Respiratory Medications

Respiratory Medications
RT 1

Pharmacology The study of substances that interact with living systems through chemical processes Especially by binding to regulatory molecules and activating or inhibiting normal body processes Basically manipulating normal human chemical mechanisms for a desired effect

Drug Any substance that interacts with a molecule or protein that plays a regulatory role in living systems. Includes oxygen and other therapeutic gases along with our inhaled aerosolized medications.

How we deliver medications
Metered Dose inhalers Portable Used with holding chamber Dry Powder inhaler No propellent Aerosol via nebulizer Given with mask or mouth piece

What types of drugs we give
Bronchodilators: Relax bronchial smooth muscle, mimic Epinephrine (adrenaline) Fast acting: Albuterol, Xopenex Long lasting: Serevent, Foradil

Bronchodilators: Relax bronchial smooth muscle Other types of bronchodilators: Atrovent: blocks acetylcholine from entering smooth muscle cells Spiriva: Long lasting anti-cholinergic

Steroids: Prevent inflammatory cell release, changes cell DNA Advair (Flovent) Symbicort (Pulmicort) Qvar Asmanex

Aerobid is now Aerospan
Flovent: DPI/MDI. 3 doses. Asmanex: twisthaler, grey or pink depending on dose Qvar: 40/80 ug dose

Pulmicort: turbahaler or respules
Advair: MDI or DPI, 3 doses, combo drug Symbicort: 2 doses, combo drug Pulmicort: turbahaler or respules

Mucoactives: Helps to molecularly break up mucus Mucomyst (pungent odor) Pulmozyme (used with Cystic Fibrosis)

Mucus Production Normal person produces 100 mL of mucus per 24 hour period Most is reabsorbed back in the bronchial mucosa 10 mL reaches the glottis Most of this is swallowed Mucus production increases with lung disease

Anti-asthma: Prevents inflammatory cell release by blocking histamine from mast cells Intal (cromolyn sodium) MDI Singulair (pill, RT’s do not typically administer)

Definitions Endogenous: Substances made inside body
Exogenous: substances made outside the body Hormones: are endogenous drugs Toxin: poisons of biologic origin

Definitions Receptors: Specific molecule, usually a protein, that interacts with a specific chemical that then causes a change in the specific molecule, causing a change in regulatory function Lock that a key fits into; ex: Lock receptor and epinephrine the key to opening the lock

Definitions Agonist: any drug that binds to a receptor and activates the receptor Drug that fits into a receptor, will then activate and a chemical reaction occurs within the cell. When agonist leaves the binding site it deactivates the receptor.

Definitions Antagonist: any drug that binds to a receptor and prevents the activation of the receptor Can be called competitive antagonist; competes with the agonist for binding site.

Definitions Absorbed: drug must be able to absorb into the body to work Delivery: Must be able to get to intended site to work; gut, intestines, liver, blood…then to site of action Elimination: drugs must be eliminated at a reasonable rate. Affected by kidney or liver problems

Terminology Names of a drug Chemical name
Generic name (assigned by US Pharmacopoeia) Proprietary name

Drug Name The chemical name is assigned according to rules of nomenclature of chemical compounds The brand name is always capitalized and is selected by the manufacturer. The generic name refers to a common established name irrespective of its manufacturer.

Example The chemical name for albuterol sulfate (albuterol sulfate inhalation solution) is α1 [(tert-butylamino) methyl]-4-hydroxy-m-xylene-α, α'-diol sulfate (2:1) (salt), and its established chemical structure is as follows:

Terminology General terms
Action (mode of action, intended drug effect) Side effect (not intended effect, nausea/tachycardia…) Half life time required for concentration of a drug in the body to decrease by 50%. Half-life also represents the time necessary to reach steady state or to decline from steady state after a change

Tolerance decrease in susceptibility to the effects of a drug due to its continued administration. Tachyphylaxis rapid decrease in response to a drug after administration of a few doses. Initial drug response cannot be restored by an increase in dose Potentiation The action of a substance, at a dose that does not itself have an adverse action, in enhancing the effect of another substance

Synergism the interaction of elements that when combined produce a total effect that is greater than the sum of the individual elements, contributions, etc. Agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist. Antagonist: blocks reaction of a agonist

Phases of Action Pharmaceutical phase
Refers to method by which a drug is administered and the form in which it is administered

Routes of Administration
Intravenous (IV) (RT will never give IV drugs, most common route of systemic meds) Inhaled (Aerosol) RT route of administration Intramuscular (IM) (includes diabetes meds, vaccines, boosters…) Subcutaneous (SubQ) (Xylocain administration, numbing agent)

Routes of Administration
Sublingual Rectal Oral (most common route outside of hospital) Topical

Pharmacokinetic Phase
Describes the time course and disposition of a drug in the body based upon absorption, distribution, metabolism, and elimination and the effects and routes of excretion of the metabolites of the drug

Pharmacokinetic Phase
Ionized drugs have minimal side effects generally; non-ionized drugs have greater side effects

Pharmacodynamic Phase
Describes the mechanism of action of a drug (how it actually works in the patients body) Effects are caused by combining a drug with a matching receptor

Receptors Adrenergics:
Beta 1 (heart, when stimulated cause contraction, increased HR)---Isoperternal, Epinephrine Beta 2 (lungs, when stimulated cause dilation)----Albuterol/Xopenex Alpha 1 (blood vessels/brain/kidney, when stimulated cause vessel constriction)—Racemic Epinephrine Alpha 2 (Sphincters, GI tract, inhibits insulin release; stimulation causes constriction) Stimulated by neurotransmitter Epinephrine/ norepinephrine *Stimulation of a receptor= agonist *Blocking of a receptor = antagonist

Receptors Cholinergic:
Nicotinic (found in the CNS and the peripheral nervous system. The neuromuscular receptors are found in the neuromuscular junctions of somatic muscles; stimulation of these receptors causes muscular contraction) Blocked with Nicotinic acetylcholine receptors can be blocked by curare; used for anesthesia and mechainical ventilation Muscarinic (found primarily in lung; G-protein-coupled receptors that activate other ionic channels via a second messenger cascade. sub types; M1-M5) responds to the binding neurotransmitter acetylcholine

Beta Receptors Tissue Receptor Subtype Heart beta1 Adipose tissue
beta1beta3? Vascular Smooth Muscle beta2 Airway Smooth Muscle Kindney-Renin release from JG cells

How Bronchodilators Work
Receptor sites Alpha sites – cause vasoconstriction and vasopressor effects, increasing blood pressure Beta1 sites – cause increase in heart rate and myocardial contractility

Receptor sites Beta2 sites – cause relaxation of bronchial smooth muscle, stimulate mucociliary activity, and have mild inhibitory effects on inflammatory mediator release

Sympathomimetics Neurotransmitters include:
Epinephrine Norepinephrine Catecholmines Dopamine Fight or Flight response allows for: Bursts of energy Increased heart rate Increased blood to brain Increased Oxygen through BRONCHODILATION

Sympathomimetics Sympathomimetic drugs given by aerosol to the lungs MIMIC fight or flight neurotransmitters and cause DIRECT bronchodilation Examples of Sympathomimic bronchodilators: Fast Acting: Albuterol, Xopenex, Racemic Epinephrine Long Acting: Serevent, Brovona

Sympathomimetics Sympathomimetic drugs can enter the blood stream and also stimulate Beta 1 receptors increasing systemic side effects such as increased HR These drugs are given for patients with reversible airflow obstruction such as Asthma and COPD

Parasympatholytic Substances that reduce the activity of the parasympathetic nervous system The PNS is part of the ANS and is often referred as the rest and digest phase. The primary neurotransmitter in this phase is: Acetycholine (Ach)

Parasympatholytic The Ach response causes: Decrease in HR
Decrease in BP Skeletal muscle contraction Bronchial smooth muscle constriction Ach causes: M3 muscarinic receptor reaction in blood vessels, as well as the lungs causing bronchoconstriction. Drugs that are parasympatholytic BLOCK M3 response and thus indirectly allow for bronchodilation

Parasympatholytic Examples of Parasympatholytics bronchodilators:
Fast Acting: Atrovent/Atropine Long Acting: Spiriva Parasymptholytic bronchodilators are referred to as anticholinergics, they are Ach antagonists Ach enters bronchial smooth muscle cells through muscanaric receptors Atrovent works by blocking all M receptors resulting in the formation of Cyclic guanosine monophosphate

Nitric Oxide Indicated for the treatment of pulmonary hypertension in neonates Causes relaxation of vascular smooth muscle, producing pulmonary vasodilation

Nitric Oxide Contraindicated in neonates with right to left shunts

Nitric Oxide Adverse effects Hypotension Formation of Methemoglobinia
Withdrawal

Exogenous Surfactant Administration
Indicated for surfactant deficiency, such as in infant respiratory distress syndrome and following lung lavage

Medication frequency BID= twice a day Ad lib= as desired TID= three times a day Q4PRN= every 4 hours as needed QID= four times a day Qh= every hour QD= once a day NS= normal saline QS= every shift m.l.= militer Q4=every 4 hours Mg= miligrams Q6= every 6 hours NPO= nothing per mouth HS= At bed time PRN= AS NEEDED EX: Albuterol 2.5 mg and 2.5 ml NS Q4 and Q2 PRN for wheezing. Oximeter check QS

Basic Concepts and Delivery Systems
Aerosol Therapy Basic Concepts and Delivery Systems

Aerosol Therapy It is important to remember that an aerosol is not the same as humidity. Humidity is water in a gas in molecular form, while an aerosol is liquid or solid particles suspended in a gas. Examples of aerosol particles can be seen everywhere: as pollen, spores, dust, smoke, smog, fog, mists, and viruses.

Aerosol Therapy Aerosol therapy is designed to increase the water content delivered while delivering drugs to the pulmonary tree Deposition location is of vital concern Some factors that affect aerosol deposition are aerosol particle size and particle number along with how the medication is instructed to be taken

Aerosol Output The actual weight or mass of aerosol that is produced by nebulization. Usually measured as mg/L/min also called aerosol density Aerosol output does not predict aerosol delivery to desired site of action.

