5. Drugs acting on respiratory system, eye and miscellaneous drugs

Locally Acting Drugs

Locally acting drugs are applied onto the skin and sometimes  on mucous membranes, the benefits include:

  1. Concentration of drug at site of application is high
  2. Systemic absorption is negligible
  3. Adverse effects are minimum as compared to systemic preparations.

Types of applications

  •       Tinctures
  •       Wet dressings
  •       Lotions
  •       Gels
  •       Aerosols
  •       Powders
  •       Pastes
  •       Creams
  •       Ointments

Tinctures and wet dressings are usually applied over oozing lesions because of drying of lesions and in descending order these preparations are applied over dry thick skin to act as lubricant.

Names of groups

  •       Demulcents
  •       Emolients
  •       Irritants/counter irritants
  •       Antiseborrheics
  •       Astringents
  •       Ectoparasiticides
  •       Anti-acne drugs
  •       Anti-warts drugs
  •       Anti-pigmentation drugs
  •       Sunscreens
  •       Drugs affecting hair growth
  •       Antiseptics/disinfectants

A. Demulcents


Means to ‘smooth down’. These are protective agents applied over skin to treat irritation.


  •       Gum acacia
  •       Tragacanth
  •       Glycyrrhiza
  •       Synthetic cellulose

-Methyl cellulose

-Carboxy methyl cellulose

  •       Glycerine
  •       Starch

-Barley starch

-Wheat starch

B. Emolients

External protective which provide lubrication.


  •       Animal fat
  •       Vegetable oils:

– Olive oil

– Cotton seed oil

– Corn oil

– Peanut oil

– Theobroma oil

  • Paraffin

Vegetable oils may be applied over skin to fight dryness to prevent itching due to thick dry skin.

C. Astringents

These are locally applied protein precipitants i.e. when applied over skin, they cause precipitation of proteins present over surface but do not destroy cells. They just cause contraction of tissues and wrinkling of tissues. Females apply astringents over oily skin because of precipitation of superficial proteins, which is helpful especially during summer season.


Metallic salts


-Al subacetate



– Tannic acid

D. Counter Irritants

Those locally acting drugs used over skin cause feeling of hotness and burning so that they mask the pain.


They are of three types:




Mechanism of Action

First degree:

When applied to the skin, there is rubfacient effect  with  feeling of heat, leading to dilation by axon reflex  and paralysis of sensory receptors, which cause stimulation of cerebral centers of  perception and consciousness by painful impression.

2nd degree:

Reddened area +inflammation

Plasma escapes  from capillaries more rapidly but cannot escape through the stratum corneum with the result that epidermis is raised producing vesicles.

Third degree:

Diapedesis of leucocytes occurs and a crop of  painful pustules around skin glands form

1. Camphor

2. Black mustard


4.Turpentine oil

5.Methyl cellulose


7.Eucalyptous oil

These are not rubbed as effects appear which are unpleasant.

E. Sclerosing Agents

Agents used to obliterate varicose veins (dilated veins due to lack of valves).


1.Obliterate varicose veins

2. Fibrosis of Haemorrhoids


Morhuate Na

Na tetradecyle sulfate


Acute thrombophlebitis

Valvular or deep venous incompetence

F.Caustics and Escharoitics

Topical agents which destroy upper thick layer of skin, and are thus not commonly used.


1.Glacial acetic acid

2.Exzicated alum



5.Trichloracetic acid


  1. Destroy warts (viral infection causing raised thick layer over skin)
  2. Keratosis
  3. Moles or Hyperplastic tissues
  4. Fungal infections & Eczema

G. Keratolytics

Desquamating agents, can cause desquamation of dermis.


Softening & removing horny layer of skin


1. Fungal infections

2. Warts & Corns

3. Eczema & certain forms of acne

4. Psoriasis (white silvery spots over skin especially over extensor surfaces, knees,  elbows, scalp due to rapid turn over of epidermis.

These agents are applied to reduce thickness.


1. Benzoic acid

2. Salicylic acid

3. Resorcinol

4. Tar (applied to patients of psoriasis)

As damage to skin occurs, these are carefully applied to warts especially salicylic acid.

H. Anti-Perspirants and Deodrants

Agents used to decrease formation of sweat are called anti-perspirants

Agents used to decrease smell from areas where sweating occurs are called deodrants.


1. Al Chlorohydrate

2. Al Cl3

3. Buffered AlSO4

4. Al Ziriconium

5. Al Formate

6. Methyl Benzethonium Cl

7. Neomycin SO4

Side Effects:

1.Contact dermatitis

2.Inactivated by Soaps

I. Anti Seborrheics

These locally applied drugs are used to decrease seborrheia.


1. Quarternary NH4 surfactants

2. Chlorinated phenols

3. Salicylic acid

4. Sulphur

5. Zn pyrithione (Head & Shoulders)

6. Selenium sulphide ( Exsel, Selsun)

7. Tar

J. Ectoparasiticides

Present over skin e.g.

Hair lice (pediculus capitis)

Scabies(sarcoptes scabei) (lies over skin causes itching especially at bed time especially winters)






K. Anti Acne Drugs

Management of acne

  •      Topical preparations for acne
  •       Oral antibiotics
  •       Hormonal treatment
  •       Retinoic acid &derivatives
  •       Tretinoin
  •       All-trans-retinoic acid

L. Melanizing Agents

In hypopigmentation caused by vertiligo, TRIOXSALEN is applied over skin but requires direct sunlight for action, patient is asked to sit in sun after applying cream over lesion. Oral preparations are also available, patient is asked to sit in sun after 2 hours of administration.

M. Anti Pigmentation Drugs

Commonly used especially in Melasina for very long time. These preparations contain:

1.Hydroxyquinones (reversible pigmentation)

2. Monobenzene (irreversible pigmentation)

Side Effects

Irritation of skin, patient is asked to apply small quantity gradually increasing strength.

