Test 1: 14-16

Question 1

where is ACh released

Answer 1

Question 2

muscarine is considered to be a –

Answer 2

‘parasympathomimetic’

will cause vagal stimulation to the heart (decrease HR?)

Question 3

how to make ACh

Answer 3

Question 4

Choline synthesized from — supplied by diet and protein metabolism

Answer 4

serine

Question 5

how is ACh made inside the nerve ending?

Answer 5

choline is brought into cell transporter (rate limiting step)

choline + Acetyle CoA (choline acetytransferase) = ACh

ACh moved into vesicle by VaCht(Vesicular acetylcholine transporter)

ACh is then moved out of nerve

there are no intracellular breakdown of ACh (unline NE)

Question 6

Answer 6

Question 7

what does botulinus toxin do?

Answer 7

blocks release of ACh into synapse

leads to flaccid paralysis

clostridium botulinum: cleaves synaptobrevin subunit to prevent export

Question 8

how is ACh broken down

Answer 8

within the synaptic cleft
very fast reaction

water and acetylcholineterase(AChE)

will cleave/hydrolyze into acetic acid and choline

choline is then brought back into the nerve to be used again (this is rate limiting step)

Question 9

how is NE vs ACh broken down in the synaptic cleft

Answer 9

NE: most NE will be taken back into the nerve to be recycled or broken down by MAO, anything left in the synaptic cleft will get eaten by COMT, bind to postsynaptic receptor, or bind to presynaptic autoreceptor(that stops reaction)

ACh: only gets broken down in the synapse, very fast hydrolization by AChE

Question 10

— is not specific for ACh, but will hydrolyze it

Answer 10

Pseudocholinesterase (pseudo-/butyro-ChE)

non specific or serum cholinesterase

made by the liver and found in blood plasma

Question 11

what is the rate limiting step of making ACh

Answer 11

choline reuptake into the nerve

Question 12

where are nicotinic sites in PNS?

Answer 12

neuromuscular junctions(skeletal)
all preganglionic fibers (ANS and adrenal medulla)

Question 13

where are the muscarinic sites in the PNS

Answer 13

where ACh is released at postganglionic fiber

all parasympathetics and sympathetic to the sweat gland

Muscarine is considered to be ‘parasympathomimetic’

nicotinic: both sympathetic and parasympathetic ganglia

Question 14

what type of receptors are nicotinic?

Answer 14

ligand-gated ion channels
(ionotropic receptors)

Question 15

what kind of receptors are muscarinic

Answer 15

GRCP
(metabotropic receptors)

Question 16

Nicotinic — receptors are ligand-gated, nonselective cation ion channels

Answer 16

ACh

Question 17

nicotinic ACh receptors will stimulate both the — and —

Answer 17

synpathetic and parasympathetic postganglionic neurons

ACh released all all pregranglionic site

Question 18

4 effects of Nicotinic ACh receptors

Answer 18

stimulates ANS: sym and para postganglionic neurons

stimulate release of EPI/NE from adrenal medulla

cause contraction of skeletal muscle (Nm)

cause CNS effects: tremor, anxiety, respiratory and circulatory center effects

Question 19

how does nicotinic receptor work?

Answer 19

5 subunits: 2⍺, 1 β𝛾δ

2 ACh binds to ⍺, pore opens, Na moves in and K moved out

Question 20

— receptor works by Binding of 2 molecules of ACh causes opening of central pore allowing the flow of ions through the pore according to their concentration gradients (Na+ and K+)

Answer 20

nicotinic ACh

Question 21

Muscarinic activation will cause:

— secretion
— contraction
relaxation of —
— of the heart

Answer 21

gland: sweat, salivary, tear, mucous

smooth muscle and pupillary constriction

sphincters: GI tract, urinary tract, biliary tract

slowing (bradycardia)

GPCR receptors

Question 22

accronym to remember muscarinic activation

Answer 22

SLUMD

Salivation, Lacrimation, Urination, Miosis(pupils contract), Defecation,

Question 23

M2 muscarinic receptors are found —

Answer 23

heart, smooth muscle, autonomic ganglia

Question 24

where are M3 muscarinic receptors found

Answer 24

Exocrine glands, smooth muscle, blood vessels (endothelium)

