Respi

pharmacology
SYLLABUS
Therapy of Bronchial Asthama (P. 1129)- Bronchodilators: (P. 1131)
Types of bronchial asthma –acute, chronic, severe acute asthma (status asthmaticus)
Classification of drugs (P. 1129), mechanism of action/pharmacological basis for the use, advantages and
disadvantages of each group, adverse effects, drugs interactions, contraindications and special features.
Therapy of COPD (P. 1136)
Therapy of Allergic Rhinitis: (P. 1139)
List the drugs, mechanism of action, advantages and limitations
Antihistaminics: (P. 1137)
Classification (P. 1138), comparison of various groups (P. 1139)
Therapy of Cough: (P. 1141)
Antitussives (P. 1142) and mucolytic agents (P. 1141)- examples for each group
Mechanism of action, usefulness and limitations
Adverse reactions and cautions
Therapy of Tuberculosis: (P. 1143) IV
Classification (P. 1144) according to antibacterial effect.
Comparison between primary and secondary antitubercular drugs.
Regimens and prophylaxis (P. 1147)
Discussion of individuals drugs under mechanism of actions.
Adverse effects, contraindications
List drugs for resistant tuberculosis, their limitations (P. 1146)

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 Pharmacology

 

IV

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PHARMACOLOGY

THERAPY OF BRONCHIAL ASTHMA Bronchial asthma

Past Questions:  It is defined as inflammatory disease characterized
1. List commonly used bronchodilators. Give the by hyperresponsiveness of trachea bronchial
basis of use of β2- agonists. (2+3=5) [10 Jan] smooth muscle to a variety of stimuli causing
2. Classify drugs used in bronchial asthma. Outline the following events.
treatment of status asthmaticus. (3+4=7) [02 June] - Narrowing of air tubes
3. Name four drugs used for the treatment of - Increased secretion
bronchial asthma. Describe briefly the - Mucosal edema
mechanism of action and adverse effect of - Mucus plugging
Salbutamol. (2 + 2 + 2 = 6) [04 June]
- Goblet cell hyperplasia
4. List drugs used in acute attack of bronchial
 Symptom: Dysnoea, wheezing, cough, chest tightness.
asthma and describe management of status
asthmaticus. (2+3=5)[03 Dec]  Physiologically, reversible narrowing of bronchial
5. Give important differences between airway and marked increase in bronchial
bronchodilators. (2+3=5) [08 Jan] responsiveness to inhaled stimuli.
6. Classify bronchodilators (2) [02 Dec] Role of receptor
7. Give the pharmacological basis for the use of: - Acetylcholine act via M1 M3 Constriction
a. Ipratropium in therapy (3)[08 Jan] - Epinephrine act via 2 Relaxation
b. Salmetrol in bronchial asthma (3) [11 July] - VIP act via VIP receptor  Relaxation
c. Inhaled Corticosteroids in bronchial asthma - No act via NK1 
(3) [09 June] - Substance act via NK2   Constriction IV
d. Corticosteroids in management of bronchial - Neurokinin A & B via NK2 
asthma. (3) [03 June] Types of Bronchial asthma
e. Theophylline in asthma (3)[08 Jan]
i. Extrinsic atopic
f. Sodium cromoglycate for bronchial asthma.
ii. Extrinsic non atopic
(3) [05 Dec]
iii. Intrinsic asthma
g. Beclomethasone aerosol in acute attack of
iv. Status asthmatics
bronchial asthma (3) [06 June]
On the basis of onset:
h. Salbutamol in bronchial asthma
i. Acute asthma
[10 July, 07 July, 06 Dec]
8. Write short notes on ii. Chronic asthma
a. Treatment of status asthmaticus (2) [08 July ] iii. Severe acute asthma (status asthmaticus)
b. Inhalation of glucocorticoids in bronchial iv. Severe chronic asthma
asthma (3) [05 June] Classification of drugs [04, 05, 08, 10]
c. Leukotriene antagonists (3) [09 Jan]
d. Steroid therapy in bronchial asthma
1. Brochodilators: [08, 10]
(3) [09 Jan] A. Sympathomimetics
e. Ipratropium (3) [03 June] I. Non selective sympathomimetics
f. Theophylline (3) [03 June] - Adrenaline
- Ephedrine
9. Management of severe from of an acute attack
of bronchial asthma. [4][013] - Isoprenaline

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II. 2 – sympathomimetics Aerosol delivery of drug

- Salbutamol  Inhalation (Topical)/systemic delivery
- Terbutaline  Topical application of drug to the lungs can be
- Bambuterol accomplished by use of aerosol (substance sealed
- Salmeterol in container under pressure and released as fine
- Formeterol spray).
- Ramiterol  This approach produces high local concentration
B. Methylxanthines in the lung with low systemic delivery.
- Aminophylline  There by significantly increasing therapeutic ratio
- Theophylline by minimizing systemic side effect.
- Etophylline Choice of inhalation device
- Oxitriphylline i. Metered dose inhaler (MDI) with a without
- Doxophylline spacer
C. Anticholinergic ii. Nebulizer
- Ipratropium bromide iii. Dry powder inhaler
- Tiotropium - Particle with diameter of 1 to 5 m allow
- Oxitropium deposition of drug in small air way and are
2. Leukotriene antagonist most effective.
- Montelukast Metered dose inhaler
- Zafirlukast - Rapid onset of action
3. Mast cell stabilizer - Small dose of drug sufficient
- Sodium cromoglycate - Low incidence of Adr.effect
IV - Ketotifen - Compact device
4. Corticosteroids - Cost effective
A. Systemic - Adapter, mouthpiece
- Hydrocortisone How to use MDI
- Prednisolone i. Shake the container thoroughly
- Betamethasone
ii. Breathe out gently
- Dexamethasone
iii. Tongue should be placed on floor of mouth
- Methyl prednisolone
of inhaler. Place between lips which are
B. Inhalational close around mouthpiece.
- Beclomethasone dipropionate
iv. The start breath slowly, canister is pressed
- Budesonide
to release the dose while patients continue
- Fluticasone propionate to breathing.
- Flunisonide v. Breath is hold for 10 sec
- Ciclesonide
vi. Exhalation should be through nose
5. Anti – Histaminic (H1) vii. Next dose is given after one minute
- Cetrizine Advantage of MDI
- Loratadine i. Multidose
6. Anti IgE antibody ii. Cheaper and portable
- Omalizumab
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Disadvantage I. Nonselective Sympathomimetics

i. Correct use require good technique Epinephrine
ii. Not useful for patient who cannot operate - Non selective 2 agonist
it. - Rapidly acting bronchodilators injected S.C.
iii. Unsafe propellant (CFC) (0.4 ml of 1:1000 soln) or inhaled as a
iv. Myocardial toxicity in high cocn. microaerosol (320 g/puff)
Advantage of use of spacer in MDI - Not given I.V because Adr. effect is more .
i. Increase effectiveness of MDI - stabilize mast cell.
ii. Coordination difficulties overcome - Max. effect in 15 min lasts for 60–90 min.
- Decrease bronchial mucosal congestion
iii. Oropharyngeal deposition reduced
- Stimulates 1, 2 receptor  so tachycardia,
iv. Low dose is required
Arrythmia and worsening of angina.
v. Local side effect minimal
Isoprenaline
Nebulizer
- Non–selective  agonist
- It produces aerosol, not much difference in
- Stimulate 1 receptor mainly.
particle size but deliver more amount of drug 5
II.  2 Selective Sympathomimetics:
– 15 mg.
- Short acting: Salbutamol, terbutaline, Pirbuterol
- More valuable in those that don't make
- Long acting: Salmeterol, formoterol, Bambuterol.
synchronization during MDI or severe form of
asthma. Short Acting:
Salbutamol [04, 06]
- Other, dry powder inhaler – use lactose/
glucose powder to carry the drug. - Rapid onset short duration of action
- Less palpitation and rise in BP
- High air flow needed.
- Used to terminate & abort the attack of asthma. IV
Bronchodilators [08, 10, 11] - Route: Rapidly effective by pressurized MD=
A. Sympathomimetics Puff, slow IV 0.25mg at rate of 5–10 min leg.
- They relax airway smooth muscle - Not suitable for round the clock prophylaxis.
- Activate adenylyl cyclase via GPCR (GC) and Terbutaline, Bitoterol, Ramiterol
increases the formation of intracellular cAMP. - Selective short acting 2 agonist
- Inhibit release of bronchoconstricting - They are effective for
mediators from mast cells.  Acute attack of asthma
- MOA:  Presentation of exercise induced asthma
ATP  During pregnancy – safe
2 agonist + AC Bronchodilation Long acting
cAMP
(Salmeterol, formeterol, Banbuterol)
+
- Selective long acting  2 agonist > 24 hrs but
Theophylline – PDE slow onset.
Bronchial tone - Formeterol has a quicker onset of action in 5
AMP
Adenosine, Ach
min and hence useful in nocturnal asthma.
+
- Bambuterol is a prodrug of short acting 2 agonist.
Theophylline, Atropine –
Note: “Regular use of 2 agonist is not adviced
AC Adenylcyclase Bronchoconstriction because they do not reduce bronchial hyperactivity
PDE Phosphodiesterase
and also downregulates the bronchial receptor.”

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Toxicity Uses:
- Due to stimulation of 2 receptor elsewhere in I. In bronchial asthma and COPD
body: II. Apnea in premature infants
 Skeletal muscle tremor - Theophylline reduces frequency and
 Vasodilatation and reflex tachycardia duration of episodes of apnea.
 Cardiac Arrhythmias - Oral or IV for 1 – 3 weeks
B. Methylxanthines [03] Action
- Theophyline,Theobromine, caffeine
I. CNS: Stimulation, sense of well being,
MOA:
alertness, improve performance,
i. Inhibitation of phosphodiesterase III, IV
enzyme which is responsible for the nervousness, restlessness insomia.
degradation of CAMP or cGMP. Hence increase II. CVS: Positive chronotrophic and inotrophic
in cAMP causes Bronchodilation. III. Smooth muscle: Relaxation
ii. Blockage of adenosine receptor (A2) IV. Kidney: Mild diuresis
Bronchodilation. V. Skeletal muscle: Enhance contractile power
ATP Bronchodilation due to sed Ca2+ release from sarcoplasmic
AC reticulum
cAMP cAMP VI. Stomach:es gastric secretion
M (–)
VII. Mast cells: Inhibits the release of
PDE III, IV sed release of cytokines, histamine and other mediator.
AMP chemokine
VIII. Metabolism:es BMR.
Decreased immune cell Adverse effects
migration and activation
- The drug has narrow margin of safety.
Pharmacokinetics (Pka) - Anorexia, nausea, vomiting abdominal
IV - Well absorbed orally, cross placenta and
discomfort, headache anxiety – > 20 mg/l.
secreted in milk.
- Seizure, ed HR, arrhythmia  40 mg/l.
- 50% bound to plasma protein
- T1/2 in adult  7–12 hrs - Many drug interaction because of inhibition
- Theophylline– 1st order to zero order CYP450 enzymes.
- Factor which need dose reduction are age > 60 yrs

EFFICACY TOXICITY

35 Death:
PLASMA CONCENTRATION

30 Convulsion, shock, arrhythmias, Delirium, worsening CVS status,

BRONCHODILATION

Increased muscle tone, extrasystoles, flashes of light seen

25
Agitation, tachypnoea, flushing hypotension
20
THERAPEUTIC Restlessness, tremors, vomiting, palpitation, diuresis
RANGE 15
Dyspepsia, headache, nervousness, insomnia
5
Minimal side effects

Adverse effects of theophylene (Methyl xanthines)

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C. Anticholinergics/Muscarinic Antagonists MOA:

- Atropinic drugs: Bronchodilation of larger airway Stimulus disturbance in cell membrane

- Muscarinic receptors: Present on Airway Phospholipid

smooth muscles, Submucosal glands, mast Phospholipase inhibitor
Phospholipase ×
cells. /corticosteroid
Arachidonic
Action: Acid
- These drug acts by LOX × Lox inhibitor/ zileuton
i. Competitive inhibition
LTC4 LTA4 LTB4
ii. Reducing vagal tone
- No action against direct effect of mediators
LTC4LTD4LTE4 LTB4– chemotaxsis
and allergen induced bronchoconstriction.
Tiptropium bromide Cysteinyl leukotrienes
- Binds to M1, M2, M3 receptor with equal × Monteleukast, zafirleukast
affinity.
 Smooth muscle
- Dissociates most rapidly from M2 receptor. contraction
 eosinophil migration
- Dose: 18 g OD.  Edema Cell membrane
Ipratropium Bromides: of airway

- Lipid insoluble, quaternary NH4+ compound Montelukast and zafirlukast

- They competitively antagonise Cys-Leukotriene
- Block M3 Muscarinic receptor on smooth IV
receptors.
muscles.
- As prophylactic therapy of mild to moderate
- It has gradual onset and late peak.
asthma as alternate to inhaled glucocorticoids.
- Dosage: 20 – 40 g, 1–2 puffs 3–4 times a day.
- It is effective in aspirin induced asthma.
Leukotriene Antagonist (09, 11) - Principle advantage is that they are taken
 More potent than Histamine in asthma orally.

 Leukotriene causes Side Effects:

- Very safe drug, produce few S/E like
- Leucocyte recruitment
headache and rashes.
- Stimulate bronchoconstriction
- Eosinophilia and neuropathy are infrequent.
- se capillary permeability - Few case of churg-strauss syndrome
- Stimulate mucus secretion (vasculitis with eosinophilia) have been
- es mucociliary clearance. reported.

 Leukotriene formed inflammatory cells in airway is Zileuton

mast cell, eosinophil, macrophage – LT C4, D4, E4. - It is a 5–Lox inhibitor, blocks LTC/D4 as well as
LTB4 synthesis.
 Act on leukotriene receptor– Bronchoconstriction.
- Clinical efficacy similar to montelukast.