Aerosol Devices Small Volume Nebulizer (AKA: Hand Held Nebulizer, Med-Neb, Free-flow…) Large Volume Nebulizer (used with bland aerosol) MDI and DPI

Prior to Administration of any Aerosolized Medication
Verify MD order Requires a frequency, dosage, modality Ex: Medication: Albuterol Dosage: 2.5mg in 3ml normal saline Frequency: QID and Q2 PRN for wheezing Modality: SVN Sign off order upon administation of drug Specify date and time of administration

Delivering a SVN Patient instruction is important for proper delivery.
Slow deep breathing replicates laminar flow, allows for better deposition Periodic breath holds (every 3rd or 4th breath is good) Using a mouth piece is best Use 8LPM on the flow meter for most medications

Particle Size The particle size of an aerosol depends on the device used to generate it and the substance being aerosolized. Particles of this nature, between and 50 microns, are considered an aerosol. The smaller the particle, the greater the chance it will be deposited in the tracheobronchial tree. Particles between 2 and 5 microns are optimal in size for depositing in the bronchi, trachea and pharynx. Particles >10 microns useful to treat nasopharyngeal or oropharygeal regions Particles 5-10 microns deposition to the more central airways Particles 2-5 lower respiratory tract Particles microns increased delivery to the lung parenchyma, terminal airways

Particle Size Heterodisperse:
aerosol with a wide range of particle sizes (medical aerosols) Monodisperse: aerosol consisting of particles similar in size (laboratory, industry)

Deposition of Particles is also affected by:
Ventilatory pattern - RCPs easily control this by simple observation and instruction. For maximum deposition, the patient must be instructed to: Take a slow, deep breath. Inhale through an open mouth (not through the nose). At the end of inspiration, use an inspiratory pause, if possible, to provide maximum deposition. Follow with a slow, complete exhalation through the mouth.

Aerosol vs. Systemic In many cases, aerosols are superior in terms of efficacy and safety to the same systemically administered drugs used to treat pulmonary disorders. Aerosols deliver a high concentration of the drugs with a minimum of systemic side effects. As a result, aerosol drug delivery has a high therapeutic index; especially since they can be delivered using small, large volume, and metered dose nebulizers.

Methods of Aerosol Delivery
Aerosols are produced in respiratory therapy by utilizing devices known as nebulizers. There are a variety of nebulizers in use today, but the most common is one in which the Bernoulli principle is used through a Venturi apparatus

Aerosol Delivery Devices
Aerosol Mask – A Face Tent – B Tracheostomy Mask – C “T” Tube – D

Metered Dose Inhalers Metered dose inhalers (MDIs) consist of a pressurized cartridge and a mouthpiece assembly. The cartridge, which contains from doses of medication, delivers a pre- measured amount of the drug through the mouthpiece when the MDI is inverted and depressed.

Metered Dose Inhalers The particle size of the drug released is controlled by two factors: the vapor pressure of the propellant blend the diameter of the actuator's opening. Particle size is reduced as vapor pressure increases, and as diameter size of the nozzle opening decreases. The majority of the active drug delivered by an MDI is contained in the larger particles, many of which are deposited in the pharynx and swallowed.

Metered Dose Inhalers Successful delivery of medications with an MDI depends on the patient's ability to coordinate the actuation of the MDI at the beginning of inspiration. Proper instruction and observation of the patient are crucial to the success of MDI of therapy. Patients need to be alert, cooperative, and capable of taking a coordinated, deep breath. A holding chamber should ALWAYS be used

Metered Dose Inhalers Be sure to shake the MDI canister well before using. Hold the MDI a few centimeters from the open mouth. Holding the mouthpiece pointed downwards, actuate the MDI at the beginning of a slow, deep inspiration, with a 4-10 second breath hold. Late actuation, or at the end of the inspiration, or stopping inhaling when the cold blast of propellant hits the back of the throat will cause the medication to have only a negligible effect. Exhale through pursed-lips, breathing at a normal rate for a few moments before repeating the previous steps. Patients should also be instructed to rinse their mouths after taking the medication.

The advantages of MDI aerosol devices include:
They are compact and portable. Drug delivery is efficient. Treatment time is short

Disadvantages They require complex hand-breathing coordination.
Drug concentrations are pre-set. Canister depletion is difficult to ascertain accurate A small percentage of patients may experience adverse reactions to the propellants. There is high oropharyngeal impaction and loss if a spacer or reservoir device is not used. Aspiration of foreign objects from the mouthpiece can occur. Pollutant CFCs, which are still being used in MDIs, are released into the environment until they can be replaced by non-CFC propellant material

Reservoir Devices for MDI’s (Spacers)
These can be used to modify the aerosol discharged from an MDI. The purposes of these spacers or extensions include: Allow additional time and space for more vaporization of the propellants and evaporation of initially large particles to smaller sizes. Slow the high velocity of particles before they reach the oropharynx. As holding chambers for the aerosol cloud released, reservoir devices separate the actuation of the canister from the inhalation, simplifying the coordination required for successful use.

Dry powder inhalers (DPIs)
Consist of a unit dose formulation of a drug in a powder form, dispensed in a small MDI-sized apparatus for administration during inspiration. Because these devices are breath- actuated, using turbulent air flow from the inspiratory effort to power the creation of an aerosol of microfine particles of drug, they don't require the hand-breath coordination needed with MDIs.

Dry powder inhalers (DPIs)
Cromolyn sodium and albuterol are the two primary drugs available in powder form. Cromolyn sodium is dispensed in a device called the Spinhaler, which pokes holes in capsules containing the powdered drug. The albuterol formulation is dispensed in a device called the Rotohaler, which cuts the capsule in half, dropping the powdered drug into a chamber for inhalation. In both cases, a single-dose micronized powder preparation of the drug in a gelatin capsule is inserted into the device prior to inhalation.

The advantages of using DPI devices for drug administration include:
They are small and portable. Brief preparation and administration time. Breath-actuation eliminates dependence on patient's hand-breath coordination, inspiratory hold, or head-tilt needed with MDI. CFC propellants are not used. There is not the cold effect from the freon used in MDIs, eliminating the likelihood of bronchoconstriction or inhibited inspiration. Calculation of remaining doses is easy.

The disadvantages encountered when relying on DPIs for drug administration include:
Limited number of drugs available for DPI delivery at this time. Dose inhaled is not as obvious as it is with MDIs, causing patients to distrust that they've received a treatment. Potential adverse reaction to lactose or glucose carrier substance. Inspiratory flow rates of 60Lpm or higher are needed with the currently available cromolyn and albuterol formulations. Capsules must be loaded into the devices prior to use.

Clips on how to perform Twisthaler (Asmanex) Aerolizer (Foradil)
Autohaler (Ventolin) Handihaler (Spiriva) Diskus (Advair, Serevent) MDI with Aerochamber (Albuterol, Xopenex…) MDI with Holding chamber mask MDI Open mouth Technique

Small volume nebulizers (SVNs)
Gas powered (pneumatic) and are a common method of aerosol delivery to inpatients. There are a variety of different SVNs available. Each has specific characteristics, especially in regard to output.

Nebs May be given inline with the ventilator (with adapter on inspiratory side), Bipap, T-piece Also combined with EZPAP, Flutter devices, Pep devices Given as blow by, by mask, mouth piece

Advantages of SVN therapy:
Requires very little patient coordination or breath holding, making it ideal for very young patients. It is also indicated for patients in acute distress, or in the presence of reduced inspiratory flows and volumes. Use of SVNs allows modification of drug concentration, and facilitates the aeorsolization of almost any liquid drug. Dose delivery occurs over sixty to ninety breaths, rather than in one or two inhalations. Therefore, a single ineffective breath won't ruin the efficacy of the treatment.

Disadvantages of SVNs include:
The equipment required for use is expensive and cumbersome. Treatment times are lengthy compared to other aerosol devices and routes of administration. Contamination is possible with inadequate cleaning. A wet, cold spray occurs with mask delivery. There is a need for an external power source (electricity or compressed gas).

Nebulizers Hand Held Nebulizers/ also know as small volume nebulizers may be given via aerosol mask, blow by, inline on the vent/bipap or by mouth piece, given on air or oxygen Small volume nebulizers contain less than 200 ml of fluid Set flow 6-8 L, a typical treatment lasts minutes, when the neb starts to sputter, shake contents

Small-particle aerosol generator (SPAG)
This is a highly specialized jet-type aerosol generator designed to for administering ribavirin (Virazole), the antiviral recommended for treating high risk infants and children with respiratory syncytial virus infections.

Advantages of Aerosol Therapy as a Whole:
Systemic side effects are fewer and less severe than with oral or parenteral therapy Inhaled drug therapy is painless and relatively convenient. Aerosol doses are smaller than those for systemic treatments. Onset of drug action is rapid. Drug delivery is directly targeted to the respiratory system.

Disadvantages as a Whole:
Special equipment is often needed for its administration. Patients generally must be capable of taking deep, coordinated breaths. There are a number of variables affecting the dose of aerosol drug delivered to the airways. Difficulties in dose estimation and dose reproducibility. Difficulty in coordinating hand action and breathing with metered dose inhalers. Lack of physician, nurse, and therapist knowledge of device use and administration protocols. Lack of technical information on aerosol producing devices. Systemic absorption also occurs through oropharyngeal deposition. The potential for tracheobronchial irritation, bronchospasm, contamination, and infection of the airway.

The common hazards of aerosol therapy are:
Airway obstruction - Dehydrated secretions in the patient's airways may absorb water delivered via aerosol and swell up large enough to obstruct airways. To avoid this, watch the patient very closely and let him progress with therapy at a reasonable rate. You may want to have suction apparatus on hand. Bronchospasms - It is common for aerosol particles to cause this condition (especially among asthmatics) and it is more prevalent when administering a cold aerosol as compared to a heated one. If a very large amount of coughing occurs, stop therapy and give the patient a rest. If this persists in farther therapy, stop treatment and notify the physician.

The common hazards of aerosol therapy are:
Fluid overload - This can occur when administering continuous aerosol therapy. It can happen quite frequently when treating infants or patients in congestive heart failure, renal failure or patients who are very old and immobile. In the infant, because of the smaller body size and possible underdeveloped fluid control mechanism, a quantity of water that an adult can easily handle will cause fluid overload. In a patient with congestive heart failure, any addition of fluid to the vascular system will put an increased strain on the heart. In a patient with renal failure who is probably already in fluid overload, it is easily seen that you will not want to increase the fluid volume. In older patients, the fluid control mechanisms may be impaired due to age.

Physician orders for aerosol therapy should contain identification of:
Type of aerosol Source gas (FI02) Fluid composition (NaCl, water, etc.) Delivery modality Duration of therapy Frequency of therapy Temperature of the aerosol

Charting should include:
time of administration duration of therapy type or composition of the aerosol (NaCl) pulse respiratory rate and pattern breath sounds characteristics of sputum if sputum was or was not produced the ease of breathing benefits observed and any other relevant observations.