Inactivated by exposure to light, applied before going to bed.

N. Sunscreens

Sunscreens – Absorb UV light.

Chemical compounds:

1.p-aminobenzoic acid


3.Physical sunscreens

PF stands for production factor. Very fair people require up to 15 SPF, below this level are not effective.

5. Drugs acting on respiratory system, eye and miscellaneous drugs

Drug Interactions

Drug interactions may create alarming situations. In most cases, monotherapy is preferred but sometimes drugs need to be given in combination e.g. in treatment of congestive cardiac failure, diuretics and vasodilators need to be combined, or in patients suffering from malignancy, coma, chemotherapy or tuberculosis. The aim is to:

  1. Reduce dose
  2. Prevent the development of resistance


When pharmacological action of a drug is altered by concurrent administration of another drug.

The adverse drug interactions may be of great clinical importance when margin of safety of drugs is small.

Sometimes clinicians allow drug interactions to occur for better actions, but  adverse reactions occur with drugs having low therapeutic index.


1.  In Vitro

2.  In Vivo

Drugs interactions can occur outside the body, e.g.

1. Incompatibilities of drug in an IV infusion

2. Use of wrong vehicle for infusion:

a) no drug should be added to blood plasma, aminoacid solutions, fat emulsions, sodium bicarbonate solution, mannitol solution (mannitol may crystalize) and to heparin infusion.

b)  Mannitol should not be mixed with electrolytes, KCl or other drugs

Highly acidic solution such as dextrose, or fructorse are unsuitable as vehicle for sodium and potassium salts of weakly acidic drugs. Such as sulfonamides, barbiturates, methicillin and novobiocin

Benzyl penicillin, ampicillin, heparin and aminophylline are unstable at the pH of these solutions.

Isotonic saline is slightly acidic or neutral and is suitable vehicle for most drug like phenytoin, diazepam

Most antibiotics become unstable and deteriorate in large volumes of fluids exceptions are amphotericin B and erythromycin.

Erythromycin lactobionate is unstable in electrolyte solution but may be diluted with 5% dextrose solutions

Amphotericin B should be diluted with 5% dextrose

Calcium salts should not be added to sodium bicarbonate

Incompatibilities in syringe

Soluble and protamine zinc  insulin: soluble insulin interacts with excess of zinc and protamine and its onset of action may be delayed

Barbiturates,, phenytoin, phenothiazine, frusemide should not be mixed with any other drug in solution

Penicillin is incompatible with gentamicin, tetracycline and hydrocortisone

Tetracycline is incompatible with calcium salts

Heparin sodium is incompatible with gentamicin and  hydrocortisone

Thiopentone sodium is incompatible with succinylcholine

In Vivo

Pharmacokinetic Drug Interactions

            Differences in plasma levels of a drug achieved by a given dose of that drug.

Pharmacodynamic Drug Interactions

            Differences in pharmacological effects produced by a given plasma level of a drug

Pharmacokinetic Drug Interactions

Drug absorption e.g. antacids

Interactions due to changes in protein binding of drugs – distribution (if highly protein bound, displace other drugs, free levels increase, leading to toxicity)

Interactions affecting drug metabolism

Interactions affecting renal excretion of drugs

Interactions Affecting Absorption

Parenteral administration

Drugs + Epinephrine

Drugs + Methacholine (vasodilator –effective drug levels not achieved)

Oral administration

Chelation  / Adsorption

Tetracycline + Ca++

Cholestyramine (adsorption) + Cardiac Glycosides

Sucralfate adsorbs, cannot give other drugs

Altered Intestinal Motility

Atropine + Acetaminophen

Metoclopramide (prokinetic) + Cimetidine (anti ulcer) (increased gastric emptying, less drug absorbed)

Inhibition of Absorption

Phenytoin and oral contraceptives + Folic acid

Colchicine + Vit B12

P-glycoproteins in intestinal wall can influence absorption, present in different cells of body, some drugs may be expelled out.

Influence of Diet

Food in Stomach

Fatty Meal

Griseofulvin has increased absorption with fally meal -EXCEPTION

pH Dependent Absorption

Weak acidic drugs e.g. NSAIDS

Weak basic drugs

Interactions Affecting Distribution

Competition for Plasma Protein Binding

Sulfisoxazole and Bilirubin (may lead to kernicterus)

Displacement from Tissue Binding Sites

Phenylbutazone and Warfarin (displace, also at level of metabolism, thus vitamin K dependent factors are impaired)

Methotrexate + Aspirin (efficacy decreased, PG inhibition, increased levels of methotrexate) so aspirin is stopped before treatment otherwise may cause methotrexate toxicity

Interactions Affecting Metabolism

Monoamine oxidase inhibitor –beneficial effect

Xanthine oxidase inhibitor (allopurinol) –beneficial effect

Enzyme inducers –adverse effects, therapeutic failure, diminished response

Interactions Affecting Excretion

Probenecid with penicillin and methotrexate

Aspirin with methotrexate

Agents that alkalinize urine –weak acid poisoning sodium bicarbonate given

Agents that acidify urine

Pharmacodynamic Drug Interactions

Receptor site down regulation or upregulation


Sulfamethoxazole & Trimethoprim

Levodopa with Carbidopa


Rifampicin and Cloxacillin

Protamine and Heparin

Combined Toxicity

Ethanol with opioids, barbiturates and benzodiazepines

5. Drugs acting on respiratory system, eye and miscellaneous drugs



Chemical Messenger having a wide range of cellular responses, causing allergies, inflammatory reactions, increased gastric acid secretion, acting as a neurotransmitter in brain

Synthesized from HISTADINE through decarboxylation.

