Transcript Inhalation

Pulmonary Disorders
Pharmacologic
Interventions
Wanda Lovitz, APRN
Obstructive Pulmonary Disease
An “Umbrella Term”
Asthma
Emphysema
Chronic Bronchitis
GENERIC NAME
albuterol
TRADE NAME
Proventil
ROUTE
CLASSIFICATION
Short-term beta² agonist
SABA
Inhaled Q4-6H
(bronchodilator)
salmeterol
Serevent diskus
Long-acting beta² agonist
LABA
Inhaled Q12H
(bronchodilator)
ipratropium
Atrovent
Anti-cholingergic
Short acting anti-cholingergic
Inhaled Q4-6H
tiotropium
Spiriva
Anti-cholingeric
Long acting anti-cholingergic
Inhaled once daily
theophylline
Theodur
Methylxanthine
(brochodilator)
PO
beclomethasone
Beclovent
Glucocorticoid
(steroid)
Inhaled Q4-6H
triamincolone
Azmacort
Glucocorticord
(steroid)
Inhaled Q4-6H
prednisone
Prednisone
Glucocorticoid
(steroid)
PO varying dose sc
fluticasone AND
salmeterol
Advair
Corticosteroid + a LABA)
Inhaled BID
*NOT a rescue inh
*INDICATED for Asth
montelukast
Singulair
(children)
Leukotriene modifier
PO daily
Leukotriene modifier
Inhaled
Obstructive Pulmonary Disease:
Pharmacology
 Two
1.

2.
Major Groups of Drugs
Bronchodilators
PREVENT/TREAT bronchoconstriction
Anti-inflammatory agents

PREVENT/TREAT inflammation

↓ inflammation will ALSO ↓ bronchoconstriction by:



↓ mucosal edema
↓ mucous secretion
↓ hyper-reactivity to various stimuli
Nervous System
Peripheral
Central
Autonomic
Brain
Spinal cord
Somatic
(Skeletal Muscle)
Parasympathetic
(cholinergic) ACh
Nicotinic receptors
Muscarinic receptors
Beta¹ receptors mainly in heart;
Beta² receptors mainly in lungs
FIGHT OR FLIGHT
↑ HR and cause bronchodilation
Sympathetic
(adrenergic) NE
Alpha ¹ & ² receptors
Beta ¹ & ² receptors
Question:
If you were giving BOTH a
bronchodilator and an antiinflammatory to the client,
which would you give first?
What is a “beta agonist”???

Beta agonists are SYMPATHOMIMETIC drugs



They “mimic” the action of the SNS ”fight or flight”
Bronchodilation
Beta Agonist Turn the SNS ON!!
Ideally have“SELECTIVE” activation of beta2-adrengeric
receptors


B2 agonist activate receptors in smooth muscle of the
lungs
B2 agonist also:
 suppress the release of histamine
 increase ciliary motility
Pharmacodynamics: Receptors



Receptor Theory of Drug Action
RECEPTORS are PROTEINS located on surfaces of cell
membranes
Are special CHEMICALS in the body that drugs interact with to produce
effects (hormones, neurotransmitter, other molecules)

When drug molecules bind with receptor molecules
→ result in a
→INITIATES
DRUG-RECEPTOR COMPLEX which
physiochemical reactions that STIMULATE/activate
OR INHIBIT normal cellular function


 agonistic (stimulates)
 antagonistic (inhibits)
Receptor – “ON” or “OFF”
Drug binds
to a receptor
and either
The light switch is either
“ON” or it is “OFF”
• MIMICS or BLOCKS
the normal physiological
activity controlled by the
receptor
Receptor Theory of Drug Action:
Antagonist

Antagonist

A drug that produces its action not by
stimulating receptors but by PREVENTING
OTHER, natural substances from stimulating
receptors

Examples:

ranitidine (Zantac) = H² ANTAGONISTBLOCKS release of gastric acid

diphenhydramine (Benadryl) = H¹
ANTAGONIST- BLOCKS action of histamine

propranolol (Inderal) = beta¹ adrenergic
ANTAGONIST – BLOCKS action of epinephrine
Adrenergic/Sympathetic Beta Receptors

