KHAN respiratory 2 exam

Traits of asthma

Airway obstruction

Mucous secretion

Inflammation

Th2 help cell

Eosinophil involvement

Bronchial hypersensitivity

How is asthma treated?

Bronchodialators and anti-inflammatroy’s

Traits of COPD

Airway obstruction

Mucous secretion

Inflammation

Cytotoxic T-Lymphocytes

Neutrophil involvement

What are the causes of COPD

-Smoking and old age

-Deficiency of alpha-1 antipyresis

What is the treatment of COPD

Beta 2 agonists and anticholinergics

What is Bronchial hyperactivity?

The bronchial is sensitive to stimulants (Pollen, animal dander, and irritant chemicals) which causes bronchoconstriction

What is the MOA of theophylline?

-Inhibits PDE → Increase in cAMP

-Adenosine antagonist

Why can’t Theophylline be used in asthma?

Has low therapeutic window

Names of the Short Acting Beta Agonists (SABA)?

Albuterol and Levabuterol

What are the names of the Long Acting Beta Agonits (LABA)?

Salmeterol

Formoterol

MOA of Beta-2 agonists?

Activating adenylyl cyclase → Increasing cAMP production

-cAMP mediates bronchodialatory effect

ADR’s of Beta-2 Agonists

1) Tachycardia

2) Skeletal muscle tremors

3) Hypokalemia

4) restlessness, apprehension, anxiety

Boxed warning of LABA

Asthma related death

Advantages of steroid and LABA combination

Reduces inflammation and increases Beta-2 expression

Can LABA be used alone in COPD?

YES

How can you ensure beta 2 selectivity?

-Catechol group

-Large R group

-resorcinol / hydroxymethol

What are the names of the three endogenous hormones secreted from the adrenal cortex?

-Glucocorticoids

-Mineralcorticoids

-Adrenal Androgen

What is the precursor of Cortical hormones?

Cholesterol

What is the rate limiting step for cortical hormone synthesis?

•cholesterol (C-27) →pregnenolone (C-21) conversion

What occurs during prolonged GC therapy?

HPA suppression

MOA of steroids

•  Steroid in circulation bound to CBG (costicosteroid binding protein →carrier protein)

•  Enters cell interact with receptor (cytosol)

•  Receptor confirmation changed

•  Steroid-receptor complex →Nuclear translocation

•  Receptor dimerization → Binds to GRE (glucocorticoid response elements) and regulate transcription

•  Glucocorticoids increase, or decrease in transcription (for example-decrease transcription of genes coding for pro-inflammatory cytokines)

Cortisol (steroids) decrease which blood cells? (immune system 1)

-Monocytes

-Basophils

-Eosinophils

-Lymphocytes

Do steroids (cortisol) increase or decrease expression of lipocortin? (immune system 2)

Increases

What is the MOA of Lipocortin?

Inhibits PLA2

A decreased expression of COX-2 leads to….

Decreased PG

Cortisol (steroids) alter expression of cytokines, which are decreased and which are increased? (immune system 3)

Increased

-Anti-inflammatory proteins (IL-10)

Decreased

-certain cytokines involved in inflammation (IL-1, TNF-alpha)

Explain Cortisol on immune system 4

Inhibition of Mast cell and basophil degranulation. decrease in IgE mediated Histamine, and LT release

Explain Cortisol on immune system 5

Decreased expression of adhesion molecules. This is helpgul because luekocytes binjd to endolthelial cells through these molecyles and move to the inflamation. —> reduced influx of luekocytes

Names of Systemic glucocorticoids

•Cortisone

•Methylprednisolone (MEDROL)

•Prednisolone (MILLIPRED, ORAPRED)

•Prednisone (RAYOS)

•Dexamethasone (DECADRON)

•Hydrocortisone (CORTEF)

•Triamcinolone (ARISTOPAN)

ADR’s of systemic glucocorticoids

Adverse effects

The most common adverse effects following short-term systemic therapy:

•Mood disturbances

•Increased appetite

•Loss of glucose control (b/c decrease glucose uptake in tissues, increased gluconeogenesis)

•Weight gain 

•Fluid retention (cause: mineralocorticoid effects® aldosterone mediated water and sodium retention)

•Hypertension (cause-as above)

•Peptic ulcer

• Long-term  systemic use: HPA suppression® taper dose to restore endogenous hormone (cortisol) production

What is significant of positions 1-2,6,9,11,16 on systemic glucocorticoids?