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PKa: Adverse Reactions

- Well & rapidly absorbed orally, not affected - Bronchospasm, throat irritation, cough nasal
by food congestion.
- Response occurs after 30 min of oral - Rarely headache, dizziness, rashes, dysuria.
administration. Uses
Contraindications: i. Bronchial asthma
i. Active liver disease ii. In Allergic condition
ii. When serum transaminase is more than 3 - Allergic rhinitis
times normal. - Allergic conjunctivitis
ADR: Hepatotoxcity
Corticosteroids [03]
Dose: 1200 mg BD daily.
 Anti–inflammatory & immunemodulatory action.
Mast cell stabilizers [05]
 Beneficial effects:
 Cromolyn sodium and Nedocromil sodium - Reduce bronchial hypersensitivity
 These are not bronchodilators; inhibit - Reducing mucosal edema
degranulation of mast cell preventing release of - Suppress inflammatory response to Ag: Ab
chemical mediator of anaphylaxis. reaction.
 Cromolyn sodium and Nedocromil, like inhaled MOA
steroid, improve lung function, reduce symptom. - Upregulation of B2 receptors in lung cells and
 Most effective in atopic. macrophages.
MOA - Inhibit release of PGs and LTs.
- Antigen and IgE (Ab) reaction on mast cell - Produce eosinopenia
IV membrane cause Ca+2influx - They inhibit the formation and release of
 cytokines and chemical mediators
Mast cell stabilizers inhibits influx of Ca2+ preventing recruitment, proliferation, and
activation of WBC.

- Stabilize the cellular lysosomal membranes.
Inhibition of degranulation thus inhibit release of
mediator release Systemic steroid therapy
- Has ability to reverse increased functional  Used in asthma under following two condition:
activation of WBC. i. Severe chronic asthma: Not controlled by
bronchodilators and inhaled steroid or when
- Suppress of activating effect of chemotactic
there is frequent recurrence of ing severity:
peptides on neutrophils, eosinophil, and
prednisolone.
macrophages.
ii. Status asthmaticus/Acute asthma: Exacerbation
- Inhibition of parasympathetic cough reflex.
 Asthma attack not responding to intensive
- Inhibition of leukocyte trafficking in airway.
bronchodilator therapy.
PKa Inhaled steroid therapy [03, 09]
- Sodium chromoglycate is not absorbed orally.
 Beclomethasone dipropionate, Budesonide,
- Poor aquous solubility-only 1% of oral dose fluticasone, ciclesonide.
- Excrete unchanged in bile.  Suppress bronchial inflammation.
- Dose: 1mg 2 puffs QID  Start with 100–200 gm BD, titrate dose upward
- Peak concentration in 15 min to max of 400m QID.

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 Peak after 4 – 7 days and persist for few weeks 4. Moderate asthma with frequent exacerbations:
after discontinuation. Step 3
Adverse Reactions 5. Severe asthma: Step 4, 5
Systemic Step–5
- Mood changes
Step–4
- Osteoporosis
- Growth retardation Step–3
Inhaled Add oral
- Bruising high predni-
- Petechiae Step–2 dose solone
glucocort +
- Hyperglycemia Low dose
icoid Add Omalizu
- Pituitary adrenal suppression gluco- Add Ipratropi mab
corticoids Leukotrie
Topical um
or
Step–1 chromolyn ne anta- bromide
- Because of oral inhalation of corticosteroids: gonists + Methyl
Inhaled sodium +
 Oral candidiasis inhaled
xanthine
short
 Dysphonia acting 2 long acting
- Treatment: Antifungals agonist 2 agonist

Anti IgE Antibody Stepdowns:

Omalizumab - When T/t aims are achieved not sooner than 3
- DNA derived humanized monoclonal Ab of IgG. months, reduce or stop oral steroid first.
- Inhibit binding of IgE to FCE R1on mast cells and Status Asthmaticus [02, 03, 08, 13]
basophils  es amount of allergen specific  Medical emergency
IgE bound to mast cells, basophil, eosinophil, IV
 Features:
monocyte, lymphocyte.
- Chest pain - Exhaustion
- This prevents the allergic reaction at very early
steps. - Cyanosis - Confusion
- On repeated administration, it lowers plasma - Bradycardia - Pulsus paradoxus
IgE to undetectable levels. - Hypotension - Coma
- Injection site reaction: Stringing, redness. Management:
MOA : Initial/Early Treatment
- Binds with IgE and prevents binding to mast - Correct dehydration
cells and thus release of Histamine.
- O2 administration
Anti – Histaminic Drug - Nebulise salbutamol & ipratropium
 New H1 receptor antagonist ketotifen, Azelostine. - Oral glucocorticoids
 Newer longer acting H1 receptor antagonist– - If poor response to above is seen in 1 hr then
Desoloratidine, rupatidine, cetrizine, levocetrizine.
following treatments are required.
Guideline to T/t of asthma  Hospitalize the patient
1. Mild episodic asthma: Step 1  Incubation and marked ventilation
2. Seasonal asthma: Step 2
 Correct dehydration – 5% glucose in saline
3. Mild chronic asthma with occasional
 Correct acidosis – IV sodium bicarbonate
exacerbations: Step 2
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 Repeat nebulised, salbutamol & - Balance of activities

ipratropium 30 min - Rehabilitation
 IV glucocorticoids – Hydrocortisone IV 200 – - Stop smoking
300 mg every 4–6 min or, methylprednisolone Management of exacerbation
30–40 mg slow IV - Antibiotic
 If improved switch to oral glucocorticoids - Controlled oxygen
50–60 mg prednisolone single morning - Bronchodilator –  agonist anticholinergic +
dose. theophylline
 IV infusion of aminophylline or salbutamol - Steroids
 Antibiotics for chest infection - Noninvasive ventilation
 Exclude pneumothorax (Chest x-ray) - Intubation
THERAPY OF COPD - Treat heart failure if present
 COPD – Is defined as state characterized by Drug delivery
presence of airflow obstruction due to chronic - Inhalation - topical
bronchitis or emphysema, the air flow obstruction - Aerosol therapy by MDI
is generally progressive, may be accompanied by - Nebulization
airway hyperreactivity, and may be partially - Dry powder inhalers
reversible. Acute Management of COPD
 Type (i) chronic bronchitis (ii) Emphysema
Controlled oxygen therapy
Chronic Bronchitis Emphysema 
a. Age: 40 – 50 yrs 50 – 75 yrs Nebulized bronchodilators salbutamol 5mg/4hr
b. Barrel chest Cachectic Appearance and ipratropium 500 ng/6hr
c. Cyanotic Pink Skin Color 
d. Increase Secretion, Abnormal distension of Steroids
IV edema, lower air ways, IV hydrocortisone 200 mg and oral prednisone 30
Bronchospasm & Bronchioles, alveoli – 40 mg
Thickened 
Bronchialwalls Antibiotics use if evidence of infection eg.
Amoxicillin 500 mg/8h
Symptoms Sign 
a. - Cough & mucoid - Hyperinflation Physiotherapy to aid sputum expectoration
sputum 
b. - Dyspnea - sed chest expansion If no response Repeat nebulizer and consider IV
c. - Wheeze - Prolonged expiration aminophylline
d. - edema - Pulmonary 
hypertension If no response to above treatment:
1. Consider nasal intermittent +ve pressure ventilation
e. - Winter exacerbation - Cyanosis & Hypercapnia
(NIPPV) if respiratory rate > 30 or pH < 7.35.
Management of COPD It is delivered by nasal mask and flow generator
COPD treatment 
- Eliminate the irritant 2. Consider intubation & ventilation of pH < 7.26
- Prevention of infection & PaCO2 is rising.
- Treat exacerbation early – antibiotics, steroids 
- Low oxygen flow 3. Consider a respiratory stimulant drug Eg.
- Bronchodilators doxapram 1.5–4 mg/min IV, see agitation,
confusion, tachycardia, nausea only for patients
- Corticosteroid
who are not suitable for mechanical ventilation.
- Mucolytics
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ANTIHISTAMINICS - Heat, cold, exposure to sunlight, x–ray

