Term
|
Definition
| Substances that help in "self remedy" |
|
|
Term
| What two drugs are considered autocoids? |
|
Definition
1. Histamine
2. Antihistamines |
|
|
Term
|
Definition
| By the decarboxylation of L-histidine |
|
|
Term
| (T/F) This substance is exclusive to mammals |
|
Definition
| False, it is also found in plants, venoms and stinging secretions |
|
|
Term
| Where is histamine found in the body? |
|
Definition
| Found in most tissues, sequestered and bound in granuls |
|
|
Term
| What two cell types is histamine especially found in? |
|
Definition
1. Mast cells
2. Basophils |
|
|
Term
| (T/F) Histamine content of tissues proportional to the tissues mast cell content |
|
Definition
|
|
Term
| Where are mast cells found? |
|
Definition
| At the sites of potential injury (nose, mouth, feet, lungs, GI mucosa) |
|
|
Term
| (T/F) Histamine is also found in other cell types in the stomach |
|
Definition
|
|
Term
| What cell types contain histamine in the stomach, and what is the function of these cells/their histamine? |
|
Definition
- Found in enterochromaffin-like cells
- Activate parietal cells to release HCl |
|
|
Term
| What is a non-mast cell source of histamine, and how does it function in this tissue? |
|
Definition
| The brain is a non-mast cell tissue that contains histamine, and it functions as a neurotransmitter here |
|
|
Term
| What is the primary cause for release of histmaine, how is release triggered? |
|
Definition
Immunological response - IgE antibody binds to Fcepsilon1 receptors on mast cells
- Ag binding to IgE causes mast cell degranulation |
|
|
Term
| What type of receptors are the cell surface receptors for histamine? |
|
Definition
|
|
Term
| How many types are there, and name them? |
|
Definition
|
|
Term
| Where is H1 located, and how does it evoke the responses in this tissue? |
|
Definition
- Found in smooth muscle (most important), endothelium and brain
- Binding of histamine causes PIP2 pathway activation (Stimulatory) |
|
|
Term
| Where is H2 located, and how does it evoke the responses in this tissue? |
|
Definition
- Found in gastric mucosa, cardiac muscle, mast cells and brain
- Increases cAMP upon ligand binding (stimulatory) |
|
|
Term
| Where is H3 located, and how does it evoke the responses in this tissue? |
|
Definition
- Found presynaptically, in the myenteric plexus and other neurons, and in the brain
- Decreases cAMP upon binding with ligand (inhibitory) |
|
|
Term
| Where is H4 located, and how does it evoke the responses in this tissue? |
|
Definition
- Found in blood cells
- Decreases cAMP in these cells |
|
|
Term
| What roles does H4 play in blood cells? (2) |
|
Definition
1. Modulates production of blood cells
2. May be involved in cytokine production |
|
|
Term
| What are the effects of histamine binding to H1 on the nervous system? |
|
Definition
| Respiratory neuron signalling is modified |
|
|
Term
| Which histamine receptor is found in bronchial smooth muscle? |
|
Definition
|
|
Term
| What does histamine binding H1 here cause? |
|
Definition
|
|
Term
| (T/F) Small histamine doses elicit major responses in sensitive individuals (ie asthma patients) |
|
Definition
|
|
Term
| Name the 3 types of histamine antagonists, and give an example of each |
|
Definition
1. Physiological antagonist - epinephrine
2. Release inhibitors - cromolyn
3. Receptor antagonists - antihistamines |
|
|
Term
| Name the two classes of H1 antagonists |
|
Definition
1: 1st generation
2. 2nd generation |
|
|
Term
| Are beclomethazone, chloropheniramine and some phenothiazines considered 1st or 2nd generation antagonists? |
|
Definition
|
|
Term
| Are loratadine, desloratadine, cetrizine, levocetirizine, and fexofenadine considered 1st or 2nd generation antagonists? |
|
Definition
|
|
Term
| (T/F) Both classes of antagonists are equally sedative |
|
Definition
| False, only 1st gen are strongly sedative |
|
|
Term
| What accounts for the difference in sedation between the two antagonist classes? |
|
Definition
| 2nd gen do not penetrate the CNS as much as 1st gen |
|
|
Term
