Cholinergic System 2 Flashcards
1
Q
Nicotinic substances
Nicotine - cholinergic agonist drug
A
- -an alkaloid contained in tobacco plant
- stimulates vegetative ganglia & medullary adrenal gland
- Acts directly on autonomic ganglia -> both on S & PS ganglia ( ganglion stimulating drug )
- stimulates nicotinic receptors
- NN nicotinic receptors are stimulated at lower doses than NM receptors
- At high doses -> stimulation of nic. rec is replaced by their blockade
- No therapeutic use
2
Q
Nicotine effects
A
- tachycardia
- increased BP
- effects on GI motility & secretions
- increased bronchial , salivary , sweat secretions
3
Q
Ganglioplegics
trimetaphan , hexamethonium
A
- paralyze vegetative ganglia ( S & PS )
- Diminish until cancellation the activity of vegetative ganglia , decreasing cholinergic + adrenergic control of various effector structures
4
Q
effects of ganglioplegic drugs
A
- most important on CV system
- on Blood vessels -> practically , innervation : adrenergic -> removal of this control -> decrease in BP with an important orthostatic component
- Decreasing sympathetic tone in vascular areas rich in β2 adrenergic receptors - heart , brain , kidneys -> causes these drugs to decrease vascular irrigation in these areas
5
Q
most important ganglioplegic drug
A
trimetaphan
- IV administration
- causes marked decrease in BP
- drug is given by continuous IV infusion -> when marked + rapid decrease in BP is needed as major hypertensive attacks , aortic dissecting aneurysm in painful crisis , controlled by hypotension to limit bleeding in the wound during very bloody surgery
6
Q
Curare derivatives
A
- class of substances that paralyze skeletal muscles by acting on nicotinic receptors in Neuro - motor junction ( NMJ)
- raw extract of the plant Chondodendron tomentosum used by native Indians to poison hunting arrows and which kills the hunted animals by paralyzing skeletal muscles , icluding respiratory muscles
- there are currently several natural / synthetic substances that cause such paralysis of the striated muscles and are mainly used in anesthesiology
7
Q
Pachycurares
- are blockers of NM receptors ,
A
- are blockers of NM receptors ,
preventing the activation of the respective receptors by endogenous Ach + depolarization of the postsynaptic membrane - antidepolarazing curare derivative ( tubocurarine ) - this causes paralysis of the neuromuscular synapse , with paralysis of skeletal muscles
Effects : can be competitively antagonized , by increasing the amount of Ach in the synaptic cleft eg anticholinesterase substances such as : neostigmine , are administered - cause paralysis of strated muscles that installs in 5-6 min and lasts depending on the drug b/w 30- 60 min
Their effect is at least partially antagonized by anticholinestarases - neostigmine
8
Q
Leptocurares
NM rec agonists
A
- act as NM rec agonists
- they stimulate these receptors - the muscle contractions that can be observed clinically in the form of muscle fasciculations
- differ in their chemicall structure of Ach and therefore are metabolised more slowly by cholinesterase so that they persist much longer in the synaptic cleft
- that means , unlike Ach , the stimulation of nicotinic rec is long - lasting .
- paralysis of respective muscles
- they are depolarizing agents
- the effect of depolarizing agonists is not antagonized by anticholinesterases but on the contrary , is potentiated by them
9
Q
leptocurares - suxamethonium ( succinylcholine )
A
- among leptocurares , is the only drug currently used
- agonist on neuromuscular nicotnic receptors
- metabolized very quickly in the blood by pseudocholinestarase
- effects of the drug installed very quickly :
1 ) latency of muscle paralysis is about 1 min
2) paralysis of striated muscles is preceded by muscle contractions -> fasciculations + duration of the effect is very short : 5-10 min - There are some people who have genetic deficiency in pseudocholinesterase : these people find it difficult to metabolise the drug -> effect of suxamethonium very intense + long lasting
- as regular theurapeutic doses can cause dangerous paralysis of respiratory muscles icluding diaphragm
- the safe use of suxamethonium ( hospitals ,ICU ) - limits effects of toxic apnea
Muscle fasciculations produced by suxamethonium can cause post- anesthetic muscle pain
10
Q
Tubocurarine ( d -tubocurarine )
A
is the first known curative and is the alkaloid contained in curare
11
Q
Gallamine
A
- is a synthetic pachycurare , with less potency than tubocurarine
- with much less expressed ganglioplegic + histamine - releasing effects
12
Q
Pancuronium
A
- synthetic agonist , with higher potency than gallamine
- very weak ganglioplegic + histamine - releasing effects
13
Q
Anticholinesterases
A
- group of substances that inhibit Ach activity
- AchE is the enzyme that degrades Ach from synaptic cleft
- some Anticholinesterase substances are ester carbamic acid - amine structure ( quaternary ammonium structure ) - reversible anticholinesterases
- organophosphates - irreversible anticholinesterase
- The reactivation of AchE requires such a long time that the disappearance of the effect of organophosphates occurs practically through the synthesis of new Ach molecules
14
Q
oxyme
obidoxime
pralidoxime - cholinesterase reactivators
A
may be useful in the treatment of organophosphates intoxication
15
Q
Neostigmine
A
- one of the least toxic anticholinesterases , can be used as systemic drug , mainly for the treatment of M.Gravis but also in other clinical conditions such as those that require :
1) an increase in intestinal transit
2) increase in bladder activity
3) for the treatment of intoxication with non-depolarizing curarizantes
