3 – Antihistamines and Antifungals Flashcards
*In which tissues is histamine released?
- **Mast cell pool
a. Stored in granules within mast cells and basophils
b. *inflammatory response, allergy, anaphylactic shock - Non-mast cell pool: GI, CNS, dermis, other tissues
a. Constant production and rapid turnover
*What receptors does histamine bind to?
- *H1: high affinity
- *H2: lower affinity
- H3
- H4
What does H1 receptor activation cause?
- Smooth muscle contraction
o Bronchioles>GIT>urinary tract - Smooth muscle relaxation
o Vasodilation of arterioles and capillaries - *clinical signs: can’t breath, peripheral swelling, heat
What is the importance of H2 receptors?
- Important in HCl secretion from parietal cells
- Activated=increase translocation of H/K ATPase pumps into apical membrane
- *lower affinity, but longer duration when activated?
What is a H2 receptor blocker drug? What is it used for in vet med?
- Things ending in ‘azole’
- Omeprazole (Gastrogard)
- Anti-ulcers: minimize acid secretion
What happens with a local cutaneous (typically) allergic response?
- Foreign antigen cross-links with IgE on dermal mast cells
- *this activation of mast cells cause degeneration=HISTAMINE RELEASE
- *cardinal signs of inflammation
*What are the primary physiological effects of histamine in allergic reactions?
- Vasodilation (redness)
- Capillary dilation (edema, swelling)
- Stimulate nerve endings (pain, pruritis
When does anaphylaxis occur?
- Severe, systemic histamine release and widespread activation of H1 receptors
o Hypotension: vasodilation, decreased peripheral resistance
o Bronchoconstriction
o *likely use epinephrine in emergency (not necessarily an antihistamine)
Histamine and neurons
- Histamine is a NT within CNS
- Peripheral release of histamine can impact sensory neurons
o Recognized as pruritus and pain
H1-blocking antihistamines: pharmacodynamics
- ‘reversible competitive inhibition’
o Compete with histamine for H1 receptor binding site
o Counteracted by high histamine concentrations - LIKELY: STABILIZE H1 receptor in NON-ACTIVE state
- *don’t care on mechanism, either way=prevents histamine/H1 receptor activation
H1 blocking antihistamines in vet med: pharmacodynamics data
- Limited
- Generally limited oral bioavailability, but lipid soluble
- High volume of distribution
- *hepatic metabolism results in ACTIVE metabolites
- *drug interactions: not an issue in vet med
o Induce hepatic microsomal enzymes (increase clearance)
o Elimination may be inhibited by P-gp substrates
Why are drug interactions with H1 blocking antihistamines not an issue in vet med?
- NOT using it chronically compared to humans
*What are the primary categories of antihistamines?
- 1st generation H1 blocking antihistamines
- 2nd generation H1 blocking antihistamines
- 3rd generation H1 blocking antihistamines
1st generation H1-blocking antihistamines effects
- Varying degree of anticholinergic effect
o Can cause sedation (low doses) OR CNS excitement (usually at higher doses)
o Ex. dry mouth
1st generation H1-blocking antihistamine examples
- Diphenhydramine (Benadryl)
- Dimenhydrinate (Gravol, Dramamine)
- *no vet approved formulations in Canada: use human injectable products
- *may not work well for cutaneous reactions
- (pyrilamine: OLD)
- (Trimeprazine)
*What are the commonly used anti-histamines in vet med?
- Diphenhydramine (Benadryl)
- Dimenhydrinate (Gravol, Dramamine)
o Diphenhydramine and 8-chlorotheophylline
2nd generation of H1 blocking antihistamines
- More selective for PERIPHERAL H1 receptors
o Less CNS distribution=less antihistamine and anticholinergic effect in CNS (‘non drowsy’? - Generally longer half-life and dosing intervals
What are some examples of 2nd generation of H1 blocking antihistamines?
- (Cetirizine: Zyrtec)
- (Loratidine: Claritin)
3rd generation H1 blocking antihistamines
- Contains only active moiety
- Generally decreased AE and increased efficacy
o Maybe faster acting?
*What are the clinical uses of antihistamines?
- ‘treatment of allergic reactions
o Modulates reaction, but WONT STOP allergen exposure or histamine release - *more useful if administered BEFORE allergen contact and subsequent histamine release
o Realistically does NOT happen - *does NOT prevent histamine from being released
EXAMWhat actually causes the clinical signs in an allergic reaction?
- *when histamine BINDS to H1, NOT when histamine is released
- Antihistamines prevent them from binding NOT preventing their release
There is limited efficacy when used for atopic dermatitis (dogs/cats)
- May DECREASE pruritus for short time
- Lots of inter-individual variability in efficacy
- Actually reduced pruritus OR just cause sedation?
o Antihistamine/anticholinergic effects
What are some other clinical uses of H1 antagonists besides for atopic dermatitis?
- Limited efficacy for reducing bronchoconstriction
- Antidotes for ‘extrapyramidal reactions’ caused by phenothiazine tranquilizers
- Adjunctive therapy for anaphylaxis, but does NOT replace sympathomimetics (EPI)
- **Adjunctive therapy for dogs with mast cell tumours
o Help prevent pruritus due to degranulation and histamine release
H1 blockers can also inhibit muscarinic receptors (anticholinergic): can produce similar but weaker effects as an anticholinergic drug (ex. atropine)
- Dry mouth and mucous membranes
- Tachycardia
- Ileus
- Mydriasis (dilated pupils)
- *PARASYMPATHOLYTIC SIGNS
H1 blockers and CNS depression or excitement. What is it due to?
- Anti-histamine OR anticholinergic OR BOTH?
o Some sort of balance between them, but variable
o Lower doses: sedation
o Higher doses: excitement