Beta receptors are a type of adrenergic receptor

B1 receptors mostly in heart and kidney

activation causes increase in HR and and increase release of renin (↑ B/P)


B2 receptors mostly in lungs and uterus



Inderal – beta 1 receptor antagonist – blocks actions of epinephrine
activation causes BRONCHODILATION and uterine relaxation
B3 receptors mostly in adipose tissue
Activation of beta receptors triggers an adrenergic response or
MIMICS the SNS


think ‘fight or flight” ADRENERGIC uses ADRENALIN
increased in HR and force, vasodilation of lungs, smooth muscle
contraction….body is ready to FLEE!
Autonomic Nervous System
Which one dominates?
B-2 receptors
Bronchodilators: Classifications
1. Beta-agonists
2. Anti-cholinergics
3. Methylxanthines
Beta-agonists: 3 Classifications
Other names: ADRENERGIC agents or SYMPATHOMIMETICS: mimic
SNS

Nonselective ADRENERGIC


(Stimulate alpha, beta¹ & beta²)
Nonselective BETA-ADRENERGIC drugs


drugs
(Stimulate beta¹ & beta²)
Selective BETA drugs


(Stimulate ONLY beta² receptors)
Cause relaxation of bronchioles
For a beta-agonist to dilate the airways of lungs, it must
stimulate beta²-adrenergic receptors located throughout the
lungs
Beta-agonists (remember agonists enhance the response)

MOA:

If stimulate beta¹ receptors: (these receptors are located mostly in the heart)


↑ rate/force of ventricular contraction (may be an adverse effect when given for bronchodilation)
If stimulate alpha receptors (mostly in heart):
↑ vasoconstriction

(what we do not want!)
If stimulate beta²-adrenergic receptors (mostly in lungs):

RELAXATION OF SMOOTH MUSCLE IN BRONCHI/BRONCHIOLES
Beta Agonists: Methods of deliver



Orally – not used as often
Most often by INHALATION
 MDI (metered dose inhaler)
 DPI (dry powder inhaler)
 Nebulizer (med in a solution and delivered with high flow oxygen to make a mist)
Short acting vs long acting inhalation




Most inhaled B2 agonist are short-acting (SABA)
Duration =Q4-6H
A commonly RX
‘LONG ACTING INHALED B2 AGONIST’ (LABA):

Salmetrol

/Serevent Diskus
Duration – 12H
Can you identify these?
Comparison of Inhalation Techniques:
Unsatisfactory Technique
Excellent Technique
Beta-agonists

Indications for Use:


Treatment of bronchial asthma, bronchitis, emphysema
Adverse Effects:
 SELECTIVE beta² agonists →


ALPHA-BETA agonists → MOST ADVERSE EFFECTS- because they are
NONSELECTIVELY stimulating cardiacreceptors as well as lung receptors


Minimal; tremors
Insomnia, restlessness, anorexia, CARDIAC STIMULATION, tremor, vascular
headache
Nonselective beta-agonists → limited to beta-adrenergic
effects/cardiac constriction effects


CARDIAC STIMULATION, tremor, ANGINAL PAIN, vascular headache
We like the SELECTIVE BETA 2 AGONISTS  they work
where we want them to work for COPD……the LUNGS!!
Beta-agonists: Common Drugs

albuterol /Proventil **

Short-acting beta² agonist (SABA): onset minutes

Inhalation

RESCUE DRUG!

Delivery method: MDI or nebulizer → FIRST LINE of
treatment for acute asthma attack!

PO → Proventil Repetabs; Proventil Syrup used for
long-term moderate to severe asthma; not to be used for
exacerbations
albuterol/Proventil Inhaler: Treatment Of
Choice For ACUTE Asthma Attack
Proventil is a RESCUE drug!

