Pharm Ch 6: Adrenergic

Front 1

What is the Clinical Indications for Adrenergic Bronchodilators?

Back 1

Relaxation of smooth airway muscle in the presence of reversible airway obstruction

Asthma

Acute, chronic, exercise-induced

Bronchitis

Emphysema

Bronchiectasis

Front 2

What is the Indication for Short-Acting Agents?

Back 2

Acute reversible airflow obstruction

Front 3

What are some short acting agents?

Back 3

a.k.a. “rescue” agents

Albuterol (brand name: proventil and Ventolin)

Levalbuterol (xopenex)

Metaproterenol

Front 4

What is the Indication for Long-Acting Agents?

Back 4

Maintenance bronchodilation, control of bronchospasm, and control of nocturnal symptoms

Front 5

What are some long acting agents?

Back 5

Salmeterol (Serevant disk)

Formoterol (Performest, symbicort)

Arformoterol (Brovana)

Indacaterol

Front 6

What are the indications for Racemic Epinephrine?

Back 6

To control airway bleeding during endoscopy

To reduce airway swelling

**vasoconstriction effect to reduce swelling

Postextubation stridor

Epiglottitis

Croup

Bronchiolitis

Front 7

Ultrashort acting

Duration?

Meds?

Back 7

Duration < 3 hours

Epinephrine and racemic epinephrine

Front 8

Short acting

Duration?

Meds?

Back 8

Duration of 4 to 6 hours

Albuterol, levalbuterol

Front 9

Long acting

Duration?

Drugs?

Back 9

Duration of 12 hours

Salmeterol, formoterol, arformoterol

Front 10

Ultralong acting

Duration?

Drugs?

Back 10

Duration 24 hours

Indacaterol- Onbrez, Arcapta Neohaler

Front 11

Sympathomimetic bronchodilators are?

Back 11

either catecholamines or derivatives of catecholamines

Front 12

Catecholamines mimic what?

Back 12

Epinephrine

(Dopamine, Isoproternal, norepi)

Front 13

Effects of Catecholamines?

Back 13

Tachycardia

Elevated BP

Smooth muscle relaxation (bronchioles and skeletal muscle blood vessels)

Glycogenolysis

Skeletal muscle tremor

CNS stimulation

Front 14

Adrenergic Bronchodilators as Stereoisomers

Back 14

Different physiological effects

Example: levalbuterol

Front 15

What is Epinephrine & it stimulates what receptor(s)?

Back 15

Potent catecholamine bronchodilator

Stimulates both α- and β-receptors

Front 16

Epinephrine side effects

Back 16

High prevalence of side effects (not B2 specific)

Tachycardia

Increased BP

Tremor

Headache

Insomnia

Front 17

Isoproterenol

Stimulates?

Used for?

Back 17

Potent catecholamine bronchodilator

Stimulates both β1- and β2-receptors

Available parenterally

Primarily used for bradycardia

Front 18

Keyhole Theory of β2 Specificity states what?

Back 18

The larger the catecholamine side chain, the more β2 specific

Epinephrine- Equal α and β

Metaproternol- Strong β, little α

Racemic Albuterol

Levalbuterol- β2 preferential

Front 19

Catecholamines are metabolized by what?

Back 19

MAO & COMT

Heat Light Air

This makes its duration of action limited. 1.5 to 3 hours

Unsuitable for oral administration

Inactivated in gut and liver (1st pass effect)

Front 20

Saligenin Agents

Meds?

Duration?

Back 20

Example: Albuterol/Slabutamol (Europe)

Duration of action 4–6 hours

Peak effect 30–60 minutes

Front 21

Saligenin Agents are available as?

Benefits?

Back 21

Available as:

MDI

Syrup

Nebulizer

Extended-release tablets

Benefits:

β2 Preference

Effective by mouth

Front 22

Levalbuterol: The (R)-Isomer of Albuterol

Back 22

Pure (R)-isomer of racemic albuterol

Available as HFA MDI and nebulizer solution

Dose:

0.31 mg/ 3 ml

0.63 mg/3 ml

1.25 mg/ 3 mil

1.25 mg/0.5 ml concentrate

Front 23

Long-Acting β-Adrenergic (LABA) Agents

Back 23

Offer less frequent dosing and nocturnal protection

(Increased compliance and maintain bronchodilation for longer time)

Extended-release albuterol:

Salmeterol

Formoterol

Arformoterol

Front 24

Salmeterol

Available as?

Effects?

Duration ?

Back 24

Available as DPI (Diskus inhaler-with VHC)

Bronchodilator effect

Slower onset than albuterol

Time to peak bronchodilating effect, 3–5 hours

Duration, 12 hours

Front 25

Formoterol

What is it?

Duration?

Back 25

β2-Selective agonist

(Only given as a combination with steroid) symbicort or dulera

Short time to bronchodilatory effect (3 minutes)

Duration of up to 12 hours

Available as MDI & DPI

Used for:

Asthma (5 years +)

Exercise-induced bronchospasm (5 years +)

COPD

Front 26

Antiinflammatory Effects:

What is used? Its effects?