Stored in mast cells

Released in response to various stimuli like after insect bites, can be released in response to bees sting, and in anaphylactic reaction.

Histamine Receptor Subtypes

 H1 – Most abundant, present in:

  1. Smooth muscles, responsible for smooth muscle contraction
  2. Endothelium, vasodilatation of blood vessels
  3. Brain neurotransmitters

Act through hydrolysis of inositol triphosphate diacyl glycerol second messenger system.H1 receptors are present on post synaptic neurons.


  1. Gastric mucosa, increase gastric acid secretion
  2. Cardiac muscle, produce hypotension, producing reflex tachycardia
  3. Mast cells,
  4. Brain

H2 receptors act through stimulation of cAMP 2nd messenger system. H2 receptors are also present on post synaptic neurons.

H3 and H4 are present pre-synaptically.

  H3 – Presynaptic: brain, myenteric plexus, other neurons

Act through inhibition of cAMP

  H4 – Eosinophils, neutrophils, CD4 T cells

Play a role in allergies.


By antihistamines we mainly refer to H1 blockers. H2 blockers are called the drugs which decrease gastric acid secretion.

Classification of Antihistamines

Antihistamines are broadly divided into two groups:

  1. 1st generation antihistamines
  2. 2nd generation antihistamines

Drugs having hysteric signs are included in 2nd generation,, rest are in 1st generation.


  •        Carbinoxamine maleate
  •        Clemastine fumarate
  •        Dimenhydrinate
  •        Diphenhydramine HCl


  •        Tripelennamine HCl
  •        Pyrilamine Maleate
  •        Antazoline

Piperazine Derivatives

  •        Hydroxyzine HCl
  •        Cyclizine HCl
  •        Meclizine HCl
  •        Cetrizine*


  •    Brompheniramine maleate
  •    Chlorpheniramine maleate
  •    Pheniramine
  •    Acrivastine*


  •    Promethazine HCl


  •             Fexofenadine*
  •             Levocabastine*
  •             Loratidine*


  •              Cyproheptadine
  •              Pheniramine

Structure of antihistamines

Structure resembles that of histamine.

Have ethylamine or carbon chain

Linked with Tertiary amine group through glycosidic bond.

To amine group, two aromatic groups are attached.

Mechanism of Action

  1st Generation block H1 receptors competitively

  2nd Generation block H1 receptors non-competitively

Pharmacological Actions

  1. Smooth Muscles

Block vasodilatation in endothelial smooth muscles. However, they are not effective in preventing bronchoconstriction because there are leukotrines and platelet activating factors involved.

  1. Capillary Permeability

Prevent capillary permeability, thus effective in preventing edema.

  1. Triple response

Antihistamines are effective in preventing triple response seen after intradermal injection of histamine, in which there is redness due to dilatation of small vessels and there is veil formation i.e. edema.

Flare is the redness around wheel. Antihistamines are effective in preventing all components of triple response.

  1. Exocrine glands

Decrease secretions of endocrine glands, including lacrimal gland, but not effective in decreasing gastric secretions.

  1. Allergy

Prevent triple response, but not effective in preventing bronchoconstriction and hypotension.

  1. Anticholinergic Effects

Most of 1st generation antihistamines are capable of antagonizing muscarinic receptors, having anticholinergic effects including

  • blurring of vision,
  • dilatation of pupils,
  • urinary retention,
  • constipation and
  • tachycardia.

Among 1st generation antihistamines, Promethazine has strongest anticholinergic activity and Mepyramine has least anticholinergic activity.

  1. Motion Sickness

Vestibular apparatus has M1 and H1 receptors, so antihistamines and anticholinergics are effective in motion sickness.

Drugs used are  Diphenhydramine and Dimenhydrinate.

1st generation antihistmaines having anticholinergic activity are effective in motion sickness.

  1. Local Anesthetic Effect

1st generation antihistamines possess local anesthetic effect in higher doses. They can block sodium channels and this local anesthetic effect is equal to procaine and lignocaine.

  1. Adrenoceptor blocking effect

1st generation antihistamines block alpha 1 receptors producing postural hypotension and flushing.

Mostly seen with Promethazine and Diphenhydramine.

  1. Serotonin blocking effect

1st generation antihistamines have ability to antagonize serotonin receptors e.g. Cyproheptadine.

  1. Appetite stimulant effect

Because of blockage of serotonin receptors, Cyproheptadine has appetite stimulant effect.

  1. Central Nervous System

1st generation antihistamines cross BBB and produce CNS depressant effect,

  • Sedation
  • Drowsiness
  • Dizziness
  • Fatigue

Almost all 1st generation antihistamines produce CNS depression except Fenandamine which produces CNS stimulation. 2nd generation antihistamines do not cross BBB.


  • Routes of Administration

Usually given through oral route and parenteral route. Topical preparations are available in form of nasal drops, eye drops. Levocabastine can be given topically.

  • Peak plasma concentration

Usually in 1-2 hours.

  • Duration of action

1st generation up to 6 hours

2nd generation up to 24 hours

However, Astimazole has more than 24 hours.

  • Distribution

1st generation antihistamines are widely distributed as are lipid soluble. 2nd generation have far less distribution.

  • Metabolism

Antihistamines are metabolized by CYT P450. Most are metabolized by cyt CA4.

  • Excretion-as metabolites

As a result converted into metabolites, e.g. Loratidine is converted into Desloratidine, Hydroxyzine is converted into Cytrazine and Terphendadrine is converted into Fexophendaine.

Mostly excreted in urine in form of metabolites. However, Cytrazine and Acrevestine are excreted as such. Sexophenadine is eliminated in feces.