Use of more than one canister per month indicates
inadequate control of asthma & need for initiating
or intensifying anti-inflammatory therapy


200 ACTUATIONS per cannister
Regularly scheduled daily use is NOT
recommended
* Also for PREVENTION of EIA (exercise induced asthma)
And now....Anticholinergics
Nervous System
Peripheral
Central
Autonomic
Brain
Spinal cord
Somatic
(Skeletal Muscle)
Parasympathetic
(cholinergic) ACh
Nicotinic
Muscarinic
REST and Digest-things get ‘wetter’
increase salivation, lacrimation, urination
Sympathetic
(adrenergic) NE
Alpha ¹ & ²
Beta ¹ & ²
Parasymphathetic Cholinergic Receptors

Cholinergic receptors- certain type of cells that respond
to a specific neurotransmitter called acetylcholine

Due to their location and reaction to acetylcholine, the
cholinergic receptors control responses that occur in the
heart, intestine, prostate, bladder

Giving ANTI-cholinergic agents results in



Turning off cholinergic response (PNS) and turning on SNS
SNS dominates = bronchodilation
Thus increasing perfusion to heart, lungs, and brain
Lungs
Heart
Anticholinergics are also used to treat OPD
Action is also BRONCHODILATION, but by a different mechanism than the Beta
Blockers
Eye
Action Sites of
Anti-cholinergics
Exocrine
glands
Bladder
GI
tract
Anti-cholinergics: Side Effects
Blockade of cholinergic receptors
Anti-cholinergic Effect
“Can’t see, can’t pee, can’t spit, can’t poop!”
Anti-cholinergics
(anti = blocking of the receptors: antagonist drugs)

MOA:


Blocks the action of ACETYLCHOLINE in bronchial smooth
muscle when given by inhalation →

keeps those MUSCLES around the large airways from tightening =
BRONCHODILATION but by a different mechanism than Beta
blockers which works on the BRONCHIOLES.
Indications for Use:

Used prophylactically/maintenance of emphysema & bronchitis
Action is SLOW and PROLONGED

NOT a RESCUE inhaler


Treatment of asthma (off label)
Anti-cholinergics

ADVERSE EFFECTS:

Dry mouth, visual difficulities,GI distress, constipation,urinary retention, anxiety


d/t blocking those cholinergic receptors
COMMON DRUGS:


Works SYNERGISTICALLY with beta agonists


may be given concomitantly
(1+1=3)
Combivent (inhalation) also known as Duoneb


Atrovent ** (qid)
ipratropium bromide /
A product that contains both albuterol & ipratropium
tiotropium bromide

(SPIRIVA) (Feb, 2004)*
First once-daily maintenance therapy for COPD
** Prototype
And finally......Methylxanthines


MOA:
 Bronchodilation 2 smooth muscle relaxation
 Also stimulate CNS & CVS (esp. heart)
Indications for Use:

SECOND-LINE agent may be added in severe OPD
(all 3)

ADVERSE EFFECTS:

TOXICITY: N/V/D, insomnia, H/A, tachycardia,
dysrrhythmias, seizures (especially in elderly)
Methylxanthines

Common Drugs:

theophylline

TheoDur, **
PO, IV or rectal

Take with food
Caffeine may ↑ side effects
Smoking → ↓ absorption

NARROW THERAPEUTIC INDEX DRUG!



Maintain serum level 5-15 mcg/ml
**PROTOTYPE
Anti-inflammatory Agents:
Classifications
Corticosteroids/Glucocorticoids
Leukotriene Modifiers
Mast cell stabilizers
Effect of Cortisol on the Body

NATURAL CORTISOL has important effects in the
body, including regulation of:

Protein, carbohydrate, lipid and nucleic acid
metabolism

Inflammation and immune response

Distribution and excretion of water and solutes

Secretion of adrenocorticotrophic hormone
(ACTH) from the pituitary gland.
Corticosteroids


Most potent &
effective antiinflammatory
medication
currently available
INDICATION: as
prophylaxis
NOT used to gain immediate control
of an ongoing acute attack
Corticosteroids

MOA: (anti-inflammatory action)
1. SUPPRESS INFLAMMATION in airways by:
 ↓ movement of fluid/protein into tissues
 ↓ migration/function of neutrophils/eosinophils


