Pharmacology Cholinergic Transmission - Test 2

Front 1

chollinergic transmission

Back 1

Cholinergic transmission involves the release of the neurotransmitter, acetylcholine

Activation of the postsynaptic receptor

Front 2

Atropine

Back 2

Atropine
Hallucinatory effects of atropine and its relatives are often sought out by recreational drug users
Prototype blocker of muscarinic receptors

Front 3

Muscarinic Receptors

Back 3

Muscarinic Receptors
Atropine is not producing any unique biological effects
Signs and symptoms are due solely to an interruption of normal cholinergic, muscarinic transmission at the various end organs
Blockade is competitive and reversible
If the concentration of acetylcholine in the vicinity of the blocked receptor can be increased, acetylcholine will displace atropine and transmission will be restored

Front 4

Atropine Overdose

Back 4

Atropine Overdose
Mad as a hatter
Blind as a bat
Dry as a bone
Red as a beet
Hot as a pistol

Front 5

Mad as a Hatter

Back 5

Mad as a Hatter
Drug-induced delirium is one of the most dangerous aspects of atropine poisoning in adults
Result in self-destructive acts, such as leaping out of windows or pulling out intravenous tubing.

Front 6

Blind as a Bat

Back 6

Blind as a Bat
Three effects on vision
Cholinergic tone to the sphincter iridis muscle of the iris tends to contract the pupil
Interruption of that tone leads to pupillary dilation (mydriasis)
Unrelenting mydriasis results in photophobia

Front 7

Dry as a Bone

Back 7

Dry as a Bone
Manifested by a blockade of cholinergic tone to the salivary glands
Decreased salivation, dry mouth, intense thirst and difficulty in swallowing

Skin is also dry because of a blockade of sweating

Front 8

Red as a Beet

Back 8

Red as a Beet
Mechanism of this response is unknown
Flushing
Not attributed to blockade of muscarinic receptors

Front 9

Hot as a Pistol

Back 9

Hot as a Pistol
Elevated body temperature
May reach life-threatening levels

Front 10

Alleviation of Symptoms of atropine OD

Back 10

Alleviation of Symptoms
Pilocarpine is in the same class of drugs as muscarine
Muscarinic agonist
Binding of atropine by muscarinic receptors is competitive and reversible, it can be antagonized by muscarinic agonists
Ophthalmic drops
Oral pilocarpine has been used to relieve the dry mouth that sometimes follows head/neck radiation treatments

Front 11

Acetylcholine

Back 11

Acetylcholine
Synthesis of acetylcholine (ACh) :

acetyl-Coenzyme A + choline ==> acetylcholine

Front 12

ACH : Receptor

Back 12

ACH : Receptor
Nicotinic receptors
Two subtypes-one at the neuromuscular junction of skeletal muscle, the other within ganglia and the CNS
Muscarinic receptors
Distributed within both peripheral and central nervous systems

Front 13

Neuromuscular-Blocking Agent (NMB)

Back 13

Cholinergic receptors are close to the enzyme acetylcholinesterase .

Front 14

Acetylcholinesterase

Back 14

Acetylcholinesterase is an enzyme that is responsible for rapid hydrolysis of ACH to acetic acid and choiline
Choline re-enters motor nerve endings to again participate in the synthesis of new acetylcholine.
Rapid hydrolysis of ACH prevents sustained depolarization

Front 15

Nicotinic Acetylcholine Receptor (nAChR)

Back 15

Nicotinic Acetylcholine Receptor (nAChR)
Up-regulation
Spinal Cord Injury, CVA, Prolonged exposure to NMB drugs, Guillain-Barre syndrome
Down-regulation
Myasthenia Gravis, Organophosphate Poisonings

Front 16

NMB – Succinylcholine (SCh)

Back 16

NMB – Succinylcholine (SCh)
Paralysis Rapidly (less than 1 minute)
Duration of Action Short


NMB – Succinylcholine (SCh)
Paralysis Rapidly (less than 1 minute)
Duration of Action Short
Phase I- Depolarizing

Front 17

Succinylcholine Anectine

Back 17

ED 90-95 :
0.3 (mg/kg)

Induction of neuromuscular blockade, During surgery as an adjunct to general anesthesia and to facilitate tracheal intubation or mechanical ventilation

Front 18

Succinylcholine (SCh)
procedure dosing

Back 18

1)  short procedures, 0.6 mg/kg IV (range 0.3-1.1 mg/kg) over 10-30 seconds2)  long procedures, 2.5-4.3 mg/min continuous IV infusion3)  long procedures, 0.3-1.1 mg/kg IV initially followed by 0.04-0.07 mg/kg at appropriate intervals4)  3-4 mg/kg IM, if suitable vein is inaccessible; MAX 150 mg