Therapeutic Uses

  1. Allergy

All kinds of allergies,

  1. acute allergies,
  2. acute rhinitis
  3. acute conjunctivitis
  4. chronic allergies
  5. chronic urticarial
  6. drug induced allergies
  7. contact dermatitis
  8. insect bites
  9. serum sickness
  10. Common Cold

Provide symptomatic release and decrease secretions.

  1. Anti Emetic Effect
  1. Pregnancy induced vomiting
  2. Radiation induced vomiting
  3. Cancer chemotherapy induced nausea, vomiting
  4. Motion sickness

Diphenhydramine and Dimenhydrinate are used.

  1. Meniere’s disease

Idiopathic disease of inner ear, affecting hearing and balance.

Promethazine and Dimenhydrinate are used.

  1. Parkinsonism

Antihistamines effect rigidity and tremors and decreases cholinergic activity. Drugs used are Orphenadrine and Diphenhydramine.

  1. Sedative, Hypnotic, Anxiolytic, Pre anesthetic medication

Can be used for sedation, hypnosis, anxiolytic effect. Can be given as pre anesthetic medication. Mostly Promethazine and Diphenhydramine are used.

  1. Appetite Stimulant

Block serotonin receptors, having appetite stimulant effect (Cyproheptadine)

  1. Carcinoid Syndrome

Cyproheptadine is used having serotonin blocking effect.

There is group of symptoms secondary to carcinoid tumor, flushing, diarrhea, bronchoconstriction.

Adverse Effects

  1. Central Nervous System

1st generation antihistamines cross BBB and produce CNS depression except Phenadrine which produces CNS stimulation. 2nd generation do not cross BBB being devoid of CNS effects.

  1. Gastrointestinal Tract
  • Can produce abdominal discomfort
  • Can alter  bowel habits
  • Anorexia
  • Cycloheptidine has appetite stimulant effect.
  1. Cardiovascular Effects

Two drugs Astamizole and Terphenadrine prolong QT interval, can produce ventricular arrhythmias. These drugs should not be given to individuals taking enzyme inhibitors.

  1. Anticholinergic effects

1st generation antihistamines can enter cholinergic receptors, producing anti cholinergic effects:

  • Dilatation of pupil
  • Dryness of mouth
  • Urinary retention
  • constipation
  1. Allergy

Topical preparations can produce allergic manifestations:

  • Dermatitis
  • Articaria
  • Rash
  1. Hematological Complications

Can produce:

  • Hemolytic anemia
  • leukopenia
  1. Teratogenic

With Piperazine derivatives, teratogenic effects are seen in experimental animals (not in humans).

  1. Mutagenicity

Some antihistamines have been found to be mutagenic, can induce fibrosarcomas and melanomas in experimental animals.

Drug Interactions

  1. Sedative Hypnotics

Can potentiate the effects

  1. Alcohol

Can potentiate the effects

  1. MAO Inhibitors

MAO inhibitors can enhance anticholinergic effects of antihistamines

  1. Ketoconazole, Itraconazole, Erythromycin

These are enzyme inhibitors, when these are combined, metabolism of antihistamines is reduced.

Astamizole and Terphenaline cardiac effects are enhanced.

  1. Grape fruit juice

Enzyme inhibitor.

Slight over dosage

With slight overdosage, there is sedation.

High Doses

In higher doses, CNS stimulation and anticholinergic effects are enhanced.

 1st generation2nd generation
Name of drug  
Chemical propertiesAromatic groups and ethylamine groupAromatic group
Mechanism of actionCompetitive antagonism of H1Non competitive antagonism
Pharmacological actionsCan cross BBB causing CNS depression(except Pheniramine)Cannot cross BBB so no CNS effects
PharmacokineticsDistributionMetabolismLipid soluble so distributed in all compartmentsNo active metaboliteLess lipid soluble so cannot enter CNS, CSFMostly converted to active metabolite e.g.Terfenadrine à FenofexadineLoratidine à Desloratidine
Local Anesthetic/Membrane Stabilizing ActivityLocal anesthetic having effect like procaine and lidocaineNo effect
Adrenoceptor blockageAlpha 1 blockageNone
Duration of actionShort (4-6 hours) except Meclizine 12-24 hoursLong 12-24 hours except Estemizole more than 24 hours.
Anticholinergic effectPresentAbsent
5. Drugs acting on respiratory system, eye and miscellaneous drugs

Anti Asthmatic Drugs

Asthma is most common respiratory tract infection. It is the reversible obstruction of large and small airways.


Bronchial asthma is characterized by hyperresponsiveness of tracheo-bronchial smooth muscle to a variety of stimuli, resulting in narrowing of air tubes, often accompanied by increased secretions, mucosal edema and mucus plugging.

  1. Inflammation
  2. Hyper reactivity
  3.  Bronchospasm

Bronchial hyper reactivity results in inflammation of bronchial wall because of increased leakiness from micro circulation, leading to edema of bronchial wall.

Because of leakage, there is plugging of bronchi with thick mucous, symptoms include wheezing breathlessness.

Parasympathetic innervation is present in fibers of walls of bronchi, when inflammation occurs, increased parasympathetic tone due to release of acetylcholine leads to bronchospasm.

Vascular smooth muscle has sympathetic innervation. Increased pulmonary blood flow occurs because of vasodilatation, ultimately leading to bronchodilatation.

Hyper reactivity is due to release of chemical mediators.

Mediators are also released from certain cells, storage granules, besides certain other cells are recruited including eosinophils, neutrophils, monocytes, which themselves release mediators contributing to inflammatory response.

The strategy these days is to address inflammation.


2 phases are present:

  1. Immediate –release of histamine leading to antigen-antibody reaction on surface of mast cells
  2. Late

IgE antibodies are synthesized within mast cells in lungs. Antigen interacts with IgE on mast cells leading to release of mediators.