↓ synthesis of histamine in mast cells
↓ production of pro-inflammatory substances
2. ↑ NUMBER/SENSITIVITY of beta² adrenergic RECEPTORS
to bronchodilators
Corticosteroids: methods of
delivery

SYSTEMIC STEROIDS work in the same way as natural
cortisol, and are prescribed for a large number of
serious diseases

They are called "SYSTEMIC" steroids if taken by mouth or
given by injection as opposed to

TOPICAL CORTICOSTEROIDS which are applied directly to

INHALED CORTICOSTEROIDS which are inhaled via a
the skin or
nebulizer or MDI
Corticosteroids

Indications for Use:

INHALED form:

CORNERSTONE OF ASTHMA THERAPY (long-term control)



(Not typically indicated for tx of COPD)
Advantage →
limited to topical site of action → the lungs
SYSTEMIC (IV or PO) form:



Used to gain prompt control of asthma when initiating long-term
therapy
Early stages of COPD → unlikely to need; however, may need
short-course therapy for episodes of respiratory distress (PO/IV)
End-stage COPD → often become “steroid-dependent”
Corticosteroids: Asthma

Used regularly to prevent symptoms, i.e. as
“PREVENTOR drug” (even if asymptomatic)


Used for maintenance therapy (not acute attacks)
ADVERSE EFFECTS:

Inhalation

Limited 2 route (sore throat, dry mouth, infection)
Teach client to rinse mouth after each administration to ↓
potential for fungal infections (ie, candidiasis*) of the
mouth

Use of SPACER also decreases med deposit in

mouth
Corticosteroids

Common Drugs:

Inhalation (Meter-Dose Inhaler)



(
beclomethasone dipropionate Beclovent
triamcinolone acetonide (Azmacort)
) **
SYSTEMIC (PO/IV)



prednisone (Prednisone)
hydrocortisone (Solu-Cortef)
methylprednisolone (Solu-Medrol)



Take with food
Follow dosing schedule exactly
3-10 day course of treatment (Lehne – “acute” use)
PROTOTYPE **
Most common SE of inhaled
corticosteroids

Oropharyngeal
candidiasis
“thrush”
Prevention:
Rinse and spit


Treatment:
Anti-fungal agent

Systemic Steroids: Short term vs
Long term

Treatment for less than ONE MONTH is considered SHORT
TERM treatment

Majority of SE seen with LONG TERM
SYSTEMIC steroids

Steroid treatment continuing for more than 3 MONTHS
is regarded as LONG TERM
SIDE EFFECTS OF SYSTEMIC CORTICOSTERIODS (will be in
covered in more detail in the stress lecture

Skin problems (infection, easy bruisng, thinning, acne)
Sleep disturbance
Increased appetite
Weight gain
Psychological effects, including ACUTE PARONIA
INCREASED OR DECREASED ENERGY
Reduction of your own cortisol production

Osteoporosis (thinning of the bones)

Redistribution of body fat:(moon face, buffalo hump,








truncal obesity = CUSHING’S SYNDROME
Increased suseptibility to internal infections (TB)
Peptic Ulcers
Combination Drug: ADVAIR

Advair – Diskus and MDI

Is a combination of fluticasone (corticosteroid)
AND salmeterol (LABA)

Caution: BLACK BOX WARNING!
Indication: Is a PREVENTOR DRUG


Approved for treatment of asthma in patients 4 years and
older. NOT approved for emphysema and bronchitis


IS NOT A RESUCE DRUG!
Indicated for MODERATE TO SEVERE ASTHMA
Advair: Black Box Warning

WARNING: ASTHMA-RELATED DEATH

Long-acting beta2-adrenergic agonists (LABAs),
such as salmeterol, one of the active ingredients in
ADVAIR HFA, increase the risk of asthma-related
death.

Should only be prescribed for moderate to severe
asthma.