Question 25

Activation of M2 receptors are --- in cardiac muscle

Answer 25

INHIBITORY due to inhibition of adenylate cyclase (decrease cAMP in the cell) and activation of K+ channels (moves K out of cell)

Question 26

Activation of M3 receptors are --- in smooth muscle

Answer 26

EXCITATORY due to the opening of plasma membrane and intracellular Ca2+ channels

Question 27

how do M2 receptors cause inhibition of cardiac muscle

Answer 27

M2 will ativate K channels, this will cause K to leave making cell less negative (decreasing action potential) M2 will also inhibit adenylate cyclase which leads to decrease in cAMP (cAMP used throughout the cell)

Question 28

how does M3 receptors excitatory to smooth muscle?

Answer 28

M3 will **open Ca channels**, (Ca will come into cell, more positive= easier to cause impulse/contraction) M3 will also **open plasma membrane channel**→ allow IP3 in which triggers more Ca into cell → contraction of cardiac muscle

Question 29

what are some parasympathomimetics drugs

Answer 29

ACh methacholine carbachol bethanecol

Question 30

what happens when you give acetylcholine

Answer 30

**No significant therapeutic** applications will trigger **both nicotinic and muscarinic sites** poorly absorbed by GI or skin if IV, rapidly **hydrolyzed by plasma cholinesterase** no CNS effect, can't get past BBB because it is + charged

Question 31

--- is a synthetic analog of acetylcholine that is more selective for Muscarinic vs Nicotinic receptor activity

Answer 31

methacholine (provocholine) less susceptibile to getting hydrolyzed by AChE used to diagnose asthma: will cause bronchial constriction can cause bradycardia and hypotension

Question 32

methacholine (provocholine) is more selective for --- receptor activity

Answer 32

Muscarinic vs Nicotinic (M>>N) ## Footnote muscarinic ACh receptors: SLUMD M2: inhibitory to cardiac muscle M3: excitatory to smooth muscle

Question 33

methacholine (provocholine) is used for

Answer 33

Used for diagnosis of asthma. * Look for exaggerated bronchial constriction after methacholine administration Cardiovascular side effects have limited its clinical use * Potential for somewhat unpredictable bradycardia and hypotension ## Footnote Muscarinic >> Nicotinic muscarinic ACh receptors: SLUMD M2: inhibitory to cardiac muscle M3: excitatory to smooth muscle

Question 34

--- are synthetic ACh that are Resistant to acetylcholinesterase (AChE) action

Answer 34

carbachol (carbamylcholine) bethanecol (myotonachol)

Question 35

what receptors do carbachol work on

Answer 35

Muscarinic and Nicotinic activity (M = N) synthetic of ACh, that is resistant to AChE degredation

Question 36

what is carbachol used for

Answer 36

* Selectively stimulates smooth muscle in the urinary and gastrointestinal tracts * Limited clinical use due to ganglionic stimulation (activates both **para- and sympathetic side**) * Used to induce miosis (**pupil constriction**) * Used in treatment of **glaucoma** to increase the outflow of aqueous humor from the eye ## Footnote resistant to AChE M=N

Question 37

bethanecol works on what receptors?

Answer 37

Muscarinic vs Nicotinic receptor activity (M >> N)

Question 38

what is bethanecol used for

Answer 38

test pancreatic function since it increases secretions Used to treat urinary retention by **stimulating contraction of bladder** ## Footnote muscarinic: **M3:** found in exocrine glands, smooth muscle and blood vessels: is **excitatory for smooth muscle**

Question 39

Answer 39

Question 40

--- is a Naturally Occurring Cholinergic Alkaloid from a south american shrub

Answer 40

pilocarpine 100x more potent then ACh M>N will cause sweating and increased salivation will cause miosis, decreases intracoluclar pressuer by increasing drainage, increases BP and causes tachycardia

Question 41

pilocarpine will cause

Answer 41

**(muscarinic effect)** will cause sweating and increased salivation will cause miosis decreases intracoluclar pressuer by increasing drainage **(nictotinic effect)** increases BP and causes tachycardia ## Footnote south american shrub that acts as parasympathomimetic that is 100 x more potent then ACh with M>N activity

