5. Autonomic Nervous System 2

Question 1

What are the 2 things that mimic parasympathetic effects?

Answer 1

1. Muscarinic receptor agonists (direct acting; carbachol, pilocarpine)
2. Acetylcholinesterase inhibitors (indirect acting; these drugs delay the breakdown of ACh and prolong its action) neostigmine

Question 2

What are the 2 things that block parasympathetic effects?

Answer 2

1. Muscarinic receptor antagonists (atropine)

2 skeletal neuromuscular junction blockers (D-tubocurarine)

Question 3

Why are the 4 uses of cholinergic agonists?

Answer 3

1. Reduce intraocular pressure in wide angle glaucoma- also uses in narrow angle glaucoma (miosis)
2. Increase the motility (peristalsis) of the gastrointestinal (GI) tract
3. Increase motility of the urinary tract (bladder contractions)
4. To increase salivary secretions-

Question 4

What are cholinesterases?

Two types?

Answer 4

Acetylcholinesterase (AChE) present in synaptic cleft on the outer membrane of postjunctional cell
Hydrolyzes ACh and the enzyme becomes acetylated

Butyrylcholinesterase (BuChE)- located at non-neuronal sites, mainly in plasma and liver
Metabolizes certain drugs (some anaesthetics and succinylcholine muscle relaxant)

Question 5

What are cholinesterase inhibitors?

Answer 5

Increase the duration of action of the released ACh and potentiate responses at muscarinic and skeletal neuromuscular nicotinic receptors

Question 6

What are the 3 chemical reactions of cholinesterase inhibition and their clinical significance?

Answer 6

Compounds that bind to cholinesterase can produce one of 3 chemical reactions;
Acetylation- caused by ACh: acetylated enzyme-recovers rapidly
Carbamylation (reversible therapeutically used drugs)- carbamylated enzyme- recovers slowly
Phosphorylation (irreversible-poisons the enzyme ex: nerve gases)

Slide 46-48 autonomic nervous

Question 7

What are the therapeutic uses of reversible ChE inhibitors?

Answer 7

Glaucoma- ups aqueous humor outflow down intraocular pressure (can cause cataracts with long term use)
CNS- treat memory loss of Alzheimer’s disease
Intestine- to stimulate peristalsis in post operative ileus, congenital megacolon
Urinary bladder- to treat urinary retention due to atony og smooth muscle

Question 8

What is botulinum toxin?

Answer 8

Toxin released by the bacteria clostridium botulinum
Botulinum toxin blocks ACh release

It is used to paralyze skeletal muscle in cases of excessive involuntary skeletal muscle tone

Clinical uses: BOTOX to remove facial wrinkles

Question 9

What are the uses of Muscarinic receptor antagonists for the;
Heart
Eyes
GI tract
Urinary bladder

Answer 9

Heart- to treat severe bradycardia
Eyes- cause pupil dilation (mydriasis) (for examination of retina)
GI tract- to treat excessive peristalsis (motility) of irritable bowel syndrome, cramping
Urinary bladder- treat 4 major symptoms of urinary incontinence: daytime urinary frequency, nocturia, urgency, and incontinence

Question 10

What is the difference between scopolamine and atropine?

Answer 10

Scopolamine is well absorbed orally, and also reaches the brain more readily than atropine
Scopolamine is approx 10 times more potent at producing CND effects

Greater fraction of scopolamine is present in a unionized form at physiological pH than atropine - facilitates it’s absorption through skin

Scopolamine is used for motion sickness as transdermal patch

Question 11

What are the 2 types of neuromuscular junction blockers?

Structure?

Answer 11

Competitive- competitively antagonize the actions of ACh at nicotinic acetylcholine receptors
Chemical structure different than that of ACh

Depolarizing agents- drug occupies and activates the nicotinic receptor (agonists) for a prolonged period of time, prevents repolarization and makes the muscle fibre refractory to further nerve impulses
Chemical structure resembles that of ACh

Question 12

What is the competitive neuromuscular junction blockers sequence of muscle paralysis?

Answer 12

Produce motor weakness leads to flaccid paralysis when 90-95% receptors occupied
Small rapidly moving muscle paralyzed first- eyes, jaw, larynx
Muscles of the limbs, trunk
Intercostal muscles
Diaphragm- respiration stops

Recovery occurs in reverse

Question 13

What do ChE inhibitors do?

