Management of status asthmaticus and Chronic Asthma

Treatment of  Status asthmaticus

Propped up position.

Oxygen inhalation by mask

Injection Hydrocortisone 200-500mg I/V routes 6 hourly Or Sodium succinate.

Nebulizer – over 5 minute repeated in 15 minutes.

Injection adrenaline subcutaneously 0.5mg (1000 dilution) 1:1000ml.

Ipratropium bromide ( 0.5mg should be added in nebulizer)

Injection Aminophylline ( 5 mg/kg intravenously very slowly)

If improved this condition then oral prednisolone 30.-60mg daily with inhaler sulbutamol.

Antibiotics if necessary.

No sedative of any kind.

Chest X-ray to exclude pneumothorax

Treatment on discharge:

• Complete the course of antibiotic
• Short course of oral prednisolone
• Inhaled beta agonist + inhaled steroid 

Treatment plan of chronic asthma

It is also called step care management of Asthma.
Step – I : Occasional use  of inhaled short acting β2 agonist bronchodilator ( once daily)
Step – II: Regular inhaled anti-inflammatory agent ( Chromolin or low dose leukotrien antagonist)
Step – III: Regular inhaled corticosteroid + regular long acting inhaled β2 agonist
Step – IV: High dose of inhaled steroid & regular bronchodilator
Step – V: Best of step + oral prednisolone

Bronchodilators administered by inhalation\

• Salbutamol
• Sulmeterol
• Formeterol
• Albuterol
• Isoproterenol
• Metaproterenol
• Terbutaline
• Ipratropium bromide
• Dexamethasone
• Beclomethasone
• Budesonide
• Flunisolide
• Di – sodium chromoglycate
• Fluticasone
• Triamcinolone

Approaches of bronchial asthma treatment, Drugs used

Approaches of bronchial asthma treatment:

1. Prevention of exposure to allergens
2. Reduction of bronchial inflammation and hyper reactivity
3. Dilatation of narrowed bronchi

Drugs used in Bronchial asthma

A. Bronchodilators:

1. Sympathomimetic drugs:

a. Selective β2 agonist.
Short acting (duration 4-6 hrs) –

• Salbutamol
• Terbutaline
• Metaproterenol

Long acting (duration 12 hrs or more) –

• Salmeterol
•  Fenoterol
• Formeterol
• Rimeterol
• Bitolterol

b. Non selective (β1 & β2)

•  Adrenaline
•  Ephedrine
• Isoproterenol (Isoprenaline).

2. Methyl xanthene group:

Natural –

• Theophylline
• Theobromine
• Caffeine (also used in neonatal apnoea)

Synthetic –

• Aminophylline. (Na salt of Theiophylin)

3. Antimuscarinic bronchodilator:

• Ipratropium
• Oxitropium

B. Anti-inflammatory

1. Corticosteroids: 

• Hydrocortisone. (Inj.)
• Prednisolone. (Oral)
• Beclomethasone
• Budesonide
• Triamcinolone
• Flunisolide
• Fluticasone
• Mometason

   

2 . Mast cell stabilizer:

• Nedocromil sodium
• Cromolyn sodium ( disodium chromoglycate) drugs 

C. Others:

1. Leukotrine pathway inhibitor –

• Zileuton
• Zafirlukast
• Montelukast

2.  Calcium channel blocker –

•  Nifedipine
• Verapamil
• Amlodipine

3. Anti IgE monoclonal antibody:

• Omalizumab

4. Histamin (H1 ) receptor blocker:

• Ketotifen

Bronchial Asthma: Pathophysiology, Immunopathogenesis, Classification

Bronchial asthma: 

 Asthma may be defined as a disorder characterized by chronic airway inflammation and increase airway responsiveness resulting in sign of wheeze, cough, chest tightness & dyspnoea.

