Antihistamines and Autocoids (Londono)

Question 1

Autocoids

Answer 1

Biological factors

Act like hormones, but act locally

Short duratio of action

Not carried in blood

Question 2

How are autocoids released

Answer 2

Response to

• Trauma
• Dust mites
• Fungus
• Mold
• Sunlight
• Chemicals

Question 3

Autacoid classes

Answer 3

1. Eicosanoids: mediate inflammatory processes

• Prostaglandins
• Leukotrienes
• Thromboxane

2. Polypeptides

• Angiotensin
• Kinins
• Substance P (modulate inflamm in human medicine)

3. Decarboxylated Amino Acids

• Histamine
• Serotonin

Question 4

Histamine:

Synthesis

Metabolism

Effects

Answer 4

Synthesized in

• Mast cells
• Basophils
• ECL cells
• CNS: neurotransmitter

​Metabolized in Liver by oxidation

Mediates

• inflammation
• anaphylaxis
• gastric acid secretion

Question 5

H1 receptors mostly responsible for

Answer 5

Vasodilation

Question 6

Tissue: Vascular smooth muscle

Effect:

Clinical Signs:

Receptor:

Answer 6

Effect:

• venule/arteriole dilation
• venoconstriction

Clinical signs:

• Erythema

Receptor:

• H1

Question 7

Tissue: Airway

Effect:

Clinical Signs:

Receptor:

Answer 7

Effect:

• Bronchoconstriction
• Increased secretion
• Mucosal edema

Clinical Signs:

• Asthma
• Reflex irritation
• Coughing/sneezing

Receptor:

• H1

Question 8

Tissue: Vascular endothelium

Effect:

Clinical Signs:

Receptor:

Answer 8

Effect:

• Contraction and separation

Clinical Signs:

• Edema
• Wheel response

Receptor:

• H1

Question 9

Tissue: Peripheral nerves

Effect:

Clinical Signs:

Receptor:

Answer 9

Effect:

• Sensitization

Clinical Signs:

• Itch
• Pain

Receptor

• H1

Question 10

Tissue: Heart

Effect:

Clnical signs:

Receptor:

* not well described don’t pay much attention

Answer 10

Effect:

• Inc in heart rate and contractility

Clinical Signs:

• Tacycardia

Receptor:

• H2

Question 11

Tissue: Stomach

Effect:

Clinical Signs:

Receptor:

Answer 11

Effect:

• Inc acid secretion

Clinical signs:

• Ulceration

Receptor:

• H2

Question 12

Tissue: CNS

Effect:

Clinical Signs:

Receptor:

Answer 12

Effect:

• Neurotransmitter

Clinical signs:

• Circadian rhythm

Receptor

• H3

Question 13

H1 Antihistamines

!st and 2nd gen

Answer 13

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

Question 14

Diphenhydramine

Answer 14

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

Question 15

Cyproheptadine

Answer 15

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

Question 16

Meclizine (antivert)

Answer 16

1st genereation H1 Antihistamine

Motion sickness

Vestibular dz: helps with the motion sickness, not dz

MOA:partially understood, CTZ

Question 17

Other H1-blockers

Answer 17

1st generation

• Promethazine: pruritic patient
• Hydroxyzine (Atarax)

Second generation

• Cetirizine (Zyrtec)

Question 18

H2-Antihistamines

Answer 18

Reversible competitive antagonists

Gastric Parietal Cells

Reduce gastric acid secretion

• Famotidine
• Ranitidine
• Cimetidine
• Nizatidine

Question 19

Famotidine (Pepcid)

Answer 19

Most potent and longest half-life

First pass hepatic metabolism

No prokinetic or antiemetic activity

Side effects uncommon

No prokinetic or antiemetic effect

Question 20

H3 and H4 Antihistamines

Answer 20

Not approved for clinical use

Experimental models

Improve attention and wakefulness

Question 21

Serotonin (5-HT)

Answer 21

Synthesized from Tyrptophan

Found in

• GI (ECL cells)
• CNS
• Platelets

Serotonergic projections

• Spinal cord
  
  • pain
  • inflammation
  • motor function
• Forebrain
  
  • mood
  • state of alertness

Question 22

Serotonin Overdose

Answer 22

Neuro signs

• seizures
• depression
• tremors
• hyperesthesia
• ataxia

GI signs

• vomiting
• diarrhea
• abdominal pain
• hypersalivation

Other

• hyperthermia
• blindness

Question 23

Pharmacology

Answer 23

MAOIs

Amphetamines

• make vesicles less likely to store serotonin

SSRIs

• decrease reuptake of serotonin into presynaptic cleft

TCAs

• decreases degradation of serotonin

Question 24

Amphetamines

Answer 24

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

Question 25

Monoamine Oxidase Inhibitors

Answer 25

Inhibitors of serotonin degradation Two types * MAOI-a * MAOI-b Reversible vs irreversible

Question 26

Selegiline (anypril)

Answer 26

Selective MAOI-b, MAOI-a at high doses TX of canine cognitive dysfunction Inc dopamine activity Cushings dz +/- 20% Adverse effects * GI signs * CNS

Question 27

Cushings

Answer 27

Inc ACTH

Question 28

Reuptake Inhibitors

Answer 28

Net inc in extracellular 5-HT Used for TX of anxiety, depression and OCD Four main classes * TCAs * SSRIs * SNRIs * NRIs

Question 29

Clomipramine (Clomicalm)

Answer 29

Tricyclic antidepressant Only FDA approved drug (dogs) TX * OCD * Anxiety * Dominance * Aggression Side effects * change in behavior

Question 30

Fluoxetine (prozac)

Answer 30

Selective-serotonin reuptake inhibitor FDA approved in dogs for TX of separation anxiety in conjuction with behavior modification plan Adverse effects * anorexia * seizures

Question 31

Mirtazapine

Answer 31

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

Question 32

Trazadone

Answer 32

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

Question 33

Cisapride

Answer 33

5-HT4 agonist Enhances acetylcholine release Prokinetic TX of * GI stasis * reflux esophagitis * constipation/megacolon (cats) Adverse effects: well tolerated

Question 34

Ondansetron (zofran)

Answer 34

Serotonin receptor agonist Potent antiemetic Receptors in vagal nerve terminals and CTZ Controversial use in cats Well tolerated in dogs