test 4

Question 1

Sites of action for cholinergic agonists

Answer 1

• All of ganglia (adrenal medulla is one giant gangilia)
• muscurinic receptor of the parasympathetic NS
• neuromuscular junction

Question 2

Cholinergic Antagonists

Answer 2

-bind to receptor and prevent ACh or any other agonist that may be present from having an effect

Question 3

Categories of Cholinergic Antagonists

Answer 3

 Selective muscarinic blockers
 Ganglionic blockers
 Neuromuscular blockers

Question 4

Selective muscarinic blockers

Answer 4

 Most clinically useful b/c they can be selective for muscurinic receptors
 Anticholinergic agents
 Antimuscarinic agents
 Parasympatholytics
 Actions of sympathetic stimulation not interrupted
-don’t block nicotinic receptors and only block muscurinic receptors

Question 5

what do Selective Muscarinic Blockers do

Answer 5

 Block muscarinic receptors
 Most can selectively block different subgroups
 Atropine cannot distinguish between subgroups
 Block sympathetic cholinergic neurons (salivary and sweat glands)
-sweat glands the one exception: activated by symp NS but they release ACh and have muscurinic receptors
 No action at neuromuscular junction (NMJ)
 No action at autonomic ganglia

Question 6

Atropine comes from

Answer 6

 Belladonna alkaloid with high affinity for muscarinic receptors

Question 7

Therapeutic uses of Atropine

Answer 7

 Relax GI tract
 Treat bradycardia
 Block respiratory secretions prior to surgery
 Antidote for organophosphate poisoning or cholinergic agonist overdose
 Enters the CNS!

Question 8

How do we use atropine clinically?

Answer 8

 Symptomatic bradycardia
 Pulseless electrical activity/electromechanical dissociation
 AV block
-typical dose = 1 mg

Question 9

what causes Chronic Obstructive Pulmonary Disease- COPD

Answer 9

• Emphysema with chronic bronchitis
• Emphysema: air spaces are destroyed and enlarged
• Bronchitis: inflammation of the airways

Question 10

what happens with Chronic Obstructive Pulmonary Disease- COPD

Answer 10

• Irreversible obstruction of airflow that is usually progressive
  * Cough
  * Excess mucus production
  * Chest tightness
  * Breathlessness
  * Difficulty sleeping
  * Fatigue
• Smoking is greatest risk factor
• Drug therapy aimed at relief of symptoms and prevention of progression

Question 11

Common Antimuscarinic Adverse Effects

Answer 11

• block parasympathetic outflow
• tachycardia
• blurred vision
• dilation of pupils
• constipation
• urinary retention

Question 12

If patient has glaucoma, don’t want to give them Antimuscarinic Adverse Effects

Answer 12

• because they don’t have adequate drainage of the aqueous humor
• muscurinic receptors in the eye help open up drainage for glaucoma

Question 13

Atropine Poisoning

Answer 13

-dry mouth
-tachycardia
-hot and flushed skin
-delirium
 Hot as a hare (high temp)
 Dry as a bone (decreased secretions, thirsty)
 Blind as a bat
 Red as a beet (flushed face)
 Mad as a hatter (confusion)
-goes straight into the CNS so that is where side effects

Question 14

Ganglionic blockers act where

Answer 14

• adrenal medulla

- pre and post synaptic neurons of symp and parasymp NS

Question 15

What do Ganglionic Blockers do?

Answer 15

 Block the entire output of the autonomic nervous system at the nicotinic receptor
 Sympathetic and parasympathetic ganglia
 Rarely used therapeutically
-only used for hypertensive emergencies
-ANS shutdown
-BP falls

Question 16

Neuromuscular Blocker Sites of Action

Answer 16

• site of neuromuscular junction of the somatic neuron (skeletal muscle)
• Different than other nicotinic receptors and that is how there can be selectivity that only blocks the NMJ

Question 17

Neuromuscular Blockers

Answer 17

 Block cholinergic transmission at neuromuscular junction
 Chemical similarities to acetylcholine and act as either:
 Antagonists: nondepolarizing, competitive
 Agonists: depolarizing
 Clinically useful for surgery
 Tracheal intubation
 Complete muscle relaxation so lower doses general anesthetic needed
 Rapid recovery from anesthesia
 Reduced postoperative respiratory depression

Question 18

Curare

Answer 18

 Nondepolarizing Neuromuscular Blockers

 first used by native South American hunters in the Amazon to paralyze prey

Question 19

Nondepolarizing Neuromuscular Blockers mechanism of action

Answer 19

 Significantly increased the safety of anesthesia
 Should not be used as an anesthesia substitute!!
 Mechanism of action:
 Low doses: competitively block ACh at nicotinic receptors
 Prevents depolarization of muscle cell membrane and inhibits contraction
 Action overcome by adding AChE inhibitors (Neostigmine, Edrophonium)
 High doses: can block the ion channels of the motor endplate
 Further weakening of neuromuscular transmission
 Action cannot be overcome by adding AChE inhibitors

Question 20

Nondepolarizing Neuromuscular Blockers process

Answer 20

 Muscles vary in susceptibility
        1. Face and eye muscles
        2. Fingers, limbs, neck and trunk muscles
        3. Intercostal muscles
        4. Diaphragm
 Muscles recover in reverse manner
 Pharmacokinetics:
         Not effective orally
         IV or IM
         Do not enter cells or cross BBB (just work at NMJ)

Question 21

Nondepolarizing Neuromuscular Blockers Major Drug Interactions

Answer 21

1. Cholinesterase inhibitors
    increase amount of ACh in the cleft so they will Antagonize effect as long as NM blocker has not entered ion channel
2. Halogenated hydrocarbon anesthetics
    Enhance effect (stabalize NMJ)
3. Aminoglycoside antibiotics
    Enhance effect (interupt Ca++ influx)
4. Calcium channel blockers
    Enhance effect (interupt Ca++ influx)

Question 22

Nondepolarizing Neuromuscular Blocking drugs vary in

Answer 22

Vary in their onset and duration of action

Question 23

Depolarizing Neuromuscular Blockers

Answer 23

 Depolarize the muscle fiber membrane similar to Ach
 Resistant to AChE and remains attached to the receptor
 Provides constant stimulation and persistent depolarization
 Hydrolyzed by psuedocholinesterase in the plasma (not at NMJ)
-rather than block the receptor, they activate the receptor
-bind to the ACh binding site and activate it and allow for the ion channels to open and Na to rush in but the cell not allowed to repolarize

Question 24

Succinylcholine Adverse Effects

Answer 24

Hyperthermia
 May induce malignant hyperthermia
Apnea
 Prolonged apnea with pseudocholinesterase deficiency
 Persian Jewish communities
 Indian Hindu communities
Hyperkalemia
 Increases potassium release from intracellular stores

Question 25

Malignant Hyperthermia (MH)

Answer 25

 Life threatening hyper-metabolism involving the skeletal muscle
 Inherited disorder triggered in susceptible individuals by succinylcholine and volatile anesthetics
 Abnormal receptor interferes with calcium regulation
 Increased CO2 production
 Heat production
 Activation of SNS
 Hyperkalemia
 DIC
 Multiple organ dysfunction
 Death