Respiratory System Flashcards
Drugs used to treat asthma
useful in the prophylactic or curative treatment of
bronchial asthma, being effective for the control of various clinical forms of asthma.
In the production and maintenance of respiratory inflammation, bronchospasm and viscous bronchial hypersecretion (components incriminated in asthma), multiple pathogenic mechanisms are involved;
1) agglomeration of various inflammatory cells and chemical produced by them,
2) epithelial lesions,
3) increased permeability of capillaries,
4) neurovegetative imbalances.
in the treatment of asthma mainly substances with ____ are used
1) bronchodilator action and
2) substances with anti-inflammatory action at bronchial level
In addition to such substances, in asthma, depending on the clinical situation, various therapeutic measures may be useful:
1) avoiding exposure to allergens and trigger factors,
2) specific desensitization,
3) administration of antibiotics,
4) administration of expectorants,
5) oxygen therapy,
6) treatment of acidosis.
Substances with bronchodilator action currently used can be divided, according to the mechanism
of action, into:
1) sympathomimetic bronchodilators,
2) parasympatholytic bronchodilators and
3) musculotropic bronchodilators.
With anti-inflammatory action, ____are mainly used in the treatment of asthma.
______are used in the prevention of asthma attacks
1) Glucocorticoids
2) Mast cell degranulation inhibitors
To these therapeutic groups are added leukotriene receptor antagonists and lipoxygenase inhibitors.
Calcium channel blockers, nitric oxide-releasing compounds or potassium channel-releasing
compounds :
are currently being studied for possible bronchodilator effects.
sympathomimetics
are among the most active substances in the treatment and prophylaxis of asthma attacks. Such compounds are included in most antiasthmatic treatment protocols
The therapeutic benefit in asthma is mainly due to
sos
The stimulation of β2 adrenergic receptors that
cause bronchodilation.
Also, at the pulmonary level, β2 adrenergic stimulation also produce :
1) increased mucociliary clearance,
2) inhibition of cholinergic neurotransmission,
3) maintenance of small vessel integrity as well as
4) inhibition of mast cell degranulation.
The formation and / or release of
histamine,
leukotrienes,
prostaglandins from mast cells, basophils and, possibly, other lung cells is prevented.
However, these actions do not significantly influence the chronic background inflammation.
Beta2-adrenergic effects are produced as a result of :
MOA
adenylate cyclase stimulation and
consequent increase in intracellular cAMP.
Cyclic adenylate via a protein kinase increases
Na +, K + - membrane ATPase activity and
decreases cytoplasmic Na + levels.
Consecutively, the Na + / Ca2 + exchange is activated, with the decrease of the available intracellular Ca2 +. Decreased intracellular Ca2 + leads to relaxation of the bronchial smooth muscles and inhibition of mast cell degranulation.
Sympathomimetics used as antiasthmatics have different affinities for adrenergic receptors.
Sympathomimetics with α and β adrenergic actions
such as adrenaline - with beta actions (both
β1 and β2) are used, but without alpha actions - for example isoprenaline - or
selective β2 agonists
- for example salbutamol, phenoterol, etc.
- the latter have the advantage of a reduced risk of side effects.
Adrenaline ( Epinephrine )
Catecholamine adrenergic agent; non-specific alpha + beta
SABA
Adrenaline
Isoprenaline
curative treatment
MABA
Salbutamol
terbutaline
phenoterol
treatment + prophylaxis
LABA
Salmeterol
is used exclusively prophylactically.
Catecholamine effects
increased HR, BP, smooth muscle relaxation. Rapid onset, short acting, quickly inactivated by COMT & MAO. Heat, light and air sensitive. Inhalation or injection (cannot be taken orally).
Non-catecholamine effects
synthetically produced modifications of catecholamines. Longer duration of action, not inactivated by COMT or MAO. Minimal Beta 1 response (^HR). Usually only acute therapy/maintenance.
Internal administration
may be useful in the case of long-term prophylactic treatment for asthma attacks, especially when aerosols cannot be used. In this case the effect is installed more slowly but is longer lasting.
The main disadvantage is the higher risk of side effects compared to aerosols (achieved plasma concentrations are much higher which can lead to loss of β2 selectivity).
Sympathomimetics can cause
vasoconstriction and hypertension (α adrenergic effects),
cardiac stimulation with tachyarrhythmias,
palpitations and
angina attacks (β1 adrenergic effects),
vasodilation,
relaxation of the uterus,
stimulation of striated muscles, increase in blood glucose (β2 effects).
Sympathomimetics can also produce psychomotor stimulation with β adrenergic anxiety and nervousness.
Headache, dizziness or fine trembling of the fingers are other side effects that can be caused by sympathomimetics.