Back 26

Salmeterol and formoterol inhibit mast cell activation

Histamines are released by mast cells which cause inflammation

In vitro results only; not clinically proven

Front 27

Arformoterol

Duration?

Used for?

Available as?

Back 27

B2-Selective agonist

(Brov?)

Single isomer of formoterol

Duration of up to 12 hours

Available as nebulizer solution

Approved for: COPD

Front 28

Indacaterol

Use?

Duration?

Back 28

β2-Selective agonist

(Arcapi neohaler)

Short time to bronchodilatory effect (5 minutes)

Duration of up to 24 hours (Ultralong)

Front 29

What is the Clinical Use of LABA’s?

Back 29

Maintenance therapy of asthma not controlled by inhaled corticosteroids (Qvar & Flovent)

COPD needing daily bronchodilator

Front 30

When are LABA use not recommended ?

Back 30

Not recommended for rescue therapy

Not recommended for treatment of breakthrough symptoms

Front 31

GERD

Back 31

Can aggravate trachea and cause asthma

Can be corrected if you get GERD under control (acid reflex treatment, weight loss, medication treatment)

Front 32

α-Receptor stimulation action

Back 32

Vasoconstriction effect – upper airway

(Racemic epi)

Decongestion effect

Front 33

β1-Receptor stimulation action

Back 33

Increased HR and contractile force

Front 34

β2-Receptor stimulation Primary action

Back 34

Relaxation of bronchial smooth muscle

Inhibits inflammatory mediator release

Stimulates mucocilliary clearance

Front 35

β-Receptor activation

Back 35

1. Adrenergic binds to β-receptor

2. Stimulates G protein

3. GDP replaced by GTP

4. Adenylyl cyclase activated by G protein

5. Increased synthesis of cAMP = smooth muscle relaxation

Front 36

α-Receptor activation

Back 36

Inhibits release of neurotransmitter from the presynaptic neuron

But may also lower the synthesis of intracellular cAMP

Front 37

Mode of action by which stimulation of the G protein–linked β receptor by a β agonist causes

Back 37

smooth muscle relaxation

Front 38

LABA- (Salmeterol, Formoterol)

Back 38

Lipophilic – approach to receptor is lateral

Approach the receptor from the aqueous phase

Approaches β-receptor laterally

Lateral attachment to receptor site provides on-going stimulation of beta receptor = LABA

Lipophilic property causes retention- longer lasting effect

Front 39

Beta adrenergic bronchodilators route of administration

Back 39

Inhalation- MDI DPI

Nebulized

Orally - Tablets Syrup

Parenterally (Epi)

Front 40

Catecholamines

Back 40

are ineffective orally

Benefits of inhalation:

Rapid onset

Smaller doses

Reduced side effects

Drug delivered directly to the target organ

Relatively safe and painless

Front 41

Limitations of catecholamines in inhaled route

Back 41

Time

Public embarrassment

Difficult to use correctly

Front 42

Continuous nebulization

Back 42

Used for management of severe asthma

Reduces need for frequent therapist attendance

Generally 10 to 15 mg/hour for adult

Front 43

Continuous Nebulization delivery methods

Back 43

Refilling SVN

Volumetric infusion pump

Large-volume nebulizer

Front 44

Continuous Nebulization toxicity and monitoring

Back 44

Potential complications

Cardiac arrhythmias, hypokalemia (albuteral can be used to lower potassium level... risk can cause arrhythmias)

hyperglycemia, tremor

Front 45

Oral route advantages

Back 45

Easy to use

Short administration time

Reproducibility and controlled dosage

Front 46

Oral route disadvantages

Back 46

Longer onset of action

More systemic side effects

Beta 2 specificity lost due to 1st pass effect through the liver

Front 47

Parenteral Route

Back 47

Used in emergency management of acute asthma

Thought to be useful when obstruction prevents penetration of aerosol to lung periphery

SQ epinephrine 0.3 mg

SQ terbutaline 0.25 mg

Front 48

Parenteral route requires

Back 48

Should be used as a last resort and requires:

Infusion pump

Cardiac monitor

Close attention for systemic side effects

Front 49

Adverse Side Effects

Back 49

Side effect: Any effect other than the intended therapeutic effect

Tremor

Cardiac effects

Tolerance to bronchodilator effect

Loss of bronchoprotection

CNS effects

Fall in PaO2

Metabolic disturbances

Propellant toxicity and paradoxical bronchospasm

Sensitivity to additives

Front 50

Asthma paradox

Back 50

Increasing evidence of asthma mortality and morbidity despite advances in treatment

Lack of steroid use?

Loss of bronchodilator effect?

Increase in bronchial hyperreactivity?

Exposure to triggers with no immediate symptoms?

Front 51

For long acting B-agonist assess

Back 51

Assess ongoing lung function

Assess the use of rescue drug and nocturnal symptoms

Assess the number of exacerbations

Assess the days absent from work/school

Assess the ability to reduce the dose of inhaled corticosteroids