Midterm - Autonomic Pharmacology

Question 1

Autonomic nervous system

Answer 1

• part of peripheral nervous system
• SNS = fight or flight
• PSNS = rest and digest

Question 2

Where are SNS and PSNS not physiological ANTagonists?

Answer 2

smooth muscle, pilomotor, glands, blood vessels

Question 3

Preganglionic vs postganglionic fibers

Answer 3

• Preganglionic is closer to CNS (from spinal cord to ganglia)
• Postganglionic is closer to tissue (innervates tissue from ganglia)

Question 4

Structure of SNS ganglia

Answer 4

• ganglia near the spinal cord
• ONE short pre- to MANY long post- ganglionic fibers

Question 5

Structuer of PSNS ganglia

Answer 5

• ganglia close to or in target tissue
• ONE long pre- to ONE short post- ganglionic fibers

Question 6

PSNS neurotransmitters

Answer 6

• cholinergic = release ACh

Question 7

SNS neurotransmitters

Answer 7

• adrenergic = release NE from postganglionic neurons (& EP from glands)

Question 8

Balance of neurotransmission in cardiac muscle

Answer 8

• Resting = PSNS = ACh is M2 (less B1 activated from SNS)
• Active = SNS = NE is activating B1 (less M2 activated from PSNS)

Question 9

ACh

Answer 9

• one step to be synthesized by ChAT or to be degraded by AChE
• activates muscarinic and nicotinic receptors

Question 10

How do nicotinic receptors act?

Answer 10

Ion influx through Na+/K+ channel = depolarization

Question 11

Norepinephrine synthesis

Answer 11

1) Tyrosine hydroxylase
2) Dopa decarboxylase
3) Dopamine Beta-hydroxylase

Question 12

Norepinephrine degredation

Answer 12

1) Re-uptake (by MAO)
2) Diffusion away from synapse (by COMT)

Question 13

Why is alpha2 different than alpha1, beta1, beta2 and M, N?

Answer 13

It is found on the PREsynaptic cleft (the others are on the POSTsynaptic)

Question 14

Beta-hydroxylase

Answer 14

Converts dopamine into NE once transported into synaptic vesicles

Question 15

Receptors of the eye

Answer 15

• Constriction = M3 contracts the sphincter
• Dilation = alpha1 contracts the dilator muscle
• Secretion = beta increases and alpha decreases
• Drainage = M3 contracts the ciliary muscle

Question 16

Receptors of the heart

Answer 16

Heart rate = M2 decreases, Beta1 increases

Question 17

Receptors of the blood vessels

Answer 17

• Vasodilation = M3, M5
• Vasoconstriction = Alpha1
• Vasodilation of the BV in skeletal muscle = Beta2

Question 18

Receptors of most organs & glands

Answer 18

• M3 = contraction and secretion
• Beta2 = relaxation of smooth muscle
• Alpha1 = constriction of sphincters

Question 19

Why are the two indirect acting cholinergic agonists different?

Answer 19

• Echothiophate = long-acting (irreversible bond to AChE)
• Physostigmine = intermediate-acting (reversible bond to AChE)

Question 20

Which direct cholinergic agonists do NOT absorb and distribute well?

Answer 20

Acetylcholine, bethanechol

Question 21

Which direct cholinergic agonists DO absorb and distribute well?

Answer 21

Muscarine, pilocarpine, nicotine

Question 22

Which cholinergic agonists activate PSNS?

Answer 22

Muscarinic (with the exception of sweat glands which activate SNS)

Question 23

Which cholinergic agonists activates both PSNS and SNS?

Answer 23

Nicotinic (initially stimulates, then blocks)

Question 24

What does nicotine do at the ganglia?

Answer 24

• activates both PSNS and SNS
• increases ACh and NE release into tissue

Question 25

Tissues where SNS dominantes

Answer 25

- blood vessels = no ACh-release (alpha1 = vasoconstriction in organs and skin, beta2 = vasodilation in skeletal muscle) - heart = rate and force increases

Question 26

Why does PSNS dominate in tissues that have both PSNS and SNS innervation?

Answer 26

Increased ACh amplifies effects at BOTH ganglia and tissue, unlike in SNS where increased ACh only amplifies at the ganglia (junction with tissue has NE not ACh)

Question 27

What do drugs that activate N receptors do?

Answer 27

Act at adrenal gland to amplify PSNS AND SNS activity: - BV = SNS only, so alpha1 vasoconstricts in organs & skin and beta2 vasodilates in skeletal - heart = increases heart rate

Question 28

What do indirect cholinergic agonists do to the heart?

Answer 28

- inhibit AChE = increase ACh at ganglia and adrenal gland = activates Nn = stimulates PSNS and SNS - increased ACh = decreased rate & force of contraction

Question 29

Symptoms of muscarinic excess

Answer 29

- Diarrhea - Urination - Miosis (pupil constriction) - Bradychardia - Bronchoconstriction - Excitation of CNS - Lacrimation (eye watering) - Sweating and salivation

Question 30

Nicotine toxicities

Answer 30

- overexcitement of CNS can cause seizure - leads to eventual downregulation of N receptors (coma, respiratory depression) - PSNS activation = muscarinic excess symptoms - increased BP and heart rate

Question 31

Why are atropine and pralidoxime used to treat organophosphate poisoning?

Answer 31

- symptoms come from muscarinic excess - these are muscarinic ANTagonists

Question 32

Atropine eye drops

Answer 32

- Used to be used for cosmetics because they dilate the pupil - BUT they block M receptors across the whole body at the same time (causes dry mouth)

Question 33

Ganglionic blockers

Answer 33

- antinicotinic - relieves pressure in vessels in emergency situations to decrease SNS activation in BV - eg. trimethaphan

Question 34

Neuromuscular blockers

Answer 34

- antinicotinic - used in surgical procedures to reduce skeletal muscle contraction -eg. D-tubocurarine

Question 35

Glaucoma treatment

Answer 35

Pilocarpine, physostigmine, echothiophate

Question 36

How does the mechanism of action differ between pilocarpine and physostigmine?

Answer 36

- Pilocarpine: direct agonist = binds and activates M3 - Physostigmine: inhibits AChE = increase ACh = increase M3

Question 37

What cholinergic drug(s) should be avoided in an individual with glaucoma?

Answer 37

Any muscarinic antagonist (atropine, D-tubocurarine, trimethaphan)

Question 38

Factors influencing heart rate

Answer 38

- cardiac output (CO) = heart rate x stroke volume - vascular tone = peripheral vascular resistance (PVR) BP= CO x PVR

Question 39

Cholinomimetics vs sympathomimetics

Answer 39

- Cholinomimetics = mimic action of ACh - Sympathomimetics = mimic action of NE/epinephrine

Question 40

Baroreceptors

Answer 40

- monitors blood pressure - BP changes = baroreceptors initiate reflex pathways = moment to moment regulation of BP

Question 41

How would baroreceptors respond to low blood pressure?

Answer 41

Signal to CNS to decrease PSNS and increase SNS (SNS innervates BV)

Question 42

How does clonidine prevent diarrhea?

Answer 42

activates alpha2 = ↓ACh release = ↓M3 receptor activation = ↓GI tract motility (more time to absorb fluid)

Question 43

Toxicities of indirect CNS agonists

Answer 43

Multiple transmitters increased and multiple receptors activated = hyperactivity, tremor, seizures, etc.

Question 44

Baroreceptor reflex response

Answer 44

- if beta1 is blocked, SNS increases by alpha1 (vasoconstriction) - if alpha1 is blocked, beta1 increases SNS (increased rate/force of contraction)