LAKSHMAN KARALLIEDDE
JANUARY 2011
1. Deliver oxygen to the cells
2.To eliminate carbon
dioxide from the body
3.To regulate the pH of
the blood
VENTILATION
Movement of air to and from the lungs
DISTRIBUTION
Air entering lungs are distributed to all parts including
the alveoli
DIFFUSION
Oxygen from the inspired air diffuses through the
walls of the alveoli to the blood capillaries surrounding
the alveoli-similarly carbon dioxide diffuses in opposite
direction
PERFUSION
Blood with high concentrations of carbon dioxide and
low in oxygen is pumped to the pulmonary arteries by
the right ventricle and after diffusion, the arterial blood
is returned to the left atrium by the pulmonary veins
PASSAGE OF OXYGEN AND CARBON DIOXIDE
SOURCE OF OXYGEN – INSPIRED AIR
SOURCE OF CARBON DIOXIDE-ALVEOLIFollowing diffusion from the blood due to metabolism
in the body.
PATHWAY FOR THE GASES:
PHARYNX
LARYNX-TRACHEA
BRONCHI
BRONCHIOLES
ALVEOLI
atmosphere
c
Carbon dioxide
o
oxygen
Right heartarteries
Left heart-arteries
Systemic circulation
Carbon dioxide
oxygen
COMMON SIGNS AND SYMPTOMS
1. COUGH
2. WHEEZING
3. SHORTNESS OF BREATH-DYSPNOEA
4. CYANOSIS
5. PAIN AROUND CHEST
COUGH – FORCED EXPIRATION AGAINST A CLOSED
GLOTTIS WHICH SUDDENLY OPENS TO EXPEL AIR AND
UNWANTED MATERIAL FROM THE RESPIRATORY TRACT
MAY BE VOLUNTARY OR INVOLUNTARY
Mucosal surface lining respiratory tract
Impulses relayed via vagus
Cough centre in brain
Efferent's
diaphragm glottis muscles of chest and
abdomen
Used in treatment of cough
The cough reflex- involves both central and peripheral nervous system as well as the smooth
muscle of the bronchial tree.
1. Irritation of the bronchial mucosa causes broncho-constriction, which stimulates
cough receptors located within the tracheo-bronchial tree.- when coughing as a
result of broncho-constriction may be relieved by bronchodilators acting simply
to dilate airways
1. Afferent nerves from these receptors via the vagus reaches multiple centres
within the medulla that are distinct from the actual respiratory centre. Drugs
acting primarily on the peripheral or central nervous system components of the
cough reflex.
2. Most effective antitussives have been shown to elevate the threshold for
coughing by poorly understood centrally mediated mechanisms.
COUGH SUPPRESSANTS
Unproductive distressing cough- central cough
depressants
e.g. pholcodine, dextromethorphan
Productive cough-do not use cough suppressants
Use expectorants and mucolytics
Expectorants-act by increasing the volume of
secretions in respiratory tract so that they may
be more easily removed by ciliary action and
coughing
e.g.ammonium salts, guaphenesin, ipecacuanha
Mucolytics- considered to affect sputum viscosity
e.g.acetylcysteine, bromhexine, carbocisteijne,
methyl cysteine
The principal non-opioid antitussive
Dextromethorphan-has a central action on the cough centre.
Morphine and related opioids depress the cough reflex , at least in part by a
direct effect on the cough centre in the medulla. Suppression of cough by such
agents appear to involve receptors in the medulla that are less sensitive to
naloxone than are those responsible for analgesia.
Structurally related to morphine but little or no analgesic properties,
And minimal (little) sedative activity.
Antitussive effects may persist for up to 5 hours.
Dextromethorphan should not be administered to patients with or at risk of
•Developing respiratory failure.