IL 4 and IL 13 are mainly responsible for bronchoconstriction and bronchospasm.

Mast cells release platelet activating factors, responsible for late phase eosinophilia.

For control of asthma, antihistamines are least beneficial especially exercise induced and allergic asthma and should be avoided. Normally leukotriene antagonists are given because:

  1. Leukotrines are contributing more in process
  2. Antihistamines cause more dryness

Bronchial inflammation differs because here hyper reactivity is the main problem.

Main goal is to treat underlying inflammation by use of anti inflammatory drugs.

Types of Bronchial Asthma

1. Extrinsic Asthma: (allergic)

It is mostly episodic, less prone to status asthmaticus

  •  Atopic (immediate due to IgE antibody).
  •  Nonatopic delayed for some hours, associated with production of precipitating antibodies

2. Intrinsic Asthma

It tends to be perennial, status asthmaticus is more common. Associated with COPD.


2 groups are present:

  1. Bronchodilators/relievers –address acute phase
  2. Anti inflammatory/controllers –address undelying



  • Salbutamol, Albuterol
  • Terbutaline,
  • Bambuterol,
  • Salmeterol,
  • Formoterol.

b. Methylxanthines:

  • Theophylline (anhydrous) (oral preparation with erratic solubility)
  • Aminophylline

500 mg diluted in 5% dextrose is given I/V very slowly, as can cause tachycardia, arrhythmias, having less therapeutic index.

c. Anticholinergics:

  • Ipratropium bromide (given inhalational, adjuvant therapy)
  • Tiotropium bromide

Leukotriene Receptor Antagonists

  • Montelukast,
  • Zafirlukast

These are 1000 times more potent mediators, they treat underlying infection, breakthrough for children.

Mast Cell Stablizers

  • Sodium cromoglycate,
  • Nedocromil,
  • Ketotifen (5HT action)

Corticosteroids(main stay)


  • Hydrocortisone,
  • Prednisolone & others.
  • Beclomethasone dipropionate,
  • Budesonide,
  • Fluticasone- propionate,
  • Flunisolide

Anti –IGE Humanized Monoclonal Antibodies

  •    Omalizumab

Approaches to Treatment

  1. Prevention of antigen-antibody reaction- avoidance of antigen, hyposensitization – possible in extrinsic asthma and if antigen can be identified
  1.  Suppression of inflammation and bronchial hyper reactivity (corticosteroids)
  2. Prevention of release of mediators (Mast cell stabilizers)
  3. Antagonism of released mediators (Leukotriene antagonists, 1000 times potent than histamines)
  4. Blockade of constrictor neurotransmitter, Acetylcholine (anticholinergics)
  5. Mimicking dilator neurotransmitter (sympathomimetics)
  6. Directly acting bronchodilators (Methyl xanthines)


Short Acting

Salbutamol, Terbutaline

Long Acting

Formeterol, Salmetrol, Bambuterol

Preferentially directly into airways by inhalation.

Onset of action via inhalational route is 1-5 minutes. Action is for 2-6 hours.

Oral administration is not preferred for bronchodilation although having prolonged action, up to 8 hours. Also

  1. Systemic side effects are produced
  2. Metabolic side effects

Although some absorption occurs through inhalational route as well, but there is not much toxicity. Beta2 drugs given in syrup form in children under 5 or elderly chronic asthmatics with symptoms aggravating. Can be given orally. Albuterol syrup

Mechanism of Action

1. Beta-2 adrenoceptor agonist, when administered binds beta 2 receptors

  1.  Stimulation of adenylate cyclase
  2.  Increase cAMP
  3.  Bronchodilation and decreased muscular tone

2. Increase potassium conductance leading to hyperpolarization and relaxation of bronchial muscle cells.

Terbutaline subcutaneous preparation is available. Usually beta 2 agonists are preferred in dyspnea with bronchoconstriction, providing symptomatic relief.

Short term drugs have quick onset of action. Salmetrol reduces possible bronchodilation for 12 hours.

3. Inhibit release of chemical mediators from mast cells, lymphocytes which have beta 2 receptors in different cells in lungs àincrease cellular cyclic AMP contributing to inflammation by preventing release of cytokines.

4. Mucociliary action -Increase mucus clearance by an action on cilia


  1. Acute asthma                           Inhalation/I/V              (short acting drugs)
  2. Chronic Asthma/ Prophylaxis              oral/Inhalation                         (long acting drugs)

Chronic treatment decreases receptor sensitization and decreases action of drug. Effective in young asthmatics, but desensitization is not observed in beta 2 receptors present on bronchial smooth muslces (resistant). Desensitization is cell specific.

Beta 2 receptors on mast cells are desensitized.

  1. COPD                                      (less benefit due to toxicity)
  2. Salmetrol also has anti inflammatory action. It acts on eosinophils. As controller Salmetrol can be added to corticosteroids, dose of which is decreased when combined.

There is risk of side effects due to genetic variations in beta 2 receptors. Patients homozygous for arginine genotype especially African-Americans. Salbutamol, Salmetrol have greater risks, affecting transcription, increasing the mortality rate.


Aminophylline, Theophylline

Theophylline is least expensive, very old drug and effective.

It is ethylated xanthine (dioxy purine) structurally related to uric acid.

Solubility of methyl xanthine is low and is enhanced by formation of complex with ethylene diamine in 1:1

Theophylline + Ethylene diamine = Aminophylline

Mechanism of Action

1. Inhibit Phosphodiestrase Enzyme (which catalyzes breakdown of cAMP). Many isoenzymes are present but isoenzyme III and IV are most effective.

  • Increase cAMP
  • Dephosphorylation of MLC
  • Bronchodilation

2. Translocation of intracellular calcium

  • Increased  intracellular calcium  lead to increased diaphragmatic contractility

3. Blockade of adenosine receptors

  • Decrease contractility of bronchiolar smooth muscles


Drug is slowly given over 20-40 minutes, otherwise death occurs due to cardiac arrhythmias.