A problem of chronic treatment with β2 stimulants is the
decrease in the duration of the bronchodilator effect over time, less the decrease in its intensity.
Tolerance is mainly due to the
decrease in the number of adrenergic receptors by inhibiting their synthesis (down regulation).
Cortisones quickly restore (in 6-8 hours) this reactivity.
In some asthma patients, the administration of selective β2 sympathomimetics may initially lead
to a decrease in arterial blood oxygen saturation.
This undesirable effect is the consequence of
the imbalance between ventilation and perfusion - the arterioles, dilated by beta2-adrenergic
action, provide an increased amount of blood to the alveoli, still insufficiently ventilated, if the
bronchodilation is not sufficiently operative. The adrenaline that produces vasoconstriction does
not cause an imbalance between ventilation and infusion.
The antiasthmatic sympathomimetics currently used belong to three structural groups:
catecholamines, resorcinols and saligenins
The differences between the three structural categories are due to
substituents on the phenolic nucleus.
the size of the substituents on the amino group is important for the action on different
adrenergic receptors.
Increasing the size of the substituent increases the selectivity for β or β2 adrenergic receptors.
Catecholamines
- adrenaline, isoprenaline, isoetarine -
due to the polar character of the
substituents, pass hard through the membranes (intestinal absorption is poor, the blood-brain
barrier passes a little). Internally administered catecholamines are largely inactivated by sulfation
in the intestine, and the small amount absorbed is practically completely degraded by methylation
to the oxidril group at position 3. This explains the ineffectiveness of the oral route. The duration
of action is short for both injected adrenaline and for preparations introduced by inhalation, due
to inactivation in the body by tissue uptake and metabolism by COMT and MAO.
Resorcinols
orciprenaline, terbutaline, phenoterol; have 2 oxidril groups substituted at positions
3 and 5 of the benzene nucleus - have higher selectivity for β2 receptors. The molecule is more
stable which makes the availability after oral administration better and prolongs the duration of
the effect.
Saligenins
- salbutamol, have a -CH2OH substituent in position 3 and a -OH group in position 4.
They have intense β2 adrenergic actions. The molecule is stable, which gives the possibility of
oral administration and prolongs the effect.
Adrenaline (epinephrine)
is used for the asthma attack treatment by subcutaneous administration. It can also be administered in aerosols. In both cases the effect settles quickly and is short-lived.
Isoprenaline -
synthetic catecholamine with predominantly beta-adrenergic action – administered
by inhalation can be used as a symptomatic treatment of asthma attack or other bronchospasm
(in bronchitis, bronchiectasis with emphysema). The effect occurs quickly and lasts 1 / 2-2 hours
Orciprenaline
(the resorcinol analog of isoprenaline) has a more lasting effect. It is used for crisis
prophylaxis administered by inhalation. The therapeutic benefit occurs quickly and lasts 3-4 hours.
It can also be administered internally (the effect appears after 15-30 minutes and lasts about 4
hours).
Terbutaline (tertiary analogue of orciprenaline)
has a higher beta2 selectivity and a slightly more
lasting effect. It can be inhalatory administered, the effect is installed after 5-30 minutes and lasts
3-6 hours. In the case of oral administration the effect occurs after 1/2 hour and lasts 4-8 hours.
Administered by injection subcutaneously the effect is evident after 6-15 minutes and is maintained for 1.5-4 hours.
- Administered by inhalation is indicated for the treatment and prophylaxis of moderate asthma attacks.
- Oral administration is appropriate when crisis are
frequent or dyspnea is continuous.
- Injectable administration is recommended for the emergency treatment of asthma attacks.
Clenbuterol
a terbutaline analogue that has two Cl- substituents instead of phenolic oxidils
has a partial agonist effect on β2 adrenergic receptors.
Clenbuterol has high potency and medium
duration effect. It is given orally or by inhalation
Phenoterol
(a resorcinol derivative) has a more lasting bronchodilator effect. It is administered
inhaler for crisis prophylaxis or internally.
Salbutamol
(a saligenin derivative) has a selective β2 action and a relatively long-lasting effect.
It can be administered inhaler or internally.
In the case of inhalation administration,
bronchodilation is evident after 15 minutes and is maintained for 3-4 hours; after internal
administration the effect begins in 30 minutes and lasts 3-4 hours.
Aerosols are useful in asthma of medium intensity.
In asthma with continuous dyspnea, internal administration is recommended.
Salmeterol
(a salbutamol-like compound) has a relatively slow and long-lasting effect.
The effect occurs 10-20 minutes after inhalation and lasts about 12 hours.
It is advantageous for the long - term prophylaxis of asthma attacks, but not stop crisis once produced.
The long duration of the effect is explained by the stable fixation of the side chain at a site on the β2 adrenergic receptor close to its active site.
Inhalatory administration.
