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PHCY 310 > L 07 Pharmacology of Asthma > Flashcards

L 07 Pharmacology of Asthma Flashcards

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1
Q

What is the Treatment goal with drug?

A

Improve ventilation
Decrease inflammation

We want ot oxygen to enrich air that does reach the alveolar space

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2
Q

If we treat with non pharmacologic option or non drug then?

A

Avoid triggers
Reduce BMI if overweight
Obesity decreases ventilation capacity

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3
Q

How air move into and out of the lunghs?

A

Through contraction and relaxation of respiratory muscles
As elastic recoil of connective tissue remains in the lungs
Any disease which cause or inhibit elasticity in recoil can cause ventilation

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4
Q

What percentage of inspired gas reaches the alveoli?

A

Around 67%

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5
Q

What affects inspiratory rate and inspiratory capacity?

A

Obstructive disease affects inspiratory rate e.g. asthma COPD
Restrictive disease affects inspiratory capacity e.g. pulmonary Fibrosis

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6
Q

What Th2 cells produce?

A

IgE by B cell, eosinophilia, mast cell recruitment

Why DCs, B cells are important?
Try to drive the response

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7
Q

What does mast cells do ?

A

Release of Bronchoconstrictors & cytokines

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8
Q

What eosinophils do?

A

Release of mediators that damage cells, contribute to remodeling

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9
Q

What is ANS?

A

Autonomic nervous system

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10
Q

Which system can be controlled or cant be controlled?

A

Somatic system can be controlled

ANS is autonomic so can not controlled which is sympathetic and parasympathetic

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11
Q

Where muscarinic receptors affects?

A

Parasympathetic function

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12
Q

What is Nicotine and how it works?

A

Nicotine is a nicotinic receptor agonist and causes sympathetic effect or parasympathetic effect both however if it affects only sympathetic receptor it may case e.g (for instance increase heart rate)

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13
Q

M3 What does it mean?

A

Muscarinic receptor type of subtype 3

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14
Q

In our lungs has Beta receptor?

A

Yes, so if we give B2 agonist then we will think that it will relax the bronchiole muscle as a result increase ventilation.

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15
Q

In our lungs also has an M2 receptor?

A

Yes, so if we give M2 antagonist then we believe that it will increase contraction. If we give an agonist then the heart rate will decrease if we give a beta antagonist heart rate increase.

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16
Q

What is Beta receptor?

A

Beta receptor is the B2 adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, β2 agonists and α2 agonists, which are used to treat high blood pressure and asthma, for example.

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17
Q

What is the selective Beta 2 agonist drug?

A

Salbutamol for treating asthma

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18
Q

What is a Beta 1 antagonist drug?

A

Metoprolol

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19
Q

The suffix for “Olol” is usually used for?

A

beta antagonist

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20
Q

What is the example of Beta antagonist?

A

Propranolol used for heart failure and hypertension and ischemic heart disease

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21
Q

In practical determination that?

A

On target, effects can be determined from a knowledge of the Selectivity of the drug for a receptor
And the prevalence of a receptor in the tissue.
So it is important to know about drug-receptor and the body’s response to it.

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22
Q

What is ANS and CNS?

A

the autonomic nervous system controls our internal organs and glands.
The central nervous system (CNS) is the brain and spinal cord only.

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23
Q

What agonists and antagonists do in a receptor?

A

Turning on or off
An agonist is a drug that activates a receptor and increases its response. ex: B2 receptor agonist is salbutamol causes activation of the receptor

An antagonist is a drug that which competes with endogenous agonist to decrease activation and creates no activity after binding B2 antagonist is metoprolol decreases sympathetic stimulation caused by epinephrine (adrenaline).

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24
Q

Some receptors and their functioning areas?

A

B1 receptors are more prevalent in cardiac tissue

B2 are more prevalent in lung tissue

M3 receptors tend to be more prevalent in the bladder
M2 are more prevalent in the heart