  1.    Acute asthma-                                   I/V (slowly)
  2.    Chronic asthma (prophylaxis)                       Oral
  3. Treatment of apnea of preterm infants as metabolized in liver and:
  • Converted in caffeine behaving as stimulant, which is exploited in treatment
  • Volume of distribution is very large
  • 2nd line drug in bronchodilation, having narrow therapeutic window.

Adverse effects

  1. Dose has to be maintained between 5-20 mcg/l, if it crosses 20 mcg/l severe CNS toxicity and convulsions occur.
  2. After 15 mcg/l GIT symptoms including pericardial pain occurs
  3. Tachycardia, palpitations

Drug monitoring is mandatory, given only in facilities having monitoring facilities.

Still theophylline is preferred in children over corticosteroids as growth retardation occurs by corticosteroids.

Sustained release preparations including 8 hourly, 12 hourly and 24 hourly preparations maintaining plasma levels for peak symptoms.


  1. Absorbed readily after oral administration, per rectal suppository has erratic absorption.
  2. Peak plasma concentration is achieved within 2 hours
  3. Volume of distribution is 0.4-0.6 l/kg, important fact is that infants have much larger Vd than adults.

Drug Interactions

Smoking, oral contraceptives, phenytoin, barbiturates increase clearance, dose adjustment is required.

In viral infections there are chances of toxicity as clearance is decreased.

Antibiotics, macrolides and cimetidine are not given with methyl xanthine as clearance is decreased

With Anti T.B drug rifampicin clearance of methyl xanthine is increased.


  • Ipratropium
  • Oxytropium
  •  Tiotropium

Selective in action, atropine is very potent but not selective so not used because of toxicity.

Mechanism of Action

  • Blockade of muscarinic receptors present in bronchi and bronchioles
  • Decrease mucus viscosity
  • Increase mucociliary clearance

In therapeutic doses, does not overcome bronchoconstriction as non muscarinic in nature.

Given as aerosol inhalation.

In lungs relieves bronchospasm.

Duration of action is up to 5 hours.

Minimal systemic effects as poorly absorbed from lungs.


  • Chronic asthma/prophylaxis                (Inhalation) (More effective & less toxicity)

Limited role in asthma, main role is to decrease bronchoconstriction in bronchitis caused by stimulation of muscarinic receptors. Antibiotics are given for secondary infections.

Mainly for COPD.

Adverse effects

Dry mouth –since not as effective given in combination with beta 2 agonists and corticosteroids, when not controlled by beta agonists alone.

Leukotriene  Receptor Antagonists

  • Montelukast     –                       oral
  •  Zafirlukast      – (Cingular)      oral administration for control of asthma

Leukotrines are products of arachidonic acid metabolism. They are released at the site of inflammation producing bronchoconstriction having contributory effect to inflammation and bronchoconstriction.

Mechanism of Action

Montelukast and Zafirlukast are competitive antagonists.

  •  Inhibits cysteinlyl leukotriene  Cys LT1 receptor relieving bronchospasm and bronchoconstriction.
  • Inhibit physiologic actions of LTC4, LTD4, LTE4
  • One drug blocks synthesis of 5 lipooxygenase and is hepatotoxic Zileuton. Half like is 2.5 hours

When Montelukast is administered, it binds cysteine leukotriene 1 receptor


  •    Prophylaxis & chronic treatment                      (oral)
    (Exercise, antigen, aspirin induced asthma)


  • Half life 10 hours
  • Bioavailability greater than 90%
  • Peak plasma binding about 99%
  • Both metabolized by cyt p450
  • Montelukast is 60-70% metabolized, having plasma life about 3-6 hours.

Side effects


  1. Inflammation at site in lungs
  2. Rarely hypersensitivity reaction
  3. Patients already treated with glucocorticoids have decreased dose.
  4. Chraug Stauss Syndrome

This is not due to drug but due to pre existing underlying disease, eosinophilia and vasculitis is seen.

Drug Interactions

Zafirleukast has drug interaction with warfarin sodium, leading to increased prothrombin time, thus dose has to be monitored.

Increase in theophylline levels, which is itself bronchodilator

Monteleukast is commonly used.

Mast Cell Stabilizers

  • Na chromoglycate                    inhalation
  • Nedocromil
  • Ketotifen-  (5HT action)             oral

Nedocromil and Ketotifen are not bronchodilators, not having direct effect. They are ineffective once antigen antibody reaction takes place.

Mechanism of Action

  1.  Inhibit transmembrance influx  of Ca provoked by antigen antibody interaction on the surface of mast cells. this is prophylactic use and have to be given before antigen enters.
  2.  Stabilize mast cells membrane and inhibit release of chemical mediators
  3.  Depress  exaggerated neuronal reflexes triggered by stimulation of irritant receptors
  4.  Depress axonal reflexes which release inflammatory neuropeptides.
  5.  Inhibit release of  cytokines from T-CELLS

Only 5% sodium chromoglycate reaches lungs, rest get accumulated leading to irritation.

Allergic conjunctivitis –nasal sprays, eye drops


Prophylaxis of allergic exercise, irritant induced asthma.

Adjuvant therapy, dose limited.

Now limited role due to leukotrines, was drug of choice in children.


  • Hydrocortisone                          I/V
  •  Prednisolone                           oral
  •  Betamethosone
  •  Beclomethasone                     inhalation
  •  Budesonide
  • Flucitasone having affinity for glucocorticoids receptors in airways

Mechanism of Action

  •  Anti inflammatory action
  •  Decrease mucosal oedema, mucus secretion and reduce capillary permeability
  •  Stabilize mast cells
  •  Block immune response, decrease antibody formation
  •  Antagonise  histaminergic and cholinergic responses
  •  Enhance beta-2 adrenoceptor responsiveness to agonists (Catecholamines)

Effects appear after 1 week, and it takes nearly 10 weeks for control of disease.