The reasons for administering aerosol therapies include:
For bronchial hygiene Hydrate dried secretions Promote cough Restore mucous blanket Humidify inspired gas Deliver prescribed medications Induce sputum lab culture

Week 3 Central and Peripheral Nervous Systems
Michael Haines, MPH, RRT-NPS, AE-C

The Nervous System Two major control systems Nervous system (hormones used to transmit signals) Endocrine system (Chapter 11) (secretion of hormones) Both systems can be manipulated by drug therapy which either mimics or blocks the usual action of the control system (That’s all pharmacology is! We either mimic or block a natural hormone response)

The Nervous System Central nervous system Brain Spinal cord
Peripheral nervous system Sensory neurons Somatic neurons Autonomic neurons * Do not control Parasympathetic branch (Acetylcholine receptors/ rest and digest reactions) Sympathetic branch (Epinephrine receptors/fight or flight reactions)

Central and Peripheral Nervous System
afferent :heat, light, pressure, pain somatic :voluntary muscle control Autonomic nervous system: involuntary control Figure 5-1 Functional diagram of central and peripheral nervous systems, indicating the somatic branches (sensory, motor) and the autonomic branches (sympathetic, parasympathetic), with their neurotransmitters. Ach, Acetylcholine; NE, norepinephrine.

Autonomic Nervous System
synapse thoracolumbar craniosacral neurons neurons

Parasympathetic Stimulation Good specificity because postganglionic fibers arise near the effector site. Sympathetic Stimulation Because fibers innervate the adrenal medulla when sympathetic activation occurs there is a release of epinephrine into the bloodstream causing a widespread reaction in the body.

Parasympathetic and Sympathetic Regulation
Parasympathetic Nervous System Essential to life Finely regulated (good specificity) Controls digestion, bladder, and rectal function Sympathetic Nervous System General alarm system “Fight or flight” response Not essential to life Increases HR and BP and causes blood flow to shift from the periphery to the core

Neutotransmitters Nerve impulses are transmitted by electrical and chemical means (neurotransmitters) Acetylcholine Neuromuscular junction Ganglia Parasympathetic end sites Sweat glands Adrenal medulla Norepinephrine Sympathetic end sites Everywhere, except

Neurotransmission Neuron: basic cell of the nervous system, provide instant method of cellular communication Don’t confuse nerve with neuron, nerve is a collection of neuron axon fibers The signals in nerves can run both ways Efferent (out) Afferent (in)

Neurotransmission Hormones such as epinephrine and AcH are stored in packets in the neuron; action potential causes these stored transmitters to release into organs, muscles… AcH: made by mitochondria as part of energy transfer (Kreb cycle) along with lecithin that contains choline. AcH is in the neuromuscular junction. Voluntary muscle movement, stimulated at nicotinic receptors to cause muscle contraction

Efferent and Afferent Nerve Fibers
Efferent: signals that are transmitted from the brain and spinal cord Autonomic Nervous System Afferent: signals that are transmitted to the brain and spinal cord Chapter 7: drugs used to block parasympathetic impulses

Example of Neurotransmission Error
Myasthenia Gravis antibodies block the nicotinic receptors in the neuromuscular junction from getting AcH. AcH is also used by the autonomic nervous system in the control of Parasympathetic smooth muscle movement (lungs, heart). The receptor here is called muscarinic

Neurotransmission AcH also found in the CNS, and affect brain and spinal cord transmissions. Catecholamines (Dopamine, norepinephrine, epinephrine): Made from the amino acid tyrosine. Located in the autonomic nervous system signals sympathetic smooth muscle movement and organ is epinephrine and norepinephrine. The receptors are alpha and beta

Neurotransmission AcH esterase breaks down AcH in the synapse. (cholinesterase) So, if we block AcH esterase, we end up with more AcH in the synapse MG patients are on cholinesterase inhibitors

Terminology Sympathomimetic = Adrenergic
Sympatholytic = Antiadrenergic Parasympathomimetic = Cholinergic Parasympatholytic = Anticholinergic

Parasympathetic Branch
Nerve Impulse Catalyzed by Cholinergic Neurotransmitter Function Ach is synthesized from Ach is concentrate in the presynaptic neuron Calcium triggers the secretion of Ach Ach attaches to receptors on the postsynaptic membrane and initiates an effect in the tissue or organ site Inactivates Ach through hydrolysis

Parasympathetic effects on the cardiopulmonary system: Heart: slows rate (vagus) Bronchial smooth muscle: constriction Exocrine glands: increased secretion Drugs can be used to block or mimic action Parasympatholytics Parasympathomimetics

Muscarinic Effects Musacrine stimulates Ach receptors at the parasympathetic terminal sites: Exocrine glands: lacrimal, salivary, bronchial mucous glands Cardiac muscle Smooth muscle: gastrointestinal tract Increase in airway secretions after the administration of Ach-like drugs

Subtypes of Muscarinic Receptors

Nicotinic Effects Nicotine stimulates Ach receptors at: Autonomic ganglia Skeletal muscle sites Effects: Increase in blood pressure Muscle tremor

Cholinergic Agents Cholinergic drugs mimic the action caused by Ach at the receptor sites in the parasympathetic system and neuromuscular junction A cholinergic drug can also activate muscarinic and nicotinic rceptors Direct-Acting Cholinergic Agents Indirect-Acting Cholinergic Agents

Cholinergic Agents Direct acting Indirect acting Mimic acetylcholine
Methacholine – diagnostic, asthma Indirect acting Inhibit cholinesterase enzyme Neostigmine – reversal of nondepolarizing muscle relaxants Tensilon – diagnostic, MG

Anticholinergic Agents
Block acetylcholine receptors Parasympatholytic (antimuscarinic) effects Bronchodilation Preoperative drying of secretions Antidiarrheal agent Prevention of bed-wetting in children (increase in urinary retention) Treatment of peptic ulcer Treatment of organophosphate poisoning Treatment of mushroom (Amanita muscaria) ingestion Treatment of bradycardia

Sympathetic Branch Adrenergic neurotransmitter function Nerve impulse
Is converted t0… Adrenergic neurotransmitter function Is converted t0… Is converted t0… NE is stored in the presynaptic neuron Calcium triggers the secretion of NE NEattaches to receptors on the postsynaptic membrane and initiates an effect in the tissue or organ site 3 ways of inactivating NE

Sympathetic Branch Enzyme Inactivation
Catecholamines: chemicals structurally related to epinephrine Two enzymes inactivate catecholamines: catechol O-methyltransferase (COMT) Monoamine oxidase (MAO) Chapter 6

Sympathetic Branch Sympathetic effects on the cardiopulmonary system:
Increased heart rate and contractile force Increased BP Bronchodilation Drugs can be used to block or mimic action Sympatholytics (antiadrenergic) Sympathomimetics (antiadrenergic)

Sympathetic Branch Sympathetic (Adrenergic) Receptor Types

Sympathetic Branch α and β Receptors α receptors: Vasoconstriction
β1 receptors: Increase the rate and force of cardiac contraction β2 receptors: Relax bronchial smooth muscle Chapter 6

Dopaminergic Receptors
Because dopamine is chemically similar to epinephrine and stimulates α and β receptors, dopaminergic receptors are classified as a type of adrenergic receptor.

Second messenger activation
drugs cause a reaction once it attaches to a receptor site, or blocks a receptor site. Second messenger activation allows complex chemical reactions to occur Drugs that affect smooth muscle use 2nd messengers

When a neurotransmitter attaches to a receptor it then activates a G protein within the cell. This then stimulates a enzyme called adenylyl cyclase to actively convert ATP to cAMP ATP is energy source that makes cAMP; increase cAMP activates many different regulatory proteins

cAMP regulates calcium within the bronchial smooth muscle cells to cause bronchodilation Cyclic AMP is made from ATP and is a second messenger. Phoshodiesterase (PDE) removes cAMP Phosphodiesterase is inhibited by caffeine (Xanthines)

Caffeine can increase cAMP Weak bronchodilator Second messenger drugs such as all of those we use as RT’s have gradual and long lasting effects. As opposed to drugs which work directly through ion channels.

Neurotransmission Epinephrine used by the sympathetic nervous system.
Also in the CNS

Airway Receptors Adrenergic receptors
Also known as sympathetic and sympathomimetic receptors Sympatholytics = block response Stimulated by epinephrine or norepinephrine Antiadrenergic drugs block receptors for norepinephrine or epinephrine (usually to slow the heart rate or decrease blood pressure)

Airway Receptors Cholinergic receptors
Also known as parasympathetic or parasympathomimetic receptors Stimulated by acetylcholine Blocked by ant-cholingergics In airway anti-musacarinic (anti-cholinergic) = bronchodilation Anti-nicotinics= neuromuscular paralysis

ACh Airway smooth-muscle cells are innervated by postganglionic parasympathetic nerves. Acetylcholine (ACh) release from these nerves triggers the contraction of airway smooth muscles. This activity is predominantly mediated by smooth-muscle M3 receptors, but activation of postsynaptic M2 receptors is also likely to contribute to this response/ ACh also leads to the activation of pre-junctional M2 muscarinic Ach receptor (mAChR) autoreceptors, which mediate the inhibition of ACh release M2 receptive for cholinersterase (we block all M receptors, so also the “good” M2)

Adrenergic Receptors The adrenergic receptors which subserve the responses of the sympathetic nervous system have been divided into two discrete subtypes: alpha adrenergic receptors (alpha receptors) and beta adrenergic receptors (beta receptors).

Adrenergic Receptors The mechanism of adrenergic receptors. Adrenaline or noradrenaline are receptor ligands to either α1, α2 or β-adrenergic receptors. Blood vessels: α1 couples to Gq, which results in increased intracellular Ca2+ which results in smooth muscle contraction. α2, on the other hand, couples to Gi, which causes a decrease of cAMP activity, resulting in e.g. smooth muscle contraction. Heart/Lung: β receptors couple to Gs, and increases intracellular cAMP activity, resulting in e.g. heart muscle contraction, smooth muscle relaxation and glycogenolysis.

