Pharm 5 - Ganglionic And Neuromuscular Blockers

Front 1

therapeutic uses of ganlionic blockers

Back 1

essential HTN or hypertensive emergency
dessecting aortic aneurysm
reduced bleeding during certain types of surge
autonoic hyperreflexia

Front 2

describe the MOA for ganlionic blockers

Back 2

non-depolarizing block of ganglion nicotinic (Nn) receptors blocking synaptic transmission at sympathetic and parasympathetic ganglia

Front 3

name two ganlionic blockers

Back 3

trimethaphan
mecamylamine

Front 4

adverse effects of ganglionic blockers

Back 4

marked hypotension
paralytic ileus
urinary retention
impotence
angina
cycloplegia
dry mouth
constipation

Front 5

name the 3 types of neuromuscular blocking agents

Back 5

depolarizing,"", non-depolarizing, ACH-release blockers

Front 6

name the 3 types of muscle relaxants

Back 6

neuromuscular blocking agents
direct acing muscle relaxants
centrally acting spasmolytic agents

Front 7

describe the primary use of neuromusc blocking agents

Back 7

surgical adjuvant to make surgical maneuvers safer and more efficient by lowering level of anesthesia needed
*non surg uses: facilitat intubation, maintence of controlled respiration, prven bone fractures during electroshock therapy, treat muscle spastiity, treak ocular disorders such as blepharospasms (uncontrolled eyelid movement) or strabismus

Front 8

name the only DEPOLARIZING blocker currently used

Back 8

succinylcholine (two mol of ACH joined end to end)

Front 9

mech of action of succinylcholine - phase I

Back 9

depolarizing block - binds to Nm receptors causing inital act like ACh, produes transient muscle fasciculations, leading to paralysis that CANNOT be overrideen by electrical stimulation; not sens to AChE = prolonged depol so m. non responsive to further stim

Front 10

can paralysis by succinylcholine be overridden by electrical stimulation?

Back 10

no

Front 11

mech of action of succinylcholine - phase II

Back 11

desensitizing block - after phase I, endplate eventual repolarized but cannot be depolarized b/c it is desensitived due to direct block of channel pore by succinyl choline

Front 12

what phase of succinylcholine mech of action can be reversed by cholinesterase inhibitors?

Back 12

phase II desensitizing block

*phase I is only augmented by cholinesterase inhibitors

Front 13

what are the adverse effects of succinylcholine?

Back 13

hyerkalemia - high serum K due to prolonged depol
increase in intraocular pressure
muscle pain
can activate cardiac muscarinic receptors
can precipitate malignant hyperthermia

Front 14

drug interation with succinylcholine

Back 14

inhaled anesthetics and aminoglycoside antibiotic potentiate neuromuscular blockade
-non-depolarings neuromusc blockers can antagonize the effect (sometimes given prior to succinylcholine to prevent fasciculations but results in need for higher dose of succinylcholine)
-increasing ACh w/chlinesterase inhibitor augmetns phase I and antagonized phase II

Front 15

pharmacokinetics of succinylcholine

Back 15

metabolized by butyrylcholinesterase
short half life (3 mins)
fast rate of recovery:
-phase I 4-8 mins
-phase II >20 mins

Front 16

what are some non-depoalrizing blockers?

Back 16

isoquinaline derivitives
-d-tubocurarine, atracurium, cisatracurium
steroid dervatives
-rocuronium, pancuronium

Front 17

can non-depolarizing blockers be overridden by electrical stimulation?

Back 17

yes

Front 18

describe the mech of action of non-depolarizing blockers

Back 18

at low doses competes with ACH
doesn't casue intitial fasciculation seen w/depolarizing blockers
at higher doses blocks channel pore
can also block presynaptic Na channels, inhibiting ACh release (larger mm. more resistant)

Front 19

in non-depolaring blockers which muscle group is last to be affected and first to recover?

Back 19

respiratory muscles

Front 20

what are pharmacokinetic considerations for non-depolarizing neuromusc blockers?

Back 20

all are quaternary ammonium compoounds - don't cross BBB
duration of action depends of method of clearance
***cmpds in metabolized by liver cleared faster
***cmpds cleared spontaneously in blood medium clearance
***cmpds excreted by kidneys have slow clearance

Front 21

succinylcholine has how fast of clearance?

Back 21

ultrafast (liver)

Front 22

mivacurium has how fast of clearnace

Back 22

fast (liver)

Front 23

atracurium has how fast of clearance

Back 23

intermediate (spontaneous)

Front 24

d-tubocuraine and pancuronium have how fast of clearance?

Back 24

slow (renal)

Front 25

what are some adverse effects of non-depolarizing blockers

Back 25

changes in BP, HR and stimulation of histamine release
*usually in non depolarizing, decr BP, incr HR and significat histamine release (tubocurarine, mivacurium)

Front 26

what non-depolarizing blockers have minimal effect on BP adn HR?

Back 26

atracurium and cis-atracurium and rocuronium (isoquiniline derivatives)

Front 27

which nondepol have minimal effect on histamine release

Back 27

rocuronium and cisatracurium

Front 28

what is special about the BP and HR effects of pancuronium and succinylcholine compared to other neuromus blocker agents?

Back 28

they both increase BP and HR

Front 29

name a ACh release blocker

Back 29

botulinum toxin

Front 30

Mech of action of botulinum toxin

Back 30

degrades SNARE proteins preventing vesicle fusion and release of NTs

Front 31

therapeutic uses of botulinum toxin?

Back 31

cosmetic, cervical dystonia, blepharospasm, strabismus, migranes, hyperhydrosis, vocal chord dysfuction

Front 32

1.name a direct acting muscle relaxant and describe it's
2.mech of action (MOA)
3. therapuetic uses
4. ROA

Back 32

1. DANTROLENE
2. inhibits excitation contraction coupling by blocking the ryanodine receptor prventing Ca release
3. treat malignant hyperthermia, spasticity due to spinal chord injury, MS, cerbral palsy
4. IV for acute tx, oral for prophylactic tx

Front 33

describe the therapeutic uses of centrally acting spasmolytics

Back 33

treatment of muscle spasm due to increase in tonic stretch reflexes associated with spinal cord injury, cerebrral palsy, MS, etc

Front 34

mech of action of centrally acting spasmolytics

Back 34

modification of stretch reflex by modulating excitatory or inhibitory synapses
*release of the NT Glu from corticospinal neurons activates excitatory AMPA receptors on the skeletal msucle motor neuron release of the NT GABA from interneurons activates inhibitory CABA A and GABA B receptors on the skeletal muscle motor neuron

Front 35

name 3 centrally acting spasmolytics and their MOAs

Back 35

dizazepam- facilitaes synaptic transmission involving type A GABA recptors

Baclofen - facilitates synaptic transmission involving GABA B receptors

Tizanidine - related to clonidine; activates Alpha-2 adrenergic receptors

Front 36

MOA of diazepam

Back 36

facilitates synaptic transmission involving GABA A receptos

Front 37

MOA of baclophen

Back 37

facilitates synaptic transmission involving GABA B receptors

Front 38

MOA of tizanidine

Back 38

related to clonidine; activats Alpha-2 adrenergic receptors