Past Questions: - Trypsin, chymotrypsin
- Venom
1. Give the pharmacological basis for the use of:
Drug that inhibit Histamine release
a. Antihistaminic in therapy [06 Dec, 05 Dec]
b. Phenylephrine in allergic rhinitis [06 June] - 2 agonist: Adrenaline, ephedrine
c. Nasal decongestants in therapy (3) [11 July] - Mast cell stabilizers: Disodium chromoglycate,
ketotifen
d. Disodium cromoglycate in allergic rhinitis
Metabolism:
[03 June]
2. Write short notes on: Histamine
a. Antihistamines (3) [10 July]
N-methyl Transferase Diamine oxidase
b. Non sedative antihistaminics.
(3) [09 July, 05 June]
N–ethyl imidazole Acetic acid
 Histamine = tissue amine 
 Widely distributed in: Urine
- Skin, GIT, mucosa, lungs, Brain, CSF, BM Pharmacological action
 Biosynthesis and storage: I. CVS
L – Histidine - Histamine act on arterioles, causes massive
  L–amino acid decarboxylase dilation  decrease BP
Histamine - Capillary permeability causing urticaria.
 On heart, it causes tachycardia (Reflex
tachycardia due to  in BP)
Heparin + protein IV
II. Smooth muscle
 Histamine is stored in mast cells and basophils.
- Severe constriction of bronchial smooth
 Non mast cell histamine is stored in
muscles
Histaminocytes.
IV. Skin: Allergic rxn Tripple response i.e. Flush,
Eg. Stomach, Histaminergic neurons in brain.
wheal, flare
Release of histamine
V. HCl Secretion (GIT stomach)

Immunological Chemical & Histaminic Receptors


release mechanical release H1
H2
H3  G–protein coupled receptors
Initial exposure

Re exposure
 H4 
No release of Release of H1Recepter:
histamine Histamine due to - Location & Action:
Ca2+ influx  Smooth muscle (intestine, Bronchi, Uterus)
Mechanical and chemical release by: – Constriction.
 Blood vessel – Vasodilation
- d – Tubocuramine
 Capillary permeability
- Pentamidine
 CNS – Neurotransmission
- Polymyxine B
 Sensory nerve ending – pain, itching.
- Succinylcholine
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MOA H4 receptor:
- G coupled receptor Location
- PIP2 Hydrolysis - Eosinophil, Neutrophil, CD4 T cells
- IP3 ,  DAG Function
2+
- Release of Ca - Chemotaxis of WBC
- Agonist (H1) Antagonist (Anti – H1) - Production of blood cell type
- 2-Methyl fluorophenyl - Triprolidine MOA
histamine - Gi coupled receptor
- 2–Thiazolyl ethylamine - Chlorpheniramine - cAMP
H2 Receptor -  Ca2+ influx
- Location & action Agonist Antagonist
 Gastric gland: Acid secretion - Imetit - Thioperamide
 Blood vessel – Vasodilation - Clozapine
  Capillary permeability Classification of H1 Antihistaminics
  HR [05, 06, 10]
  Force of contraction A. 1st generation H1 Anti-histaminic:
 Brain neuro transmission - Cross BBB and causes sedation
MOA I. Highly sedative
- Gs protein coupled receptor - Diphenhydramine
- Dimenhydrinate
- cAMP
- Promethazine – commonly used
IV Agonist (H2) Antagonist (Anti – H2) - Hydroxyzine
- Dimaprit - Ranitidine II. Moderately sedative
- Pheniramine
- Impromidine - Famotidine - Cyproheptadine
H3 Receptor: - Meclizine
- Cinnarizine
- Brain – presynaptic (Autoreceptor)
III. Mild sedative
-  Histamine, NE - Chlorpheniramine
-  Ach release - Dexchlorpheniramine
-  Secretion - Triprolidine
- Cyclizine
- Blood vessel dilation
- Clemastine
MOA
B. 2nd Generation [05, 09]
- Gi coupled protein - Does not cross BBB so it does not cause
- cAMP sedation.
-  Ca2+ influx  Fexofenadine
 Levocetrizine
-  Opening of K+ channel
 Loratadine
Agonist Antagonist  Rupatadine
- R methyl-histamine - clobenpropit  Desloratadine
- Imetit - Thioperamide  Cetirizine–Commonly used

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Clinical uses of H1 Anti-histamine Non sedative 2nd generation

I. Allergic disorders: Immediate type of allergic-  Newer anti-histaminic
reaction: Itching, urticaria, allergic  Cannot cross BBB, so there is no sedation
conjunctivitis, angioedema
 Drugs are given in classification
II. Common cold = (Allergic rhinitis)
Uses
III. Vertigo
- Allergic reactions
- Cinnarizine (Anti cholinergic, anti-5HT,
- Acute allergic reactions to drugs, foods
sedative and vasodilators properties
- Pre–anesthetic medication
- Calcium channel blocking activity
- Inhibit vestibular sensory nuclei in the inner
Adverse Drug Reactions:
ear, suppresses postatory labyrinthine - Cardiotoxicity associated with astemizole and
reflex by reducing stimulted influx of Ca2+ terfenadine
into vestibular sensory cells. Other drug: - Disturbance of ocular accommodation
cyclizine, promethazine (labyrinthine - Gastrointestinal upsets
suppressants) Difference between 1st and 2nd
IV. Motion sickness Generation drugs [03, 05, 08]
- Milder effect, taken one hr. before journey nd
I. 2 generation donot have any direct chemical
- Drug used: Promethazine, resemblance to histamine as unique
diphenhydramine, cyclizine substitutions have been made on the
V. Pruritus ethylamine core histamine.
VI. Parkinsonism: Due to anticholinergic and II. 2nd generation are more polar, they donot
sedative properties, mild symptomatic relief cross the BBB to any appreciable extent.
Eg. promethazine III. 2nd generation has greater affinity for IV
VII. Acute muscle dystonia peripheral H1 receptor as compared to the
- Due to central anticholinergic activity of central H1 receptors and have negligible
drug Eg.promethazine, hydroxyzine potential of causing sedation (nonsedating
VIII. Cough: anti- histaminic)
- Antitussive effect IV. They are all specific for H1 receptors and have
Eg.chlorpheniramine, diphenhydramine poor anticholinergic, antiadrenergic action, in
turn reduces unwanted effects.
IX. As sedative/hypnotic/Anxiolytic  CNS
depressant effect. V. It donot potentiate alcohol or benzodiazepines

Adverse effects of H1 anti histaminics VII. Several active metabolites of 2nd generation
antihistamine are used as therapeutic agent.
- Sedation
E.g. Terfenadine (PD)  Fexofenadine (T1/2 –
- Photosensitivity
11.16 hr)
- Motor incoordination
Hydroxyzine (PD)  Cetirizine (T1/2 – 7–9 hr)
- Tachycardia
- Dryness of mouth ALLERGIC RHINITIS
- Prolongation of Q.T. interval  Allergic Rhinits is inflammation of mucous
- Alteration of bowel movements membrane of nose due hypersensitivity rxn in
- Urinary hesitancy nasal mucosa from repeated allergen exposure
- Blurred vision (atopy).