M1 and M4 typically more prevalent to CNS

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25
Selectivity depends on the drug?
Dose-dependent because bigger the dose less selective
26
What does Beta 2 agonist selectivity for salbutamol mean?
It has a full activity for B2 but very little for B1 and No activity for Alpha receptor
27
Long acting Beta agonists mean?
The drug associates with a lipophilic site which holds the drug close to the receptor. It appears therefore to have a long action due to a high local concentration near the binding site. Despite systemic half-life may be shorter but Just remember that the concentration of the drug at biophase are higher and the duration of activity is longer.
28
What is biophase is?
Biophase is a generic term used to describe "a region that surrounds the receptor". The BioPhase may have a different pharmacokinetic profile than the drug concentration in the plasma.
29
Long acting M antagonists gives effects like?
The drug slowly dissociates from the binding site so the longer the duration of activity is due to the slower off binding.
30
Write FOUR beta-agonist drugs name use as bronchodilator?
Salbutamol Salmeterol Formoterol Terbutaline
31
Write FOUR M antagonist drugs used for bronchodilation?
Ipratropium Tiotropium Glycopyrronium Umeclidinium
32
Which inhalers are funded in NZ for asthma?
Only short-acting muscarinic antagonists are funded in nz for asthma.
33
What are the on-target side effects of inhaled bronchodilators?
Beta agonist low dose: | i) Increased heart rate
34
What SE may occur if we give Beta agonist high dose:
i) Increased heart rate ii) Nervousness iii) Decrease plasma potassium iv) Sleep disturbances
35
What M antagonist do for heart:
i) Increased heart rate | ii) Dry mouth
36
Write some name of corticosteroids?
Budesonide inhaler Fluticasone inhaler Oral prednisone
37
What are the side effects of chronic inhaled corticosteroids?
With low dose: Less than 500mcg/day budesonide equivalents Oral candidiasis Through Inhaled high dose:>1200mcg/day budesonide equivalent Oral candidiasis Growth delays HPA axis suppression (occasional) Oral Prednisone 5mg/day: Edema Dyspepsia Cushingoid symptoms
38
What is Hypoxia?
a systemic issue that causes breathlessness, and the inability to complete a sentence
39
What is the sympathetic nervous system responsible for?
Fight or flight mechanisms
40
What is the parasympathetic nervous system responsible for?
Rest and digest mechanisms
41
B2 agonist in the lungs will cause
Smooth muscle relaxation = improved ventilation
42
M2 antagonist in the lungs will cause
M2 endogenous agonists will cause contraction, therefore an antagonist will reduce this contraction = improved ventilation
43
Side effects of giving a Beta agonist for asthma.
- Is this for both B1 and B2? | Increased heart rate. B1 more so than B2
44
What are the effects of a muscarinic agonist and a muscarinic antagonist on heart rate?
Muscarinic agonist: heart rate will decrease | Muscarinic antagonist: heart rate will increase
45
Define agonist + asthma example
An agonist is a drug that activates a receptor to produce an increase in response. e.g B2-receptor agonist (e.g salbutamol) causes activation of the receptor
46
Define antagonist + heart example
An antagonist is a drug that competes with endogenous agonists to decrease activation. They have no activity themselves at the receptor once bound. e.g a B1-receptor antagonist (e.g metoprolol) will decrease sympathetic stimulation caused by adrenaline
47
Define selectivity
Selectivity is defined as a (relative) 100 fold difference in affinity between receptor subtypes (e.g B1 vs B2 receptors)
48
What is the benefit of choosing a selective drug
It reduces on-target side effects (on target not because we are aiming for them, but because they are predictable)
49
Are drugs selective for receptor type or receptor subtype?
Selectivity is only between subtypes. A B-receptor agonist will usually have no effect on x-receptors, but will have an affect on B1 and B2 (if does big enough)
50
Why are LABAs long acting? What is the systemic half-life vs local?
The drug is associated with a lipophilic site that holds the drug close to the receptor. Systemic half life: shorter than expected because only the biophase concentrations (local) are prolonged (i.e plasma conc is not the same as the binding site conc)
51
Why are LAMAs long acting?
LAMAs are long acting because of their kinetics. The drug slowly dissociates off the binding site therefore is more potent (more potent = lower dose required for long acting, as potency is opposite to binding)
52
on target side effects vs on target therapeutic effects
On target side effects are predictable effects but that are unwanted. On target therapeutic effects are predictable and beneficial to the therapy.
53
5 examples of B-agonists
``` Salbutamol Terbutaline Salmeterol Formoterol Vilanterol ```
54
Short acting B2 agonists ex
Salbutamol and terbutaline
55
Long-acting B2 agonists ex
Salmeterol, formoterol and vilanterol are...
56
4 examples of M-agonists
ipratropium glycopyrronium tiotropium umeclidinium
57
On target side effects of high dose inhaled B-agonists
- Increased heart rate - Tremor (rhythmic shaking movement in one or more parts of your body) - Nervousness - Peripheral vasodilation - Sleep disturbances - Decreased plasma potassium
58
Are there any side effects from low dose B agonists and M antagonists?
No, side effects from inhaled doses are rare
59
What are the systemic effects of inhaled corticosteroids like?
The systemic effects of inhaled corticosteroids are considerably less than oral or injected steroids
60
Potential on target side effects of chronically inhaled corticosteroids?
Oral candidiasis Potential growth delays (reversible but controversial evidence) Occasional HPA axis suppressive effects
61
Variability in beneficial effects for patients using inhaled drugs is due to... and why is this?
Variability in beneficial effects for patients using inhaled drugs is due to the use of the device rather than the PK. This is because they act locally.
62
Variability in side effects for patients using inhaled drugs is due to... and why is this? How do you reduce this?
Variability in side effects for patients using inhaled drugs is due to absorption and disposition (PK) You can reduce variability by teaching patients how to use their devices correctly.
63
What is the proportion of The systemic availability of salbutamol in the lungs compared to oral dose?
is ~50% of the equivalent oral dose.
64
Knowledge of the ANS enables therapeutic responses to be?
to be predicted.
65
variability in inhaled drugs tends to be due to ... and ... more so than .....
Variability in inhaled drugs tends to be due to technique and device more so than pharmacology.
66
What study types are at the top of the hierarchy of evidence for finding research results?
Meta-analyses and systematic reviews

PHCY 310 (65 decks)

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