Patient teaching a MUST! Not a rescue drug
Leukotriene Modifiers

Fairly new class of asthma medication; first in over 20
years

Leukotrienes



Cause inflammation, bronchoconstriction, & mucous
production
MOA of leukotriene modifiers:
Anti-inflammatory action



PREVENTS leukotrienes from attaching to receptors
(block inflammation) by:



(1) inhibiting enzymes
(2) inhibiting proteins or
(3) blocking receptors
Leukotriene Modifiers

INDICATIONS FOR USE:

PREVENTOR DRUG:



Oral prophylaxis & chronic treatment of asthma in adults &
children 6 years old
NOT MEANT FOR ACUTE ASTHMA ATTACKS!!
ADVERSE EFFECTS:

Headache, dyspepsia, nausea, dizziness, insomnia
Leukotriene Modifiers

Common drugs (oral):



zafirlukast /Accolate** - for adults
montelukast/ Singulair** – once
daily dose for children
Improvement seen ≈ 1 week
**PROTOTYPE
Mast Cell Stabilizers

Common drugs:


cromolyn (Intal)** – first agent developed
MOA: (anti-inflammatory action)

Stabilize membranes of mast cells & prevent release of
bronchoconstrictive/ inflammatory substances


when mast cells are confronted with allergens/other stimuli they release
mediators of inflammation
Indications for Use:

PREVENTOR DRUG

Used for prophylaxis of acute asthma attacks in clients with chronic
asthma (prior to exercise or known allergen)
Mast Cell Stabilizers

Use may allow ↓ dosage of bronchodilators &
corticosteroids


Use 15-20 min prior to known trigger


PROPHYLAXIS USE ONLY!
exercise, pollutants, etc.
Adverse Effects:


Very safe drug
Occ cough, sore throat, bronchospasm
Two Categories of Medications Used
to Prevent & Treat OPD,
(Particularly Asthma)
1. Long-term control medications

AKA:



Long-term preventive
Controller
Maintenance
2. Quick-relief (RESCUE) medications

AKA:


Reliever
Acute rescue
OPD Medications:
Routes of Administration

Two routes:
1. Inhaled “aerosols”


Major advantages:
 Higher concentrations can be delivered more
effectively to airways
 Systemic adverse effects are avoided or minimized
 Onset of inhaled bronchodilators < oral
bronchodilators (5-15 minutes)
‘Rinse
& spit’ following inhalation
2. Systemic

Oral or parenteral
Inhaled Medications:
A Variety of Devices

Metered-dose inhaler (MDI)
 Actuation during a slow, deep inhalation (3-5 secs)

Followed by 10-second breath-holding;
Wait one minute between each puff

Do bronchodilator BEFORE anti-inflammatory agent



Open-mouth technique (1-2 inches) vs. closed-mouth
technique
Population: > 5 years
Inhaled Medications:
A Variety of Devices

Breath-actuated MDI



Slow inhalation (3-5 secs) - followed by 10-second breathholding
400 inhalations/cannister
Indicated for clients unable to coordinate inhalation and
actuation

cannot be used with spacer/holding chamber devices

Population: > 5 years

“Maxair Autohaler”
Inhaled Medications:
A Variety of Devices

Spacer/holding chamber

Slow (3-5 secs) inhalation or tidal breathing immediately
following actuation

Easier to use than MDI alone

Recommended for anyone using MDI!

Population: > 4 years,  4 years with face mask
Inhaled Medications:
A Variety of Devices

Nebulizer

Slow tidal breathing with occasional deep breaths

tightly fitting face mask for those unable to use mouthpiece

Less dependent on client coordination/cooperation

DELIVERY METHOD OF CHOICE for cromolyn in children & for
high-dose beta² agonists/anticholinergics in MODERATE-TO-
SEVERE EXACERBATIONS IN ALL CLIENTS
Moving on
Drugs to treat Tuberculosis
Drugs to KNOW: Drugs to Treat TB





isoniazide/INH
pyrizinamide/PZD
rifampin/Rifadin
ethambutol/Myambutol
Streptomycin
Pharmacological Treatment of TB