FAST TRAC KBASIC SCIENCE MBBS -1139-

 Pharmacology

 Etiology Nasal Decongestants [11]

- Hereditary I. Adrenergic drugs
- Psychological – emotion & Anxiety - Work well for congestion, for running nose
- Endocrinal – puberty, pregnancy, menopausal - No effect of itching on sneezing
period Eg. Oxymetazoline, Xylometazoline, Naphazoline
- Ventilation & seasonal - Relativity selective 2 agonist
 Precipitation factors - Long duration of action
- Inhalants: Inhalation of pollens, smokes and - Available as nasal sprays
dusts, house dusts, tobacco smoke - Long term use  atrophic rhinitis, insomnia
- Ingestion: Eggs, Crabs, Brinjals, bacterial - Can enter systemic circulation, & BP,
allergy. depression
- Drug Aspirin, Iodine, Antibiotic II. Pseudoephedrine
- Synthetic material
-  agonist, poor 2agonist
- Insomnia
- Vasoconstriction in skin and mucosa
 Symptoms - Fewer CNS, Cardiac side effects
- Watery nasal discharge - Better combined with antihistaminic,
- Nasal congestion mucolytic, antitussive and analgesic esp. in
- Repetitive sneezing common cold
- Itchy eyes, nose, ears and throat - May cause BP especially in hypertensive.
- Nose rubbing III. Phenylephirne [06]
- Allergic state - Is selective 1 adrenergic agonist weak action.
IV - Headache - Constrict the dilated arterioles in the nasal
- Sinusitis mucosa.
Alergic rhinitis therapy i.e. shinkage of mucosa and reduces airway
I. Avoidance of triggers resistance.
II. Medication - When administrated as an aerosol. If has a
I. Avoidance of triggers rapid onset of action and show few systemic
effects, thus provides quick relief.
- No carpeting or upholstered furniture
- No furry or feathered pets Non–Steroidal nasal sprays [03]

- Maintain heating/cooling system - Cromolyn (= Disodium cromoglycate: Mast cell

stabilizer)
- Non smoking
- It is mast cell stabilizer that inhibits
II. Medication
degranulation of mast cell.
- Prophylaxis
- Chemotaxis of inflammatory cell is inhibited.
- Antihistamines
- Very safe drug.
- Nasal decongestants
- Good for prevention of symptoms if given
- Nonsteroidal nasal spray before exposure.
- Steroid nasal sprays - Cromoglycate is not a nasal decongestant, but
- Anticholinergic nasal sprays irregular 4 times daily prophylactic dose as a
- Antileukotriene nasal spray produces symptomatic
- Vit. C, Vit. B complex improvement in many patients.
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 Respi

Topical Nasal corticosteroids THERAPY OF COUGH

- Reduce mucosal inflammation and all nasal Past Questions:
symptoms. 1. List drugs used for treatment of: [04 June]
- Use with persistent rhinitis at the lowest a. Dry cough (2)
effectiveness
2. List mucolytics. Give important differences
 Beclomethasone between bronchodilators.
 Budesonide (2+3=5) [08 Jan3]
 Fluticasone 3. List cough suppressants. List important
differences between cough suppressants.
 Mometasone
(2 + 3 = 5) [06 Dec]
 Triamcinolone
4. List the drugs for the treatment of:
Anticholnergic nasal spray (Ipratropium bromide)
(5 × 2 = 10)[04 June]
- Good for running nose.
a. Dry cough [05]
Antileukotriene (montelukast)
b. Mucolytic agents [10 Jan]
- Helpful for running nose or congestion
c. Mucolytics in therapy [07 July, 05 Dec]
- Not first line therapy
d. Antitussives [10 July]
Stepwise approach for allergic rhinitis
e. Expectorants [08 Jan]
 Avoidance of allergic factors and irritants is the
 Cough is a protective reflex which help to expel
first step in management.
irritant matters, respiratory secretion or foreign
 Mild intermittent symptoms: Non sedating
IV
bodies from respiratory tract.
antihistamine and /or decongestants as needed
 Types:
 Persistent mild to moderate symptoms:
I. Productive cough (useful) Associated with
- Intranasal steroid therapy 1–2 weeks prior to large amount of sputum.
season.
II. Nonproductive and dry cough  sputum is
- Nonsedative antihistamine and decongestant not produced
as needed.
Classification [04]
- Topical ocular antihistamines with or without
I. Pharyngeal demulcents
vasoconstrictor or topical ocular mast cells
stablizer. - Lozenges, cough drops, glycerine

 Severe Symptoms II. Expectorants (Mucokinetics) [07, 08]

- Topical nasal corticosteroids a. Bronchial secretion enhancer: Sodium or

potassium citrate, potassium iodide,
- Non sedating anti histamine and/or
Guaiphenesin, Ammonium chloride
decongestant if needed
b. Mucolytics [03, 05, 07, 10]
- Short term brust of oral corticosteriods.
Bromohexine, Ambroxol, Acetyl cysteine,
carbocisteine

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 Pharmacology

III. Antitussives (cough center suppressants) [10] - Side effects:

a. Opoid: Codeine, Pholcodeine  Rhinorrhoea
b. Nonopoids: Noscapine, Dextromethorphan,  Lacrimation
chlorphedianol  Gastric irritation
c. Antihistamines: Chlorpheniramine,  Hypersensitivity
Diaphenhydramine, promethazine - Dose: 8–10 mg TDS 4mg/5ml
IV. Adjuvant anti-tussives Acetylcysteine
Bronchodilator: salbutamol, Terbutaline - Act on disulfide bond in mucoproteins
I. Pharyngeal Demulcents present in sputum, makes it less viscid.

- Useful in cough due to irritation of the - Administrated directly into respiratory tract
pharyngeal mucosa above the epiglotis. - Can be nebulished directly in tracheal tube.
- Sooth the throat and reduce afferent impulses Carbocisteine
from the inflamed irritated pharyngeal mucosa, - Action is similar to acetylcysteine
(Symptomatic relief in dry cough) - Dose: 250–750 mg TDS orally
II. Expectorants (Mucokinetics) - S/E: G.I irritation and rashes
- It includes the drug which increase bronchial III. Antitussives [10, 11]
secretion or reduce its viscosity facilitating its - The drugs inhibits cough reflex complex
removal by coughing. directly or indirectly by acting on the cough
- Loosen cough and make more productive Centre in medulla and are useful in
symptomatic relief of dry irritant cough.
Guaiphenesin
- Reduce intensity and frequency of cough.
- Directly es bronchial secretion and
IV mucosal ciliary action after absorption from
- Used only for dry unproductive cough or if
cough is unduly tiring, disturb sleep or is
gut.
hazardous.
- And they are secreted by tracheobronchial
Opoids:
glands.
Codeine
- Dose: 50–200 mg
- An opium alkaloid similar or less potent
- S/E: Gastric upset than morphine
Mucolytics [03, 05, 07, 10] - More selective for cough Centre
- These drugs are used for making the sputum - An effective cough suppressant and
thin and less viscid, so that it can be easily suppresses cough for about 6 –8 hr.
expectorated. - Abuse liability is low but present if
Bromhexine [07, 10] continued.
- Is potent mucolytic and mucokinetic, - Antitussive action is blocked by naloxone.
capable of inducing copious bronchial - Drawback:
secretion.  Constipation
- Reduce viscosity of sputum by dissolving  Respiratory depression (at high dose)
mucopolysaccharide fibres directly and also
 Drowsiness
by liberating lysosomal enzymes.
- Contraindication: Asthmatics patients
- Useful if mucous plug is present
- Dose: 10–30 mg