Beta Receptors Beta Receptors Beta receptors have been further subdivided into beta1 and beta2 receptors. beta3 and beta4 receptors have recently been isolated, cloned and characterized. The beta3 receptor may be involved in regulating the metabolism of fatty acids. This receptor could be the site of antiobesity drugs in the future. The functions of the beta4 receptor remain to be discovered. The classification of beta receptors is based on the interaction of a series of drugs with these receptors.

Beta Receptors Beta Receptor Systems
Most tissues express multiple receptors. However, the receptor mainly utilized by the sympathetic nervous system to affect myocardial function in the normal heart is the beta1 receptor; while in vascular and nonvascular smooth muscle it is the beta2 receptor.

Respiratory Pharmacology Adrenergics

Airway Receptors Adrenergic receptors
Also known as sympathetic and sympathomimetic receptors Sympatholytics = block response Stimulated by epinephrine or norepinephrine Antiadrenergic drugs block receptors for norepinephrine or epinephrine (usually to slow the heart rate or decrease blood pressure)

Also known as parasympathetic or parasympathomimetic receptors Stimulated by acetylcholine Blocked by ant-cholingergics In airway anti-musacarinic (anti-cholinergic) = bronchodilation Anti-nicotinics= neuromuscular paralysis

ACh Airway smooth-muscle cells are innervated by postganglionic parasympathetic nerves. Acetylcholine (ACh) release from these nerves triggers the contraction of airway smooth muscles. This activity is predominantly mediated by smooth-muscle M3 receptors, but activation of postsynaptic M2 receptors is also likely to contribute to this response/ ACh also leads to the activation of pre-junctional M2 muscarinic Ach receptor (mAChR) autoreceptors, which mediate the inhibition of ACh release M2 receptive for cholinersterase (we block all M receptors, so also the “good” M2)

Adrenergic Receptors The adrenergic receptors which subserve the responses of the sympathetic nervous system have been divided into two discrete subtypes: alpha adrenergic receptors (alpha receptors) and beta adrenergic receptors (beta receptors).

Adrenergic Receptors The mechanism of adrenergic receptors. Adrenaline or noradrenaline are receptor ligands to either α1, α2 or β-adrenergic receptors. Blood vessels: α1 couples to Gq, which results in increased intracellular Ca2+ which results in smooth muscle contraction. α2, on the other hand, couples to Gi, which causes a decrease of cAMP activity, resulting in e.g. smooth muscle contraction. Heart/Lung: β receptors couple to Gs, and increases intracellular cAMP activity, resulting in e.g. heart muscle contraction, smooth muscle relaxation and glycogenolysis.

Beta Receptors Beta Receptors Beta receptors have been further subdivided into beta1 and beta2 receptors. beta3 and beta4 receptors have recently been isolated, cloned and characterized. The beta3 receptor may be involved in regulating the metabolism of fatty acids. This receptor could be the site of antiobesity drugs in the future. The functions of the beta4 receptor remain to be discovered. The classification of beta receptors is based on the interaction of a series of drugs with these receptors.

Beta Receptors Beta Receptor Systems
Most tissues express multiple receptors. However, the receptor mainly utilized by the sympathetic nervous system to affect myocardial function in the normal heart is the beta1 receptor; while in vascular and nonvascular smooth muscle it is the beta2 receptor.

Beta Receptors Tissue Receptor Subtype Heart beta1 Adipose tissue
beta1beta3? Vascular Smooth Muscle beta2 Airway Smooth Muscle Kindney-Renin release from JG cells

Beta Blockers Beta Blockers used as anti arrthymia agents for A-fib, A-flutter beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction and hypertension Ex: Labetalol, Esmolol. Metoprolol…

Muscarinic drugs stimulate acetylcholine receptors specifically at parasympathetic nerve-ending sites Anticholinergic drugs block receptors for acetylcholine

Receptor sites Alpha sites – cause vasoconstriction and vasopressor effects, increasing blood pressure Beta1 sites – cause increase in heart rate and myocardial contractility

Receptor sites Beta2 sites – cause relaxation of bronchial smooth muscle, stimulate mucociliary activity, and have mild inhibitory effects on inflammatory mediator release

Autonomic System We give drugs that:
1. increase sympathetic nervous system response (increase BP/HR/bronchodilate) 2. drugs that increase the parasympathetic response (induce bronchoconstriction, slow heart, increase muscle contraction) 3. drugs that block the sympathetic nervous system response (decrease HR/BP) 4. drugs that block the parasympathetic response (prevent bronchoconstriction)

Autonomic System Sympathetic nervous system: fight or flight. Half of ANS system Parasympathetic nervous system: rest and digest, other half of ANS system Sympathetic agonist: simulate fight/flight Parasympathetic agonist: simulate rest/digest Antagonists block response Sympathetic agonist have similar response as parasympathetic antagonist

Sympathomimetic Mimic, imitate, increase sympathetic nervous system response. Sympathetic agonists Albuterol, Xopenex, Racemic Epinephrine, Serevent, Brovona, Foradil Most cardiac stimulators

Sympatholytic Decrease the sympathetic nervous system response. Block or decrease sympathetic nervous system response Sympathetic antagonists Drugs that block beta receptors to decrease heart rate/BP Contraindicated with Asthma/COPD

Parasympathomimetic Mimic, imitate, increase parasymoathetic nervous system response Parasympathetic agonists Methocholine (induces bronchoconstriction) Medications to slow heart/BP

Parasympatholytics Block parasympathetic response
Parasympathetic antagonist Example: Atrovent (block AcH), Atropine (increase HR), Spiriva

You DO NOT control ANS (automatic) ANS controls functions of organs automatically, many drugs that affect the ANS affect many organs causing side effects (such as Albuterol/Xopenex) ANS drugs affect: Heart, blood vessels, pancreas, ureters, bladder, eyes, pupils, lungs, salivary glands

Sympathomimetics Substances that mimic effects of the sympathetic nervous system Part of the autonomic nervous system (not under conscious control) Activated by “fight or flight” response

Sympathomimetics Neurotransmitters include:
Epinephrine Norepinephrine Catecholmines Dopamine Fight or Flight response allows for: Bursts of energy Increased heart rate Increased blood to brain Increased Oxygen through BRONCHODILATION

Sympathomimetics Sympathomimetic drugs given by aerosol to the lungs MIMIC fight or flight neurotransmitters and cause DIRECT bronchodilation Examples of Sympathomimic bronchodilators: Fast Acting: Albuterol, Xopenex, Racemic Epinephrine Long Acting: Serevent, Brovona

Sympathomimetics Sympathomimetic drugs bind to Beta 2 receptor sites on bronchial smooth muscle cells producing an adrenergic agonist response 1. Once attached to a β2 receptor in bronchial smooth muscle the drug then attaches to the intracellular Gs protien which stimulates adenly cyclase to form cAMP from ATP which then decreases Ca2+↓ and Myosin resulting in SM relaxation . 2. Also activate β receptors on mast cell mb. , thus used in prophylaxis of allergic asthma .

Sympathomimetics Sympathomimetic drugs can enter the blood stream and also stimulate Beta 1 receptors increasing systemic side effects such as increased HR These drugs are given for patients with reversible airflow obstruction such as Asthma and COPD

Parasympatholytic Substances that reduce the activity of the parasympathetic nervous system The PNS is part of the ANS and is often referred as the rest and digest phase. The primary neurotransmitter in this phase is: Acetycholine (Ach)

Parasympatholytic The Ach response causes: Decrease in HR
Decrease in BP Skeletal muscle contraction Bronchial smooth muscle constriction Ach causes: M3 muscarinic receptor reaction in blood vessels, as well as the lungs causing bronchoconstriction. Drugs that are parasympatholytic BLOCK M3 response and thus indirectly allow for bronchodilation

Parasympatholytic Examples of Parasympatholytics bronchodilators:
Fast Acting: Atrovent/Atropine Long Acting: Spiriva Parasymptholytic bronchodilators are referred to as anticholinergics, they are Ach antagonists Ach enters bronchial smooth muscle cells through muscanaric receptors Atrovent works by blocking all M receptors resulting in the formation of Cyclic guanosine monophosphate

Parasympatholytic cGMP inhibits constriction and mucus production
cGMP acts as a secondary messenger much like cAMP but instead of converting ATP, cGMP prevents neurotransmitters from entering the bronchial smooth muscle cell Unlike sympathometic bronchodilators, Atrovent/Spiriva do not cross the blood brain barrier and thus have essentially no systemic side effects (both are derivatives of Atropine, but are quaternary amines) Slower bronchodilator effects and less intense than adrenergics

Adrenergic bronchodilators ATP converts to cyclic 3’5’-adenosine monophosphate (cAMP) cAMP produces bronchodilation

Anticholinergic agents Parasympathetic stimulation of the muscarinic sites leads to production of guanosine triphosphate (GTP) GTP converts to cyclic guanosine monophosphate (cGMP)

Anticholinergic agents Anticholinergic agents block the parasympathetic stimulation at the muscarinic site

Xanthines In the presence of phosphodiesterase, cAMP denatures to form GMP Xanthines inhibit the action of phosphodiesterase, prolonging bronchodilation

Adrenergic Bronchodilators
Short acting bronchodilators Includes catecholamines Indicated for relief of acute reversible airflow obstruction Also known as “rescue” bronchodilators Primary drugs Albuterol and Xopenex

Short acting bronchodilators Rapid onset (3-5 minutes) Rapidly metabolized, resulting in short duration of action (3-8 hours) Common side effects: increased HR, trembling, nervousness If HR increases by 20+ stop treatment

Long acting bronchodilators Indicated for maintenance bronchodilation and control of bronchospasm Used to control nocturnal symptoms Slower onset Long duration of action, generally 12 hours Include Serevent, Brovona, Foradil

Catecholamines Ultra short
Epinephrine (not given as a bronchodilator usually, used to stop bleeding, primary cardiac stimulator) Adrenaline Cl Alpha Beta1 Beta2 SVN: 1% solution (1:100), 0.25 – 0.5 ml, qid MDI: 0.2 mg/puff, puffs as ordered Onset: 3 – 5 minutes Peak: 5 – 20 Duration: 1 – 3 hours Racemic (airway swelling) Micro-Nefrin, Asthma-Nefrin SVN: 2.25% solution, 0.25 – 0.5 ml, qid Duration: 0.5 – 2 hours Isoproterenol (not used as a bronchodilator any longer) Isuprel SVN: 0.5% solution (1:200), 0.25 – 0.5 Onset: 2 – 5 Peak: 5 – 30 Duration: 0.5 – 2 hours Isoetharine (weak, rarely used) Bronkosol SVN: 1% solution, 0.25 – 0.5 ml, qid Onset: 1 – 6 Peak: 15 – 60 Duration: 1 – 3

