Pharm 1 - Respiratory Pharm I And Ii

Front 1

Pathophys of asthma - General

Back 1

Genetic component and environmental exposures

SM contraction leading to significant airway narrowing.

Massive inflammation in mucosa/submucosa leading to mucus plugging of narrow airways.

Front 2

TH1 or 2 more common in asthmatics?

Back 2

They tend to do a TH2 response.

Mast cells are also important.

Front 3

Which mediator probably causes muscle spasm?

Back 3

Histamine

Front 4

Which mediators probably initially cause inflammatory exudate in the submucosa?

Back 4

Leukotrienes, thromboxanes, PGs

Inflammation and mucus then contributes to occlusion of the lumen.

Front 5

One thing to definnitely ask about in dx asthma

Back 5

Nocturnal sx

Front 6

Asthma vs. COPD

Back 6

Asthma - Reversible bronchial SM contraction, epithelial edema.

COPD - Hypertrophied submucosal bronchial glands much more than asthma, increased risk of infection.

Front 7

Big diff in short acting and long acting beta2 agonists

Back 7

Short - Short duration of action but quick onset. (acute crisis)

Long - longer duration of action and slower onset (chronic use)

Front 8

Beta 2 receptor

Back 8

Linked to adenyl cyclase to increase cAMP and this brings down intracellular calcium to mediate bronchodilatation.

Enhances mucociliary clearance

Decreases microvascular permeability

Suppresses mediator release from inflammatory cells.

Front 9

Main benefits of inhaled

Back 9

Less dose so less systemic toxicity

Quicker onset of action.

Front 10

Beta2 agonist metabolism

Back 10

COMT/MAO

Front 11

Why does tolerance/tachyphylaxis develop with beta2 agonists?

Back 11

With constant receptor stimulation, arrestin protein signals internalization of the beta2 receptor.

Front 12

AEs of beta2 agonists

Back 12

Tachycardia, palpitations, flushing, exacerbation of angina/arrythmias, vasodilation of pulmonary artery leading to perfusion of non-ventilated areas (V/Q mismatch)

Tremor/anxiety (beta2 affects on muscle), headache, insomnia

Hypokalemia, hyperglycemia (normal beta2 response).

Front 13

Beta2 agonists used for...

Back 13

i think asthma and COPD

Front 14

Strucutre of long-acting beta2 agonists

Back 14

Longer side chains and two rings.

Front 15

Always rx long acting beta 2 agonists with...

Back 15

steroids to reduce risk of inflammation and hypocia causing death.

Front 16

Two long-acting beta2 agonists

Back 16

salmeterol and formoterol.

Front 17

Short acting beta2 agonist

Back 17

Albuterol

But there is also metaproterenol, bitolterol, pirbuterol, terbutaline, fenoterol.

("you dont have to memorize all these")

Front 18

Anticholinergics (3)

Back 18

ipratropium
oxitropium
tiotropium (long-acting/once a day)

these allow SM to dilate.

Front 19

Anticholinergics vs. beta-agonists

Back 19

Slower onset of action and less bronchodilation.

Front 20

Anticholinergic SEs

Back 20

Anticholinergic effects only at high doses.

Bitter taste (this is the main one)

Paradoxical bronchoconstriction due to a preservative that some pts are sensitive to.

Drying of secretions in the lungs DOES NOT OCCUR!

Front 21

Methyl Xanthine drug

Back 21

theophylline

Front 22

Theophylline mechanism of action

Back 22

Inhibition of phosphodiesterase (normally breaks down cAMP)

Block the inhibition that adenosine produces of adenylate cyclase

IT BASICALLY INCREASES cAMP!!!

Front 23

Pharmacodynamics of methyl xanthines (theophylline)

Back 23

Relax SM (vasodilate and bronchodilation)
Increased CNS and CV stimulation.
Less skeletal muscle fatigue
Diuresis

Front 24

Main toxicity issues with theophylline

Back 24

N/V

CV at relatively high doses or CNS toxicity at very high doses.

Has lots of drug interactions

Front 25

All the drugs in this lecture can be used for...

Back 25

Asthma/COPD

Front 26

Drugs that are cromokalim derivatives

Back 26

Sodium cromoglycate
Nedocromil

They prevent mast cell degran.

Front 27

Inhaled steroids

Back 27

Beclomethasone
Fluticasone

Front 28

Systemic steroids

Back 28

Hydrocortisone
Prednisone
Prednisolone
Methylprednisolone

Front 29

Uses of sodium cromoglycate

Back 29

Proph. in antigenic and exercise induced asthma.
Also good in allergic rhinitis and conjunctivitis.

VERY GOOD TO TAKE THIS BEFORE EXERCISE.

Front 30

Mechanism of sodium cromoglycate

Back 30

Doesn't directly bronchodilate
Inhibits release of inflamm. mediators from mast cells
Supresses effects of kinins of inflamm cells.
Inhibits sensory C-fiber endings to reduce cough.

Front 31

SEs of cromoglycate

Back 31

very rare
occasional coughing/wheezing/HA/nausea.

They aren't used over steroids just because they are a little less effective.

Front 32

Use of systemic steroids (hydrocortisone and prednisone)

Back 32

Acute and severe asthma (although it takes hours to work so it is used prophylactically)

Front 33

Uses of inhaled steroids (beclomethasone and fluticazone)

Back 33

Prophylaxis in mild/moderate asthma.
Can be combined with systemic steroids to reduce their dose (in chronic severe asthma)

Front 34

Mechanism of corticosteroids (systemic and inhaled)

Back 34

Lipophilic, hits a receptor and goes to DNA and...

Prevents proinflammatory mediators and induces things that fight inflammation.

Front 35

Cells that steroids work on

Back 35

lymphocytes, endothelial cells, monocytes, basophils.

Front 36

Length of effect of steroids

Back 36

Last way past drug life in body because so many processes are modulated.

Front 37

Inhaled steroids - pharmacokinetics

Back 37

Only 10% reaches bronchi.

Metab by CYP3A

Low systemic concentrations.

Front 38

Inhaled steroids SEs

Back 38

Local thrush and dysphonia

At high systemic doses you can get HPA-axis suppression, bruising, cataracts, inhibition of bone growth, behavioral disturbances (especially in kids)

Front 39

Steroids - relationship of anti-inf potency and mineralo potency

Back 39

More anti-inf, less mineralo (where you will have less water retention and rise in blood glucose)

Front 40

Acute SEs of systemic steroids

Back 40

CNS, metabolic (hyperglycemia and salt/water retention), proximal myopathy, infection

Front 41

Chronic SEs of systemic steroids

Back 41

HPA axis suppression, cushing appearance, infection (opportunistic)