Beneficial effects are observed with inhalted 500 mcg.

Maximum therapeutic range is 500 mcg/ml.


Systemic toxicity occurs when steroid is inhaled, more than 1500 mcg.

Even with 500 mcg dose there are chances are

  1. Osteoporosis
  2. Dysphonia
  3. Oropharyngeal candidiasis

Uses and Routes of Administration

Bronchodilator is given immediately because:

  1. It takes about 1 week for effects to appear.
  2. Due to constriction, drug cannot reach lungs so bronchodilator is given

a. Acute severe asthma (status asthmaticus)

Hydrocortisone                                             I/V

b. Acute asthma –                                    oral


c. Chronic asthma –(Prophylaxis)   Inhalation

Beclomethasone etc


Prodrug, when absorbed drug is acted upon by esterases in bronchial epithelial cells, less amount of drug absorbed gets bound to glucocorticoid receptors, bones, skin, eyes, and there are less chances of osteoporosis and cutaneous thinning.

It has some role in people predisposed to cataract and osteoporosis.

Status Asthmaticus

  • Status asthmaticus is an acute exacerbation of asthma that remains unresponsive to initial treatment with bronchodilators.
  • It is a life threatening form of asthma, because it can lead to respiratory failure and cardiac arrest.
  • Status Asthmaticus requires immediate treatment (corticosteroids are essential as immediate treatment)
  • Air trapping strains on breathing muscle which are fatigue and exhausted
  • Status asthmaticus is frequently associated with metabolic acidosis, and acidosis reduces the effectiveness of beta agonist.
  1. I/V NaHCoadded if pH is below 7.5 in patient with refractory status asthmaticus, but there is risk of hypercapnia, in children.
  2. decrease in PCO level corrected with nasal/Face mask oxygen (Helium)
  3. Continuous nebulization of albuterol for the first few hrs
  4. Switched to intermittent albuterol very 02 hrs. I/V
  5. corticosteroids, inhaled ipratropium every 06 hrs

Treatment of last resort used in status asthmaticus include:-

  • Providing G.A with inhaled anaesthetic which are potent bronchodilators.
  • I/V ketamine, is also helpful.
  • However help of an anesthesiologist is required.


The best way to decrease the possibility of having a severe attack is to take medication regularly as prescribed:-

  •  Never to stop taking inhaled steroids
  •  Leukotriene modifiers / “Controller” unless instructed to do so

Monoclonal Antibodies

Can be given to patients having severe forms of disease.

They bind to IgE antibodies present on mast cells. If administered I/V or subcutaneously, humanized monoclonal antibodies decrease levels of IgE antibodies, decreasing tendency of severe asthma, in both phases (immediate/delayed).

Also improve nasal/conjunctival symptoms, allergic manifestations. These are reserved for severe cases, if want to reduce dose of corticosteroids as there are undetectable levels of IgE antibodies in plasma and no antigen antibody reaction occurs.

5. Drugs acting on respiratory system, eye and miscellaneous drugs

Drug Treatment of Glaucoma

Glaucoma is from Greek word “Glaukoma” meaning clouded or blue green hue.

Glaucoma is a group of diseases characterized by progressive form of optic nerve damage

It is associated with raised intraocular pressure, rise should be more than 21 mmHg.

Etiology –exact cause is not known, however there are usually many risk factors.

Chief therapeutic measure is to reduce intraocular pressure either by decreasing formation of aqueous humor or increasing outflow.

Production and Drainage of Aqueous Humor

Produced by ciliary body behind iris, then flows through pupil and drains at angle between iris and cornea (drainage angle).

Within drainage angle, a porous tissue, the trabecular meshwork from where goes into canal of Schlemn, then drains into the veins under conjunctiva.

Most of the aqueous humor leaves the eye through this conventional pathway.

Rest drains through the non-conventional pathway or uveoscleral pathway i.e. leaves through ciliary body.


Normal Intraocular Pressure

10-20 mm Hg


According to:


  • Primary
  • Secondary


  1.  Open angle
  2.  Closed angle


  1. Congenital or infantile
  2. Adult type

Glaucoma based on Morphology

Angle closure glaucoma


Occurs in individuals having narrow iridiocorneal angle or shallow anterior chamber.

Intraocular Pressure

Remains normal until an attack is precipitated by mydriasis.

Intraocular pressure rises very rapidly to high values and  becomes emergent condition. Failure to lower this IOP can result in loss of sight.

Risk factors

There are many risk factors:

  1. Old age
  2. Physiological enlargement of lens
  3. Hyper opia –far sightedness
  4. Prolonged uveitis
  5. Diabetes mellitus
  6. Drugs causing pupillary dilatation –sympathomimetics, anticholinergics, antihistamines, TCA, quinine and quinidine


  • Severe throbbing pain in eye along with blurring of vision.
  • Dilated pupil not responding to light
  • Cornea discoloured or steamy.
  • Redness of eye.
  • May be accompanied by abdominal discomfort, nausea, vomiting


Made on basis of symptoms and tonometry.


Definitive treatment is surgery or laser iridotomy.

Vigorous medical therapy is employed to decrease intraocular pressure.

Drugs used are:

  1. Acetazolamide 500 mg I/V followed by 250 mg.
  2. Mannitol I/V à decongests eye, once I/V given
  3. Pilocarpine, drug is instilled after every 10 minutes for 1st one hour, then 4 times daily.
  4. Topical beta blockers like Timolol are instilled after every 12 hours.
  5. Apraclonidine
  6. Latanoprost
  7. PGF2 alpha analog

Once intraocular is decreased then surgery or laser iridotomy is done, hole is made in iris which facilitates flow of aqueous humor.