Short Acting Bronchodilators
Albuterol (asthma COPD, pulmonary e Proventil, Ventolin, Pro-air Beta2 SVN: 0.5% solution, 0.5ml, 2.5MG with 3ml NS tid, qid MDI: 90 µg/puff, 2 puffs, tid, qid Onset: 15 minutes Peak: 30 – 60 minutes Duration: 5 – 8 hours Levalbuterol Xopenex SVN: mg/3 ml, tid 1.25 mg/3 ml, tid 0.31mg MDI 45 ug/puff, 2 puffs tid/qid

Short Acting Bronchodilators
Terbutaline (used now as a anti contraction med to prevent early delivery) Brethaire Beta2 MDI: 200 µg/puff, 2 puffs, q4 – 6 hours Tab: 2.5 or 5 mg, q6 hours Onset: 5 – 30 minutes Peak: 30 – 60 Duration: 3 – 6 hours Pirbuterol Maxair (automatic MDI actuation) Onset: 5 minutes Peak: 30 minutes Duration: 5 hours Bitolterol Tornalate SVN: 0.2% solution, 1.25 ml, bid – qid MDI: 370 µg/puff, 2 puffs, q8 hours Onset: 3 – 4 minutes Duration: 5 – 8 hours

Long Acting Bronchodilators
Salmeterol (combined with Flovent to make Advair) Serevent Beta2 DPI: 50 µg/blister, twice daily Onset: 20 minutes Peak: 3 – 5 hours Duration: 12 hours Formoterol (combined with pulmicort to make symbicort) Foradil DPI: 12 µg/inhalation, Onset: 15 minutes Peak: 30 – 60 minutes Arformoterol (has a short acting component) Brovana SVN: 15 µg/2 ml unit dose, twice daily

Primary drug given for acute and chronic bronchospasm Used frequently for all sorts of conditions. Even hyperkalemia (although you need >20 mg in 15 minutes)

Adverse effects Bronchospasm (some patients have allergic reaction) Dizziness Tachycardia

Adverse effects Nausea (common with almost all drugs) Worsening ventilation/perfusion ratio Tachyphylaxis

Albuterol Sulfate Albuterol is used to prevent and treat wheezing, difficulty breathing and chest tightness caused by lung diseases such as asthma and chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways). Albuterol inhalation aerosol is also used to prevent breathing difficulties during exercise. Albuterol is in a class of medications called bronchodilators. It works by relaxing and opening air passages to the lungs to make breathing easier.

Albuterol Albuterol comes as a tablet, extended-release (long-acting) tablet, and a syrup to take by mouth and as an aerosol, a solution (liquid), and a powder-filled capsule to inhale by mouth. The solution is inhaled using a nebulizer, and the powder-filled capsules are inhaled using a special dry powder inhaler. Albuterol tablets and syrup are usually taken three or four times a day, and extended-release tablets are usually taken twice a day. For the treatment or prevention of asthma symptoms, the oral inhalation is usually used every 4 to 6 hours as needed. For the prevention of bronchospasm during exercise, the oral inhalation is used 15 minutes before exercise. The nebulized solution is used three or four times a day. Albuterol is often mixed with other drugs specifically Atrovent when given to COPD patients

Albuterol Generic Name: Albuterol
Trade Name: Proventil, Ventolin, Salbuterol (International name) Classification: Fast acting front door bronchodilator, Beta- 2 Adrenergic Sympathomimetic Bronchodilator Purpose: Relaxation of the bronchial smooth muscle resulting in bronchodilation, Quick onset time within 15 minutes, peak effect minutes and lasts 5-8 hours How it works: Stimulates intracellular production of cyclic 3’5’- AMP which causes dilation of bronchial smooth muscle, promotes bronchodilation via the neurotransmitter norepinephrine, which is similar to epinephrine (Adrenaline). Receptor Sites: Beta 1 (Cardiac smooth muscle stimulation) +1, Beta 2 (Bronchial smooth muscle stimulation) + 4, Alpha (Vasoconstriction) 0 Delivery Device: Primarily as an Aerosol for RT’s lasts minutes, MDI (metered dose inhaler), Liquid syrup or as a tablet Doses: Unit Dose and most common is 2.5 mg mixed with 2.5 ml of saline given TID, QID, Q4, or Q6. As an MDI given with the same frequency but usually with 2 to 4 puffs using a spacer.

Xopenex XOPENEX is a short-acting beta-agonist used to treat and prevent bronchospasm in children and adults. Medicines like XOPENEX, called bronchodilators, relax the tightened muscles around the airways in the lungs when bronchospasm occurs allowing the airways to open. Similar to Albuterol but believed to have less cardiac effects with a longer duration, making it the ideal choice for front line fast acting bronchodilation except that the drug is relatively new and costly. There is two ways of giving the drug, aerosol and MDI. The MDI is relatively new (2006) and is called XOPENEX HFA™ (levalbuterol tartrate) Inhalation Aerosol is a short-acting beta-agonist and has been approved by the FDA for the treatment or prevention of bronchospasm in patients 4 years of age and older. By subtracting the (S)-isomer from racemic albuterol, it differs from Albuterol.

Xopenex Generic Name: Levalbuterol
Trade Name: Xopenex, Chemical name: Racemic Albuterol Classification: Fast acting front door bronchodilator, Beta- 2 Adrenergic Sympathomimetic Bronchodilator Purpose: Relaxation of the bronchial smooth muscle resulting in bronchodilation, Quick onset time within 1-5 minutes, peak effect minutes and lasts 6-8 hours How it works: Stimulates intracellular production of cyclic 3’5’- AMP which leads to activation of protein kinase A, which inhibits phospholylation of myosin and lowers intracellular ionic calcium concentrations resulting in relaxation of all the airways (trachea, bronchi and bronchioles). Receptor Sites: Beta 1 (Cardiac smooth muscle stimulation) +1, Beta 2 (Bronchial smooth muscle stimulation) + 4, Alpha (Vasoconstriction) 0 Delivery Device: Primarily as an Aerosol for RT’s lasts minutes, MDI (metered dose inhaler) Doses: 0.31mg/3mL (Infants), 0.63mg/3mL (Children, Adults) & 1.25mg/3mL (Adults) unit dose vials

Is Xopenex Better than Albuterol
It’s not completely clear. When Xopenex was first developed, animal studies suggested that S-albuterol caused inflammation in the lungs, which could possibly worsen asthma. It was also thought that as more racemic albuterol (mixture of the R and S-albuterol isomers) was taken, the S-albuterol isomer would accumulate within the lungs and result in contraction of the smooth muscles around the lungs, thereby worsening asthma symptoms. Xopenex was therefore expected to work better at treating asthma symptoms than racemic albuterol.

Early studies did show that Xopenex was better at treating asthma than albuterol, since less Xopenex was needed to achieve control of asthma symptoms than comparable amounts of albuterol. Since Xopenex is the active half of albuterol, one would expect that half the dose of Xopenex would be equivalent to twice the dose of albuterol; however, these studies suggested that only one-fourth of the dose of albuterol was needed to achieve the same result when using Xopenex. This was thought to be due to the lack of the S-albuterol isomer in Xopenex, which was working against the R-albuterol isomer.

Recent data on Xopenex, however, along with an overview of all of the available data, suggests that Xopenex is no better at treating asthma than would be expected. The dose of Xopenex required to achieve the same result of treating asthma does appear to be approximately one-half, which is what is expected since it contains the active isomer (R-albuterol). The S-albuterol isomer appears to be inert, meaning that it does not act for or against the treatment of asthma symptoms.

Albuterol is well-known to cause certain side effects, including muscle tremors, jitteriness, palpitations and increased heart rate. Early studies on Xopenex suggested that because far less medicine was needed to achieve the same benefit as albuterol, fewer side effects would occur. In addition, it was initially thought that the S-albuterol isomer was primarily responsible for many of the albuterol side effects, and therefore Xopenex, which does not contain the S-albuterol isomer, would cause few side effects.

Recent studies suggest, however, that the side effects of Xopenex are equivalent to albuterol, since it is actually the R-albuterol isomer that is responsible for the albuterol side effects. The S-albuterol isomer is inert, meaning is does not contribute to side effects. The package insert for Xopenex states that the rate of the above mentioned side effects are similar for equivalent doses of Xopenex and albuterol.

Ultra Short Bronchodilator (Racemic Epi)
Slightly different chemically from epinephrine. Stimulates both alpha and beta adrenergic receptors with a slight preference for the beta2 receptors in the lungs. This results in bronchodilation and a decrease in mucus secretion. It also helps in relieving the subglottic edema associated with croup when administered by inhalation. Croup, or acute laryngotracheobronchitis, is the most common cause of upper airway obstruction in children. Croup produces subglottic edema to varying degrees and affects children between the ages of 6 months and 12 years, with a peak incidence of 2 years of age. The clinical syndrome consists of hoarseness and barky cough, with or without inspiratory stridor. Preceding symptoms often include congestion, runny nose, and fever. Severe cases may present with cyanosis and respiratory distress.

Racemic Epi Croup is caused by several viruses, of which the most common are parainfluenza type I and III, respiratory syncytial virus, and influenza. The natural course of the illness includes peaking of symptoms between 24 and 48 hours after the onset of barky cough with expected resolution of all symptoms over a week. Current emergency management for moderate to severe croup consists of cool mist therapy, steroids, and/or nebulized racemic epinephrine. The literature on croup has convincingly demonstrated benefit from steroid treatment with respect to improvement of croup scores, decreased need for further therapy, and decreased hospitalization rates DECADRON Inhaled/nebulized steroid

Racemic Epi Generic Name: Racemic Epinephrine
Trade Name: Micronefrin,VapoNefrin Classification: Alpha-adrenergic Sympathomimetic effect Purpose: Treats croup, stridor, post extubation, laryngeal tumor or swelling, bronchiolittis, or any other upper airway edema causing swelling and inflammation. How it works: Mucosal vasoconstriction decreases subglottic edema. Bronchodilation, increases heart rate, increases cardiac contractile force. Receptor Sites: Strong Alpha effect which causes vasoconstriction, Alpha +4, Beta 2 +2, Beta 1 +2 Delivery Device: Inhalation only (small-volume nebulizer).