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 Respi

Pholcodeine - Specially promoted for cough in respiratory

- Similar efficacy as codeine allergic state.
- No addicting property and longer acting > - Second generation anti-histamines are
12 hr. ineffective.
- Dose: 10 – 15 mg - Drug used:
Non opioids  Chlorpheniramine 2 – 5 mg
Dextromethorphan [02, 05]  Diphenhydramine: 15 – 25 mg
- Acts centrally and elevates the threshold of  Promethazine 15 – 25 mg
cough centre. Bronchodilator
- d – isomer has selective antitussive action - It is used when there is bronchospasm induced
(last for 5 – 8 hrs) and aggravated cough.
- As potent as codeine in controlling cough. - Helps in clearing secretion by increasing
- Does not suppress respiration, more safer, surface velocity of airflow during cough.
no constipation, no addiction. - Eg. Salbutamol, terbutaline
- Antitussive actionsnot blocked by
naloxone so, action is not exerted through THERAPY OF TUBERCULOSIS
opioid receptor. Past Questions:
- Side Effects: 1. a. List antitubercular drugs.
 Dizziness b.Write the regimen used in the treatment of
 Nausea category I of tuberculosis.
 Drowsiness c. List two adverse drug reactions of rifampin.
 Ataxia (2+4+2=8, 2+3+3=8) [09 July, 08 July]
IV
- Dose: 10 – 20 mg 2. a. List the drugs used in the treatment of
Noscapine (= Narcotine) tuberculosis (2) [06 June]
- An opium alkaloid of the benzoisoquinoline b. Write one regimen for the treatment of each
series. category of tuberculosis (6) [06 June]
- Depresses cough but is non – narcotic and 3. List the drugs used in tuberculosis. Write regimen
no dependence inducing properties. used in treatment of category I. (8) [07 July]
- Equipotent antitussive as codeine  useful 4. List the drugs used in treatment of tuberculosis.
for spasmodic cough Write short term regimen for the treatment of
smear positive tuberculosis. (2+3=5) [05 June]
- Side Effects:
5. List the drugs used in treatment of tuberculosis.
 Headache
Write important adverse effects of first line drugs
 Nausea in tuberculosis (2+4=6) [02 Dec]
 Bronchoconstriction in asthmatic due to 6. Give reasons:
release of histamine
a. Rifampicin in short course chemotherapy of
- Dose: 15 – 30 mg tuberculosis (3) [05 Dec]
Antihistamine b. Combination of drugs in treatment of
- It decreases cough by inhibiting post nasal drip tuberculosis. (3) [10 Jan, 03 June]
by virtue of their anticholinergic action and c. Antimicrobial combinations in tuberculosis
sedative effect.
(3) [10 July]
- But lack selectivity for cough centre.
FAST TRAC KBASIC SCIENCE MBBS -1143-
 Pharmacology

Classification of antitubercular drugs - Act on extracellular and intracellular TB bacilli.

[02, 05, 07, 08, 09] - Mutation in catalase-peroxidase gene
preventing conversion of prodrug isoniazide to
 Drugs are classified based on their clinicalutility:
its active metabolite (Resistance).
I. First line drugs/Primary anti-tubercular drugs
Mechanism of Action
- Drugs have high antitubercular efficay and
- Inhibit biosynthesis of mycolic acid, a important
low toxicity
constituents of myco-bacterial cell wall.
- Are used routinely
- Resistance: Inh A gene encode mycolic acid.
- Drugs are:
It’s mutation is responsible for resistance
 Isoniazid (H)
- Most atypical mycobacteria are not
 Rifampin (R) inhibited by INH.
 Pyrazinamide (Z) PKa
 Ethambutol (E) - Given orally, completely absorbed
 Streptomycin (S) - Concentration similar to plasma in
II. Second line drugs /secondary antitubercular cerebrospinal fluid is present only in
drug inflamed meninges.
- Drugs have either low antitubercular - Metabolized in liver
efficacy or high toxicity or both.  Fast acetylator (t1/2 – 1 hr)
- Used in special circumtances only.  Slow acetylator (t1/2 – 3hr)
- Drugs are: Dose:
 Thiacetazone (Thz) - 5mg /kg / day
 Para-aminosalicylic acid (PAS) - Max dose: 300 mg/day
IV  Ethionamide (Eto) Interaction:
 Cycloserine (Cs) - Aluminum hydroxide inhibits INH absorption.
 Terizidone (Trd) - PAS inhibit INH metabolism & prolong its T1/2.
 Rifabutin Adverse Drugs Reactions
 Fluoroquinolones - Peripheral neuritis: INH interferes with
 Ofloxacin (Ofx) utilization of pyridoxine to nerve and 
excretion of pyridoxine.
 Levofloxacin (Lvx/Lfx)
Treatment: 100 mg/day pyridoxine.
 Moxifloxacin (Mfx)
- Hepatotoxicity: Hepatocellular damage and
 Ciprofloxacin (Cfx)
necrosis
 Injectable drugs
- CNS: Psychotic behaviour
 Kanamycin (Km)
Rifampin (R) [05, 08, 09]
 Amikacin (Am)
- Broad spectrum anti tubercular drug
 Capreomycin (Cm)
- Highly effective antibiotic
Isoniazid (H) MOA
- It is the antitubercular drug which is primarily - Both extracellular and intracellular organisms
tuberculocidal, however, it is bacteriostatic for are affected.
resting bacilli and bactericidal for rapidly
- Inhibit DNA dependent RNA polymerase 
dividing organism
exert bactericidal effect.
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 Respi

PKa - MOA
- Well absorbed orally Given at least 1/2  Inhibits mycolic acid synthesis by interacting
hr before breakfast, penetrates cavities with a different fatty acid synthase
caseous masses, placenta and meninges. encoding gene.
- Microsomal enzyme inducer,  metabolism - Resistance: Mutation in the PnCA.
of OCP HIV protease inhibitor, Ritonavir, - PKa:
indinavir  Oral absorption
Adverse Drugs Reactions [08, 09]
 Good penetration of drug into CSF
- Hepatitis
- Dose:
- Respiratory syndrome
 20–30 mg/kg/day
- Flu syndrome
 For > 50 kg – 1500 mg
- Abdominal syndrome
- Cutaneous syndrome - Adverse Drug Reactions
- Purpura, hemolysis, shock and renal failure  Hepatotoxcity
- Orange red coloration of urine and body  Hyperuricemia: due to inhibition of uric acid
secretion (harmless) secretion
Other indications of Rifampin  Gout can occur
- Leprosy  Drug fever
- Prophylaxis of meningococcal & H.  Contraindications: Liver disease
influenzae meningitis.
Ethambutol (E)
- 2nd /3rd choice drug for MRSA,
- Is selective tuberculostatic drug
diphtheroids and legionella infection.
- Combination of doxycycline and rifampin
MOA IV
 1st line drug therapy of brucellosis - Inhibit arbinoglycan synthesis
Contraindications: - Suppress the growth of most INH and
- Alcoholics streptomycin resistant tubercle bacilli.
- Chronic liver disease - Along with other drug it prevents or delay
- Vasculitis the emergence of resistant bacilli.
- Old age PKa
Dose:
- Cross BBB when meninges inflammed
- 10 mg/kg/day (for > 50 kg body wt) sufficiently.
- Max. wt: 600 mg/day Dose
Resistance: - 15 – 20 mm/kg/day
- Mutation of Repo B gene
- For 50 kg, 100 mg
Pyrizinamide (Z)
ADR
- It is chemically similar to INH and weak
- Optic neuritis
tuberculocidal drug
- More active in acidic mediaShow inflammation - visual acquity  unable to differentiate
- Lethal to intracellular bacilli red from green
- Highly effective during first 2 months of - It is not recommended for children under
therapy when inflammatory changes are 5yr of age.
present.
FAST TRAC KBASIC SCIENCE MBBS -1145-
 Pharmacology