•Do not administer to patients on monoamine oxidase inhibitorsrisk of severe reactions-hyperpyrexia, fatalities
PHOLCODINE
CENTRALLY ACTING COUGH SUPPRESSANT
UNLIKE CODEINE, THERE IS LITTLE OR NO METABOLISM
TO MORPHINE
LONGER HALF-LIFE THAN CODEINE- DOSES MAY BE GIVEN ONCE
OR TWICE A DAY
ANTIHISTAMINES E.G. DIPHENHYDRAMINE
OFTEN USED AS ANTI-TUSSIVES
MODE OF ACTION – UNCERTAIN
SUGGESTIONS-
a. Reduction in cholinergic transmission
b. Suppression of cough because of sedative action
c. Reduces nasal secretions and therefore the post-nasal
drip that causes cough
d. Should not be used to treat productive cough as it
increases the viscosity of the mucus
The viscosity of pulmonary mucus secretions depends on the concentrations of mucoproteins
and deoxyribonucleic acid (DNA).
While mucoprotein is the main determinant of viscosity in normal mucus, in purulent
inflammation the mucoid concentration of DNA increases (due to increased cellular debris)
and so does its contribution to mucoid viscosity.
Some patients with respiratory tract disease, the bronchial inflammation
will be associated with the presence of large amounts of relatively viscous, inflammatory exudate
and mucus which is firmly attached to the lining of bronchioles and bronchi.
This would in practical terms increase bronchial wall thickness.
Adverse effects of increased mucus accumulation are
1. Increase the "lumen narrowing" effects of bronchial constriction
2. Enhance the overall inflammatory process
3. Potentiate persistent coughing.
Mucolytics would be useful in facilitating recovery/relief of
symptoms
The two most frequently prescribed mucolytics
• bromhexine hydrochloride
• Acetylcysteine-probably reduces viscosity by splitting the
disulphide bonds in mucoproteins
• Other forms:
Normal saline, directly administered to the airways by
effective nebulisation therapy-extremely effective mucolytic
and expectorant
DORNOSA ALFA
ACTS AS A MUCOLYTIC
BY HYDROLYSING DNA THAT HAS ACCUMULATED IN THE
SPUTUM FROM DECAYING NEUTROPHILS
USED AS A NEBULIZING SOLUTION IN PATIENTS WITH
CYSTIC FIBROSIS
Physiological bronchial tone
mediated by three neuro-endocrine systems:
1. Parasympathetic system: dominant efferent pathway providing the baseline tone of
mild broncho-constriction - characterizes the normal respiratory tract
2.Sympathetic system -mediates these inherent broncho-constrictive effects through
a. beta 2-adrenergic-mediated broncho-dilation
b. alpha 1-mediated broncho-constriction
c. possibly beta 2-mediated reduction of parasympathetic broncho-constriction
3. The non-adrenergic, non-cholinergic (NANC) system:
a. mediates broncho-dilation through various neurotransmitters e.g. Vaso-active
intestinal peptide.
BRONCHODILATION ACHIEVED
• via anticholinergic agents- ipratropium bromide 0.5 mg nebulised
repeat every six hours (including beta 2 agonists),
• beta 2 adrenergic receptor agonists –nebulised salbutamol (2.5-5.0
mg every two to six hours, terbutaline
• agents such as the methylxanthines which produce
bronchodilation at least in part due to increased intracellular
cAMP levels in bronchial smooth muscle.
•Inhaled anti-inflammatory agents- corticosteroidsbeclomethasone or budenoside 100-400 micrograms twice daily
• Oral corticosteroids-40-60 mg once daily
•Intravenous hydrocortisone- 200 mg every six hours
Adrenergic agonists
All adrenergic agonists have variable alpha and beta receptor affinity.
Due to the distribution of alpha and beta receptorsnon-selective beta receptor agonists such as isoprenaline or
mixed alpha and beta receptor agonists such as adrenaline
are more likely to produce cardiovascular side effects than similarly administered selective beta agonists.
THEREFORE DRUGS WITH PREFERENTIAL AFFINITY FOR BETA 2 RECEPTORS PROVIDE MORE EFFECTIVE
BRONCHODILATION WITH FEWER SIDE EFFECTS.
A possible exception may be with the treatment of acute allergic bronchospasm.
The M-2 receptor-mediated inhibition of cholinergic bronchospasm may be helpful.