Pathophysiology of bronchial asthma:

Occurs due to external stimulus, such agents are –

•      Biological agents
•      Environmental /chemical agent
•      Virus

Immunopathogenesis of Bronchial Asthma:

• When a person exposed to antigen it stimulates production of antibody ( reaginic antibody – IgE) and bound to mast cell surface. 
• When re-exposure to that antigen than antigen –antibody reaction occur and triggers release of some chemical mediators from stored granules of mast cell and also helps in the synthesis and release of other mediators.

Types of bronchial asthma: 

There are various types of bronchial asthma.

1. Asthma associated with specific allergic reaction:

Criteria:

• Very early onset.
• Extrinsic type.
• Atopic individual.

Avoid of allergens – we prevent asthma. Here type I reaction occur involving IgE Antibody.

2. Asthma not associated with known allergy:

Criteria:

• Late onset.
• Intrinsic type.
• Non-atopic. (Not individual) occurs in a group.

3. Exercise induced asthma: Criteria: Within a few minutes asthma develops.

4. Asthma associated with chronic obstructive pulmonary disease.

• Chronic bronchitis
• Pulmonary emphysema

Asthma may also be classified into:

1. Intermittent
2. Persistent –

• Mild
• Moderate
• Severe

3. Acute

• Mild
• Moderate
• Severe ( Status asthmaticus)

4. Special variant –

• Seasonal
• Drug induced 
• Exercise induced
• Cough variant and Pregnancy asthma

Drugs Used In Prostatic Hyperplasia and Erectile Dysfunction

Drugs Used in Benign Enlargement of Prostate

Principle:  

Capsular and stromal tissue of Prostate gland is rich in α1 adrenoceptors, and glandular tissue under the influence of androgens. Both these, the α receptors and androgens, and androgens, are targets for drug therapy. Because the bladder itself has a few α receptors, it is possible to use selective α1-blockade without affecting bladder contraction.

Drugs:

α –adrenoceptor blockers:

•     Prazosin
•     Alfuzosin
•     Indoramin
•     Terazosin
•     Doxazosin
•     Tamsulosin

All are selective for α1 receptor.

Others:

•     Finasteride

Mechanism of drugs used in BHP: 

α1 receptor blockers cause significant increases (compared to placebo) in objective measures such as maximal urine flow rate and drugs also improve semi-objective symptom scores. In normotensive men, falls in blood pressure are generally negligible; in hypertensive patients, the decline in pressure can be regarded as an added bonus.

Tamsulosin is a competitive α1 receptor blocker with a structure quite different from that of most other α1 receptor blockers. Long half life of 9-15 hrs. it has higher affinity for α1A and α1D receptors than for the α1B subtype.

Advantages of tamsulosin over other alfa receptor blockers:

•     Long half life
• Greater potency in inhibiting contraction in prostate smooth muscle versus vascular smooth muscle
• Drug efficacy in BHP suggests that the α1A subtype may the most important alfa subtype mediating prostate smooth muscle contraction.
• Less effect on standing blood pressure

Adverse effects:

• Dizziness
• Asthenia
• Nasal stuffiness

But Tamsulosin has fewer side effects.

Finasteride: 

An alternative drug is the type II 5α-reductase inhibitor; it inhibits conversion of testosterone to its more potent metabolite, dihydrotestosterone.  It doesn’t affect serum testosterone, or most non-prostatic responses to testosterone. It reduces prostatic volume by 20% and increases urinary flow rates by a similar degree.

Drug used in erectile dysfunction:

• Sildenafil
• Tadalafil
• Vardenafil

Sildenafil
Mechanism of action:

Erectile response mediated by release of nitric oxide (NO) from nerves supplying vessels in corpora cavernosa. This increases intracellular cGMP levels which cause vasodilatation. Effects terminated by phosphodiesterase type 5 enzymes. Which is inhibited selectively by sildenafil, which enhances vasodilatory action of NO.