Answer 13

Up in ACh

Used clinically to reverse neuromuscular block caused by competitive inhibitors

Question 14

What are the 3 main side effects of competitive neuromuscular blockers?

Answer 14

Ganglionic blockade- fall in blood pressure, tachycardia

Block of vagal responses

Histamine release- bronchospasm, hypotension, up in bronchial and salivary secretions

Question 15

What do depolarizing neuromuscular junction blockers do?

Answer 15

Bind to and activate muscle nicotinic receptors
Not metabolized by AChE
Causes persistent receptor stimulation

Succinylcholine- short duration of action
Rapid hydrolysis by plasma butyrylcholinesterase

Used in surgical anaesthetics to obtain relaxation of skeletal muscle, particularly in abdominal wall!!

Question 16

What are the side effects of depolarizing neuromuscular junction blockers?

Answer 16

Depolarizing agents can release K+ rapidly from intracellular sites 
Cause hyperkalemia (dangerous in heart failure patients in diuretics) rhabdomyolysis and cardiac arrest

Malignant hyperthermia

Depolarization blockers should be avoided in patients with soft tissue trauma or burns

Not given to children under 8

Question 17

What is malignant hyperthermia?

Answer 17

Seen after certain anaesthetics and neuromuscular blockers (succinylcholine)
Can be life threatening
Ups Ca2+ release from the sarcoplamsic reticulum of skeletal muscle

Contracture, rigidity, heat production from skeletal muscle, hyperthermia, accelerated muscle metabolism, metabolic acidosis, and tachycardia

Question 18

What are the 4 things that mimic sympathetic effects?

Answer 18

1. Adrenergic receptor agonists (direct acting)
2. Norepinephrine uptake blockers (indirect acting)
3. Monoamine oxidase and COMT inhibitors (these drugs delay the breakdown of NE and prolong its action)
4. NE releasing agents (from nerve terminal, indirect acting) mean

Question 19

What is the one thing that can block sympathetic effects?

Answer 19

Adrenergic receptor antagonists

Question 20

How do you terminate norepinephrine action at the synapse?

Answer 20

Reuptake into nerve terminal

Released transmitter is taken up back into presynaptic nerve terminal

Uptake 1 can be blocked by several drugs including cocaine
Uptake 1 blockers will increase sympathetic activity

Slide 72 oct 3

Question 21

What is the heart response in change of blood pressure?

Answer 21

Baroreceptor control of blood pressure and heart rate. SNS, sympathetic nervous system, PNS, parasympathetic decoys system

SLIDE 73 oct 3

Question 22

What are adrenergic receptor agonists?

3 Types, what each type activates

Answer 22

Epinephrine- equipotent at α and β receptors
NE- can activate α and β1 receptors, has little activity at β2 receptors
(Is a little less potent than epinephrine at α receptors)
Dopamine too

Question 23

What is epinephrine and norepinephrines effect on;
Heart rate?
Blood pressure?
Peripheral resistance?

Answer 23

Epinephrine:
Heart rate- raises it
Blood pressure- if high already it will raise it, if low already it will lower it
Peripheral resistance- drops it

Norepinephrine:
Heart rate- lowers it (reflex bradycardia)
Blood pressure- raises it
Peripheral resistance- raises it

Slide 75 oct 3

Question 24

What are the 3 therapeutic uses of adrenergic drugs (agonists)?

Answer 24

Allergic reactions- anaphylactic shock (epinephrine EPIPEN) increases heart rate and contractility, constricts some and dilates some vessels to maintain BP

Bronchodilators (asthma)- albuterol, a β2 agonist

As pressor agents (hypotension)- Epi or NE (hypovolemic shock)

Question 25

What are the 4 therapeutic uses of adrenergic receptor blockers?

Answer 25

Hypertension- α2 such as clonidine decreases sympathetic outflow from CNS in treatment of hypertension

Myocardial infarction, angina pectoris- propranolol

Cardiac arrythmia- propranolol

Migraine headache- propranolol

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Question 26

What are the therapeutic effects in one organ limited by?

Answer 26

Therapeutic effects in one organ are limited by side effects in other organs