Streptomycin (S) Para amino salicylic acid (PAS)

- First clinically effective drug - Chemical properties and MOA are related to
- Acts only on extracellular bacilli sulfonamides.
Given by IM dose – 15 mg/kg, 750mg above 50 - Competitively inhibits folate synthesizing
yr of age enzyme and prevents the formation of
- Does not cross BBB normally but reaches CSF in tetrahydrofolic acid (THFA) which is required
inflamed meanings upto 20% of plasma cocn. for growth and multiplication of bacteria.
- Not commonly useddue to need of IM - Have tuberculostatic effect.
injection.
- Rapidly abserved orally and widely distributed
- Low safety margin So, ADR are:
- Poor penetration of BBB
 Ototoxicity
- PAS reduces absorption of rifampicin from gut
 Nephrotoxicity
and competitively inhibits the acetylation of
 NM blockage INH thus increasing plasma level of INH
- Resistance develops when rapidly used alone
Dose:
Uses
- 10–12 gm/day in divided dose with meal.
 Serious form of T.B.
ADR
 Disseminated TB, meningitis
- Poor patients acceptability: Anorexia,
 TB with hepatic disease
nausea, epigastric pain
Second line drugs - Rashes, fever, malaise
Thiacetazone (Thz) - Liver dysfunction, blood dyscrasias
- Tuberculostatic - Goiter
- Cost of drug is low and efficacy is also low
Cycloserine (Cs)
IV - Use along with isoniazid for delay resistance
- Tuberculostatic drug
but need prolonged therapy
- But have serious CNS S/E
- Dose: 150 mg orally
ADR  Sleepiness
- Hepatitis, Anorexia, loose motion  Headache
- Not used in HIV infected with TB – due to  Tremor
serious and fatal adverse drug reactions:
 Psychosis
 Steven's Jonhson syndrome
 Suicide in some case
 Toxic epidermal necrolysis
- Adverse effects limit usefulness of drug.
Ethionamide (Eto)
- Tuberculostatic, chemically related to INH Kanamycin (Km), Amikacin (Am),
- Inhibition of cell wall synthesis (mycolic acid) Caperomycin (Cm)
- Recommended dose: 1 gm/day but more than - Kanamycin and amikacinAmynoglycoside
500 mg not tolerated. - Caperomycin Polypeptide
ADR - Given by IM route
- Anorexia, nausea, vomiting are common - All exhibit Nephrotoxcity, ototoxicity so never
- Hepatitis combined together or with streptomycin.
- Peripheral/optic neuritis
- Used when not responding to usual therapy or
- It is seldom used only in case of resistance infection by atypical mycobacteria.
to better tolerated drugs.

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 Respi

Rifabutin  Category – 3 has been removed in recent

- Related to rifampin in structure and MOA regimen
- Are hepatic microsomal enzyme inducers but in  Category – 4
lesser degree. - Failure of treatment of previous category II
- Lesser interaction with protease inhibitors, so - Multi Drug Resistant Tuberculosis
dose of rifabutin sed 300 mg to 150 mg/day.  Treatment pattern: Treated in 2 phases
- Used in TB with HIV
Initial phase (2 month) Continuous phase (4 – 6
- Prophylaxsis of MAC infection in HIV infected month)
individual.
- Rapid killing of TB - Fewer drug takes lower
Fluoroquinolones (FQs) bacilli time
- Ciprofloxacin, ofloxacin.
- Infectious patients - Drugs eliminate the
 Inhibitory activity against mycobacterium become non remaining T.B bacilli
tuberculosis and MAC infection. infectious within 2 - Prevents relapse
Uses wks. Vast majority
become –ve within 2
- Salvage therapy for MAC infection in HIV
months
patients
- Ciprofloxacin, clarithromycin, Rifabutin and National treatment regiment for each patient
amikacin. treatment category
- Tuberculosis therapy with quinolone Treatment Tuberculosis Initial phase Continuous
reserved for patent with MDR TB or those category patients phase
who cannot tolerate 1st line drug. Category - - New smear 2 HRZE(S) 4 HR/4H3R3
- Macrolides – clarithromycin, Azithromycin 1 +ve PTB IV
 Clarithromycin more active than - Smear –ve
Azithromycin by 4 times. PTB
 For MAC infection: Clarithromycin 500mg - Extra PTB
BD or azithromycin 500mg OD + ethambutol cases
with or without rifabutin. Category - - Relapse 2HRZES + 5 HRE
 T/t should be continued throughout life 2 - Treatment 1HRZE
time of HIV patient. failure
Standardized Treatment Categories - Return after
[06, 08, 09] default

 Category - 1 WHO treatment regimen for TB [06]

- New sputum '+ve' PTB TB category Initial Continuation Total
- Sputum smear '–ve' phase phase duration
(Daily /3×
- Extra-pulmonary TB
per week)
 Category - 2
Category-1 2 HRZE (S) 4 HR/4H3R3 6
- Relapse
- Treatment failure Category-2 2 HRZES + 5HRE or 8
1HRZE 5H3R3E3
- Return after default

