Pharm of the Somatic Nervous System II

What is Myasthenia like syndrome?

A Syndrome in which Ach receptors are blocked or destroyed resulting in lack of muscle contractions leading to weakness and fatigue that is progressive w/ exertion

What are some etiologies of Myasthenia like syndrome?

1. Autoimmune agains Nm receptors

2. Paraneoplastic thymoma

3. Methimisole

4. Congenital

What is paraneoplastic mean?

Cancer that causes a different physiological response of non-affected cells.

Pyridostigmine and neostigmine are _____ for acetylcholinesterase?

Competitive antagonists

Pyridostigmine and neostigmine are _____ for Nm receptors?

Physiological agonists

Why does Pyridostigmine and neostigmine work against myasthenia like syndrome?

The drugs attach to acetylcholinesterase and result in a longer reset time for the enzyme meaning it degrades less Ach and the concentration can result in more receptor signaling

What is Neostigmine most commonly used for? What is it off label for?

Usage: Reversal of neuromuscular blockade

Off label: Dx and tx of myasthenia like syndrome

What is Pyridostigmine's label use?

What is its off-label use?

Label - Myasthenia like syndrome in dogs

Off Label - Myasthenia like syndrome in cats

How does the administration of Pyridostigmine and Neostigmine differ?

Pyridostigmine- PO

Neostigmine- IV

What is the central compartment of the body?

Circulatory, liver, kidney, lungs

What is the direct route to the central compartment of the body?

IV

What are indirect routes of a drug that must be absorbed into the blood to get into the central compartment?

Oral

Transdermal

Respiratory

How do we sample drug levels?

Blood draw via central compartment

Drugs will common distribute and redistribute between central and peripheral compartments to do what?

Maintain equilibrium

The amount of drug that binds to the target receptors is ____ compared to the amount of available drug?

Negligible

What is the duration of a drugs effect directly relate to?

Time the drug will bind to the receptor

What will decrease the effect of a drug in the body?

The drug will be cleared from the body due to equilibrium between peripheral and compartments

What are exceptions to drug effects decreasing w/ blood levels?

-Covalently bound drugs

- Drugs that alter gene expression (corticosteroids)

What is the most common method of drug administration?

Oral (Enteral/PO)

What are drug factors affecting oral administration of a drug?

Soluability,

Dissolution

Concentration

Isoelectric point (pKa)

What are body factors affecting oral administration of a drug?

Blood flow

Absorbing surface

Contact time

pH

Most drugs are absorbed in the ____ because?

Small intestine,

It is long well perfused and has thin mucosa

What leads to greater absorption?

Longer GI transit

Drugs that go through the GI system will go through ___ circulation and get to the ___ first?

Portal circulation,

Liver

Name a few disadvantages of oral administration?

Emesis (Vomiting)

Destruction via stomach acid/ enzymes

Metabolism to bacterial

Exposure to liver first

Binding to food and excreted

Absorption rate ____ on route, Elimination _____ on route?

Depends

Doesn't depend

What is bioavalibility?

fraction of drug that is absorbed

Why doesn't 100% of a drug not get into circulation when given PO

1. Inactivation in GI

2. Transport back into GI lumen

3. Metabolism in the GI/ liver

Metabolism in the GI mucosa/ liver is also known as what?

First pass effect

How is bioavailability calculated?

(AUC oral / AUC IV ) x 100%

How do most drugs get into circulation?

Simple diffusion

Most drugs are _____?

Weak acids or bases

A drug has to be ____ to cross the lipid bilayer?

Uncharged

Molecules that are used to remove a drug from the body are often?

Nonspecific active transporters

A weak acid in an ____ is ____ and more likely to be absorbed?

Acidic medium (stomach)

Less charged

A weak base in an ____ is ____ and more likely to be absorbed?

Basic medium (small intestine)

Less charged

Explain ion trapping?

Accumulation of a drug on one side of the membrane b/s environmental pH is different on opposite sides

Ex penicillin is acidic and will be absorbed in the stomach's acidic environment, the blood being more basic than the stomach will mean penicillin can not transfer back into the stomach

A weak acid accumulates in ____ environments

A weak base accumulates in ___ environments

Basic

Acidic

Weak acids are better absorbed in ___ stomachs

Weak bases are better absorbed in ____ stomaches?

Carnivore

Herbivores

Ion trapping is very rarely used to what?

Increase drug excretion in the urine (ONLY FOR EMERGENCIES)

Ammonium chloride is used to ____.

Sodium bicarbonate is used to ____.

Elimination of bases

Elimination of acids