Autacoids Flashcards
H1-mediated effects
Contraction of the smooth muscles of the GI, bronchioles, uterus, and large blood vessels
Vasodilation of capillaries, arterioles, and venules then contraction leading to increased permeability, edema, hypotension, and hypovolemic shock
Positive inotropic effect
Stimulation of exocrine secretion
H2-mediated effects
Gastric acid secretion
Positive inotropic effect and increased heart rate
H3-mediated effects
Inhibiting release of histamine, serotonin, norepinephrine, and acetylcholine
H1 antagonists 1st generation
Ehylenediamines Ethanolamines Alkylamines Piperazines Phenothiazines Methyl piperidines
H1 antagonists 2nd generation
Non-sedating, more receptor selectivity, some exhibit non-competivtive antagonism, antiinflammatory effects by stabilizing mast cells
Piperidines
Ketotifen
Pharmacokinetics of H1 antagonists
Readily absorbed orally
Wide distribution including the brain, except the 2nd generation
Metabolized by liver and excreted in urine
Most are enzyme inducers
Therapeutic uses of H1 antagonists
Allergy and anaphylaxis
Antimotion sickness
Ketotifen is available as ophthalmic for treatment of allergic conjunctivitis, and orally as adjunctive for prevention of asthma
Side effects of H1 antagonists
1st generation causes sedation
Anticholinergic effect
Gastrointestinal irritation
Alpha-adrenergic blocking effect
H2 antagonist drugs
Cimetidine
Ranitidine
Famotidine
Nizatidine
MOA of H2 antagonists
Competitive antagonists to H2 receptors
Cimedtidine has immunomodulatory effects including inhibiting suppressor T cells and enhancing cell-mediated immunity
Ranitidine and Nizatidie, not Cimetidine or Famotidine, have cholinergic activity by inhibiting acetyl cholinesterase, stimulating gastrointestinal motility
Uses of H2 antagonists
Peptic ulcer
Gastric erosive disease
Gastroesophageal reflux disease
Duodenal ulcer
Cimetidine is used in the treatment of equine melanoma (as immunomodulator)
Ranitidine and Nizatidine can be used as prokinetic
Serotonin (5-HT) Agonist drugs
Cisapride Fluoxetine Cyproheptadine Ondansetron Metoclopramide Mirtazapine Trazodone
Cisapride
- MOA
- Use
5-HT Agonist
MOA = 5-HT4 recptor agonist in enteric neurons
Use = prokinetic (stimulates GI motility)
Fluoxetine
-MOA
5-HT Agonist
Selective serotonin reuptake inhibitor (SSRI) antidepresant
Acts by increasing serotonin levels in the brain
Increasing serotonin levels improves signs of depression in humans
Fluoxetine
-Clinical use
5-HT Agonist
Approved for treatment of canine separation anxiety in conjunction with a behavior modification plan
Used in dogs and cats to treat behavioral disorders (aggression, obsessive compulsive, anxiety)
Used in treatment of cats with inappropriate elimination and urine marking
Fluoxetine
-Side effects
5-HT Agonist
Nausea, anorexia, irritability, and sleeping disturbances
Cyproheptadine
-MOA
5-HT Agonist
Blocks H1 receptors
Blocks serotonin receptros
Inhibition of serotonin inhibits ACTh
Cyproheptadine
-Uses
5-HT Agonist
Antihistamine
Stimulate appetite in small animals
Treatment of “serotonin syndrome” in dogs and cats
Ondansetron
- MOA
- Use
5-HT Agonist
MOA = 5-HT3 receptor antagonist (central and peripheral)
Use = Prevention and treatment of anticancer chemotherapy-induced nausea and vomiting
Metoclopramide
- MOA
- Use
5-HT Agonist
MOA = 5-HT3 receptor antagonist; D1 and D2 receptor antagonist
Use = Antimetic (effective against vomiting and nausea)
Mirtazapine
-MOA
5-HT Agonist