FAST TRAC KBASIC SCIENCE MBBS -1147-

 Pharmacology

DOTS plus Guideline: Treatment of MDR TB Extensively Drugs Resistant TB

[03, 10] - These are MDR – TB cases that are also
- MDR-TB is defined as resistance to both H and resistant to FQs as well as one of the injectable
R, and may be any number of other (1st line) 2nd line drugs and may be any number of other
drug(s) drugs.
- MDR-TB has more rapid course with with - The bacilli thus are resistant to at least 4 most
worse outcomes. effective cidal drugs, viz, H,R,FQ and one of
- Its treatment requires complex multiple 2nd line Km/Am/Cm.
drug regimens which are longer, more - XDR-TB is very difficult to treat, has a rapid
expensive and more toxic.
course and high mortality.
- The general principle of treatment of MDR-TB are:
- However, to prevent further amplification of
 The regimen should have at least 4 drugs
resistance, the standardized MDR regimen
certain to be effective. Often 5 – 6 drugs are
must be immediately stopped when XDR-TB is
included, since efficacy of some may be
detected or suspected.
uncertain.
- An expert panel may decide on institutintg
 Reliance about efficacy may be placed on
category V treatment, including group V drugs.
survey of similar patients who have been
treated, DOT results (applicable to H.R. Km, - Group V are drugs with uncertain efficacy; not
Am, Cm, FQs), and the anti – TB drugs used recommended for MDR-TB; may be used in
previously in that individual. extensively drugs resistant TB. (XDR–TB).
 Avoid combining cross resistance drugs, e.g. - Group V Drugs:
two FQs, Km with Am or Eto with Pto. Or Cs  Thiacetazone
with terizidone.
IV  Clarithromycin
 The RNTCP has devised a ‘standardized’
treatment regimen (also called category IV  Clofazimine
regimen) of 6 drugs intensive phase lasting  Linezolid
6 – 9 months and 4 drugs continuation  Amoxicillin/clavulanate
phase of 18 months, which is used in all
 Imipenem/cilastatin
confirmed or suspect MDR – TB cases.
Intensive phase (6 – 9 Continuation phase
TB with pregnancy and Lactation
months) (18 months) - 2HRZ + 4HR
1. Kanamycin (KM) 1. Ofloxacin or - Isoniazid, rifampin, pyrazinamide, Ethambutol
Levofloxacin are safe in pregnancy
2. Ofloxacin (OfX) or 2. Ethionamide - Ethambutol can be added in 3rd trimester not
levofloxacin (Lfx) earlier.
3. Ethionamide (Eto) 3. Cycloserine - T/t should not be withheld due to pregnancy
4. Cycloserine (Cs) 4. Ethambutol and Lactation
5. Pyrazinamide (Z) - In Lactation: Full course of T/t should be given
6. Ethambutol (E) infant should be given chemoprophylaxis.
+ pyridoxine 100 mg/day

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 Respi

SPECIAL POINTS FOR MCQs

Bronchial Asthma
1. B2 sympathomimetic Bronchodilators
- Salbutamol, Terbutaline
 Short acting
 Used in Acute attack
 Show no antiinflammatory effects.
- Salmeterol, Bambuteral, formeterol
 Long acting
 Used for prophylaxis
 Show no anti – inflammatory effects
2. Side effects of sympathomimetic bronchodilators are:
Hypokalemia, Hyperglycemia, Tolerance, tachyphylaxis
3. Methylxanthines (Theophylline &Doxophyline)
- MOA: Inhibits phosphodiesterase III, IV and es cAMPcocn.
 Blocks adenosine receptor IV
 2 agonist
 Mucociliary movement stimulator
- At high does, kinetics changes from 1st order to 2nd order.
- Erythromycin inhibits metabolism of theopylline
- Cross placenta & secreted in milk.
- Smoking, Phenytoin, rifampin, phenobarbitone plasma levels of theophylline.
- Erythromycin, ciprofloxacin, cimetidine, allopurinol, es levels of theophylline.
4. Ipratropium & Tiotropium
- Anti cholinergic bronchodilators.
- Bronchodilaters of choice in COPD / COAD.
5. Mast cell stabilizer (Sodium chromoglycate)
- Inhibits mast cell deregulation
- Ineffective in acute attack
- Used in prophylaxis
- Not absorbed orally, given as aerosol.

FAST TRAC KBASIC SCIENCE MBBS -1149-

 Pharmacology

6. Leukotriene Antagonist (Monteleukast):

- Used in maintenance therapy of asthma and relief of seasonal allergies.
- It is not useful in acute attack.
- Usually administered orally.
- Montelukast is a cysLT1 antagonist i.e. blocks action of Leukotriene D4 on the cysteinyl LT
receptor (CYSLT1) in lung and bronchial tubes by binding to it.
- Its use is associated with higher incidence of churg–strauss syndrome.
- Zafirlukast is taken once daily.
- 5 – lipooxygenase inhibitor is Zileuton.
7. Steroids
- Are anti inflammatory
- lipocortin levels
- Blocks phospholipid breakdown
- Not bronchodilators
- Have no role in acute attack or status asthamaticus.
- Reduce airway inflammation.
- Best route to treat steroid dependent asthmatic case is Inhalational
- Inhalational steroids cause oropharyngeal candidiasis.
- Topical steroids causes: Glaucoma.
IV - Parenteral steroids: Cataract
- Posterior subscapular cataract  commonest type of steroid induced cataract.
- Steroids are contraindicated in herpetic corneal ulcer.
8. Omalizumab
- Humanized IgE Ab
- Reduces frequency of Asthma exacerbations.
9. Antihistaminic – H1
- Divided into
i. 1st generation  sedative
ii. 2nd generation  non sedative
10. H3-receptors are mainly located in Brain &myenteric plexus.
- On H3 – receptor activation, does not cause release of Dopamine but causal of release of
histamine, serotonins, Nor-epinephrine.
11. Nizatidine
- H2 receptor antagonist
- Stimulates contractile activity of stomach
- Inhibits enzyme cholinesterase

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12. Slowest acting antistaminic drug: Astemizole

13. Fastest acting antistaminic drug: Terfendine
14. Potent bromchoconstrictor is Bradykinin
15. Anti-tubercular drug
- Drugs 
 1st line
 2nd line
 Newer
- 2nd line drugs are used only for the treatment of patients with tuberculosis resistant to first line
drugs.
16. Tuberculocidal drugs Tuberculostatic drugs
- Isoniazid - Ethambutol
- Rifampin - Thiacetazone
- Pryizinamide - PAS
- Streptomycin - Ethionamide
- Cycloserine
17. MOA anti tubercular drug
Drug MOA
i. Isonizid - Inhibits mycolic acid synthesis
IV
ii. Rifampin - Inhibits RNA polymerase
iii. Ethambutol - Inhibits Mycolic acid incorporation into cell wall
iv. Pyrizinamide - Inhibit Mycolic acid
v. Streptomycin - Inhibit protein synthesis
18. Adr. & Resistance anti tubercular drug
Resistance is due to
Drugs Adr
mutation
i. Isoniazid InhA gene mutation - Irritation Neuritis (peripheral neuritis)
Hepatoxcity @ INH
i. Rifampin Repo B gene mutation - Respiratory syndrome, cutaneous syndrome,
Flu like syndrome, Abdominal syndrome @
Remember as syndrome
iii. Pyrazinamide Pnc A gene mutation - Hepatotoxcity, Hyperuricemia,
Hypeglycemic [@ 3H]
iv. Ethambutol emb gene - Optic neuritis, Retinal damage blue vision
v. Streptomycin 16 SrRNA gene mutation - Ototocicity, NM blockage nephrotoxicity

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19. Antitubercular drug which act intracellular  Pyrazinamide

20. Antitubercular drug which acts at low pH  Pyrazinamide
21. Antitubercular drug which penetrates meninges (BBB) Pyrazinamide,INH, Rifampin.
22. Antitubercular drug, which is contraindicated in renal failure: Ethambutol, streptomycin.
(MCQs KU 2012)
23. Isoniazid
- Acts as Bacteriostatic against in resting bacilli and bactericidal against rapidly multiplying
organism.
- Peripheral neuritis associated with isoniazid relates to interference with pyridoxine (vit. B6)
metabolism. This can be reduced with prophylactic administration of 10 to 50 mg of
pyridoxine daily.
24. Rifampin is semisynthetic derivative of streptomyces mediterranei.
25. INH drug has metabolism under genetic control.
26. Streptomycin + ethambutol is preferred in severe hepatic failure.
27. Most hepatotoxic is pyrazinamide.
28. Streptomycin is contraindicated in TB in pregnancy.

IV

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