PNS & Autocoids Pharmacology

Chemicals that act like local hormones

Short lived

Rapidly degraded

What is an autocoid?

Biogenic Amines

Histamine

Serotonin

Eicosanoids

Prostanoids

Leukotrienes

Polypeptides

Bradykinin

Angiotensin

Cytokines

What are the classes of autocoid?

1. Histamine receptor antagonists

2. Prostaglandin receptor agonists

3. Serotonin receptor agonists/antagonists (Metaclopramide)

4. Monoamine & Serotonin reuptake inhibitors (Fluoxetine e.g. Prozac)

5. Angiotensin II receptor antagonists (Telmisartan)

6. Angiotensin Converting Enzyme (ACE) inhibitors (Enalopril)

3-6 covered in other lectures

Types of autocoid drugs used in veterinary practice

- Gastric secretion - stimulate gastric acid production (H2)

- Smooth muscle effects - H1 receptors stimulate contraction

- Allergic reactions & anaphylaxis

- Inflammation

- Neurotransmission

What are the normal functions of histamine?

Diphenhydramine (1st gen)

Loratidine (2nd gen)

Inhibits vasodilation

Inhibiting itches

Relaxes smooth muscle

Sedation

Give examples of H1 receptor blockers and their main effects

- Pruritis

- Anaphylaxis

- Antiemetic

CNS depression

Dry mouth, urine retention

Allergies

What can H1 receptor blockers be used to treat? What are their side effects?

H2 receptor blocker

Treats gastric ulcers, gastritis & reflux

Side effects are very rare

What is the mechanism of action of Ranitidine? What does it treat? Side effects

Inhibits histamine release from mast cells by hyperpolarising Cl channels (H2 blocker)

Pulmonary & nasal allergic conditions

Allergic conjunctivitis

Local irritant

What is the mechanism of action of Sodium Chromoglycate? What does it treat? Side effects

Synchronise oestrus

Induce abortion/parturition

What are PGF2a receptor agonists used for?

Misoprostol

Cyto-protection of gastric mucosa

Inhibit gastric acid secretion

What are PGE receptor agonists used for?

Prevents contraction of skeletal muscle

Manages muscle spasms

General muscle weakness

Dantrolene

Mode of action

Main effects

Adverse effects

Depolarising - ACh agonists

Non-depolarising - ACh antagonists

What are the two types of Neuromuscular blocking drugs?

Flaccid muscle paralysis

Used with anaesthetics to give muscle relaxation

hypotension = non-depolarising

bradycardia & raised intraocular pressure = depolarising

Main effects and adverse effects of Neuromuscular blocking drug?

Edrophonium & Organophosphates

AChE inhibitor

Treatment of myaesthenia gravis (wears off in 5 secs)

Nausea, vomiting, diarrhoea, salivation

Anticholinesterases

- name

- main effects

- adverse effects

Stimulate postganglionic muscarinic receptors

Decreases CO & HR

Smooth muscle contractor

Increases salivation & lacrimation

Pupil constriction

Cramps, salivation, bradycardia

Muscarinic Agonists

- mechanism of action

- main effects

- adverse effects

Inhibit postganglionic muscarinic receptors

Increase HR

Bronchodilation

Decrease salivary & gastric secretion

Pupil dilator

Tachycardia

Dilated pupil

Constipation

Muscarinic Antagonists

- mechanism of action

- main effects

- adverse effects

α1 – Vasoconstriction, relaxation of GI smooth muscle, salivary secretion, hepatic glycogenolysis

α2 – Inhibition of neurotransmitter release

β1 – Increased cardiac rate & force

β2 – bronchodilation, vasodilation, inhibition of GI smooth muscle, hepatic glycogenolysis

β3 – lipolysis, thermogenesis & detrusor relaxation

Main effects of activation of receptors:

α1

α2

β1

β2

β3

Contraction of smooth muscle (except GI)

Relax GI muscles

Glycogenolysis

Treat urinary incontinence

Inhibitory on nerve terminals

Restlessness & hypertension

α-Adrenoceptor agonists

- Uses

- adverse effects

Treats urethral spasms

Treat severe hypertension

Reverse sedation from alpha agonists

Hypotension

Miosis

Tachycardia

α-Adrenoceptor antagonists

- Uses

- adverse effects

Relaxes GI muscle

Broncho & Vasodilation

Increase HR

Glycogenolysis & lipolysis

Myometrial relaxation

Hypotension, tachycardia, fine tremor

β-Adrenoceptor agonists

- Uses

- adverse effects

Stop bronchodilation

Block ionotropic & chronotropic effects on heart

Manage cardiac arrythmias

Bradycardia

Hypotension & syncope

Hypoglycaemia

Bronchospasm

β-Adrenoceptor antagonists

- Uses

- adverse effects

Stimulates noradrenaline release

Treats hypotension & urinary incontinence

Ephedrine

- mode of action

- What it treats