Histamine Flashcards
Where are histamine located?
Found throughout many tissues, MAINLY in Mast cells (Highest amounts are found in the lung, skin, nasal; gastrointestinal mucosa)
How is Histamine synthesized and stored?
Formed by decarboxylation of the amino acid histidine and stored in granules
How are Histamines released?
Released along with several chemical mediators during episodes of trauma, allergies, anaphlyaxis, colds, bacterial toxins, bee sting venom, drugs
What are the two types of histamine release?
- Cytolytic: plasma membrane is damaged causing leakage of cytoplasmic contents (no energy dependent, no calcium required)
- Noncytolytic: exocytotic release from granules (no damage to mast cell, requires energy and calcium - IgE antibodies bind to antigen and release histamine)
What drugs are inducers of Cytolytic release of Histamine?
- Phenothiazines
- Narcotic analgesics
What substances and drugs stimulate Histamine release from Mast cells?
- Radiocontrast media
- D-Tubocurare
- Mast cell degranulation protein (from bee venom)
- Morphine
- Codeine
- Succinylcholine
- Protamine
- Doxorubicin
- Vancomycin
What is Red Man Syndrome? What are associated S/Sx? How do you treat?
Related to reactions with Vancomycin may cause:
- Flushing
- Pruritus
- Chest pain
- Muscle spasm
- Hypotension
Pretreatment with antihistamine attenuates the symptoms
Which drugs are Mast cells stabilizers (prevent noncytolytic degranulation and histamine release)?
- Cromolyn
- Nedocromil
How are Cromolyn and Nedocromil administered?
Inhalation of a powder
T or F: Cromolyn and Nedrocromil is useful in management of acute asthma attacks.
F; Only used prophylactically to BLOCK asthmatic reactions, DEC symptoms of allergic rhinistis, Effective only if used before a challenge not during.
How many types of histamine receptors are known? What are they?
4 different types:
- H1: phospholipase C mechanism
- H2: adenylyl cyclase mechanism parietal cell acid secretion
- H3: inhibit the release of histamine on neurons (feedback inhibitions)
- H4: Proinflammatory activity
What is histamines role in Allergies and Anaphylaxis?
- Stimulation of secretions
- Constriction of smooth muscle
- Stimulation of sensory nerve endings
How does Histamine stimulate secretions at H1 receptors?
INCs mucus in nasal cavity and bronchi (results in respiratory symptoms)
How does Histamine stimulate secretions at H2 receptors?
Stimulates gastric acid secretion
How does histamine constitute constriction of smooth muscle?
H1 receptors constrict bronchi and intestines (causes cramps and diarrhea)
T or F: Healthy human’s histamine will causes hyperreactivity
F; healthy human’s histamine is not especially potent but in patients with asthma the bronchi are hyperreactive.
Which histamine receptor is responsible dilation of smooth muscle in blood vessels; How does histamine affect these processes?
H1; DEC blood pressure and INC nitric oxide (vasodilation)
Which histamine receptors stimulate heart rate and contractility? How does histamine affect these processes?
H1 & H2; Directly INCs via INC influx of calcium, Indirectly INC via baroreceptor-mediated INC in sympathetic tone
Where are catacholamines released from in the body?
Adrenal glands
Which histamine receptors are responsible for dilation and INC’d permeability of capillaries? How does histamine affect these processes
H1 & H2; causes endothelial cells to contract and expose permeable basement membrane (leaks protein and fluid)
What is the “Triple response of Lewis”?
Positive skin test, challenge with an allergen (bugbite, histamine, allergy test)
What are the three presentations of “Triple Response of Lewis”?
- Red Line/Spot (Dilates arterioles where injected)
- Flare (Histamine stimulates nerve endings which leads to dilation of arterioles)
- Wheal (INC in capillary permeability due to local edema)
What are the principal targets in a hypersensitive reaction?
- Mast cells
- Basophils
What happens in an allergic response?
Antigen produces formation of IgE antibodies bind with high affinity receptor specific for IgE and activate tyrosine kinase –> INC in intracellular calcium (triggers exocytosis of secretory granules in the mast cells)
What other mediators of inflammation are released?
Phospholipase A2: produces leukotrienes (contract smooth muscles of the bronchi) and prostagladins
What are the main differences are between allergic reactions and a anaphylatic response?
- Releasing locations
- Rates of release
T or F; Response remains localized if histamine release is in a specific area.
T
What will happen if histamine is released rapidly and diffuses into the blood?