Most changes occur in these positions

Structure of cortisol

Structure of cortisone

Structure of Prednisone

Structure of Prednisolone

Which systemic glucocorticoids are active?

-Cortisol

-Prednisolone

What are the positions on Triamcinolone and what do they effect?

F at position 9= Increases GCC and MCC

OH at position 16= decrease in MCC

Names of the inhaled glucocorticoids

•Beclomethasone (BECLOVENT)

•Triamcinolone (AZMACORT)

• Flunisolide (AEROBID)

• Budesonide (PULMICORT)

• Fluticasone (FLOVENT)

ADRs of inhaled glucocorticoids

•Oropharyngeal candidiasis (b/c of localized immunosuppression and allowing opportunistic infections)

•Hoarseness of the voice

On an inhaled glucocorticoid, Budenoside, what does Acetal group on 16,17 do?

-Increase lipophiliocity

-Decreased mineralcorticoid activity

Inhaled glucocorticoid, Beclomethasone, 9 alpha chloro, 16 beta methyl results into what?

9 alpha chloro increases GCC and MCC

16 Beta methyl Decreases MCC activity

What is the Cromolyn effect?

Its a mast cell stabalizer

BUT has bad taste

How is LTA4 synthesized?

Arachidonic acid is converted to LTA4 through 5-lipoxygenase

What are the names of the luekotriene modifiers?

Leukotriene Receptor Antagonists

•Zafirlukast

•Montelukast (SINGULAIR)

Leukotriene Synthesis Inhibitor

•Zileuton

MOA of Leukotriene modifiers ANTAGONISTS

•Selective, high-affinity, competitive antagonists of CysLT1 (cysteinyl leukotriene 1) receptor

ADR’s of Leukotriene modifiers ANTAGONISTS

•Hepatotoxicity (hepatitis, enzyme elevation)

•Neuropsychiatric events

MOA of Leukotriene modifiers INHIBITION

•Inhibits 5-lipoxygenase

•Leukotrienes results from the action of 5-lipoxygenase on arachidonic acid and are synthesized by a variety of inflammatory cells in the airways

ADR’s of Leukotriene modifiers INHIBITION

•Hepatotoxicity

•Neuropsychiatric events

MOA of Omalizumab

•The anti-IgE monoclonal antibody (targeted against the portion of IgE that binds to its receptors on inflammatory cells)

•Clears unbound, circulating IgE from the circulation

•IgE-Anti-IgE complexes are cleared from the blood

•Does not activate IgE already bound to cells

•Does not provoke mast cell degranulation

ADR’s of Omalizumab

•Anaphylaxis can occur during tx or at a later time

•Malignancy

What are the muscarinic receptor names?

•Ipratropium (Atrovent)

•Tiotropium (Spiriva)

MOA of Muscarinic antagonists

–Decreases mucous secretion

–Decreases bronchoconstriction® bronchodilation

Do muscarrinic receptor antagonists have CNS effect?

NO

What is the most common ADR of Muscarinic antagonists?

DRY MOUTH

Are Muscarinic antagonists? used in Asthma or COPD

COPD

Why do Muscarinic antagonists have no systemic effect?

Low systemic absorption

MOA, Metabolite, of Roflumilast

MOA:•PDE4 inhibitor → increases cAMP levels in the lungs

Metabolite: roflumilast N-oxide, it is pharmacologically active