Contra indications:

• Severe hepatic impairment
• BP<90/50 mmHg
• Recent stroke or MI
• Patient who are taking organic nitrates

Adverse effects:

• Headache
• Flushing
• Dyspepsia
• Nasal congestion
• Green / blue tingling of vision (3%)

Drugs used for osteoporosis:

• Alendronate
• EtidronateIbandronate
• Pamidronate
• Risedronate

Drugs for obesity:

• Orlistat
• Phentermine
• Sibutramine

Oral Hypoglycemic Drug- Sulphonylureas: Mechanism, Indication, Side Effects

Mechanism of action of Sulfonylureas (Glibenclamide) / oral hypoglycemic drug:

I. Pancreatic action: 

a. They are effective only in the presence of functioning pancreas at least 30% β- cell should be active.
At pancreatic beta cell membrane there is ATP dependent K+ channel. Sulfonylurea bind to sulfonylurea receptor and blocks the ATP dependent K+ channel. So inhibits the efflux of K+ ion, through the channel resulting depolarization. Depolarization causes opening of voltage gated Ca++ channel leading to influx. This Ca++ then induces insulin secretion. This endogenous release insulin then lowers the blood glucose level. Sulfonylurea acts only in presence of viable pancreatic beta cell that is when at least 30% pancreatic beta cell is viable. It is indirect action of sulfonylurea.

b. Reduction of serum glucagons concentration:
Increase release of both insulin and somatostatin causes inhibition of α cells which leads to reduction of glucagons release

II. Extra pancreatic action:
Sulfonylurea binds to its receptor in K+ channel in extrapncreatic tissue also and may potentiate the action of insulin by –
o    Increase number of insulin receptors in tissue
o    Increase binding affinity of insulin receptor for insulin
o    Increase glucose transport into the cell by glucose transporter
o    Decrease release of catecholamines
o    Inhibit glycogenolysis by inhibiting phosphorylase enzymes

Three mechanism of Sulfonylureas action have been proposed. Sulfonylureas indirectly decrease blood sugar:
By –
1. Release of insulin from pancreatic beta cell.
2. Reduction of serum Glucagon level.
3. Potentiate the action of insulin on its target tissue & extra pancreatic effect.

Adverse effect of Sulfonylureas:

1. Hypoglycaemia.
It is not frequently occurs but when occurs tends to be prolong. It is particularly seen with Chlorpropamide, Glibenclamide & elderly patient with impaired hepatic & renal function.

2. GIT upset.

• Nausea
• Vomiting.
• Diarrhea

3. Haemotological reaction.

• Neutropenia
• Agranulocytosis
• Thrombocytopenia
• Aplastic anemia

4. Cholestatic jaundice & intolerance to alcohol Chlorpropamide can induce hepatic microsomal enzyme particularly in high doses & due to disulfiram like reaction.

5. Allergic skin reaction – skin rash, exfoliative dermatitis

6. Weight gain – due to increase appetite

7. Muscular weakness, ataxia, dizziness, mental confusion

8. Teratognensis

9. Drug interaction:  Sulfonylureas are protein-binding drug so drug interaction occurs with protein binding drugs.

• Sulfonamide
• Salicylate
• Phenylbutazone
• Warfarin

These drugs displace Sulfonylureas & produce antidiabetic effect & cause hypogylcaemia.

Indications of Sulfonylureas:

1. Sulfonylureas are used for the treatment of NIDDM who can’t be controlled by diet, exercise & weight reduction. It is usually used in non-obese non-insulin dependent patient.

Contraindications of Sulfonylureas:

1. In insulin dependent diabetes mellitus (IDDM).
2. Diabetes with complication e.g. diabetic keto acidosis, diabetic nephropathy etc.
3. Diabetes with surgery.
4. Diabetes with pregnancy & lactation.
5. Hepatic & renal impairment.

N.B:
Combined therapy with Sulfonylureas & insulin: 
It is used in cases where daily insulin requirement is very high. Since Sulfonylureas drug not only increase the pancreatic beta cell secretion of insulin but also increase peripheral tissue sensitivity to insulin. So use of Sulfonylureas has been advocated to reduce the total insulin dose.