Respiratory pharmacology

Question 1

Pharmacological management of asthma

Answer 1

Acute Symptom Relief:
B2 agonists
Parasympathetic antagonists

Corticosteriods

Question 2

Prophylactic treatment

Answer 2

Long acting beta agonists
Cromoglicates
Leukotriene synthesis and receptor inhibitors

Question 3

biochemistry of inflammation and brochoconstriction

Answer 3

During inflamation Arachidonic acid is produced which causes release of cycloxygenase 1 and 2 to produce prostaglandins which cause inflammatory response.

Lipoxygenase also released which produces leukotrines (LTD4) resulting in brochocontriction.

Question 4

How does corticosteriods work

Answer 4

Reduces inflammatory response by breaking down the arachidonic acid.

Also results in production of COX 1 and 2 inhibitors which inhoboit cycloxygenase enzyme to reduce prostaglandin levels to stop inflammation

Question 5

What are gluco-corticoids (steriods)

Also called corticosteroids

Answer 5

Glucocorticoids binding to glucocorticoid receptors (GRs) in target cells.
The glucocorticoid receptor complex then enters the nucleus and binds to DNA, expressing certain functions:
* Anti-inflammatory effects: Reducing the production of pro-inflammatory cytokines, enzymes (like COX-2), and immune cell activation.
* Metabolic effects: Stimulating gluconeogenesis, increasing protein breakdown, and fat redistribution.
* Immunosuppression: Suppressing immune responses, which is beneficial in treating autoimmune diseases but can increase susceptibility to infections.

Question 6

Examples of corticosteroids

Answer 6

prednisolone and dexamethasone
Hydrocortisone

Question 7

Side effects of Steriods

Answer 7

Bone Health: Osteoporosis and increased fracture risk due to inhibition of bone formation and calcium absorption.

Metabolic: Weight gain, hyperglycemia (can lead to steroid-induced diabetes), and fat redistribution

Immune System: Increased risk of infections due to immune suppression.

Skin: Thinning of the skin, delayed wound healing, and easy bruising.

Hypertension: Steroids can cause fluid retention and increase sodium levels, leading to higher blood pressure.

inhaled steroids have less side effects than oral unless longer duration

Question 8

Adrenergic Beta 2 receptor activity

Answer 8

When a catecholamine (like Adrenaline or salbutamol) binds to a β₂ receptor:

1. The receptor undergoes a conformational change, activating an associated G protein
2. This activation stimulates adenylyl cyclase, an enzyme that converts ATP into cAMP.
3. Increased cAMP levels activate protein kinase A (PKA), which then phosphorylates various target proteins inside the cell.
4. In smooth muscle cells, this leads to relaxation (e.g., bronchodilation or vasodilation), while in other tissues (like the liver and adipocytes), it promotes metabolic processes like glycogenolysis and lipolysis.

Question 9

Parasympthetic NS and bronchiole dilater regulation

Answer 9

Acetylcholine binds to M3 G protein receptor which causes the cell to release calcium ions which result in smooth muscle contraction.

So when this process in inhibited smooth muscles are relaxed.

Question 10

Examples of anti-cholinergic drug receptor binding
(Anti-muscurinics)

Answer 10

Ipratropium bromide is a non selective muscarinic antagonist and therefore blocks M1,M2 and M3 receptors

Tiotropium is a potent, and long-lasting muscarinic antagonist that has a selectivity for M1 and M3 receptors because it dissociated very quickly from M2 receptors.

Question 11

Anti-muscurinics side effects

Answer 11

Dry mouth
constipation
urinary retention glucoma (especially when nebulised)
Atrial fibrillation
Supraventricualr tachycardia

Question 12

Phospho diesterase inhibitors

Answer 12

phosphodisterase enzymes responsible for breaking down cyclic nucleotides like cyclic AMP (cAMP) and cyclic GMP (cGMP). By inhibiting phosphodiesterase, these drugs increase the levels of cAMP or cGMP in various tissues, which can lead to a range of therapeutic effects.

e.g smooth muscle relaxation, increased blood flow and antiinflammatory actions

Question 13

Examples of phosphodiesterase inhibitors

Answer 13

Theophylline
Aminophylline

Question 14

Xolair (omalizumab)

Answer 14

IgE monoclonal antibody
Given to patients that test positive for allergenic asthma

NICE: recommend the use of Xolair (omalizumab) in adolescents
(12 years of age and over)

Administered via sub cut

Question 15

WHat does xolair medication do

Answer 15

Binds IgE and inhibits IgE binding to Mast cells. This prevents inflammation and other factors such as cytokines and leukotrienes which result in bronchoconstriction

Question 16

Theopyline

Answer 16

Has low therapeutic index.
Short half life (4-5 hours), care needs to be taken in liver and cardiac failure
Prone to dose dumping, increased drug release when taken with fatty meals or alcohol.
A problem normally associated with SR preparations

Question 17

Side effects of theophylline

Answer 17

mostly stimulatory,
Cardiac; tachycardia, and arrhythmias,
Neuro insomnia convulsions (especially IV)
GIT; nausea and diarrhoea.

Question 18

Leukotriene Receptor antagonists

Answer 18

Affects LTD4 to stop bronchoconstriction

Question 19

Adverse drug reactions of LTRAs

Answer 19

Anxiety, depression, sleep disturbance, hallucinations, suicidal thinking and suicidality, tremor, dizziness, drowsiness, neuropathies and seizures.
The immune system reaction , in particular, cases of Churg-Strauss syndrome (Eosinophilic Granulomatosis with polyangiitis: vascular inflammation)
hypersensitivity reactions, including anaphylaxis and eosinophilic infiltration.
hepatobiliary, (including fatal hepato-toxicity) pancreatic and urine production disorders.

Question 20

Side effects of Xolair

Answer 20

Injection site reaction (45%)
Viral infection (23%)
U Resp Tract Infection (20%)
Sinusitis (16%)
Headache (15%)
Pharyngitis (11%)