Front 19

Intubation (SCh) dosing

Back 19

Intubation
1)  0.6 mg/kg IV (range 0.3-1.1 mg/kg) over 10-30 secondsRapid sequence intubation
1)  1.5 mg/kg IV

Front 20

Rapid sequence intubation(SCh) dosing

Back 20

Rapid sequence intubation
Adverse 1)  1.5 mg/kg IV
Effects

Front 21

Adverse effefts (SCh)

Back 21

Muscle rigidity, Prolonged Myalgia, Raised intraocular pressure,
Bradyarrhythmia, Tachyarrhythmia (especially in children),
Hyperkalemia, Malignant hyperthermia, Hypersensitivity reaction
Rhabdomyolysis with myoglobinemia in children, Prolonged
neuromuscular block, Respiratory depression, Apnea

Front 22

Mivacurium

Back 22

Mivacurium Short-acting non-depolarizing 

ED 90-95 :
0.07 (mg/kg)

Induction of neuromuscular blockade, During surgery as an adjunct to general anesthesia and to facilitate tracheal intubation or mechanical ventilation

Front 23

Mivacurium dosing

Back 23

1)  initial, for intubation, 0.15 mg/kg IV bolus over 5-15 sec OR 0.2 mg/kg IV bolus over 30 sec OR 0.25 mg/kg IV bolus in divided doses (0.15 mg/kg followed in 30 sec by 0.1 mg/kg)2)  maintenance, 0.1 mg/kg IV bolus 15-25 min after initial dose3)  maintenance, 9-10 mcg/kg/min continuous IV infusion after initial dose, upon early evidence of spontaneous recovery4)  maintenance, 4 mcg/kg/min continuous IV infusion if initiated simultaneously with administration of initial dose

Front 24

Mivacurium SE

Back 24

Adverse Effects
Flushing, Bradyarrhythmia, Cardiac dysrhythmia, Hypotension, Tachyarrhythmia, Prolonged neuromuscular block

Front 25

RocuroniumIntermediate-

Back 25

RocuroniumIntermediate-Acting non-depolarizing


ED 90-95 : Onset 1 -2 minutes, last 25-30 minutes
0.3 (mg/kg)

Induction of neuromuscular blockade ventilation

Front 26

Rocuronium
Induction of neuromuscular blockade ventilation

Back 26

Induction of neuromuscular blockade ventilation
1)  initial, 0.6 mg/kg IV 2)  maintenance, 0.1-0.2 mg/kg IV repeated as needed
3)  maintenance, 0.01-0.012 mg/kg/minute continuous IV infusion

Front 27

Rocuronium Intubation

Back 27

Intubation
1)  initial, 0.6 mg/kg IV2)  maintenance, 0.1-0.2 mg/kg IV repeated as needed3)  maintenance, 0.01-0.012 mg/kg/minute continuous IV infusion

Front 28

Rocuronium Rapid sequence intubation

Back 28

Rapid sequence intubation
1)  0.6 to 1.2 mg/kg IV
Premedication for anesthetic procedure, Preinduction defasciculating dose (Non-FDA labeled indications )
1)  0.05 to 0.06 mg/kg IV 1.5-3 min prior to succinylcholine administration

Front 29

Rocuronium Adverse Effects

Back 29

Adverse Effects
Injection site pain, Cardiac dysrhythmia (rare), Hypertension, Hypotension, Tachyarrhythmia (rare), Anaphylaxis (rare)

Front 30

AtracuriumIntermediate-

Back 30

AtracuriumIntermediate-Acting Non-depolarizing


ED 90-95 :
0.2 (mg/kg)

Front 31

Atracurium
Induction of neuromuscular blockade

Back 31

Induction of neuromuscular blockade
1)  initial, 0.4-0.5 mg/kg IV bolus2)  maintenance, 0.08-0.1 mg/kg IV bolus 20-45 min after initial dose, then every 15-25 min as needed3)  maintenance, 5-9 mcg/kg/min (range 2-15 mcg/kg/min) continuous IV infusion after initial dose, upon early evidence of spontaneous recovery; in ICU, 11-13 mcg/kg/min (range 4.5-29.5 mcg/kg/min) continuous IV infusion

Front 32

Atracurium
Adverse Effects

Back 32

Adverse Effects
Flushing, Bradyarrhythmia, Edema, Hypotension (At larger than
recommended doses), Tachyarrhythmia ( At higher doses), Erythema, Hives, Anaphylaxis (rare), Hypersensitivity reaction (rare), Muscle Weakness, Paralysis Bronchospasm (rare), Laryngeal spasm

Front 33

Cisatracurium

Back 33

Cisatracurium


ED 90-95 :
0.05 (mg/kg)