| (T/F) Following this trend, 1st gen antagonists are more effective than 2nd gen antagonists in periphery tissues as well |
|
Definition
| False, they are equally as effective |
|
|
Term
| What are H1 antagonists primarily used for? |
|
Definition
| Control/treatment of allergic reactions |
|
|
Term
|
Definition
| A resp disease/set if disease involving inflammation of airways and increased resistance to airflow |
|
|
Term
| How is asthama characterized, clinically? (4) |
|
Definition
- Shortness of breath
- Tightness in chest
- Coughing
- Wheezing |
|
|
Term
| What 3 factors contribute to the increased airway resistance experienced in asthma? |
|
Definition
1. Contraction of bronchiolar smooth muscle
2. Mucosal edema
3. Bronchiolar secretions |
|
|
Term
| (T/F) All 3 of these pathways can be targeted for effective drug treatment of asthma |
|
Definition
|
|
Term
| Describe the FEV1 vs Time graph seen during diagnosis of asthma patients. |
|
Definition
| See an early reaction, where FEV1 drops to at least 70%. Then there is a recovery of FEV1, before the late reaction occurs and reduces FEV1 again |
|
|
Term
| Which two cell types mediate the early reaction of asthma? |
|
Definition
|
|
Term
| What is the function of mast cells in the early response? (3) |
|
Definition
- Releases vasoactive amines that vasodilate vessels
- Releases inflammatory mediators that bronchoconstrict (PGD2, LTC4, PAF)
- Releases chemotactic cytokines |
|
|
Term
| What two cell types mediate the late phase reaction? |
|
Definition
1. Eosinophil
2. Neutrophils |
|
|
Term
| What do eosinophils release, and what does it cause? |
|
Definition
| ECP and MBP -> increase vessel permeability |
|
|
Term
| What do neutrophils release, and what does it cause? |
|
Definition
| PAF and proteases -> Increase mucous secretions and increase smooth muscle contraction |
|
|
Term
| Describe tissue responses to inhaled irritants, that do not rely on the nervous system? |
|
Definition
| The irritant itself causes tissue response - directly causes degranulation and the resulting responses |
|
|
Term
| Describe tissue responses to inhaled irritants, that rely on the nervous system? |
|
Definition
| Inhaled irritant acts on a sensory receptor, which then has its signal relayed by the vagal afferent to the CNS. The CNS then sends a resonse via the vagal efferent, which then causes the inflammatory response |
|
|
Term
| How are anti-asthma drugs often administered, and why? |
|
Definition
| Inhalation; because this way the drug is delivered to the site of action with the lowest possible dose - systemic responses are avoided |
|
|
Term
| What are acute anti asthma drugs used for? |
|
Definition
| Termination of asthma attack |
|
|
Term
| What are prophylactic anti asthma drugs used for? |
|
Definition
|
|
Term
| Name the 7 classes of anti-asthmatic drugs |
|
Definition
1. Cromolyn sodium
2. Sympathomimetics
3. Steroids
4. Anticholinergics
5. Methylxanthines
6. Leukotriene pathway inhibitors
7. Anti IgE antibody |
|
|
Term
| Describe the mechanism, administration, therapeutical use and response time of cromolyn sodium |
|
Definition
M: Decreases release of bronchoconstrictor chemicals
A: Inhalation, powder or liquid
T: Used prophylactially
R: Days to a month - patient compliance |
|
|
Term
| (T/F) cromolyn sodium is absorbed if taken orally |
|
Definition
|
|
Term
| Describe the mechanism, administration, and therapeutical use sympathomimetics |
|
Definition
M: Beta2 and alpha stimulation
A: Injection or inhalation
T: In an emergency |
|
|
Term
| (T/F) Different sympathomimetics are used to achieve different action times |
|
Definition
|
|
Term
| What is a SABA, a LABA, and a uLABA? How long does each last? |
|
Definition
1. SABA: Short acting beta 2 agonist (3-4 hours)
2. LABA: Long acting beta2 agonist (12 hrs)
3. uLABA: ultra long acting beta2 agonist (24 hours) |
|
|
Term
| What are common side effects of sympathomimetics? |
|
Definition
| Insomnia, anxiety, tremor |
|
|
Term
| Describe the mechanism, administration, therapeutical use and response time of steroids |
|
Definition
M: Anti inflammatory -> decrease eicosanoid synthesis
A: Inhaled