Racemic Epi Doses: Racemic Epinephrine (2.25%) nebulizer form, Child under 6 months: 0.25 ml, Child: 0.5 ml, Adolescent: 0.75 ml, usually mixed with 2-3 cc of normal saline.Effect dissipates in 2 hours, Effects last 90 to 120 minutes Precautions: Avoid too frequent use due to tachyphylaxis, Observe 2-4 hours after racemic Epinephrine Contraindications: Epiglottitis, hypersensitivity to the drug, severe tachyarrhythmias Side effects: Headache, angina, palpitations, tachycardia. Use precaution with use with antihistamines or tricyclic antidepressants may cause adverse cardiac effects.

LABA SEREVENT Indication: Treatment and prevention of bronchospasm. Serevent is not intended for the treatment of acute asthma exacerbations or for symptoms that can be managed with occasional use of short- acting inhaled Beta 2 agonists. 2. Dosage: (MDI version D/C’d after ) - DPI: 1 inhalation (50mcg) twice daily, 12 hours apart 3. Onset: min 4. Peaks: 3-4 hours 5. Duration of action: 12 hours Typically combined with Flovent to Make ADVAIR

LABA Brovana (arformoterol) is a bronchodilator. It works by relaxing muscles in the airways to improve breathing. Brovana is used to prevent bronchoconstriction in people with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Brovana will not treat a bronchospasm attack that has already begun.

LABA Foradil (formoterol) is a long-acting bronchodilator that relaxes muscles in the airways to improve breathing. Foradil is used to prevent bronchospasm in people with reversible obstructive airways disease, including symptoms of night-time asthma. It is also used in people with chronic obstructive pulmonary disease (COPD) such as emphysema and chronic bronchitis.

Respiratory Pharmacology Anticholinergics and Mucolytics

Only effective if bronchoconstriction exists due to cholinergic activity USED FOR COPD PATIENTS only May also be used for asthmatics during an attack

In combination with beta-agonist in patients with COPD on regular treatment regimen who require additional bronchodilation If you give Spiriva, you DO NOT also give Atrovent. Spiriva given QD Kp672Y

Adverse effects Dry mouth Cough EXTREMENLY RARE SYSTEMIC SIDE EFFECTS AS IT DOES NOT CROSS BLOOD BRAIN BARRIER Nervousness Headache, dizziness

Adverse effects Pharyngitis Dyspnea

Atrovent “Back door bronchodilator” that is used in conjunction with a front door bronchodilator such as Albuterol or Xopenex. It works by opening up the air passages in your lungs by preventing cholinergic responses. It is not to be used alone for treating an acute attack of breathing problems, as it takes some time to work and is usually given as a maintenance drug that excels the use of Albuterol or Xopenex for people with COPD. Ipratropium is only for inhalation by mouth through an inhaler device or for inhalation by a nebulizer.

Atrovent Generic Name: Iprtropium Bromide Trade Name: Atrovent
Classification: Anticholinergic agent How it works: It relaxes airway muscles by impacting neurotransmitters sent to the autonomic nervous system, a process different than how beta-agonist drugs act. Sometimes given in addition to shorter-acting bronchodilator therapy, if the shorter-acting meds are not doing enough. Tends to have longer-lasting effect than beta-agonist drugs. Delivery Device: As an aerosol used in a nebulizer or as a DPI as SPIRIVA® HandiHaler® (tiotropium bromide inhalation powder) Doses: Unit dose is 0.5 mg or 0.02%, usually mixed with Albuterol or Xopenex. Side Effects: Fever, infection, headache, skin rash or hives, swelling of lips, tongue or face, vomiting, cough, blurred vision, dry mouth Contraindications/Percautions- If the following exist take precaution when initiating treatment:

Combo Drugs Albuterol and Atrovent DuoNeb (Nebulizer solution)
Combivent (MDI)

Ipratropium bromide Atrovent MDI: 17 µg/puff, 2 puffs four times daily SVN: 0.02% solution, 0.5 mg, three to four times daily Nasal Spray: 0.03%, 0.06% solution, 2 sprays per nostril, 2 to 4 times daily Onset: 15 minutes Peak: 1 – 2 hours Duration: 4 – 6 hours and Albuterol Combivent DuoNeb MDI: Ipratropium 18µg/puff, Albuterol 90 µg/puff, 2 puffs four times daily SVN: Ipratropium 0.5 mg and Albuterol 2.5 mg. Tiotropium bromide Given with handi haler Spiriva DPI: 18 µg/inhalation, 1 inhalation daily Onset: 30 minutes Peak: 3 hours Duration: 24 hours

Mucus controlling drugs
The general term for medications that are meant to affect mucus properties and promote secretion clearance is “mucoactive.” These include expectorants, mucolytics, mucoregulatory, mucospissic, and mucokinetic drugs Mucoactive medications are intended either to increase the ability to expectorate sputum or to decrease mucus hypersecretion

Expectorants Expectorants are defined as medications that improve the ability to expectorate purulent secretions. Medications that increase airway water or the volume of airway secretions, including secretagogues that are meant to increase the hydration of luminal secretions (eg, hypertonic saline or mannitol) and abhesives that decrease the adhesivity of secretions and thus unstick them from the airway (eg, surfactants).

Mucolysis Mucolysis is the breakdown of mucus.
Mucolysis is needed in diseases in which there is increased mucus production: Cystic Fibrosis COPD Bronchiectasis Respiratory Infections Turberculosis

Mucolysis These diseases result in a marked slowing of mucus transport
Changes in properties of the mucus Decreased ciliary activity Both

Mucolytics Acetylcysteine sodium bicarbonate (NaHCO3) Dornase alfa
Pulmozyme

Airway Anatomy

Mucus Layer Gel (1 to 2 mm): Gelatinous and sticky (flypaper)
Sol (4 to 8 mm): Watery, Cilia in this layer Total layer thickness: 5 to 10 mm thick Surface Epithelial Cells Pseudostratified ciliated columnar Surface goblet cells (6,800/mm2) Serous cells – Sol layer Clara cells – Unknown function (enzymes?) Submucosal Gland Bronchial Gland

Mucus Layer Bronchial Gland Found in submucosa
Found down to terminal bronchioles Parasympathetic control (Vagus nerve) Provide the majority of mucus secretion Total volume 40 times greater than goblet cells

Mucus vs. Sputum Mucus is the total secretion from mucous membranes including the surface goblet cell and the bronchial glands. Sputum is the expectorated secretions that contains mucus, as well as oropharyngeal and nasopharyngeal secretions (saliva).

Mucociliary Escalator
Mucosal Blanket Sol layer Gel layer Cilia 200 per cell 6 mm in length Beat 1000/min Move mucus 2 cm/min Paralyzed by cigarette smoke

Function of Mucociliary Escalator
Protective function Remove trapped or inhaled particles and dead or aging cells. Antimicrobial (enzymes in sol/gel) Humidification Insulation (prevents heat and moisture loss) NOTE: No cilia or mucus in lower airways (respiratory bronchioles on down) Mucus also protects the epithelium from toxic materials.

Structure and Composition of Mucus
95% water Need for water intake to replenish Mucus doesn’t easily absorb water once created 3% protein and carbohydrates 1% lipids Less than 0.3% DNA

Factors that Impair Ciliary Activity
Endotracheal tubes Temperature extremes High FiO2 levels Dust, Fumes, Smoke Dehydration Thick Mucus Infections

Facilitation of Mucus Clearance
Provide adequate hydration Increase fluid intake orally or IV Remove causative factors Smoking, pollution, allergens Optimize tracheobronchial clearance Use Mucolytics Reduce Inflammation

Dairy Intake No evidence to support the common belief that drinking milk increases the production of mucus or phlegm and congestion in the respiratory tract There is a loose cough associated with milk intake

Secretion Management Increase the depth of the sol layer
Water Saline Expectorants Alter the consistency of the gel layer Mucolytics Improve ciliary activity Sympathomimetic bronchodilators Corticosteroids

Bland Aerosols “Dilutes” mucus molecule Also known as wetting agents
Function may be more of an irritant than a wetter Types Sterile & Distilled Water Humectant Dense aerosols and asthmatics Normal (isotonic) Saline Hypertonic Saline Increase mucus production Hypotonic Saline

Expectorants Iodides Unclear function
SSKI (Saturated Solution of Potassium Iodide) Guifenesin At high doses, stimulates bronchial gland secretion Robitussin Not typically given by RTs

Cough Suppressants Vagal stimulation causes a cough.
Irritation of pharynx, larynx, and bronchi lead to a reflex cough impulse. If the cough is dry and non-productive, it may be desirable to suppress its activity. Cough suppressants depress the cough center in medulla Narcotic preparations (codeine) Non-Narcotic preparations (dextromethorphan) Nebulized Xylocain Caution in patients with thick secretions.

Function of Mucolytics
Weakening of intermolecular forces binding adjacent glycoprotein chains Disruption of Disulfide Bonds Alteration of pH to weaken sugar side chains of glycoproteins Destruction of protein (Proteolysis) contained in the glycoprotein core of proteolytic enzymes Breaking down of DNA in mucus

Disruption of Disulfide Bonds acetylcysteine breaks the bonds by substituting a sulfhydril radical –HS

Alteration of pH Sodium Bicarbonate 2% NaHCO3 solutions are used to increase the pH of mucus by weakening carbohydrate side chains Can be injected directly into the trachea or aerosolized (2-5 mL)

Proteolysis Dornase alfa (Pulmozyme) Attacks the protein component of the mucus

Hazard of Mucolytics The problem with all three mucolytics is that they destroy the elasticity of mucus while reducing the viscosity. Elasticity is crucial for mucociliary transport. The patient must be able to cough adequately to remove the mucus.

acetylcysteine Indications
Mucolytic by aerosol or direct instillation into the ET tube. Given orally to reduce liver injury with acetaminophen (Tylenol) overdose. Mix with cola or given by NG tube.