For this reason, the use of an adrenergic agent with both alpha 2 and beta 2 agonist activity may be
beneficial in the peracute management of allergic bronchospasm.
Due to risks associated with administering systemic non-selective adrenergic agonists to a hypoxic and
already tachycardic patient, it is preferable for them to be administered by inhalation.
Selective beta 2 agonists- lead to rapid and effective pulmonary beta 2 receptor activation with low
systemic drug concentrations by inhalation of small doses of the drug in aerosol form.
METHYLXANTHINES
POSSIBLE ACTIONS
1.Relaxation of smooth muscle, particularly bronchial smooth muscle
2.Stimulate the central nervous system
3.Weakly positive chronotropes and inotropes
4.Mild diuretics.
Naturally occurring methylated xanthines
Caffeine, theophylline and theobromine - relatively insoluble. Solubility enhanced by the
formation of complexes with a wide variety of compounds e.g. aminophylline which is the
ethylenediamine
complex of theophylline with differing quantities of water of hydration.
When dissolved in water, aminophylline readily dissociates to its parent compounds.
Theophylline has a low therapeutic index- Therefore dose rates should be determined on lean
body mass.
The dose rate of theophylline varies depending on the preparation used.
OPIOID ANTITUSSIVES
Widely available at present- codeine phosphate and hydrocodone.
Codeine has a high oral-parenteral potency with oral administration providing around 60% of its
parenteral efficacy. Once absorbed, codeine is metabolized by the liver . Inactive metabolites
excreted predominantly in the urine. In man approximately 10% of administered codeine is
demethylated to form morphine -and both free and conjugated forms of morphine can be
found in the urine of patients receiving therapeutic doses of codeine.
In man, codeine's plasma half-life is around 2 to 4 hours.
Codeine phosphate is contained in numerous "over the counter" analgesic preparations as well
as in 30 and 60mg tablets which have restricted scheduling.
Hydrocodone is generally marketed in combination with homatropine as both an elixir and tablet
formulations. The addition of homatropine is designed to enhance any reduction in respiratory
secretions, which may come about as a result of the administration of hydrocodone.
BENZONATATE
Cough suppressant believed to act both centrally and peripherally.
Related to amethocaine ( a local anaesthetic) and therefore has a local anaesthetic action on
the mucosa.
.
LEUKOTRIENE RECEPTOR ANTAGONISTS
Inflammation of the respiratory tract is frequently characterised by
the classical markers of inflammation;
•accumulations of inflammatory cells
•exudate.
•associated with varying degrees of bronchoconstriction
•and, or, bronchospasm.
• Additionally "airway hyper reactivity" may become a standard
response of sensitised patients to various inhaled compounds.
Although glucocorticoids remain the "gold standard" in controlling
this inflammatory-induced bronchoconstriction, the leukotriene
receptor antagonists represent a new class of drugs which may
facilitate management of these various forms of bronchoconstriction.
DEMULCENTS
INDIRECTLY ACTING COUGH
SUPPRESSANTS
? MODE OF ACTION
POSSIBLY BY PROVIDING A
PROTECTIVE COATING OVER
THE SENSORY RECEPTORS IN
THE PHARYNX
EXAMPLES- GLYCEROL, HONEY,
LIQUORICE AND SUCROSE
SYRUPS
HYDRATION
1.LIQUEFYING MUCUS
2.DEMULCENT EFFECT
3.METHODS
DRINK PLENTY OF FLUIDS
STEAM INHALATION
INHALATION OF AEROSOLS CONTAINING
WATER, SODIUM BICARBONATE, SODIUM
CHLORIDE,
SURFACTANTS E.G. TYLOXAPAL
PROTEOLYTIC ENZYMES E.G.