Question 42

--- is made from the betel nut and turns teeth black

Answer 42

arecoline M=N effect previously used to treat tapeworm cause it increased GI movement

Question 43

arecoline is used for

Answer 43

no current uses previously used to treat tapeworm infections can be addictive and turn teeth black made from betel nut M=N receptors

Question 44

muscarine is made from ---

Answer 44

mushroom amanita muscaria poisonous from M>>>N response - marked lacrimation, salivation, sweating, miosis - severe abdominal pain - frequent watery and painful bowel evacuations - cardiovascular collapse - vertigo, weakness, confusion, coma, convulsions - death in few hours antidote atropine

Question 45

muscarine acts on what receptors?

Answer 45

M>>>N cause: marked lacrimation, salivation, sweating, miosis - severe abdominal pain - frequent watery and painful bowel evacuations - cardiovascular collapse - vertigo, weakness, confusion, coma, convulsions - death in few hours poisionous mushroom

Question 46

what does muscarine cause

Answer 46

- marked lacrimation, salivation, sweating, miosis - severe abdominal pain - frequent watery and painful bowel evacuations - cardiovascular collapse - vertigo, weakness, confusion, coma, convulsions - death in few hours

Question 47

antidote for muscarine

Answer 47

muscarinic receptor antagonist **atropine** ## Footnote muscarine is from poisonous mushroom

Question 48

side effects of atropine

Answer 48

Tachycardia - Decreased intestinal contraction and motility - Drying of airway and sinuses and brochodilation - Pupillary dilation (mydriasis) - Tremor - CNS delusion ,excitement, life-like dreams ## Footnote atropine is an anticholinergic with M>>>N effects

Question 49

what receptors does atropine work on?

Answer 49

M>>>N with nonselective M1-6 activation

Question 50

--- is made from deadly nightshade

Answer 50

atropine

Question 51

what are some therapeutic uses for atropine

Answer 51

atropine is a **antimuscarinic agent:** decrease respiratory secretions after intubation used in cold medications: decreases lacrimal and nasal gland secretions antiasthmatic (blocks ACh mediated bronchoconstriction

Question 52

scopolamine is used for

Answer 52

motion sickness sedate mentally ill patients antimuscarinic agent

Question 53

tropicamide is used for

Answer 53

causes mydriasis (dilates pupil for very short time) ## Footnote synthetic antimuscarinic agent: stops ACh receptors

Question 54

contraction of radial iris muscles causes

Answer 54

dilation (mydriasis) innervated by SYM only

Question 55

contraction of the circular iris muscles will cause

Answer 55

constriction of pupil (miosis) innervated by the PARA

Question 56

the iris is under both para and sym control, which one is stronger?

Answer 56

para para controls circulear muscle (keeps eye slightly contricted at all times→ **miosis**)

Question 57

to cause miosis what kind of drug

Answer 57

muscarinic agonists miosis/constriction controlled by PARA

Question 58

to cause mydriasis what type of drug

Answer 58

**muscarinic antagonist** mydriasis/dilation controlled by SYM **tropicamide** will cause short term dilation of the eye

Question 59

cililary muscle is controlled by ---

Answer 59

PARA muscle is always slightly contracted

Question 60

contraction of the ciliary muscle causes

Answer 60

lens to bulge, used for near vision ## Footnote controlled by PARA: always slightly contracted

Question 61

relaxation of the ciliary muscle will cause the lens to ---

Answer 61

flatten used for far vision under control of PARA

Question 62

--- is paralysis of the ciliary muscles

Answer 62

cycloplegia can be from to little or too much ACh lens shape is controlled by contraction of ciliary muscle which is under PARA control and always slightly contracted

Question 63

paralysis of accommodation of the cililary muscle is caused by ---

Answer 63

muscarinic antagonist= too little ACh ciliary muscles kept slightly contracted by PARA, if you block this muscle relax and lens flattens= **farsighted**

Question 64

spasm of accomodation of the ciliary muscle is cause by

Answer 64

muscarinic agonist or AChE inhibtors or too much ACh ciliary muscle under control of PARA, kept slightly contracted, if you increase stimulation will lead to constant state of max contraction= **nearsighted**

