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49 Cards in this Set

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chollinergic transmission
Cholinergic transmission involves the release of the neurotransmitter, acetylcholine

Activation of the postsynaptic receptor
Atropine
Atropine
Hallucinatory effects of atropine and its relatives are often sought out by recreational drug users
Prototype blocker of muscarinic receptors
Muscarinic Receptors
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
Atropine Overdose
Atropine Overdose
Mad as a hatter
Blind as a bat
Dry as a bone
Red as a beet
Hot as a pistol
Mad as a Hatter
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.
Blind as a Bat
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
Dry as a Bone
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
Red as a Beet
Red as a Beet
Mechanism of this response is unknown
Flushing
Not attributed to blockade of muscarinic receptors
Hot as a Pistol
Hot as a Pistol
Elevated body temperature
May reach life-threatening levels
Alleviation of Symptoms of atropine OD
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
Acetylcholine
Acetylcholine
Synthesis of acetylcholine (ACh) :

acetyl-Coenzyme A + choline ==> acetylcholine
ACH : Receptor
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
Neuromuscular-Blocking Agent (NMB)
Cholinergic receptors are close to the enzyme acetylcholinesterase .
Acetylcholinesterase
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
Nicotinic Acetylcholine Receptor (nAChR)
Nicotinic Acetylcholine Receptor (nAChR)
Up-regulation
Spinal Cord Injury, CVA, Prolonged exposure to NMB drugs, Guillain-Barre syndrome
Down-regulation
Myasthenia Gravis, Organophosphate Poisonings
NMB – Succinylcholine (SCh)
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
Succinylcholine Anectine
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
Succinylcholine (SCh)
procedure dosing
1)  short procedures, 0.6 mg/kg IV (range 0.3-1.1 mg/kg) over 10-30 seconds 2)  long procedures, 2.5-4.3 mg/min continuous IV infusion 3)  long procedures, 0.3-1.1 mg/kg IV initially followed by 0.04-0.07 mg/kg at appropriate intervals 4)  3-4 mg/kg IM, if suitable vein is inaccessible; MAX 150 mg
Intubation (SCh) dosing
Intubation
1)  0.6 mg/kg IV (range 0.3-1.1 mg/kg) over 10-30 seconds Rapid sequence intubation
1)  1.5 mg/kg IV
Rapid sequence intubation(SCh) dosing
Rapid sequence intubation
Adverse 1)  1.5 mg/kg IV
Effects
Adverse effefts (SCh)
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
Mivacurium
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
Mivacurium dosing
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 dose 3)  maintenance, 9-10 mcg/kg/min continuous IV infusion after initial dose, upon early evidence of spontaneous recovery 4)  maintenance, 4 mcg/kg/min continuous IV infusion if initiated simultaneously with administration of initial dose
Mivacurium SE
Adverse Effects
Flushing, Bradyarrhythmia, Cardiac dysrhythmia, Hypotension, Tachyarrhythmia, Prolonged neuromuscular block
Rocuronium Intermediate-
Rocuronium Intermediate-Acting non-depolarizing


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

Induction of neuromuscular blockade ventilation
Rocuronium
Induction of neuromuscular blockade ventilation
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
Rocuronium Intubation
Intubation
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
Rocuronium Rapid sequence intubation
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
Rocuronium Adverse Effects
Adverse Effects
Injection site pain, Cardiac dysrhythmia (rare), Hypertension, Hypotension, Tachyarrhythmia (rare), Anaphylaxis (rare)
Atracurium Intermediate-
Atracurium Intermediate-Acting Non-depolarizing


ED 90-95 :
0.2 (mg/kg)
Atracurium
Induction of neuromuscular blockade
Induction of neuromuscular blockade
1)  initial, 0.4-0.5 mg/kg IV bolus 2)  maintenance, 0.08-0.1 mg/kg IV bolus 20-45 min after initial dose, then every 15-25 min as needed 3)  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
Atracurium
Adverse Effects
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
Cisatracurium
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
Cisatracurium dosing
1)  initial, 0.15-0.20 mg/kg IV bolus as component of a propofol/nitrous oxide/oxygen induction-intubation technique 2)  maintenance, 0.03 mg/kg IV 3)  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
Cisatracurium
Adverse Effects
Adverse Effects
Bradyarrhythmia (rare), Hypotension (rare), Bronchospasm (rare
Vecuronium
Vecuronium Intermediate-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
Vecuronium dosing
1)  initial, 0.08-0.1 mg/kg IV bolus 2)  maintenance, 0.01-0.015 mg/kg IV 25-40 min after initial dose, repeat every 12-15 min as needed 3)  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
Vecuronium
Adverse Effects
Adverse Effects
Hypotension (rare), Tachyarrhythmia (rare), Anaphylaxis (rare)
Prolonged Muscle weakness, Prolonged neuromuscular block Apnea
(rare), Bronchospasm (rare
Long-Acting Nondepolarizing NMB
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
Pancuronium ED
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
Pancuronium dosing
1)  endotracheal intubation, 0.06-0.1 mg/kg IV 2)  initial, 0.04-0.1 mg/kg IV; later incremental doses starting at 0.01 mg/kg may be used 3)  maintenance, 0.01-0.06 mg/kg IV 80-150 min after initial dose if needed; repeat doses every 30-45 min as needed
Pancuronium
Adverse Effects
Adverse Effects
Salivation finding, Tachyarrhythmia Prolonged neuromuscular block, Apnea, Bronchospasm
Doxacurium ED
Doxacurium (long-Acting)

ED 90-95 :
0.025 (mg/kg)

GeneralAnesthesia (Adjunct)
Doxacurium dosing
1)  initial, 0.05 mg/kg and 0.08 mg/kg IV to provide neuromuscular block for an average 100 min and 160 min, respectively 2)  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 IV 2)  (with succinylcholine) initial, 0.025 mg/kg IV
Doxacurium Adverse Effects
Adverse Effects
Flushing, Prolonged Paralysis
Increase neuromuscular blocking effect
Aminoglycosides, Clindamycin, Colistin, Desflurane, Isoflurane, Lincomycin, magnesium,Piperacillin, Sevoflurane Suxamethonium, Ketamine, Digoxin (arrhythmias)

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


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