A TCA that enhances noradrenergic and serotonergic activity by antagonizing central presynaptic alpha2-adrenergic inhibitory autoreceptors and heteroreceptors
A potent antagonist of 5-HT2 and 5-HT3 receptors
Mirtazapine
-Use
5-HT Agonist
Antidepressant
Antimetic
Trazadone
-MOA
5-HT Agonist
Serotonin antagonist reuptake inhibitor (SARI)
Blocks 5-HT2A and alpha-adrenergic receptors
Inhibits reuptake of serotonin by blocking SERT (serotonin transporter)
Increases serotonin levels in the brain
Trazadone
-Uses
5-HT Agonist
Extra label in dogs and cats for treatment of behavior disorders such as separation anxiety and other anxiety, such as fear of fireworks, and post-surgical cage confinement
Trazadone
-Side effects
5-HT Agonist
Vomiting, diarrhea, lethargy, sedation, hyperactivity shaking, and agitation
Used with caution in male breeding dogs because it can cause priapism (prolong erection) in humans
Large doses may cause seizures
Neuokinins Antagonists
Maropitant citrate
Maropitant citrate
-MOA
Neuokinin Antagonist
The neuropeptide (tachykinin) substance P (SP) is involved in integration of pain, stress, anxiety, psychologic stress, and vomiting
Maropitant blocks neuokinin 1 (NK1) receptors preventing substance P from binding resulting in antiemetic effect
Maropitant citrate
-Use
Neuokinin Antagonist
Used only in dogs (over 16 weeks of age) as tablets or injection for the prevention of acute vomiting due to motion sickness and may be effective in treating vomiting due to viral infections and anticancer chemotherapy
Renin activity
A proteolytic enzyme
Converts angiotensinogen to angiotensin I
Stimulation of renin secretion
Hypotension
Decreased renal blood flow
Low Na of Cl in the blood
Sympathetic stimulation (B1-adrenergic receptors)
Inhibition of renin secretion
Angiotensin II ADH Hypertension Increased reabsorption of sodium B1-adrenergic blockers
Angiotensin II activity
A potent vasoconstrictor
Stimulates aldosterone secretion
Inhibits renin release
Angiotenisn II Antagonists
ACE Inhibitors = Captopril, Enalapril, Lisinopril, Benazepril
Angiotensin II-receptor antagonists = Losartan (blocks Angiotensin II type 1 receptors)
Prostaglandins
Misoprostol Dinoprost tromethamine Cloprostenol Fenprostalen Fluprostenol Latanoprost Travoprost Bimatoprost
Misoprostol
- MOA
- Use
MOA = A synthetic prostaglandin E1 that causes GI cytoprotection and decreases acid secretion Use = Given orally as an anti-ulcer drug
Fluprostenol
- MOA
- Use
Prostaglandin
MOA = cause leuteolysis; stimulate motility of the smooth muscles of the reproductive tract
Use = in reproduction
Latanoprost, Travoprost, Bimatoprost
- MOA
- Use
Prostaglandins
MOA = PG agonists that increase uveoscleral outflow by stimulating FP receptors in the eye
Use = used topically on the eye in the treatment of open-angle glaucoma or ocular hypertension
Prostaglandin Inhibitors
Cyclooxygenase Inhibitors - NSAIDs
Phospholipase A2 Inhibitors - Corticosteroids (also inhibit COX-2)
Prostaglandin Antagonist
-Class
Galliprant
Non-cyclooxygenase (COX) inhibiting, NSAID in the piprant family (prostaglandin receptor antagonist, PRA)
Galliprant
- MOA
- Use
Prostaglandin Inhibitor
MOA = Selective PGE2 EP4 receptor antagonist
Use = Osteoarthritis pain and inflammation in dogs
Janus Kinase (JAK) Inhibitor
- Drug
- MOA
Oclacitinib
Inhibits pruritogenic and pro-inflammatory cytokines by inhibiting JAK1 and JAK3 without inhibitin cytokines involved in hematopoiesis that are dependent on JAK2
Oclacitinib
-Use
Used for the control of pruritus associated with allergic dermatitis and atrophic dermatitis in dogs over 12 months