Question 65

farsightedness is caused by --- of accommodation

Answer 65

paralysis too littel Ach= relaxation and flat lens

Question 66

nearsightedness is caused by --- of accomodation of the ciliary muscle

Answer 66

spasm too much ACh= max contraction and lens bulges

Question 67

Inducing miosis with --- and --- drugs can increase drainage

Answer 67

**pilocarpine** (miosis= contraction controlled by PARA) **physostigmine**

Question 68

β antagonist (---) decrease aqueous humor production

Answer 68

timolol

Question 69

nicotine causes ---

Answer 69

a bunch of stuff- **No significant therapeutic uses for nicotine** hard to determine cause nicotinic receptors( NM > NN) on **PARA and SYM** nicotinic receptors also **desensitize with increased dose**

Question 70

--- Specifically blocks ganglionic Nicotinic receptors (NN) not as active against NM

Answer 70

hexamethonium (C6) Use is limited since it blocks both sympathetic and parasympathetic ganglia

Question 71

--- is a ganglionic blocker of nictonic agents and Has been used in veterinary medicine to lower blood pressure during surgery

Answer 71

trimethaphan (arfonad)

Question 72

what will AChE inhibitors do

Answer 72

increase effect of ACh throughout, will have sym, somatic and para effects

Question 73

AChE inhibtors block the breakdown of ACh and are ---

Answer 73

parasympathomimetics will have more ACh activation of both muscarinic and nicotinic receptors

Question 74

--- type of anti-AChE with Quaternary nitrogen that binds **reversibly** to the anionic site on AChE

Answer 74

reversible inhibitor

Question 75

--- type of anti-AChE with Substrate for AChE and occupy active site for **extended** time

Answer 75

carbamylating inhibitor

Question 76

--- type of anti-AChE that Covalently binds to and **irreversibly** inactivates AChE

Answer 76

phosphorylating inhibitors

Question 77

edrophonim (tensiolon) works as a reversible anti AcHE by ---

Answer 77

**competitive inhibitor** for binding sites no covalent attachment means **rapidly reversible** ## Footnote used to diagnose myasthenia gravis

Question 78

edrophonium (tensilon) is used to diagnosis ---

Answer 78

myasthenia gravis reversible Anti- AChE- simple competitive inhibitor ## Footnote Myasthenia Gravis is a neuromuscular disease characterized by weakness of skeletal muscle contraction as a result of a decrease in ACh receptor density at the neuromuscular junction

Question 79

how is edrophonium/tensilon used to diagnose myasthenia gravis

Answer 79

MG→ autoantibodies cause ACh receptors to be internalized edrophonium will block the degrade of ACh allowing for a greater chance of ACh to bind to the receptor that are left will have short response →**transient improvement** increase ACh= increase muscle contraction

Question 80

how does carbamylated inhibitors of AChE work?

Answer 80

this drug will bind to same enzyme that breaks down ACh, but it will get stuck for 30 minutes substrate will sit in active site of AChE for **extended** time

Question 81

how does physostigmine(eserine) work?

Answer 81

carbamylated inhibitor of AChE will sit in AChE binding site and prevent it from working for 30 minutes made from West African plant Physostigma venenosum

Question 82

physostigmine (eserine) was originally used to treat MG, --- and --- poisoning.

Answer 82

glaucoma atropine increases ACh available physostigmine is a carbamylated inhibtor of AChE that sits in AChE binding site for extended period

Question 83

how does DFP work

Answer 83

phosphorylating inhibitor of AChE will bind to AChE but will not let go, inactivating the enzyme → increases ACh avialable

Question 84

how to overcome phosphorylating inhibitors of AChE

Answer 84

these drugs break AChE by binding and never letting go body needs to make new AChE enzymes which could take weeks. toxic exposure when 80-90% of all AChE is inactivated

Question 85

nerve gas, sarin and VX gas work by

Answer 85

Phosphorylating Inhibitors of AChE permently inactivate AChE leads to overflow of ACh in the body →**SLUMD and then paralysis and respiratory failure**

Question 86

2-PA M does not work against --- inhibitors

Answer 86

carbamylating AChE (PNPD) does not cross BBB, only works on non-aged complex will give atropine after to prevent extra ACh in mus. recp