Mucomyst Draw up with a syringe and instill into nebulizer

Acetylcysteine Indicated for treatment of accumulated airway secretions Chronic obstructive pulmonary disease Bronchiectasis Acute tracheobronchitis

Acetylcysteine Used to treat or prevent liver damage in acetaminophen overdose (patient drinks it) Reduces viscosity of mucus by substituting sulfhydryl group for disulfide group

Acetylcysteine May be directly instilled during bronchoscopy to remove mucus plugs Normal dosage via SVN: 3 – 5 ml

Acetylcysteine Side effects
Airway obstruction secondary to rapid liquefaction of secretions Disagreeable odor (rotten eggs) Nausea Rhinorrhea Bronchospasm

Acetylcysteine Discard 96 hours after opening, usually refrigerated
Should not be administered in the presence of thin secretions ALWAYS GIVE WITH A BRONCHODILATOR

Dosage of acetylcysteine
Concentration 10% or 20% Dosage 3-5 mL of a 20% solution TID or QID Maximum dose 10 mL 6-10 mL of a 10% solution TID or QID Maximum dose 20 mL 1-2 mL of a 10% or 20% for direct instillation

Hazards of acetylcysteine
Bronchospasm Asthma – may be a problem during an acute asthma attack. Anecdotal; lack of evidence If used with asthma, use 10% and mix with a bronchodilator (preferably a short-acting agent). Increase mucus production Be prepared to suction a patient who cannot cough or who is intubated.

Hazards of acetylcysteine
Do not mix with antibiotics in the same nebulizer (incompatible). Nausea & Vomiting Disagreeable odor (smells like rotten eggs) due to the hydrogen sulfide. Open vials should be used within 96 hours to prevent contamination.

sodium bicarbonate Weak base.
Increasing the pH of mucus weakens the polysaccharide chains. Available as 1.4%, 5%, and 7.5% solutions. Dosage: 2-5 mL of a 2.5% solution Q4-Q8. Mix 5% solution with equal volume of sterile water. Can be irritating (especially the 5 & 7.5% solutions).

dornase alfa Pulmozyme
Clone of the natural human pancreatic DNase enzyme which digests extracellular DNA. Dornase alfa is a solution of recombinant human deoxyribonuclease (rhDNase) Approved by FDA in 1994

dornase alfa – Pulmozyme
Indications Reduce viscosity of secretions during an infection by breaking down extracellular DNA. Used in cystic fibrosis, chronic bronchitis or bronchiectasis. Maintenance therapy in CF Has no effect on non-infected sputum.

Infection Increased WBCs – neutrophils WBCs contain DNA
WBCs release DNA when they die which increases the viscosity of secretions Decreases the effectiveness of antibiotics Pancreas produces an enzyme called deoxyribonuclease (DNase) which breaks down the DNA

Function of rhDNase

Common Side Effect of Pulmozyme
Voice Alteration Pharyngitis/Laryngitis Rash Chest pain Conjunctivitis Contraindicated in patients hypersensitive to Chinese Hamster Ovary cell products.

Concentration and Dosage
Supplied in single dose vials (unit dose). Concentration is 1 mg/mL (0.1% solution). Each vial contains 2.5 mg /2.5 mL. Administer one unit dose vial (2.5 mL) daily. Some patients may benefit from BID administration. Do not mix or dilute with other drugs. Nebulizer specific (per manufacturer).

Mucus-Controlling Agents
Dornase alfa (Pulmozyne) Indicated for the treatment of cystic fibrosis (CF) to reduce number of infections and improve pulmonary function Breaks down DNA material from neutrophils found in purulent secretions Normal dosage via SVN: 2.5 mg/ampule, 1 ampule daily

Dornase Alfa Side effects (does not cause bronchospasm) Pharyngitis
Laryngitis Chest pain

Sodium Bicarbonate Not commonly used, but changes the pH of mucus. Aerosolized a. Action: Adjusts the pH of mucus, decreasing the surface tension to facilitate mucolytic action. b. Indication: tracheal irrigation c. Dosage: - irrigation: 2-5 ml of 2-8.4% NaHC03 in 2-5 ml NS d. Precaution: mucosal irritation

Ethyl Alcohol Ethyl Alcohol 30-50% (Ethanol) a. Indication:
- pulmonary edema (OLD treatment) Defoaminant b. Precautions: - mucosal irritation - intoxication - vasodilation

Aqueous Aerosols (bland aerosols, non medicated)
Indications Thin secretions Used as diluent for medications May be used to induce sputum (hypertonic saline); >0.9% saline. Normal saline is 0.9% and has no effect in the airway, used a diluent to most medications

Aqueous Aerosols Distilled water Osmolarity – hypotonic
Will be absorbed into interstitial space May cause or contribute to edema Hypotonic rarely given, if it is given, use a ultra sonic nebulizer

Aqueous Aerosols Isotonic saline (0.9%)
Osmolarity – equal to lung tissue Also known as normal saline Used as diluent for medication

Aqueous Aerosols Hypotonic saline (<0.9%, commonly 0.45% or half normal) Osmolarity – less than that of lung Used in ultrasonic nebulizers – due to evaporation, solution will become isotonic by the time it reaches the airway Can increase resistance due to swelling of secretions

Aqueous Aerosols Hypertonic saline (>0.9%)
Osmolarity – greater than that of lung tissue Used for sputum induction

Aqueous Aerosols Hypertonic saline (>0.9%)
Draws fluid from interstitial space to mucus bed, thinning secretions May cause bronchospasm, especially in hyperactive airways

Chapter 8 Xanthines

Clinical Uses of Xanthines
Asthma COPD Apnea of prematurity

Clinical Indications for the Use of Xanthines
Use in asthma Theophylline: maintenance therapy (step 2 or alternative in step 3 with ICS) of mild, persistent asthma Patients older than 5 years of age Side effects and narrow therapeutic index may make it a poor choice vs. other agents

Clinical Indications for the Use of Xanthines (cont’d)
Use in COPD Theophylline: recommended by GOLD as alternative to β2-agonist and anticholinergics Not used in acute exacerbations Use in apnea of prematurity First-line treatment Theophylline most extensively used, but caffeine citrate may be a better choice (safer, higher therapeutic index)

Specific Xanthine Agents
Also known as methylxanthines Found as alkaloids in plant species Theophylline Tea leaves Theobromine Cocoa seeds or beans Caffeine Coffee beans and kola nuts

General Pharmacological Properties
Effects on humans CNS stimulation Cardiac muscle stimulation Diuresis Bronchial, uterine, and vascular smooth muscle relaxation Theophylline is generally classified as a bronchodilator Peripheral and coronary vasodilation Cerebral vasoconstriction Used in headache remedies

General Pharmacological Properties (cont’d)
Structure-activity relations Theophylline Methyl attachments at N-1 and N-3 enhance bronchodilation/increase side effects Caffeine Additional methyl group at N-7 decreases bronchodilation Dyphylline Derivative of theophylline with methyl attachment at N-7 that weakens bronchodilation Enprofylline Not available in the United States Potent bronchodilator Large substitution at the N-3 position

General Pharmacological Properties (cont’d)
Proposed theories of activity Exact mechanism of action is unknown Smooth muscle relaxation via inhibition of phosphodiesterase (?) Antagonism of adenosine (?) Catecholamine release (?)

Proposed Mechanism of Action
Figure 8-3 Two proposed mechanisms of action by which theophylline and xanthines reverse airway obstruction. A, Inhibition of phosphodiesterase. B, Blockade of adenosine receptors. AMP, Adenosine monophosphate; ATP, adenosine triphosphate.

Titrating Theophylline Doses
Individuals metabolize theophylline at different rates Equivalent doses of theophylline salts Anhydrous theophylline = 100% theophylline Salts of theophylline not pure by weight

Titrating Theophylline Doses (cont’d)
Serum levels of theophylline <5 μg/mL: No effects seen 10 to 20 μg/mL: Therapeutic range >20 μg/mL: Nausea >30 μg/mL: Cardiac arrhythmias 40 to 45 μg/mL: Seizures Asthma 5 to 15 μg/mL COPD 5 to 10 μg/mL

Dosage schedules Used to titrate drug levels Rapid theophyllization: 5 mg/kg lean body weight oral loading dose of anhydrous theophylline (if patient was not previously receiving theophylline) Each 0.5 mg/kg = 1 μg/mL serum level Slow titration: 16 mg/kg/24 hr or 400 mg/24 hr (whichever is less)

Methods of titration: Clinical reaction of patient Serum drug levels 1–2 hours after administration (immediate release) 5–9 hours after administration (sustained release)

Theophylline Toxicity and Side Effects
Narrow therapeutic margin Distressing side effects may occur at therapeutic levels Inhaled theophylline is being studied Common side effects: Gastric upset Not recommended in patients with peptic ulcer or acute gastritis Headache Anxiety Diuresis

Factors Affecting Theophylline Activity
Conditions affecting liver/kidneys Interactions with other drugs (see Box 8-2 in the textbook) Conditions that increase theophylline levels: Viral hepatitis Left ventricular failure Condition that decreases theophylline levels: Smoking Additive effect: β-Agonists

Clinical Uses Asthma COPD Use debated
Only after other relievers and controllers have failed COPD If ipratropium bromide and β2-agonist fail to provide control

Nonbronchodilating Effects of Theophylline
Increase in force of respiratory muscle contractility Increase in respiratory muscle endurance Increase in ventilatory drive Cardiovascular effects Increased cardiac output Decreased pulmonary vascular resistance Antiinflammatory effects

Use in Apnea of Prematurity
Xanthines are the first-line choice when nonpharmacological methods are unsuccessful Caffeine citrate is preferred over theophylline Loading dose of caffeine citrate is 20 mg/kg Daily maintenance dose of 5 mg/kg

STEROIDS

Inhaled Steroids Mode of action at the tissue level
Restoration of epithelium Reduction of thickening of basement membrane Reduction of mucosal edema Reduction of leukocyte infiltrate Reduction of mast cell number

Inhaled Steroids Mode of action at the molecular level:
Blockage of active sites of pro-inflammatory genes Mode of action at the cellular level: Inhibition of release of pro-inflammatory molecules

Inhaled Corticosteroids
Mode of action Modify response of the cell in order to inhibit inflammatory response of the airway May require hours to days to gain full benefits Daily compliance is essential to maximizing effects

Indications Anti-inflammatory maintenance therapy of persistent asthma and COPD Control of seasonal allergic or non-allergic rhinitis May be administered as orally inhaled aerosol or intranasal aerosol

Aerobid is now Aerospan
Flovent: DPI/MDI. 3 doses. Asmanex: twisthaler, grey or pink depending on dose Qvar: 40/80 ug dose

Pulmicort: turbahaler or respules
Advair: MDI or DPI, 3 doses, combo drug Symbicort: 2 doses, combo drug Pulmicort: turbahaler or respules

Adverse effects Decrease type and severity of side effects compared to systemic administration Adrenal insufficiency Acute asthma

Adverse effects (systemic mostly) Osteoporosis Growth suppression Oropharyngeal infections

