Antihistamines and Autocoids (Londono) Flashcards
Autocoids
Biological factors
Act like hormones, but act locally
Short duratio of action
Not carried in blood
How are autocoids released
Response to
- Trauma
- Dust mites
- Fungus
- Mold
- Sunlight
- Chemicals
Autacoid classes
- Eicosanoids: mediate inflammatory processes
- Prostaglandins
- Leukotrienes
- Thromboxane
- Polypeptides
- Angiotensin
- Kinins
- Substance P (modulate inflamm in human medicine)
- Decarboxylated Amino Acids
- Histamine
- Serotonin
Histamine:
Synthesis
Metabolism
Effects
Synthesized in
- Mast cells
- Basophils
- ECL cells
- CNS: neurotransmitter
Metabolized in Liver by oxidation
Mediates
- inflammation
- anaphylaxis
- gastric acid secretion
H1 receptors mostly responsible for
Vasodilation
Tissue: Vascular smooth muscle
Effect:
Clinical Signs:
Receptor:
Effect:
- venule/arteriole dilation
- venoconstriction
Clinical signs:
- Erythema
Receptor:
- H1
Tissue: Airway
Effect:
Clinical Signs:
Receptor:
Effect:
- Bronchoconstriction
- Increased secretion
- Mucosal edema
Clinical Signs:
- Asthma
- Reflex irritation
- Coughing/sneezing
Receptor:
- H1
Tissue: Vascular endothelium
Effect:
Clinical Signs:
Receptor:
Effect:
- Contraction and separation
Clinical Signs:
- Edema
- Wheel response
Receptor:
- H1
Tissue: Peripheral nerves
Effect:
Clinical Signs:
Receptor:
Effect:
- Sensitization
Clinical Signs:
- Itch
- Pain
Receptor
- H1
Tissue: Heart
Effect:
Clnical signs:
Receptor:
* not well described don’t pay much attention
Effect:
- Inc in heart rate and contractility
Clinical Signs:
- Tacycardia
Receptor:
- H2
Tissue: Stomach
Effect:
Clinical Signs:
Receptor:
Effect:
- Inc acid secretion
Clinical signs:
- Ulceration
Receptor:
- H2
Tissue: CNS
Effect:
Clinical Signs:
Receptor:
Effect:
- Neurotransmitter
Clinical signs:
- Circadian rhythm
Receptor
- H3
H1 Antihistamines
!st and 2nd gen
1st
- Allergy meds that cause drowsiness: cross the BBB
- Lipophilic
2nd
- Allergy meds that don’t cross the BBB
- Not lipophilic
Use
- Allergy
- dermatitis
- nausea: CRTZ
Limited role
- asthma: don’t reach brochial tree?
- anaphylaxis: no great effect
Diphenhydramine
1st gen H1 Antihistamine
use
- acute allergic reaction
- antipruritic
- prevent reactions (vaccines, chemo)
- motion sickness
- mast cell tumor
crosses blood brain barrier
Adverse effects
- CNS
- anticholinergic
- dry mouth
- retention of urine
- inc secretion in gut
- inc secretion in lungs
- Cants can be hyper
Cyproheptadine
H1-Antihistamine
Acts on
- Serotonin
- appetite stimulant
- Alpha-receptors
- histamine
1st generation
NOT VERY ANTIHISTAMINIC: not for itchy dogs
Horses
- head shaking
- cushings (not first choice)
Adverse effects
- CNS
- Anticholinergic
- Cats may get excited
Meclizine (antivert)
1st genereation H1 Antihistamine
Motion sickness
Vestibular dz: helps with the motion sickness, not dz
MOA:partially understood, CTZ
Other H1-blockers
1st generation
- Promethazine: pruritic patient
- Hydroxyzine (Atarax)
Second generation
- Cetirizine (Zyrtec)
H2-Antihistamines
Reversible competitive antagonists
Gastric Parietal Cells
Reduce gastric acid secretion
- Famotidine
- Ranitidine
- Cimetidine
- Nizatidine
Famotidine (Pepcid)
Most potent and longest half-life
First pass hepatic metabolism
No prokinetic or antiemetic activity
Side effects uncommon
No prokinetic or antiemetic effect
H3 and H4 Antihistamines
Not approved for clinical use
Experimental models
Improve attention and wakefulness
Serotonin (5-HT)
Synthesized from Tyrptophan
Found in
- GI (ECL cells)
- CNS
- Platelets
Serotonergic projections
- Spinal cord
- pain
- inflammation
- motor function
- Forebrain
- mood
- state of alertness
Serotonin Overdose
Neuro signs
- seizures
- depression
- tremors
- hyperesthesia
- ataxia
GI signs
- vomiting
- diarrhea
- abdominal pain
- hypersalivation
Other
- hyperthermia
- blindness
Pharmacology
MAOIs
Amphetamines
- make vesicles less likely to store serotonin
SSRIs
- decrease reuptake of serotonin into presynaptic cleft
TCAs
- decreases degradation of serotonin
Amphetamines
Inhibitors of serotonin storage
Displaces 5-HT, domapine and norepinephrine from storage vesicles
In humans used for depression and ADHD
*No application in vet med
Monoamine Oxidase Inhibitors
Inhibitors of serotonin degradation
Two types
- MAOI-a
- MAOI-b
Reversible vs irreversible
Selegiline (anypril)
Selective MAOI-b, MAOI-a at high doses
TX of canine cognitive dysfunction
Inc dopamine activity
Cushings dz +/- 20%
Adverse effects
- GI signs
- CNS
Cushings
Inc ACTH
Reuptake Inhibitors
Net inc in extracellular 5-HT
Used for TX of anxiety, depression and OCD
Four main classes
- TCAs
- SSRIs
- SNRIs
- NRIs
Clomipramine (Clomicalm)
Tricyclic antidepressant
Only FDA approved drug (dogs)
TX
- OCD
- Anxiety
- Dominance
- Aggression
Side effects
- change in behavior
Fluoxetine (prozac)
Selective-serotonin reuptake inhibitor
FDA approved in dogs for TX of separation anxiety in conjuction with behavior modification plan
Adverse effects
- anorexia
- seizures
Mirtazapine
Atypical antidepressant
5-HT2 and 5-HT3 inhibitor
Central alpha-2 receptor inhibitor (net inc NE)
Appetite stimulant
Antiemetic
Adverse effects
- drowsiness/sedation
- voalization
- tachycardia
Trazadone
5-HT2 inhibitor and SSRI
Adjuctive anxiolytic
TX of hospitalization-related anxiety and post-op recovery
Adverse effects:
- GI signs
- ataxia
- hypotension
Less cardiovascular effects
Cisapride
5-HT4 agonist
Enhances acetylcholine release
Prokinetic
TX of
- GI stasis
- reflux esophagitis
- constipation/megacolon (cats)
Adverse effects: well tolerated
Ondansetron (zofran)
Serotonin receptor agonist
Potent antiemetic
Receptors in vagal nerve terminals and CTZ
Controversial use in cats
Well tolerated in dogs
