurane and sevoflurane can cause nephrotoxicity
Hypotension: decreases in MAP due to decreases in SVR with isoflurane, desflurane, and sevoflurane

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