Muscarinic And Nicotinic Blockers Flashcards
The efferent (motor) division of the PNS is sub-divided into ______ Nervous System and the ______ Nervous System.
Somatic
Autonomic
The somatic nervous system innervates the ______ muscles.
The ANS supplies motor impulses to ____ muscle, _____ muscles and to the glandular epithelium.
skeletal
cardiac; smooth
The ANS is divided into ______ and ______ systems.
sympathetic and the parasympathetic
Autonomic efferent pathway uses ___ neurons arranged in ___ to integrate CNS to the peripheral organs.
Somatic efferent pathway, however, uses _____ neuron for the integration of CNS to the skeletal muscles
two; series
a single
Cholinergic Transmission: Site Differences
Skeletal Muscle
Neurotransmitter:_______
Receptor type: _______
Acetylcholine
Nicotinic
Cholinergic Transmission: Site Differences
Autonomic Effectors
Neurotransmitter: _______
Receptor type:_________
effector coupled to receptor by _______
Acetylcholine
Muscarinic
a G protein
Cholinergic Transmission: Site Differences
Autonomic Ganglia
Neurotransmitter: ______
Receptor type: _____
Acetylcholine
Nicotinic
Nicotinic Receptor Agonists
These are drugs that mimic the action of acetylcholine at __________ receptor sites.
Examples include: ???
nicotinic acetylcholine
nicotine, acetylcholine, choline, epibatidine, lobeline, varenicline and cytisine
Ganglion stimulants
These are drugs which stimulate the ___ receptors in ___________ ganglia.
nicotinic
both sympathetic and parasympathetic
Ganglion stimulants
The dominant receptors are the _________.
In addition, there are subsidiary ___________________________________ receptors
nicotinic NN
M1, M2, adrenergic, dopaminergic, aminergic and peptidergic
autonomic ganglion is a one transmitter – one cell junction system
T/F
F
autonomic ganglion is not merely a one transmitter – one cell junction, but a complex system
therapeutic application of ganglion stimulants??
There is no therapeutic application of ganglion stimulants , as no useful purpose could be served by stimulating both sympathetic and parasympathetic ganglia concurrently.
Ganglion stimulants
Nicotine is available as ________ for treating nicotine dependence and as an aid to smoking cessation.
It ameliorates the symptoms of _________ but does not completely ______
transdermal patches
nicotine withdrawal
suppress craving.
Varenicline:
As a ___________, it reduces both the __________ and ________ of cigarettes and other tobacco products. Through these mechanisms it can assist some patients to quit smoking.
partial agonist
craving for and the pleasurable effects
ANTICHOLINERGIC DRUGS
Also known as Cholinergic Antagonists, ___________
Parasympatholytics
ANTICHOLINERGIC DRUGS
If via the nicotinic receptors, they are referred to as “______,” and “________.”
Ganglion blockers
Neuromuscular blockers
Muscarinic Receptor Subtypes:
M1
Location: ____ neurones , _____
Functions: Improves learning, memory, motor functions
Gastric glands:____ release, ___ secretion
Salivary: ____eased secretion
Clinical Effects: _____ Secretion
Clinically Selective Anticholinergic Drugs:
____,_____,____,______
CNS; Stomach
histamine; acid ; incr
Hydrogen Ion
Pirenzepine, Telenzepine, Dicyclomine, trihexyphenidyl
M1 is It is primarily a _____ receptor
neuronal
M2:
Location: ____,_____
- Functions: SA node: ____polarization, (enhanced or reduced?) rate of impulse generation
- AV node: (enhanced or reduced?) conduction velocity
- Atrium: (shortening or lengthening ?) of APD, (enhanced or reduced?) contractility
- Ventricle: (enhance or reduced?) contractility
- Presynaptic terminals/Cholinergic nerve endings of peripheral and central neurones : reduced ACh release
- CNS: tremor, analgesia
Heart, CNS
hyper ; Reduced; reduced
Shortening; Reduced
Reduced
M2 receptor exert (excitatory or inhibitory?) effects, mainly by increasing ___ conductance and by (stimulating or inhibiting?) _____ channels. Thus, its activation is responsible for the vagal ____ of the heart, as well as presynaptic ______ in the CNS and periphery.
inhibitory
K+; inhibiting; calcium
inhibition
inhibition
M2:
Clinical Effects: ______
Clinically Selective Anticholinergic Drugs: _______,_________
Bradycardia
Tripitamine, Methoctramine
M3:
Effects mainly (excitatory or inhibitory?) , except on the ______ muscle, where its activity is mediated through the release of ___, to produce vaso______.
excitatory; vascular smooth; NO
dilatation
M3:
- Location : ______,_____,_______,_____
Clinical Effects
CNS - Visceral smooth muscle (contraction or relaxation?)
- Iris (pupillary (constriction or dilatation?)
Smooth muscles, endocrine glands, lungs, pancreas
Contraction
Constriction
M3
Clinical effects
-Ciliary muscle (contraction or relaxation)
- Exocrine glands (______)
- Vascular endothelium (release of ___ to produce vaso____)
Clinically Selective Anticholinergic Drugs:
Mention 4
Contraction
Secretion
NO; dilatation
Darifenacin, Solifenacin, oxybutynin, tolterodine.