Open Angle Glaucoma

More common/dangerous than closed angle because of no signs/symptoms usually.


Due to changes in trabecular meshwork that occurs with advancing age

Genetic Predisposition

Genetically predisposed condition due to mutations in myocilin, genes are present on chromosome 1, which encodes myocilin glycoproteins present in meshwork.

Optic nerve/optic disc damage, increase in cup disc ratio, if more than .2-.3 then suspicion of glaucoma is made.


Usually no complains of hallows around light, central vision remains intact till last and there is loss of peripheral vision.


Made on visual field examinations, on tonometry and optic disc examination.

Drug Treatment of Glaucoma

Beta-adrenergic Antagonists

Are one of the 1st line drugs. However, nowadays, PGF2 alpha analogs have replaced them.

Beta-1 nonselective

Timolol  maleate (0.25, 0.5%) bid

Timolol Hemihydrates (5-12 mg/ml) bid

Levobunolol HCL (0.25, 0.5%) bid

Metopranolol  (0.3%) bid

Carteolol HCL (1.0%) bid

Beta-1 selective

Betaxolol HCL (0.25, 0.5%) bid

Mechanism of Action

These block beta receptors in ciliary epithelium and decrease aqueous humor production by inhibiting adenylyl cyclase, so decrease intraocular pressure.

Have secondary effect, i.e. decrease intra ocular blood flow.


There are a few advantages over meiotics:

  1. No change in pupil size
  2. No headache or pain
  3. No fluctuations in IOP
  4. Convenient to be used, given once daily or twice daily.



  1. Dryness
  2. Redness of eye
  3. Blurring of vision
  4. Corneal hypo esthesia
  5. Allergic blepharoconjunctivitis


Systemic effects occur when beta blockers act through nasolacrimal duct.

  1. Severe bronchospasm in asthmatics
  2. Bradycardia
  3. Enhancement of heart blocks
  4. Congestive heart failure

Adrenergic agonists

Nonselective adrenergic agonists

Epinephrine  (0.25,0.5,1.0,2.0%) bid

Epinephrine HCL (1.0,2.0%) bid

Epinephryl borate (0.5, 1.0,2.0%) bid

Epinephrine bitartrate (2.0%) bid

Dipivefrin (0.1%)

Alpha2– selective adrenergic agonist

Apraclonidine  HCL (1.0%) (0.5%) pre and post laser tid

Brimonidine tartrate (0.2%)

Brimonidine has selective actions on alpha 2 receptors than apraclonidine, has lesser adverse effects than apraclonidine.

Mechanism of Action

  1. Initially produce vasoconstriction and decrease aqueous humor production,
  2. later on also increase outflow of aqueous humor

Dipivefrin is prodrug, activated while it transverses the cornea, has less systemic effects than epinephrine.



  1. Allergy
  2. Follicular conjunctivitis
  3. dermatoconjunctivitis


Mainly on cardiovascular system;

  1. Arrhythmias
  2. Tachycardia
  3. hypertension

Parasympathomimetic Drugs

Cholinergic agents

  • Pilocarpine HCL (0.25 -10.0%) bid to qid
  • Pilocarpine Nitrate (1.0,2.04.0%) bid to qid
  • Carbachol (0.75,1.5,2.25,3.0%) bid to qid



  • Echothiophate Iodide (0.03,0.06, 0.125, 0.25%) bid
  • Demecarium Bromide (0.125, 0.25%) bid
  • Physostigmine (0.25%) (0.25, 0.5%) bid

Mechanism of Action

  1. Act by contraction of ciliary muscles
  2. Cause opening and re-alignment of trabecular meshwork
  3. Facilitate drainage of aqueous humor

Adverse effects

Contact allergy is possible to pilocarpine. Since produce meiosis, interfere with visual acuity and should not be given for longer time since Echothiophate produces cataract formation if given for prolonged period because of degradation of proteins.


  • Latanoprost  (0.005%) bid
  • Bimatoprost
  • Travoprost

Mechanism of Action

Increase uveoscleral outflow of aqueous humor, exact mechanism is not known.

Said to be due to relaxation of ciliary muscles as well as remodeling of elements of ciliary muscles.

Side effects

  1. Thickening and darkening of eye lashes
  2. Darkening of iris
  3. Redness of eyelids
  4. Redness of eyes
  5. Blurring of vision
  6. Macular edema

Carbonic Anhydrase Inhibitors


Acetazolamide (125, 250 mg) bid to qid (500mg)

Acetazolamide  (500 mg)  6-8 hr


Dichlorphenamide (50mg) bid, tid

Methazolamide  (25, 50 mg) bid, tid       


Dorzolamide  (2.0%) tid

Brinzolamide (1.0%) tid

In health it is production of bicarbonates that drain sodium and then water follows by osmosis.

These carbonic anhydrase inhibitors inhibit production of bicarbonate inhibiting aqueous humor production.

Side effects

Systemic effects are common with drugs used parentally.

Dorzolamide has more topical adverse effects than Brinzolamide.

  1. Anorexia
  2. Hypokalemia
  3. Metabolic acidosis
  4. Renal stone formations
  5. Lethargy
  6. paresthesias

Hyperosmotic agents

  • Mannitol parenteral (5-25% solution) 2g/kg

Mechanism of Action

Osmotic agents are inert in humans. They increase blood plasma osmolarity and in this way drain water from eyes into plasma and decrease vitreous volume and intraocular pressure.

Side effects

  1. Headache
  2. Back ache
  3. Diuresis
  4. Ataxia

Sometimes cerebral hemorrhage.