Induction of neuromuscular blockade, During surgery as adjunct to general anesthesia and to facilitate endotracheal intubation or mechanical ventilation in the ICU

Front 34

Cisatracurium dosing

Back 34

1)  initial, 0.15-0.20 mg/kg IV bolus as component of a propofol/nitrous oxide/oxygen induction-intubation technique2)  maintenance, 0.03 mg/kg IV3)  maintenance, initial continuous IV infusion rate of 3 mcg/kg/min may be required to rapidly counteract spontaneous recovery from initial bolus dose; thereafter, 1-2 mcg/kg/min continuous IV infusion; in ICU, infusion range of 0.5-10.2 mcg/kg/min

Front 35

Cisatracurium
Adverse Effects

Back 35

Adverse Effects
Bradyarrhythmia (rare), Hypotension (rare), Bronchospasm (rare

Front 36

Vecuronium

Back 36

VecuroniumIntermediate-acting

ED 90-95 :
0.05 (mg/kg)
Induction of neuromuscular blockade, During surgery as adjunct to general anesthesia and to facilitate endotracheal intubation or mechanical ventilation in the ICU

Front 37

Vecuronium dosing

Back 37

1)  initial, 0.08-0.1 mg/kg IV bolus2)  maintenance, 0.01-0.015 mg/kg IV 25-40 min after initial dose, repeat every 12-15 min as needed3)  1 mcg/kg/min continuous IV infusion 20-40 min after initial intubation dose, after early evidence of spontaneous recovery; then adjust to maintain 90% suppression of twitch response; range 0.8-1.2 mcg/kg/min

Front 38

Vecuronium
Adverse Effects

Back 38

Adverse Effects
Hypotension (rare), Tachyarrhythmia (rare), Anaphylaxis (rare)
Prolonged Muscle weakness, Prolonged neuromuscular block Apnea
(rare), Bronchospasm (rare

Front 39

Long-Acting Nondepolarizing NMB

Back 39

Long-Acting Nondepolarizing NMB
Pancuronium
Onset of action 3-5 minutes
DOA= 60-90 minutes
Do not use in hepatic failure or renal failure
Increased risk of cardiac dysrhythmias

Front 40

Pancuronium ED

Back 40

ED 90-95 :
0.06 (mg/kg)

Induction of neuromuscular blockade, During surgery as adjunct to general anesthesia and to facilitate endotracheal intubation or mechanical ventilation in the ICU

Front 41

Pancuronium dosing

Back 41

1)  endotracheal intubation, 0.06-0.1 mg/kg IV2)  initial, 0.04-0.1 mg/kg IV; later incremental doses starting at 0.01 mg/kg may be used3)  maintenance, 0.01-0.06 mg/kg IV 80-150 min after initial dose if needed; repeat doses every 30-45 min as needed

Front 42

Pancuronium
Adverse Effects

Back 42

Adverse Effects
Salivation finding, Tachyarrhythmia Prolonged neuromuscular block, Apnea, Bronchospasm

Front 43

Doxacurium ED

Back 43

Doxacurium(long-Acting)

ED 90-95 :
0.025 (mg/kg)

GeneralAnesthesia (Adjunct)

Front 44

Doxacurium dosing

Back 44

1)  initial, 0.05 mg/kg and 0.08 mg/kg IV to provide neuromuscular block for an average 100 min and 160 min, respectively2)  maintenance, 0.005 mg/kg and 0.01 mg/kg IV to provide neuromuscular blockage for an average of 30 min and 45 min, respectively
Intubation
1)  0.05 mg/kg IV2)  (with succinylcholine) initial, 0.025 mg/kg IV

Front 45

Doxacurium Adverse Effects

Back 45

Adverse Effects
Flushing, Prolonged Paralysis

Front 46

Increase neuromuscular blocking effect

Back 46

Aminoglycosides, Clindamycin, Colistin, Desflurane, Isoflurane, Lincomycin, magnesium,Piperacillin, Sevoflurane Suxamethonium, Ketamine, Digoxin (arrhythmias)

Hypermagnesemia
Hypocalcemia
Hypokalemia

Front 47

Decrease neuromuscular blocking effect

Back 47

Decrease neuromuscular blocking effect
Anticholinesterases, carbamazepine(Except Mivacurium), phenytoin, Theophylline


Hypercalcemia
Hyperkalemia

Front 48

Why Use NMB?

Back 48

Why Use NMB?
Poor Oxygenation or patient-ventilator interaction despite adequate sedation
Dangerous movements in patient that persists regardless of sedation
To allow intubation

Front 49

Things to Know

Back 49

Things to Know
Adequate sedation and analgesia must be achieved before starting a paralytic, sedation around the clock
Train-of-Four (baseline first, 1-2 twitches)
Concurrent medications and disease states