Nicotinic Antagonists Flashcards
Nicotine structure and how it works
Plant alkaloid that depolarizes ganglia and blocks them (persitent depolarization)
In high doses, essentially a blocker
At low doses, “positive” CNS effects
Positive CNS effects of nicotine
Increase arousal, attnetion, and learning
Dependence producting
Most prevalent is on presyhnaptic receptor*****
Permissive action on NT in the nucleus accumbens (dopamine, glutamate)
Make presynaptic CNS notinic recpeotrs targets for smoking cessation (alpha 7s)
How is nicotine ingested?
Accidental cigarrette ingetions in kids
Spill as insecticide
Smoker
Ganglionic blockers effects on veins, arteries heart
Arteries - vasodilation and hypotension (normally under SNS)
Veins - dilation, decreases blood returning (SNS)
Heart - tachycardia (PNS)
Iris/eye GI Bladder Salivary glands Sweat glands
Affects of ganglionic blockers
Mydriasis (PNS) Constipation (PNS) Prevent filling (SNS) Xerostomia (PNS) Anyhydrosis (SNS)
General affects of ganglionic blockers
Affect symp and para
Depress ALL autonomic functions
Inhibitors of nicotinic recpeotrs
Nonspecific
NMJ blocker general effects
Devoid of central effects so still need anesthesia and analgesia
Used during surgicla and critical care to maintain paralysis
NMJ blocker interactions
Aminoglycoside ABs - decrease Ach so additive effect
Volatile anesthetics - stabiliz NMJ which decreases signlaing - additive effect
Classifications of NMJ blocks
Succinylcholine - depolarizing
Pancuronium - non-depolarizing
NMJ blockers effects on muscles
Block nicotinic recpetors on striated muscles
Decrease O2 use and shivering
Facilitate mech ventilaiton
Need to use less anesthesia because the muscles are paralized
improves recovery time
Atnagonists vs. agonists
Antagoists do not depolarize
Agonists depolarize so first fasciulations, then flaccid paralysis
Curare
Non-depolarizing that blocks Ach receptors
Pancuronium is an example
Some release histamines
Can have ganglionic blocking effect
Order of organ sensitivity for curare like and hwo t oovercome
Small muscles around eye and face
Neck and limbs
Intercostals
Diaphragm
Ovecome with AchE inhibitors
Types of nondepolarizing blockrs
Isoquinolines - most release histamines (renal)
Steroids - do not release histamines but can be vagolytic (pancuronium - kidney and slower elimination)
Succinylcholine
Depolarizing agent that blocks NMJ
First get opening, then desensitized and muscle repolarizes but unresponsive
Used for rapid intubation
Hydrolized by butyrylcholinesterases
Succinylcholine other
Not reversible by AChE inhibitors
Can stimulate ganglion NT and muscarinic receptor in heart so arrythmias
Can get hyperkalemia
Depolarizing NMJ blockers in general
Very rapid onset
SHort duration of acion
Some release histamine
Metabolized by butyrylcholinesterase (circulating levels determine duration of action)
Malignant hyperthermia can occur in patients with mutant plasma cholinesterase given succinylcholine
CV Adverse effects of depolarizing NM blockers
CV - negative ionotropic and chronotropic effects at large doses
Arrythmias with halothane
Hypotension from ganglion NT
Venous pooling
Hyperkalemia and GI, other effects of depolzriing NMJ blocker
Should not be used in patients with burns, soft tisue damage or NM dz
Increase intragastric pressure and risk of emesis and aspiration
Muscle pain
Increased salivary and bronchial secretion
May trigger malignant hyperthermia - use dantrolene
Centrally acting muscle relaxers and uses
Work in spinal cord to increase inhibitory tone on reflex arc
Fibromyalgia, MS , cerebral palsy, stroke, chronic back pain and sprains
Cyclobenzaprine and methocarbamol
High potential for abuse but better tha nplacebo
Dantrolene
Works in muscles to decrease Ca levels attained during contration but decreasing Ca induced Ca release…less contracitons, less spasms, less pain
Not central acting
Depressing polysynaptic spinal cord reflexes with
Centrally acting GABA agonists relieves pasticity and pain
Drugs permeate tissues depending on
Charge present hydrophilicyt and lipophylicity
