Pharmacology of the Autonomic Nervous system I

Adverse effects are typically either?

Predictable or Bizarre

What some kinds of predictable adverse effects?

Overdose,

Normal reactions on undesired tissues

Chronic effects

Delayed effects

Withdraw effects

What are the kinds of overdose (hormesis)

Iatrogenic - human caused

Competition of multiple drugs for plasma proteins (warfarin)

Decreased metabolism or elimination

A doctor recommends giving diphenhydramine for allergic reactions but warns about drowsiness. What kind of adverse effect is this?

Predictable normal reaction on off target tissue

A dog had a severe flare up of IVDD and was given prednisone for a month. The dog saw a loss of natural steroid hormones. What kind of adverse effect is this?

Predictable chronic drug effect

A dog had a severe flare up of IVDD and was given prednisone for a month. The owner abruptly stopped the prednisone after two weeks after the dog got better and the dog became very lethargic showing signs of Hypoadrenocorticism. What kind of adverse effect is this?

Withdraw effect

What is a Bizarre adverse effect?

Drugs that activate multiple receptors

A quantal dose response curve will represent what?

The dose for a population

What is a trend of a quantal dose response curve?

Bell curve as some are sensitive at low or high doses but most will be in the middle

What is a ED50?

effective dose for 50% of the population

What is the LD50?

lethal dose for 50% of the population

How do you calculate Therapeutic index?

TI = LD50/ED50

The ____ the TI the ____ the drug?

Higher, safer

Name the two most common Adverse effects of Pyridostigmine bromide?

Tolerance - down regulation of Nm receptors

Intussusception - intestine eats intestine (Too much GI activity)

What do we do if an animal becomes tolerant to a drug? Why could this be a problem?

Increase the dose, risk toxicity

Tolerance will occur when?

W/ chronic administration

What are the two much types of tolerance?

Pharmacokinetics - drug induces own metabolism

Pharmacodynamics - body downregulates receptors

The autonomic nervous system pertains to what?

Unconscious control, visceral function to maintain physiological homeostasis

What is the most important parasympathetic nerve?

vagus nerve

What is the craniosacral efferents?

Parasympathetic innervation in which preganglionic fibers are long and post ganglionic are very short

What is the Thoracolumbar efferents?

Sympathetic innervation, preganglionic fivers are short and postganglionic fibers are long

Cholinergic receptors will accept what endogenous neurotransmitter?

Ach

What systems have cholinergic receptors?

BOTH sympathetic and parasympathetic

Adrenergic use what kind of neurotransmitters?

Multiple neurotransmitters like epinephrine

What systems have adrenergic receptors?

Sympathetic

What are two nicotinic receptors?

Nm - at neuromuscular junctions

Nn - at post synaptic ganglion junctions and adrenal medulla

What is an M receptor?

A cholinergic receptor presant in all parasympathetic post-sympathetic junctions

Besides post sympathetic parasympathetic junctions where might we find an M receptor?

Sympathetic post synaptic junctions of sweat glands not in horses

Where can we see Alpha 1 receptors?

vasculature

GI

urinary bladder,

male genetalia

spleen,

piloerector muscles

Where can we see Alpha 2 receptors?

Presynaptic sympathetic nerver terminals.

Pancresus islets and kidneys

Where do we find B1 receptors?

Heart (stimulatory)

GI

Urinary bladder,

Kidney

Uterus

(NOT VASCULATURE)

Where are B2 receptors found?

Bronchioles

Heart

Vasculature

Sympathetic pre-synaptic nerve terminals

In the ANS neurotransmitters are Agonists of what?

G-protein coupled receptors

How does a G-protien get activated?

Agonist binding to a receptor will make G protein in the cytoplasm to GTP which activates G protein

Gs proteins will _____ cAMP production

Gi proteins will _____ camp production?

Stimulate

Inhibit

What will a Gq Protein cause?

Ca2+ release

How does Gq cause Ca2+ release?

Gq activated Phospholipidase C in the membranes which will hydrolyze Inositol head group of a phospholipid into IP3 and DAG

IP3 will stimulate what?

Ca2+ release

DAG will stimulate what?

Protein kinase C

Label what secondary messengers there are for the cholinergic receptors?

Nm

Nn

M

Nm Ligand gated

Nn Ligand gated

M Gq

Label what secondary messengers are for the adrenergic receptors?

a1:

a2:

b1:

b2:

a1: Gq

a2: Gi

b1: Gs

b2: Gs