1. PERSONS WITH ACTIVE TB

At least 6 months of tx with multiple agents

Multiple drug regimens for 6-12 months

Treatment may last up to 24 months…especially with multi-drug
resistant TB
2. PERSONS WITH CLOSE CONTACT TO CASES OF
ACTIVE TB and persons with positive PPD but no active
disease (prophylactic treatment)
 SINGLE DRUG REGIMEN: INH FOR 6-
9 MONTHS
American Thoracic Society:
3 Principles On Which Treatment For TB Are Based
1. Regimens must include MULTIPLE DRUGS to
which the organisms are susceptible
2. The drugs must be taken REGULARLY
3. Drug therapy must continue

for a sufficient time to provide

safest/most effective therapy in shortest possible
period
Antitubercular Agents:
5 First-Line Primary Agents

isoniazid (INH) *

rifampin (Rifadin) **

pyrazinamide (PZA) **

ethambutol (Myambutol) **

Streptomycin **
* Prototype
** Know adverse effects of drug
isoniazid (INH)*
Mainstay of treatment of TB
MOA:
 Inhibits cell wall synthesis of mycobacterium
 depletes pyridoxine (B6) (needed for cell to multiply)
 SE/Adverse Reactions:
 Hepatoxicity
 Peripheral neuropathy
 Tx for neuropathy may include:
 pyridoxine (Vitamin B6) q day
* PROTOTYPE
Why would a patient receiving INH therapy
take vitamin B6?

Vitamin B6 (pyridoxine) is needed for nerve conduction
and the synthesis of neurotransmitters

A decrease in B6 levels can result in nerve damage

Nerve damage can cause “peripheral
neuropathy”


Peripheral" means nerves further out from the center of the body, distant from the
brain and spinal cord."Neuro" means nerves."Pathy" means abnormal)
Neuropathic symptoms:

Pain, burning, numbness, pins and needles sensation
isoniazid (INH)
Prophylaxis  use alone 6 months – 1 year
Active TB  use with 1 – 2 other drugs – minimum 6
months and up to 2 years for resistant TB
 Monitor liver function tests (LFT’s)
rifampin (Rifadin)
 MOA:
 Inhibits protein synthesis (cell
cannot divide)
 SE/Adverse Reactions:
 Induces hepatic microsomal
enzymes & accelerates
metabolism of numerous drugs
 MONITOR LFTS AND
ASSESS FOR JAUNDICE
AND ENLARGED LIVER
  ½ life/therapeutic effects
of some drugs
 Causes harmless redorange discoloration of
body fluids
pyrazinamide (PZA)
 Used WITH other antibtubercular agents in
treatment of clinical TB
 MOA:
 Unknown ? inhibits lipid synthesis ?
 SE/Adverse Reactions:
 Hepatoxicity (Check LFT’s)
ethambutol (Myambutol)
MOA:
 Inhibits protein synthesis of mycobacterium cell
wall
SE/Adverse Reactions:
Optic neuritis (infection of the optic nerve)
  visual acuity &  ability to differentiate red from
green
 reversible with discontinuation of drug therapy
streptomycin
 Aminoglycoside ANTIBIOTIC
 1944 – first TB drug
 Used today WITH COMBINATIONS ONLY 2° drug toxicities:
 Hepatoxicity
 Otoxicity
 Nephrotoxcity
 Given parenterally (IM)
MOA:
 Inhibits protein synthesis
TB: Sample Drug Plan

Drug-susceptibility tests
performed



Once test results
available, meds
adjusted accordingly

Active disease? Will
feel better in 2-3
weeks
Culture may take 2-12
weeks
Before results are known,
client is started on 4-drug
regimen (’s possibility of
resistant organisms):

isoniazid

rifampin

pyrazinamide

ethambutol or streptomycin
What is DOT Therapy?
Direct Observation Therapy (DOT)

Advocated by the World Health Organization (WHO)

Form of treatment that requires that another person
actually watch the client as the prescribed drugs are
taken


Can ↑ compliance to near 100%
Can be conducted with regimens given once daily, 2
times weekly, or 3 times weekly
THE END OF THE ROAD FOR TODAY!