Autacoids

Question 1

H1-mediated effects

Answer 1

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

Question 2

H2-mediated effects

Answer 2

Gastric acid secretion

Positive inotropic effect and increased heart rate

Question 3

H3-mediated effects

Answer 3

Inhibiting release of histamine, serotonin, norepinephrine, and acetylcholine

Question 4

H1 antagonists 1st generation

Answer 4

Ehylenediamines
Ethanolamines
Alkylamines
Piperazines
Phenothiazines
Methyl piperidines

Question 5

H1 antagonists 2nd generation

Answer 5

Non-sedating, more receptor selectivity, some exhibit non-competivtive antagonism, antiinflammatory effects by stabilizing mast cells
Piperidines
Ketotifen

Question 6

Pharmacokinetics of H1 antagonists

Answer 6

Readily absorbed orally
Wide distribution including the brain, except the 2nd generation
Metabolized by liver and excreted in urine
Most are enzyme inducers

Question 7

Therapeutic uses of H1 antagonists

Answer 7

Allergy and anaphylaxis
Antimotion sickness
Ketotifen is available as ophthalmic for treatment of allergic conjunctivitis, and orally as adjunctive for prevention of asthma

Question 8

Side effects of H1 antagonists

Answer 8

1st generation causes sedation
Anticholinergic effect
Gastrointestinal irritation
Alpha-adrenergic blocking effect

Question 9

H2 antagonist drugs

Answer 9

Cimetidine
Ranitidine
Famotidine
Nizatidine

Question 10

MOA of H2 antagonists

Answer 10

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

Question 11

Uses of H2 antagonists

Answer 11

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

Question 12

Serotonin (5-HT) Agonist drugs

Answer 12

Cisapride
Fluoxetine
Cyproheptadine
Ondansetron
Metoclopramide
Mirtazapine
Trazodone

Question 13

Cisapride

• MOA
• Use

Answer 13

5-HT Agonist
MOA = 5-HT4 recptor agonist in enteric neurons
Use = prokinetic (stimulates GI motility)

Question 14

Fluoxetine

-MOA

Answer 14

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

Question 15

Fluoxetine

-Clinical use

Answer 15

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

Question 16

Fluoxetine

-Side effects

Answer 16

5-HT Agonist

Nausea, anorexia, irritability, and sleeping disturbances

Question 17

Cyproheptadine

-MOA

Answer 17

5-HT Agonist
Blocks H1 receptors
Blocks serotonin receptros
Inhibition of serotonin inhibits ACTh

Question 18

Cyproheptadine

-Uses

Answer 18

5-HT Agonist
Antihistamine
Stimulate appetite in small animals
Treatment of “serotonin syndrome” in dogs and cats

Question 19

Ondansetron

• MOA
• Use

Answer 19

5-HT Agonist
MOA = 5-HT3 receptor antagonist (central and peripheral)
Use = Prevention and treatment of anticancer chemotherapy-induced nausea and vomiting

Question 20

Metoclopramide

• MOA
• Use

Answer 20

5-HT Agonist
MOA = 5-HT3 receptor antagonist; D1 and D2 receptor antagonist
Use = Antimetic (effective against vomiting and nausea)

Question 21

Mirtazapine

-MOA

Answer 21

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

Question 22

Mirtazapine

-Use

Answer 22

5-HT Agonist
Antidepressant
Antimetic

Question 23

Trazadone

-MOA

Answer 23

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

Question 24

Trazadone

-Uses

Answer 24

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

Question 25

Trazadone | -Side effects

Answer 25

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

Question 26

Neuokinins Antagonists

Answer 26

Maropitant citrate

Question 27

Maropitant citrate | -MOA

Answer 27

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

Question 28

Maropitant citrate | -Use

Answer 28

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

Question 29

Renin activity

Answer 29

A proteolytic enzyme | Converts angiotensinogen to angiotensin I

Question 30

Stimulation of renin secretion

Answer 30

Hypotension Decreased renal blood flow Low Na of Cl in the blood Sympathetic stimulation (B1-adrenergic receptors)

Question 31

Inhibition of renin secretion

Answer 31

``` Angiotensin II ADH Hypertension Increased reabsorption of sodium B1-adrenergic blockers ```

Question 32

Angiotensin II activity

Answer 32

A potent vasoconstrictor Stimulates aldosterone secretion Inhibits renin release

Question 33

Angiotenisn II Antagonists

Answer 33

ACE Inhibitors = Captopril, Enalapril, Lisinopril, Benazepril Angiotensin II-receptor antagonists = Losartan (blocks Angiotensin II type 1 receptors)

Question 34

Prostaglandins

Answer 34

``` Misoprostol Dinoprost tromethamine Cloprostenol Fenprostalen Fluprostenol Latanoprost Travoprost Bimatoprost ```

Question 35

Misoprostol - MOA - Use

Answer 35

``` MOA = A synthetic prostaglandin E1 that causes GI cytoprotection and decreases acid secretion Use = Given orally as an anti-ulcer drug ```

Question 36

Fluprostenol - MOA - Use

Answer 36

Prostaglandin MOA = cause leuteolysis; stimulate motility of the smooth muscles of the reproductive tract Use = in reproduction

Question 37

Latanoprost, Travoprost, Bimatoprost - MOA - Use

Answer 37

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

Question 38

Prostaglandin Inhibitors

Answer 38

Cyclooxygenase Inhibitors - NSAIDs | Phospholipase A2 Inhibitors - Corticosteroids (also inhibit COX-2)

Question 39

Prostaglandin Antagonist | -Class

Answer 39

Galliprant | Non-cyclooxygenase (COX) inhibiting, NSAID in the piprant family (prostaglandin receptor antagonist, PRA)

Question 40

Galliprant - MOA - Use

Answer 40

Prostaglandin Inhibitor MOA = Selective PGE2 EP4 receptor antagonist Use = Osteoarthritis pain and inflammation in dogs

Question 41

Janus Kinase (JAK) Inhibitor - Drug - MOA

Answer 41

Oclacitinib Inhibits pruritogenic and pro-inflammatory cytokines by inhibiting JAK1 and JAK3 without inhibitin cytokines involved in hematopoiesis that are dependent on JAK2

Question 42

Oclacitinib | -Use

Answer 42

Used for the control of pruritus associated with allergic dermatitis and atrophic dermatitis in dogs over 12 months