Anaphylatic reaction (systemic response)
What will a patient presents with who is experiencing a hypersensitiveity reaction?
- Intense warmth
- Skin reddens
- Marked effec on palms, hands, face, scalp and ears
- Hives
- Nausea
- DEC BP
- INC HR
- Bronchospasm
- Constriction
How can (true) anaphylaxis reaction treated?
Epinephrine
Which drugs are considered 1st Generation Histamine H1 Blockers?
- Triprolidine
- Diphenhydramine
- Promethazine
- Hydroxyzine
- Chlorpheniramine
Which drugs are considered 2nd Generation Histamine H1 Blockers?
- Loratadine
- Desloratadine
- Azelastine
- Cetirizine
- Fexofenadine
What are differences between 1st and 2nd generation H1 blockers?
-
1st generation
- anticholinergic
- short-acting
- CNS penetration
-
2nd generation
- no anticholinergic activity
- Long-acting
- no CNS penetration (does not cross BBB)
What are characteristics of H1 blockers?
Antagonize all actions of histamine (reversible, competitive blockers of H1 receptors – action via H2 receptor still active) mainly blocking the effects of histamine on:
- INC permeability
- Edema formation
- Itching
T or F; H1 blockers have great effect on actions bronchoconstriction and vasodilation
F; these actions are predominantly caused prostaglandins and leukotrienes
Does H1 Blockers have tolerance to suppressive effects on skin test reactivity to allergens? Tolerance to sedative effects?
No, concentration achieved at sites unknown with significant inhibition of wheal and flare response for 26 hours (residual suppression may last for up to 7 days after discontinuation of H1 blockers following 1-2 week regular use); Tolerance to sedative effects may occurs (theraputic effect may be restored with swith to another antihistamine class)
What is the importance of active metabolites of 2nd generation H1 blockers?
Theraputic uses (Desloratadine=Clarinex, Fexofendaine=Allegra)
T or F: All FDA-approved antihistamines do not prolong the QT interval
T
What are theraputic uses for antihistamines?
- Allergic reactions
- Prevention of Motion Sickness
- Prevention of Nausea/Vomiting
- Sedative
- Antiparkinsonism
- Local anesthetic action
How are antihistamines useful in preventing motion sickness?
Possibly related to anticholinergic effects; administered 1 hour prior to anticipated motion
What antihistamine medications are available for prevention of motion sickness? Which are most effective?
- Promethazine (most effective)
- Scopolamine (most effective, non-antihistamine)
- Diphenhydramine
- Mecilizine
- Cyclizine
What antihistamine medications are available for prevention of nausea/vomiting? How do these medications work?
Block dopamine D2 receptors
- Promethazine
- Timeprazine
What antihistamine medications are available as sleep medications?
- Diphenhydramine
- Doxylamine
- Doxepin
What is the limit for tolerance of antihistamines medications used for sedative purposes?
10 consecutive nights of use
What antihistamine medications are available that have antiparkinsonism effects?
- Diphenhydramine
What antihistamine medications are available with local anesthetic actions? How do these medication have this effect?
Block sodium channels
- Promethazine (sunburn preparation)
- Magic Mouthwash (TX oral ulcers, infections, inflammation, and pain)
What are all the actions of diphenhydramine?
- H1 Blocker (1st Generation)
- Motion Sickness
- Sedative effects (Sleep medication)
- Antiparkinsonism effects
What are all the actions of Promethazine?
- H1 Blocker (1st Generation)
- Motion Sickness
- Nausea/Vomiting
- Local Anesthetic
What are ADRs for Antihistamines?
- Antimuscarinic
- Sedative actions (absent/lower with 2nd generation H1 Blockers)
What sedative effects might a patient present with when taking antihistamines?
- Fatigue
- Dizziness
- Blurred vision
What determines the CNS sedation of a person on Antihistamines?
Effect correlates with H1 receptor binding in the brain (i.e. Doxepin=50-90% CNS bound, Fexofenadine 0% bound)
What antimuscarinic effects might a patient present with when taking antihistamines?
- Dry mouth and nasal passages
- Constipation
- Blurred vision
- Urinary retention
T or F: Paradoxial excitation may occur in children taking antihistamines.
T
What drug interactions are known with antihistamines (H1 blockers)?
Could potentiate other CNS depressants
What are possible toxicities with antihistamines (H1 antagonist)?
OD is rare but acute poisoning is relatively common (esp. in children)
What are acute poisoning effects experienced with antihistamines?
- Initial excitement
- Ataxia and convulsions
- Coma and cardiorespiratory collapse
