Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHARM 311 Respiratory System > 5. Medicinal Chemistry of Antihistamines & Bronchodilators > Flashcards

5. Medicinal Chemistry of Antihistamines & Bronchodilators Flashcards

1
Q

Allergy

  • Early phase reaction
  • Late phase reaction
A

Local/systemic inflammatory response to allergens

Early phase reaction occurs within minutes of exposure to an allergen & lasts for 30-90 minutes

Late phase reaction begins 4-8 hours later & can last for several days, often leading to chronic inflammatory disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Allergic reactions - synthesis/release of histamine

A

Histamine is a chemical messenger that mediates several cellular responses & also a neurotransmitter

  • Synthesised by decarboxylation of histidine (AA) by histidine decarboxylase
  • Stored as granules/quickly inactivated by histamine-N-methyltransferase & diamine oxidase
  • IgE antibodies that respond to foreign antigens in the body cause release of histamine from mast cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Histamine Receptors

A

H1:

  • Found on smooth muscle, endothelium & CNS tissue
  • Activation results in vasodilation, bronchoconstriction, smooth muscle activation, & separation of endothelial cells

H2:

  • Found on parietal cells
  • Regulates gastric acid secretion

H3:

  • Found in the CNS
  • Regulates the release of other neurotransmitters

H4:
- Recently discovered in different parts of the body including organs of digestive tract, basophils & bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Antihistamines - mechanism

A

When released, histamine reacts with H1 receptors resulting in:

  • Dilation of arterioles & capillaries increasing air flow
  • Increased permeability of capillaries resulting in outwards passage of fluid into EC spaces, leading to oedema (congestion) & other secretions (runny nose & watery eyes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Allergic reactions to antihistamines

A
  • Extensive arteriolar dilation
  • Decreased BP
  • Skin flushed & oedematous (accumulation of water in cells, tissue or body cavities)
  • Itching, constriction & spasm of bronchioles
  • Pulmonary & gastric secretions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Antihistamines

A
  • Reversible H1 receptor antagonists (inverse agonists)
  • Block the binding of histamine to receptors

3 generations of antihistamines

  • Each generation improved on the previous one
  • Share general characteristics & properties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

1st generation antihistamines

A

Small lipophilic molecules that could cross the BBB - not specific to the H1 receptor

Groups:
- Ethylenediamines
- Ethanolamines
- Alkylamines
- Piperazines
- Tricyclics
E.g. Chlorphenamine, Brompheniramine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Structural features of 1st generation antihistamines

A
  • 2 aromatic rings connected to a central carbon, nitrogen or CO
  • Spacer between the central X & the amine
  • Usually 2-3 carbons in length
  • Linear, ring, branched, saturated or unsaturated
  • Amine is substituted with small alkyl groups e.g. CH3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Second generation antihistamines

A

Modifications of the 1st generation antihistamines to eliminate side effects - less able to cross BBB, but more selective for peripheral H1 receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pharmacokinetics of Second-Generation antihistamines

A

Relatively rapid onset

Elimination half lines:

  • Loratadine - up to 28 hours
  • Fexofenadine - 14 hours
  • Cetirizine - 8 hours

Children metabolised cetirizine faster, but rates are similar for others

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Side effects: 1st gen vs 2nd gen

A

1st gen:

  • Anticholinergic CNS reactions
  • Gastrointestinal reactions
  • Common side effects: Sedation, dizziness, tinnitus, blurred vision, euphoria, lack of coordination, anxiety, insomnia, tremor, nausea & vomiting, constipation, diarrhoea, dry mouth & dry cough

2nd gen:
- Common side effects: Drowsiness, fatigue, headache, nausea & dry mouth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Next (3rd) generation antihistamines

A
  • Metabolite derivatives or active enantiomers of existing drugs
  • Safer, faster acting or more potent than 2nd gen drugs

E.g.:

  • Fexofenadine
  • Desloratadine
  • Levocetirizine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cold vs Allergy - Which antihistamine?

A

Common cold - 1st generation antihistamine for short term use & fast onset of action

Allergic rhinitis - 2nd generation antihistamine for long term use & longer duration of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Asthma

A

Bronchospasm/bronchoconstriction results when the lung tissue is exposed to extrinsic or intrinsic factors that stimulate a bronchoconstrictive response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Asthma - causes

A
  • Humidity
  • Air pressure changes - Temperature changes - Smoke fumes
  • Emotional upset
  • Allergies
  • Dust
  • Food
  • Some drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Asthma - symptoms

A
  • Airway hyper-reactivity – abnormal sensitivity of the airways to wide range of external stimuli
  • Inflammation
  • Swelling
  • Thick mucus production
  • Bronchospasm (constriction of the bronchial muscles)
17
Q

Aims of anti-asthmatic drugs

A
  • To relieve acute episodic attacks of asthma (bronchodilators, quick relief medications)
  • To reduce the frequency of attacks, & nocturnal awakenings (anti-inflammatory drugs, prophylactic or control therapy)
18
Q

Bronchodilators

A

Quick relief medications are used to relieve acute attack of bronchoconstriction – improve airflow by relaxing bronchial smooth muscle cells

19
Q

Non-selective beta2 agonists

A

Epinephrine:

  • Potent bronchodilator, rapid action (max effect within 15 minutes)
  • Aerosol or nebuliser
  • Has short duration of action (60-90 minutes)
  • Drug of choice for acute anaphylaxis (hypersensitivity reactions)

Isoprenaline

20
Q

Selective beta2 agonists (preferable)

A
  • Drug of choice for acute asthma attack
  • Mainly given by inhalation – metered dose inhaler or nebuliser
  • Can be given orally, parenterally
21
Q

Short acting beta2 agonists

A

Short acting beta2 agonists (SABA):

  • Rapid onset of action (15 – 30 min)
  • Short duration of action (4 – 6 hours)
  • E.g. Salbutamol (aluterol) & Terbutaline

Structure-activity relationship – the alkylamine group makes these compounds selective for beta receptors

22
Q

Long acting beta2 agonists

A
  • 12 hours of action
  • High lipid solubility (creates depot effect)
  • Given by inhalation
  • E.g. Salmeterol & Formoterol
23
Q

Muscarinic antagonists

A
  • Quaternary derivatives of atropine
  • Act by blocking muscarinic receptors
  • Given by aerosol inhalation
  • Do not diffuse into blood
  • Do not enter CNS, minimal systemic side effects
  • Delayed onset of action
  • Ipratropium has short duration of action: 3 – 5 hours
  • Tiotropium has a longer duration of action: 24 hours
24
Q

Methylxanthines

A

Structurally similar to caffeine

Mechanism of action:

  • Are phosphodiesterase inhibitors
  • Increase cAMP which causes Bronchodilation
  • Adenosine receptor antagonists (A1)
  • Increase diaphragmatic contraction
  • Stabilisation of mast cell membrane

E.g. Theophylline & Aminophylline
- Aminophylline – mixture of theophylline & ethylene diamine in a 2:1 ratio

25
Q

Summary - Antihistamines

A
  • H1 receptor antagonists/inverse agonists
  • 3 generations
  • Generations show less side effects & act at different rates
26
Q

Summary - bronchodilators

A
  • Cause smooth muscle relaxation by increasing cAMP
  • Beta2 agonists or phosphodiesterase inhibitors
  • Quick relief medications

PHARM 311 Respiratory System (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions