SM57_PharmacologyofPNS

Question 1

Somatic division of PSN has its cell bodies in the _____

Answer 1

spinal cord

Question 2

Skeletal nueormuscular transmission is mediated by what type of channel?

Answer 2

Nicotinic ACh receptors - fast ligand gated channels

Question 3

Fusion machine connecting calcium channels and ACh vesicles contain:

Answer 3

SNARES - responsible for priming the vesicles (making them fusion competent)

Synaptotagmins - Ca2+ sensors wrapped around snares

+other proteins not discussed

Question 4

The drug that blocks voltage gated Na+ channels, preventing initiation of action potentials in both nerve and skeletal muscle

Answer 4

TTX - tetrodotoxin

Does not affect cardiac and smooth muscle as much as skeletal muscle

Question 5

Factors that reduce Ca influx at presynaptic terminal of NMJ

Answer 5

Impermeant polyvalent cations compete with Ca2+ (Mg2+, Co2+, Mn2+, Cd2+, Ld3+)

Aminoglycoside antibiotics (neomycin, kanamycine, amikasin, gentamicin, tobramycin) reduce Ca2+ entry through voltage gated channels

Question 6

What pharmacologic agent prevents Ach release at NMJ but interacting with SNAREs (+ clinical relevant example)

Answer 6

Botulinum toxins – cleaves the SNAREs, preventing priming of ACh release machinery.

Botox A cleaves SNARE SNAP-25 and is used clinically yo treat spasticity

Question 7

Types of nicotinic receptor blockers

Answer 7

Non-depolarizing blockers (competitive inhibitors at the skeletal NMJ): tubocurarine - indian poison arrow, curoniums - surgical procedure muscle relaxant

Depolarizing blockers: succinylcholine (SUX)
-binds to nicotinic receptors and depolarized the muscle before blocking the receptor

Question 8

Disease related to post synaptic nicotinic receptors

Answer 8

Myasthenia Gravis: nicotinic receptors are destroyed by circulating antibodies and the MG patient is already fatigued

Question 9

Names and effect of Acetylcholinesterase inhibitors

Answer 9

Effect: enhances synaptic transmission by inhibiting degradation of ACh

Neostigmine (reversible inhibitor) - disease treatment for impaired synaptic transmission due to nicotinic receptor deficit

Sarin (irreversible inhibitor) - aka nerve gas

Question 10

Common characteristics of both divisions of ANS

Answer 10

1. Preganglionic and postganglionic nerve fibers. Preganglionic nerves are myelinated and cell bodies of preganglionic nerve fibers are completely within CNS. Postganglionic cell bodies all lit within autonomic ganglia
2. Preganglionic nerve fibers synapse in the autonomic ganglia; both divisions have nicotinic receptors (fast ligand gated) at this neuro-neuronal site
3. Formation of neuroeffector junctions between postganglionic fibers and effector organs

Question 11

Key differences between divisions of ANS

Answer 11

1. Receptor type at neuroeffector junction:
   Sympathetic division - norepinephrine NT acts on alpha and beta adrenoreceptors.
   Parasympathetic - acetylcholine NT acts on muscarinic cholinergic receptors
2. Length of preganglionic and postganglionic fibers: longer postganglionic for sympathetic system –> can figure out the rest of them
3. Anatomic definitions:
   Sympathetic - fibers emerging from thoracic and lumbar regions of spinal cord
   Parasympathetic - emerging from cranial and sacral regions of CNS

Question 12

Major difference in synaptic transmission between NMJ and in ANS (@ neureffector junction)

Answer 12

Cholinergic (parasympathetic): same except postsynaptic receptors are GPCRs (muscarinic not nicotinic)

Adrenergic (sympathetic):

1. NT released into synapse is NE not ACh
2. Innervated receptors are alpha-1 and beta-1 adrenoreceptors (GPCRs) not nicotinic OR muscarinic
3. Termination of NE action via norepinephrine transporter (NET aka SLC6A2) vs. acetylcholinesterase mediated hydrolysis