Adverse effects Dysphonia Cough Bronchoconstriction

Corticosteroids Used in Aerosol Administration
Beclomethasone dipropionate QVAR MDI: 40 and 80 µg/puff. Adults > 12 years: 40 to 80 µg twice daily, or 40 to 160 µg twice daily Children > 5 years: 40 to 80 µg twice daily Triamcinolone acetonide (No longer made) Azmacort MDI: 100 µg/puff. 2 puffs three times of four times daily Children > 6 years: 1 or 2 puffs three or four times daily Flunisolide Aero-Bid MDI: 250 µg/puff Adults and children > 6 years: 2 puffs twice daily; adults no more than 4 puffs; children < 15 years no more than 2 puffs daily

Fluticasone propionate Flovent MDI: 44, 110, and 220 µg/puff Adults > 12 years: 88 µg twice daily; 88 – 220 µg twice daily; or 880 µg twice daily Children 4 – 11 years: 88 µg twice daily DPI: 50, 100, and 250 µg Adults: 100 µg twice daily; 100 – 250 µg twice daily; or 1000 µg twice daily Children 4 – 11 years: 50 µg twice daily Budesonide Pulmicort DPI: 200 µg/actuation 200 – 400 µg twice daily; 400 – 800 µg twice daily Children > 6 years: 200 µg twice daily SVN: mg/2 ml; 0.5 mg/2 ml Children 1 – 8 years: 0.5 mg total dose once daily or twice daily in divided doses 1 mg given as 0.5 mg twice daily or once daily

Fluticasone propionate/ salmeterol Advair Diskus Advair HFA DPI: 100 µg fluticasone / 50 µg salmeterol 250 µg fluticasone / 50 µg salmeterol 500 µg fluticasone / 50 µg salmeterol Adults and children > 12 years: 100 µg fluticasone / 50 µg salmeterol, one inhalation twice daily, about 12 hours apart Children > 4 years: 100 µg fluticasone / 50 µg salmeterol, one MDI: 45 µg fluticasone / 21 µg salmeterol 115 µg fluticasone / 21 µg salmeterol 230 µg fluticasone / 21 µg salmeterol 2 inhalations twice daily, about 12 hours apart Budesonide / formoterol fumarate Symbicort MDI: 80 µg budesonide / 4.5 µg formoterol 160 µg budesonide / 4.5 µg formoterol 160 µg budesonide / 9 µg formoterol twice daily; maximum daily: 640 µg budesonide / 18 µg

Advair Advair Diskus combines an inhaled corticosteroid and an inhaled long-acting bronchodilator in one easy-to-use device. Advair Diskus does not replace fast-acting inhalers for sudden symptoms. Advair Diskus effectively treats the two main components of asthma at the same time: constriction, the tightening of the muscles around the airways, and inflammation, the swelling and irritation of the airways. Constriction and inflammation cause the airways to narrow and reduce airflow into the lungs, which may result in symptoms such as wheezing, coughing, chest tightness, or shortness of breath. The combination of fluticasone (Flovent-steroid) and salmeterol (Serevent-bronchodilator) is used to prevent wheezing, shortness of breath, and breathing difficulties caused by asthma, but also be prescribed for COPD.

Advair Generic Name: fluticasone propionate and salmeterol xinafoate
Trade Name: Advair (Advair Diskus) How should Advair Asthma Medication be Used? 1. OPEN Hold the DISKUS in one hand and put the thumb of your other hand on the thumbgrip. Push your thumb away from you as far as it will go until the mouthpiece appears and snaps into position. 2. CLICK Hold the DISKUS in a level, horizontal position with the mouthpiece towards you. Slide the lever away from you as far as it will go until it clicks. The DISKUS is now ready to use. Every time the lever is pushed back, a dose is ready to be inhaled. This is shown by a decrease in numbers on the dose counter.

Advair To avoid releasing or wasting doses: • Do not close the DISKUS. • Do not tilt the DISKUS. • Do not play with the lever. • Do not advance the lever more than once. 3. INHALE Before inhaling your dose of Advair Diskus, breathe out as far as is comfortable, holding the DISKUS level and away from your mouth. Remember, never breathe out into the DISKUS mouthpiece. Put the mouthpiece to your lips. Breathe in quickly and deeply through the Advair Diskus, not through your nose.

Combos Symbicort (Contains formoterol, a long-acting beta2-adrenergic agonist (LABA) and budesonide (steroid); given BID, two doses 160/4.5 mcg, 80/4.5 mcg; MDI) Dulera (mometasone furoate/ formoterol fumarate dihydrate, BID, 100/5 or 200/5 mcg dose MDI)

Non-Steroidal Anti-Asthma Drugs
Mast cell stabilizers Indicated for prophylactic control of mild to moderate asthma Inhibits degranulation of mast cells in response to allergic and non-allergic stimuli Used typically as alternatives to inhaled corticosteroids, especially in children

Leukotriene inhibitors Indicated for prophylactic control of mild to moderate asthma Used in combination with inhaled steroids to reduce the dose of the steroid

Cromolyn sodium Intal Nasalcrom MDI: 800 µg / actuation Adults and children > 5 years: 2 inhalations four times daily SVN: 20 mg / ampule or 20 mg / 2 ml Adults and children > 2 years: 20 mg inhaled four times daily Spray: 40 mg / ml (4%) 1 spray each nostril, 3 to 6 times daily every 4 – 6 hours Nedocromil sodium Tilade MDI: mg / actuation Adults and children > 6 years: Zafirlukast Accolate Tablets: 10 and 20 mg Adults and children > 12 years: 20 mg twice daily, without food Children 5 – 11 years: 10 mg twice daily

Montelukast Singulair Tablets: 10 mg; 4 and 5 mg chewable; 4 mg packet of granules: Adults and children > 15 years: one 10 mg tablet daily Children 6 – 14 years: one 5 mg chewable tablet daily Children 2 – 5 years: one 4 mg chewable tablet daily Children 6 – 23 months: one 4 mg packet of granules daily Zileuton Zyflo Tablets: 600 mg Adults and children > 12 years: one 600 mg tablet four times per day

Aerosolized Anti-Infective Agents
Pentamidine isethionate (Nebupent) Indicated for the prevention of Pneumocystis carinii pneumonia (PCP) Not recommended for use in treatment of PCP (however typically given)

Pentamidine Isethionate (Nebupent)
Action: The drug interferes with protozoal nuclear metabolism inhibitionof DNA, RNA, phospholipid and protein synthesis. It is known to have activity against pneumocystis carinii. Indication: Prevention of Pneumocystis carinii pneumonia (PCP) in high risk, HIV-infected patients. Dosage: 300mg once every 4 weeks (nebulized)

Pneumocystis pneumonia (PCP)
Pneumocystis pneumonia (PCP) form of pneumonia, caused by the yeast-like fungus (which had previously been erroneously classified as a protozoan) Pneumocystis jirovecii Pneumocystis is commonly found in the lungs of healthy people, but being a source of opportunistic infection it can cause a lung infection in people with a weak immune system. Pneumocystis pneumonia is especially seen in people with cancer, HIV/AIDS and the use of medications that affect the immune system. also known as Pneumocystis jiroveci[i] pneumonia

Pentamidine Isethionate
Adverse effects Cough Bronchial irritation, bronchospasm Shortness of breath Given using a scavenger nebulizer/SPAG

Pentamidine Isethionate
Adverse effects Fatigue Pharyngitis Chest Pain

Ribavirin (Virazole) Indicated as anti-viral agent to treat respiratory syncytial virus (RSV) Administered via small particle aerosol generator (SPAG)

Ribavirin-injection Ribavirin is also used with an interferon medication to treat hepatitis C in people who have not been treated with an interferon before. Ribavirin is in a class of antiviral medications called nucleoside analogues. It works by stopping the virus that causes hepatitis C from spreading inside the body. It is not known if treatment that includes ribavirin and another medication cures hepatitis C infection, prevents liver damage that may be caused by hepatitis C, or prevents the spread of hepatitis C to other people.

Ribavirin Adverse effects Skin rash Eyelid erythema
Occlusion of endotracheal tube Deterioration of pulmonary function

Tobramycin (Tobi) Indicated for management of chronic infection with Pseudomonas aeruginosa; typically seen with CF and immune suppressed patients Treat or prevent colonization

Tobi Action: Aminoglycoside antibiotic disrupts protein synthesis eventually resulting in cell death (gram negative organisms). Dosage: One 5 mL ampule contains 300mg of tobramycin. Given B.I.D. / Q12 with recommended nebulizer (Pari type neb)

Tobramycin Adverse effects Ototoxicity and tinnitus Bronchospasm
Fetal harm (deafness)

Zanamivir (Relenza) Indicated for treatment of uncomplicated illness due to influenza virus

Relenza used in the treatment and prophylaxis of influenza caused by influenza A virus and influenza B virus. The bioavailability of zanamivir is 2%. After inhalation, zanamivir is concentrated in the lungs and oropharynx, where up to 15% of the dose is absorbed and excreted in urine. Dosing is limited to the inhaled route. This restricts its usage, as treating asthmatics could induce bronchospasms

Zanamivir Adverse effects Bronchospasm
Under treatment of bacterial infection appearing as viral infection

Amphotericin B Indicated for the treatment of fungal infections, especially in lung transplants

amphotericin B amphotericin B binds the main component of fungal cell membranes, forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl−) leakage, which is the primary effect leading to fungal cell death.

Amphotericin B Adverse effects Nausea Vomiting Bronchoconstriction

Pentamidine isethionate Nebupent 300 mg powder in 6 ml sterile water, once every four weeks Ribavirin Virazole 6 g powder in 300 ml sterile water (20 mg / ml solution); given every 12 – 18 hr / day for 3 – 7 days by SPAG Tobramycin TOBI 300 mg / 5 ml ampule: Adults and children > 6 years: 300 mg bid, 28 days on drug, 28 days off drug Zanamivir Relenza DPI: 5 mg / inhalation: Adults and children > 7 years: 2 inhalations (one 5 mg blister / inhalation) bid, 12 hours apart for 5 days Amphotericin B Fungizone 10 mg three times per day for six to 8 weeks

Nitric Oxide Indicated for the treatment of pulmonary hypertension in neonates Causes relaxation of vascular smooth muscle, producing pulmonary vasodilation

Nitric Oxide Contraindicated in neonates with right to left shunts

Nitric Oxide Adverse effects Hypotension Formation of Methemoglobinia
Withdrawal

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