lecture 5

Question 1

local anesthetic

Answer 1

agent that interrupts pain impulses in a specific region of the body without a loss of patient consciousness – completely reversible

Question 2

Ao fibers are ___ and encode ____. C fibers are ____ and encode _____.

Answer 2

fast (myelinated), first pain; slow (not myelinated), second painful stimulus

Question 3

TRPV1 channel responds to

Answer 3

noxious heat, capsaicin

Question 4

erytheromelagia

Answer 4

burning all the time, mutation is vg sodium channels

Question 5

prostoglandins

Answer 5

promote pain and inflammation by enhancing activity of sodium channels thus APs

Question 6

first drug to treat pain

Answer 6

cocaine

Question 7

cocaine does what

Answer 7

blocks impulse conduction along axons and inhibits reuptake of neurotransmitters

Question 8

synthetic procaine

Answer 8

novocaine

Question 9

bc of the ester linkage in cocaine,

Answer 9

the effects are short acting and they are hydrolyzed by pseudo-cholinesterase and have a short half life.

Question 10

bupivacaine? amide linked local anesthetics?

Answer 10

metabolized in the liver sooo longer elimination half-life, lidocaine, bupivacaine for epidural! less motor block

Question 11

mechanism of local anesthetics

Answer 11

block nerve conduction by reducing the influx of sodium ions into the nerve cytoplasm

Question 12

unionized drugs

Answer 12

diffuse freely across membrane

Question 13

drugs get in through where

Answer 13

nodes of ranvier to prevent salatory conduction of myelin

Question 14

why are Ao fibers blocked easier

Answer 14

drugs can block nodes, but unmyelinated C fibers are harder

Question 15

3 factors that affect action of LAs

Answer 15

diameter of nerve (small fibers easier bc smaller distance), presence of myelin, firing frequency (Ao and. C fibers are small diameter that fire high, so theyre blocked sooner with lower. concentrations than are A alpha fibers)

Question 16

harder to block second or first pain

Answer 16

second bc they’re C fibers

Question 17

use dependence

Answer 17

nerves that fire at a higher frequency are blocked more easily by LAs

Question 18

tonic block

Answer 18

low frequency stimulation where LA bind to resting or closed Na channels

Question 19

phasic block

Answer 19

high frequency stimulation where injured regions fire at high frequency and are blocked more effectively (use dependent)

Question 20

differential blockade

Answer 20

the ability of the LA to block sensory impulses while sparing motor and propioception - generally first pain

Question 21

Procaine

Answer 21

Novocaine - short acting ester. low hydrophobicity so rapidly removed

Question 22

Lidocaine

Answer 22

moderate hydrophobicity. nerve block, infiltration, epidural and topical. co adminster epinephrine - vasoconstriction

Question 23

bupivacaine

Answer 23

hydrophobic and potent. epidural as more nociception than motor activity. cardiac toxicity

Question 24

alkalinization

Answer 24

when sodium bicarbonate is added to LA solutions to increase the fraction of nonionized LA molecules. mostly done w epi to increase shelf life (and for speeeeed)

Question 25

local anesthetic do what to blood vessels

Answer 25

dilate

Question 26

systemic actions of LAs

Answer 26

CNS excitation --> tremor, seizure at highlevels -->. coma, respiratory arrest LAs decrease myocardial excitation, decrease conduction rate and decrease force of contraction

Question 27

NSAIDs

Answer 27

nonsteroidal anti-inflammatory drugs willow bark- salicylic acid--> aspirin

Question 28

aspirin

Answer 28

acetylsalicylic acid - reduced irritant properties of salicylic acid

Question 29

NSAIDs inhibit ______(enzyme)

Answer 29

cyclooxygenase (COX), that makes prostaglandins

Question 30

NSAIDS do not act on the ___ enzyme

Answer 30

Lipooxygenase, which also makes an inflammatory product. (leukotrienes)

Question 31

Aspirin mechanism

Answer 31

acetylates serine on COX1 to irreversibly inactivate. COX-2 is prostaglandin synthesis is also turned off, but still produce antiinflmamatory lipoxins

Question 32

thromboxinate 2 (TXA2)

Answer 32

vasoconstriction, knocking down platelet TXA2 --> platelet disaggregation and vasodilation

Question 33

PGI2

Answer 33

prevents blood clotting

Question 34

aspirin inhibits PGI2 and TXA2 for what

Answer 34

control of platelet aggregation

Question 35

COX-1 vs COX-2

Answer 35

COX-1 houskeeping, expressed under normal conditions in most tissues, plays imoprtant role in protection of GI lining, renal function, and platelet aggregation COX-2 expressed primarily in CNS under normal conditions, expression is induced under inflammatory conditions, reuslting in the intitiaon of inflammtory response bad PGS

Question 36

NSAIDs inhibit COX1 and COX2. Which one produces serious side effects?

Answer 36

COX-1

Question 37

NSAIDs examples

Answer 37

aspirin, ibuprofen, naproxen (aleve)

Question 38

GPCRs

Answer 38

7 transmembrane receptors that have 2nd msngers heterotrimeric structures catecholamines: E, NE, and dopamine all derived from tyrosine

Question 39

D1 and D2 dopamine effects on cAMP - P210

Answer 39

D1 - activate adenylyl cyclase --> can phosphorylate NMDA and AMPA receptors to promote activity D2 - decrease adenylyl cyclase --> decrease cAMP --> decrease PKA --> decrease phosphorylation

Question 40

parkinson's disease dopamine mechanism

Answer 40

direct pathway inhibited and indirect pathway activated, both leading to reduced movement

Question 41

GPCR mchanism

Answer 41

GDP connected to unit. alpha subunit binds GTP instead of GDP so G protein is now activated. alpha subunit can activate different effectors like adenlyl cyclase. GTP gets hydrolyzed back to GDP eventually.

Question 42

cholera

Answer 42

secretory diarrhea and is caused by V. cholera found in costal esturine waters - contaminated food or drinking water

Question 43

cholera toxin catalyzes covalent modification of __. mechanism?

Answer 43

Gsa ADP-ribose is transferred from NAD+ to an arginine residue at the GTPase active site of Gsa. ADP-ribosylation prevents GTP hydrolysis by Gsa, so the stimulatory G protein is PERMANENTLY activated!

Question 44

pertussis toxin (PTX) mechanism and what does it cause

Answer 44

whooping cough. same thing - ADP-ribosylating but this time with GDP so the GDP-bound form (inactive state) is stuck forever

Question 45

whooping cough transmission

Answer 45

respiratory disease by bacteria. respiratory droplets. DTaP vaccines! and Tdap vaccines for addults

Question 46

cholera toxin still allows ____ receptor to let ___ ions to flow out, Na+ and H2O following it

Answer 46

CFTR; chloride

Question 47

CFTR helps to control

Answer 47

bulk water flow across epithelia

Question 48

cholera treatment

Answer 48

isotonic solution of NaCl, dextrose, etc.