Somatic Nervous System (2)

What is myasthenia-like syndrome?

weakness/fatigue that progresses with exertion’

many etiologies (autoimmune attack against NM receptors, paraneoplastic, methimazole tx, congeital)

What does myasthenia-like syndrome cause muscle weakness?

less receptors mean can’t have as great of a response

How does an acetylcholinesterase inhibitor increase muscle contractions?

prevents breakdown of acetylcholine so effect lasts longer

recovers action potential in muscles to recover contraction

What is neostigmine?

IV

reversal of neuromuscular blockage

dx (and tx) of myasthenia-like syndrome (extra label)

tx of GI/bladder atony after SX (sheep, swine, cattle, horses)

What is pyridostigmine?

labeled for management of canine myasthenia-like syndrome

extra label use in cats

PO

Neostigmine/pryidostigmine are examples of ________ antagonists

physiological

do not interact with receptor itself

How is neostigmine used of neuromuscular junction blockage reversal?

increases longevity of acetylcholine so can outcompete atracurium

What is the central compartment of pharmacokinetics?

circulatory system, liver, kidneys, lungs

highly perfused tissues

drug is absorbed into it and then either distributed to peripheral of eliminated

only direct route is IV

The ______ compartment is the only convenient way to sample drug levels

central

What is the peripheral compartment of pharmacokinetics?

all other tissues (ie bone, spleen, brain)

most drugs act here

What is characteristic at blue, green, and red arrows?

blue - instant peak concentration after IV dose

green - distribution (initial drop off of drug concentration as moves from central → peripheral compartment)

red - eliminiation (via metabolism or excretion)

The amount of drug bound to target receptors is _______ compared to amount of available drug

negligible

tiny concentration to get effect but need huge concentration to get it to WHERE it causes effect

What is the duration of a drug effect related to?

the time drug is bound to receptor

What happens with decreasing blood levels?

regardless of potency efficacy will also decrease

except with covalently bound drugs or drugs that alter gene expression

What are drug factors that affect absorption?

solubility, dissolution, concentration, and pKa

What are some body factors that affect absorption?

blood flow, absorbing surface, contact time, pH

What is the primary site of enteral absorption?

small intestine

long, well perfused and thin mucosa

Longer GI transit times lead to ________ absorption

greater

cowers longer than cats and vary within species

Once the drug is absorbed by the intestine where does it go first?

enters portal circulation and exposed to liver first

Rank the routes of administration from greatest to best absorption

pulmonary

oral

percutaneous

T/F Elimination depends on administration route

False - only absorption cares about route

What is bioavailability?

fraction of drug absorbed

100% of IV but rarely that much of PO

What are some reasons 100% of PO drugs don’t make it to circulation?

inactivation in GI, transport of drug back into GI lumen, metabolism in GI mucosa/liver (first pass effect)

What is the first pass effect?

drug follows first pass of blood through system

will go into liver via portal system and metabolized then some may make it into circulation

How is bioavailability calculated?

area under curve oral admin X 100

area under curve IV

How do drugs enter the central compartment? Why?

simple diffusion

transporters in membrane are specifc as body regulates what comes into body very carefully

A drug must be what to cross bilayer?

uncharged and nonpolar

most drugs are weak acids/bases and will have charge depending on pH

A weak acidic drug is more acidic medium is what?

less charged

more lipid soluble

more rapidly absorbed

What is the equation to measure the amount of charged/uncharged weak acid?

pH - pKa = log (A-)/(HA)

A weak basic drug in more basic medium is what?

less charged

more lipid soluble

more rapidly absorbed

What is the equation to measure the amount of charged/uncharged weak base?

pH - pKa = log (B)/(HB+)

What is ion trapping?

accumulation of drug on once side of membrane due to pH differences across membrane

weak acids accumulate in basic environments

weak bases accumulate in acidic environments

Carnivores have more ______ stomach while herbivores have more ______ stomach

acidic, basic

dogs/cats - 1-3 pH

equine stomach - 2-6 pH (more acidic towards pylorus)

cows more basic in rumen (7 pH) and acidic i nabomasum (3.5)

How can ion trapping be used to increase drug excretion in urine?

make more acidic urine by ammonium chloride increases base elimination

make more basic urine by sodium bicarbonate increases acid elimination