CHYMOTRYPSIN, TRYPSIN
BTS GUIDELINES FOR MANAGEMENT OF
ASTHMA
1. INHALED SHORT-ACTING BETA-2
AGONIST AS REQUIRED
2. ADD INHALED STEROID-200800MICROGRMS/DAY
3. ADD INHALED LONG-ATINGBETA 2
AGONIST- CONSIDER INCREASING
STEROID INHALED DOSE
4. CONSIDER USING LEUKOTRIENE
RECEPTOR ANTAGONIST OR
THEOPHYLLINE
ADAPTED FROM THORAX 2008;63 (suppl
4):
ACUTE BRONCHITIS
TREATMENT USUALLY NOT REQUIRED IN
PREVIOUSLY HEALTHY PATIENTS BELOW
AGE 60
EXACCERBATION OF COPD-START WITH
DOXYCYCLINE 200MG OD -SECOND LINEAMOXICILIIN (OR CO-AMOXICLAV)
BRONCHIECTASIS-CO-AMOXICLAV 1.2 G
TDS IV OR IF AVAILABLE PIPERICILLIN +
TAZOBACTAM 4.5 G TDS
CYSTIC FIBROSIS- CIPROFLOXACIN
500MG BD ORALLY OR 400MG BD IV IF
PSEUDOMONAS IS SUSPECTED
Adapted from Pocket Prescriber
ADVERSE EFFECTS OF INHALED
CORTICOSTEROIDS EXAMPLE
BECLOMETASONE
1. ORAL CANDIDIASIS ( decreased by
rinsing mouth with water after use)
2. HOARSE VOICE3. RARELY GLAUCOMA
4. INCREASING DOSES MAY CAUSE
ADRENO-CORTICAL SUPPRESSION,
CUSHING’S
5. DECREASE IN DENSITY OF BONES
6. DECREASE IN GROWTH HORMONE ?
7. Very rarely-paradoxical bronchospasm
Adapted from Pocket Prescriber
SALBUTAMOL
BETA 2 AGONIST- SHORT ACTING
ACTIONS:
1. DILATES BRONCHIAL SMOOTH MUSCLE
2. RELAXES UTERINE SMOOTH MUSCLE
3.INHIBITS MAST-CELL MEDIATOR RELEASE
BEWARE USE -IN CARDIO-VASCULAR DISEASE Esp. arrhythmias-susceptibility to
increased QTc
- DIABETES MELLITUS- MAY INCREASE RISK OF DIABETIC
KETO-ACIDOSIS
- MAY INCREAE THYROXINE LEVELS
SIDE EFFECTS- FINE TREMOR, HEADACHE, NERVOUSNESS
INCREASE IN HEART RATE, PALPITATIONS, ARRHYTHMIAS
DECREASE IN SERUM POTASSIUM
MUSCLE CRAMPS
Prolonged treatment -? Increased risk of glaucoma
THEOPHYLLINE
METHYLXANTHINE BRONCHODILATOR- Additive effects with beta 2 agonists but
increases risk of hypokalaemia
Beware – caution in patients with
• Cardiac disease especially risk of arrhythmias,
• Epilepsy
• Peptic ulcer
• Hypertensive heart disease
• Fever
• Porphyria
• In acute febrile illness
• Glaucoma
• Diabetes mellitus
THEOPHYLLINE
SIDE EFFECTS• ARRHYTHMIAS
• SEIZURES
• GASTRO-INTESTINAL UPSET- NAUSEA
• RESTLESSNESS, INSOMNIA
• HEADACHE
• LOWERS SERUM POTASSIUM
MONITOR- SERUM POTASSIUM, BLOOD LEVELS 6 HR AFTER
ADMINISTRATION
TOXIC EFFECTS MAY OCCUR EVEN WITH NORMAL BLOOD
LEVELS E.G. 10-20MG/L
MONTELUKAST
LEUKOTRIENE RECEPTOR ANTAGONIST
CAUTION
1. ACUTE ASTHMA
2. CHURG-STRAUSS SYNDROME (asthma with + or – rhinitis, sinusitis with
sytemic vasculitis and increased eosinophil counts
MONTELUKAST
SIDE EFFECTS
1. HEADACHE
2. GASTRO-INTESTINAL UPSET
3. MYALGIA
4. DRY MOUTH/THIRST
MONITOR
FULL BLOOD COUNT
WATCH FOR VASCULITIS
PERIPHERAL NEUROPATHY
INCREASED CARDIAC AND RESPIRATORY SYMPTOMS