T: Prophylactically
R: Hours |
|
|
Term
| How do steroids carry out their actions? |
|
Definition
| Alteration of transcription |
|
|
Term
| (T/F) Often times, steroids are used in conjunction with long acting bronchodilators |
|
Definition
|
|
Term
| Describe the structure of anticholinergics? |
|
Definition
| Quaternary N analogs of atropine |
|
|
Term
| Describe the mechanism, administration, therapeutical use of anticholinergics |
|
Definition
M: Block cholinergic bronchoconstriction
A: Inhaled
T: For acute reaciton |
|
|
Term
| Why are anticholinergics inhaled? |
|
Definition
| To reduce the systemic effects of blocking cholinergic receptors |
|
|
Term
| Describe the mechanism and therapeutical use of methylxanthines |
|
Definition
M: Bronchodilation without involving ACh or adrenergic receptors; blockade of adenosine receptors; others possible
T: Prophylactically - long term control |
|
|
Term
| (T/F) Methyxanthines only act in a certain area of the body |
|
Definition
| False, they act in a multitude of locations |
|
|
Term
| Describe their actions in the airways |
|
Definition
|
|
Term
| Describe their actions at the heart |
|
Definition
| Stimulates HR and force of contraction |
|
|
Term
| Describe their actions in the CNS |
|
Definition
- Stimulation/increased alertness
- Stimulation of resp centre |
|
|
Term
| What infantile condition are methylxanthines used to treat? |
|
Definition
|
|
Term
| What occurs with high doses of methylxanthines? |
|
Definition
| Convulsions, with resistance to anticonvulstants -> can lead to death |
|
|
Term
| Describe their actions in the GIT |
|
Definition
| Induce acid/pepsin secretion |
|
|
Term
| Describe the involvement of beta agonists, theophylline, and muscarinic antagonists in treatment of asthma |
|
Definition
- All are bronchodilators
- Beta agonists: increase production of cAMP by CA stimulation
- Theophylline: blocks adenosine interacitions with bronchiolar smooth muscle, and prevents metabolism of cAMO
- Muscarinic antagonists: prevent ACh actions at muscarinic receptos |
|
|
Term
| (T/F) Leukotriene inhibitors are used to treat asthma |
|
Definition
|
|
Term
| Why is this? How does it work? |
|
Definition
| Preventing the production of leukotrienes decreases inflammatory responses; leukotrienes are potent vasoconstrictors, |
|
|
Term
| How does zileuton act in leukotriene inhibition? |
|
Definition
|
|
Term
| How does montelukast/zafirlukast act in leukotriene inhibition? |
|
Definition
| CysLT1 receptor antagonists (counteract LTC4/LTCD4/LTCE4 actions) |
|
|
Term
| How are leukotriene pathway inhibitors taken? How an this be advantageous over inhaled anti-asthmatics? |
|
Definition
| Orally; better for patients with poor compliance |
|
|
Term
| (T/F) Omalizumab is an example of anti-IgE antibody |
|
Definition
|
|
Term
|
Definition
| Prevents binding of IgE to mast cells by binding the FceR1 epitope, which prevents action |
|
|
Term
| (T/F) Anti-IgE Ab is used for mild asthma |
|
Definition
| False, only for moderate to severe cases |
|
|
Term
| (T/F) Severe anaphylactic reactions are a potential hazard with this type of anti-asthmatic |
|
Definition
|
|
Term
| Name the 3 different was that Omalizumab combats asthmatic responses |
|
Definition
1. Decreases FceR1 expression
2. Decreases mediator release
3. Decreases allergic inflammation and prevents exacerbation/reduces symptoms |
|
|
Term
| Desribe the asthma management continuum for treatment |
|
Definition
1. Diagnosis
2. Environmental control
3. SABA on Demand (if controlled) or SABA/LABA/ICS (if uncontrolled)
4. Inhaled corticosteroids
5. Add LABA (if teen) or increase ICS (if child) to ICS
6. LTRA addition
7. Anti IgE
8. Prednisone |
|
|
Term
| Give 4 examples of future asthma targets |
|
Definition
1. Cytokine
2. CAM antagonists
3. Protease inhibitors
4. Immunomodulators |
|
|
Term
| What would the role of immunomodulators (cytokines) do, and how would this help? |
|
Definition
| Shift from TH2 to TH1 - less antibody mediated response |
|
|
Term
| How would cytokines be targeted? |
|
Definition
| Abs that target IL -4,-5,-13 would be made |
|
|
