Lecture 36/37 Flashcards
Nicotinic, Ganglionic, Neuromuscular Blockers
Nicotine as an Agonist
- Stimulates parasympathetic and sympathetic ganglia resulting in:
1. Increased BP due to symp. NS - epi. release from adrenal and NE from nerve terminals on blood vessels not innervated parasympathetically
2. GI and Urinary Tract - increases peristalsis and secretions due to parasympathetic activation over sympathetic - *Rapidly enters CNS - addictive**
Ganglionic Blockers
- Specifically block parasymp. and symp. ganglia’s nicotinic receptors
- No selectivity over one over the other, makes responses complex and unpredictables
- No effect on NMJ
- Drug class = non-depolarizing, noncompetitive ganglia antagonist (Mecamylamine)
- RARELY used therapeutically
Predominating System
-Ganglionic blockers uncover the dominant system since it blocks ALL autonomic ganglia
Tissue + Dominant System/Effect
- Arterioles/Veins ==> Symp./Vasodilation (Thera. use)
- Sweat glands ==> Symp./Anhidrosis (can’t sweat)
- Heart ==> Parasymp/Tachycardia
- Iris/Ciliary Muscle ==> Parasymp./Mydriasis/Cycloplegia
- GI Tract ==> Parasymp./Hypomotility
- Urinary Bladder ==> Parasymp./Urinary Retention
- Salivary Glands ==> Parasymp./Xerostomia (dry mouth)
Mecamylamine
- Inversine
- Oral ganglion blocker that decreases BP in normal and hypertensive patients
- Noncompetitive antagonists of nic. ACh receptors in ganglia
Mecamylamine Therapeutic Uses
- Moderately severe to severe essential hypertension
- Malignant hypertension (sudden and rapid development of extremely high BP) - diastolic raises up to >130 mmHg, 1% of hypertensive patients have this and can be related to women with toxemia of pregnancy and those with kidney/collagen vascular disorders
Mecamylamine SE/Information
- Start at low dose and adjust up to dose that is just below causing mild, postural hypotension
- D/C slowly since it may cause fatal cerebral vascular accidents or acute CHF; sub. with other hypertensives
Side Effects
- GI: Ileus, constipation, dry mouth, N/V
- CV - orthostatic hypotension, dizziness
- NS/Psychiatric - Convulsions, tremor, sedation
- Urogenital - Urinary retention
Drug Classes + Muscle Function
- NM Blocking Drugs - competitive (non-depolarizing) or non-competitive (depolarizing)
- Centrally acting muscle relaxants (antispasmodics)
- Peripherally acting skeletal muscle relaxants (dantrolene)
Skeletal Muscle Relaxants - Nic. Antagonists
-Block neurotransi=mission of nic. chol. receptor
Two Types:
1. Nondepolarizing blocking agents - competitive antagonists for ACh at nicotinic receptor in skeletal muscle
2. Depolarizing blocking agents - Initially stimulate at junction to get contraction and then create NM blockade
ACh Receptor in NMJ
- (Alpha1)2/(Beta1)yo
- Abundance of these receptors and AChE in NMJ
Curare
- Used in poison dart by South American indians in early 1800s, causes respiration to shut down
- Developed to be used in tetanus/spastic disorders and muscle relaxation during anesthesia in 1932 and 1942 respectively
- Substitutes and more potent version of the drug discovered in the late 40s into the 60s
Non-Depolarizing Blockers
- Competitive
1. Pancuronium (Pavulon) - increases HR
2. Tubocurarine - prototype replaced by other drugs due to side effects
3. Cisatracurium (Nimbex) - spontaneously degrades in plasma, no dose adjustment needed in renal failure
4. Atracurium (Tracrium)
5. Rocuronium (Zemuron) - rapid onset (1 minute), used for tracheal intubation
6. Vecuronium (Norcuron) - commonly used for mechanical ventilation in the ICU
Non-Depolarizing Blocker Uses
- Used in anesthesia during surgery to relax skeletal muscle
- “Balanced” anesthesia so that a lower dose is needed
- Shorter acting drugs used to facilitate tracheal intubation
- Provide skeletal muscle relaxant in ICU
Plane 2
Initial signs of paralysis of intercostals
Plane 3
Full paralysis of intercostals
Plane 4
Paralysis of diaphragm
Sequence of Paralysis
Fingers, Orbit (Small muscles) ==> Limbs ==> Trunk ==> Neck ==> Intercostals ==> Diaphragm
Recovery goes in reverse
Breathing Muscles
- Intercostal muscles - contract and pull rib cage out to draw air in and relax to push air out
- Diaphragm - contracts to bring air in and relaxes to push air out
NM Blockade in ICU
- Limited use due to prolonged weakness and complications
- Want to maximize use of sedative and analgesic infusions first
- Vecuronium - commonly used
Vecuronium
- Norcuron
- Facilitates in mechanical ventilation
- Assist in control of elevated intracranial pressures
- Decreases oxygen comsumption
- Prevents muscle spasms in neuroleptic malignant syndrome, tetanus, etc.
- Protects surgical wounds or medical device placement
Long-Term Complications with NM Blockers
- Associated with inactivity - muscle wasting, edema, corneal drying
- Associated with inability to assess patient - recall, anxiety, unrelieved pain
- Associated with loss of respiratory function - asphyxiation from ventilation malfunction or atelectasis, pneumonia, etc.
- Prolonged paralysis or acute NM blockade myopathy - decreases membrane excitability or muscle necrosis, increased risk if used with steroids
Non-Depolarizing Blockers + Doses
- Prevents ACh binding at low doses and inhibits skeletal muscle contraction - can be overcome by high concentrations of ACh, ChE inhibitors can also decreases its duration (Neostigmine, Pyridostigmine, or Edrophonium)
- High doses - may block ion channel and weaken NM transmission - decreases the ability of ChE inhibitors to reverse the drug action
Comp. NM Blocker Drug Choice
-Depends on how quickly you need the muscle relaxation
Factors to Consider
- Liver: Vercuronium and Rocuronium are deacetylated in liver, CL prolonged with liver disease
- Renal - Pancuronium is excreted unchanged in urine, CL prolonged with kidney disease
- Cisatracurium - spontaneously degrades in plasma, is safe to use in liver and renal diseased patients
All drugs possess 2+ Quat. amines, must be given IV, no oral effectiveness or CNS effects
Adverse Effects - minimal, Pancuronium increases HR