Somatic Nervous System (1)

How do drugs cause effects?

act through receptors

Agonist

drugs that activate receptor

bind same site as natural ligands

reversible

How do agonists bind to receptors?

electrostatic interactions, H bonds, van der waals, and/or hydrophobic interactions

What represents drug-receptor affinity?

dissociation constant Kd

Why does a drug with higher concentration have greater receptor occupancy?

greater concentration means can bind more receptors

response is proportionate to number of receptors occupied

Agonists cause the ____ response as natural ligands

same physiological

When is maximum response reached?

when drug is bound to all available receptor

once all bound additional drug does not increase response

What is threshold dose?

minimum dose that causes response

What is EC50?

concentration for 50% effect

indicates potency (lower = more potent/lower doses)

The _____ the affinity the ______ the EC50

higher, lower

What is a saturable drug?

has a maximal effect (efficacy)

What is the difference between a full agonist and partial agonist?

full = 100% effect

partial < 100% effect

What happens if you combine partial agonist + full agonsti?

both will compete at binding site

decreased efficacy

What happens if partial agonist has lower affinity than full agonist?

more likely to get full response (full agonist will bind more often/more tightly)

What if the partial agonist with lower affinity is present in higher amount than full?

reduced efficacy

able to outcompete via higher concentration

What happens if the partial agonist has higher affinity than full?

reduced efficacy

Graded, dose response curves describe ______ mediated pharmacodynamics

receptor mediated

Non-receptors mediated pharmacodynamics are based on what?

physical properties

ie osmotic agents, some biologics (therapeutic antibodies), some chemotherapies

What are competitive antagonists?

compete with natural ligand at its receptor binding site

have zero intrinsic activity (efficacy)

What is a non-competitive antagonist?

bind receptors covalently (irreversibly) or at allosteric site

uncommon in vet med

What are physiological antagonists?

act on different receptor to produce opposing physiological effect

What are chemical antagonists?

neutralize chemically (like therapeutic antibodies)

If agonist concentration is _____ enough effect of antagonist can be _______

high enough, overcome

maximum response by agonist/ligand does not change

Antagonists ____ agonist affinity

decrease

increase Kd and EC50

Motor nerves release __________ which activate receptors in _________________

acetylcholine, skeletal muscles neuromuscular junctions

What are acetylcholine receptors?

ligand gated ion channels (Na+ channels)

aka N_M receptors

activated (opened) by acetylcholine

How does acetylcholine cause muscle contraction?

ACH binds NM receptor and depolarizes end plate

when voltage change reaches threshold then muscle depolarizes and releases intracellular Ca2+ for contraction

What stops contraction?

ACH broken down and stops signaling

acetylcholinesterase breaks down ACH and NM receptors reset

What is atracurium besylate?

N_M competitive antagonist (neuromuscular blocking agent)

causes progressive paralysis

How is atracurium used?

IV administration

perioperatively for muscle relaxation in dogs, cats, small mammals, and horses

provides NO analgesia

all uses extra label

What is the order of muscle recruitment in progressive paralysis?

small muscles → larger muscles (ie limbs) → deglutition/laryngeal/abdominal intercostal muscles → respiratory muscles

recovery in opposite direction

Pancuronium and vecuronium bromide are used in what animals?

dogs and cats