M4:
They function as (inhibitory or excitatiry?) autoreceptors for ACh.
When activated M4 receptors (inhibit or stimulate ?) ACh release in the striatum. Antagonist:_______
inhibitory
Inhibit
Himbacine
Atropine
Is sufficiently lipid (soluble or insoluble?)
Soluble
Atropine -from _______(_____)
Hyoscine- from ________-(_____).
Both are ______\ compds
Atropa belladonna
deadly nightshade
Datura stramonium
thorn apple
tertiary ammonium
Atropine
readily penetrate the BBB.
T/F
T
Semi-synthetic derivatives: Homatropine, Atropine methonitrate, Tiotropium, Ipratropium (quaternary amine) and Hyoscine butyl bromide
Synthetic: Cyclopentolate, Propantheline, Oxyphenonium, Glycopyrolate, Dicyclomine, Valethamate, Pirenzepine and Tropicamide (quaternary amine
Lmao
Atropine (prototype)
Effect on heart rate: causes ______, but in low doses it causes a _______, which results from a central action, increasing vagal activity.
Eye: Pupillary dilatation (mydriasis), which makes the eye _______. Relaxation of ______ causes paralysis of accommodation (cyclopegia), as a result, ___ vision is impaired.
tachycardia; paradoxical bradycardia
unresponsive to light
ciliary muscle
near
Effects of atropine
GIT: (enhanced or Reduced ?) motility
Other smooth muscles: ______,____, and _______ tract are all relaxed by atropine
Reduced
Bronchial, biliary and urinary
Effects of atropine
CNS: Atropine produces mainly (inhibitory or excitatory?) effects.
Low doses cause _______, higher doses cause ________
These central effects could be opposed by _________ drugs
Excitatory
mild restlessness
agitation and disorientation.
anticholinesterase
__________ is an effective antidote to atropine poisoning
Physostigmine
Hyoscine (low dose) causes marked ____ but is similar to ______ in high dosage.
sedation
atropine
Hyoscine also useful as an _____ and used in _____ sickness.
antiemetic
motion
Atropine-like drugs affect ________ system, reducing _______ movement and ______ in Parkinson’s disease.
Body temperature: (Increase or decrease)
Local anaesthestic: Atropine produces a mild anaesthetic action on the ___
extrapyramidal
involuntary
rigidity
Increase
cornea
Pharmacokinetics of atropine
Absorption: is (slow or rapid?) after ____ and local admn of the tertiary amines.
Systemic absorption of inhaled quaternary dugs is _____
Elimination: Atropine (__% is metabolised in the liver and the remaining ————-
Half-life: approx. __
Rapid; oral
Minimal
50
excreted unchanged in the urine.
4h
Between hyoscine and atropine , which penetrates the BBB better and which is more completely metabolized?
Hyoscine is more completely metabolized and penetrates the BBB better.
Summary of AntiCholinergic Effects
In the CNS- list 5
In the eye- list 3
In the heart- at low and high dose
In the bronchioles- list 2
Sedation, hallucination, drowsiness, antiparkinsonism, amnesia
Mydriasis, cyclopegia, lacrimal glands become dry and sandy
Initial bradycardia at low doses then tachycardia
Bronchodilation, decrease in bronchial secretions
Summary of AntiCholinergic Effects
In the GIT- tone, motility, emptying time
Urinary tract- tone, emptying
Relaxation, decrease motility, antidiarrheal, prolongs gastric emptying time
Relaxation of the bladder wall, urinary retention
Summary of AntiCholinergic Effects
Glands
Skeletal muscles
Decrease secretion, salivation, lacrimation, sweating
None
Anticholinergic Toxicity
Symptoms Mnemonic
-____ as a hare ( ______ )
-____ as a bone (___)
- ____ as a beet (____)
- ____ as a bat (____)
- ____ as a hatter (______)
Hot; Hyperthemia
Dry; dry skin
Red; flushed
Blind; mydriasis
Mad; delirium
Management of anticholinergic Toxicity
1) Control hyperthemia using _______
- Agitation may require
-____________
-________(Benzodiazepines) - If ingested, ____
- Antidote: ________ (1-3 mg s.c or i.v arrests both central and peripheral effects)
cold sponging or ice bags
physical restraints
- chemical restraints
gastric lavage
Physostigmine
Why physostigmine as antidote and not Neostigmine
Neostigmine is ineffective for central effects
Clinical uses of Anticholinergic drugs
As Antispasmodic:
Useful for intestinal and renal colic, ____
For _______ diarrhoea, but not _____ diarrhoea
Spastic constipation, _______ syndrome
Urinary frequency and urgency, ______ in children
_________
abdominal cramps
nervous and drug-induced ; infective
irritable bowel
enuresis
Dysmenorrhoea
Clinical uses of Anticholinergic drugs
Bronchial asthma, Chronic Obstructive Pulmonary Disease (COPD):
- They produce broncho_____ and dry up _______ in the respiratory tract
dilatation
excessive secretions
Clinical uses of Anticholinergic drugs
As Antisecretory:
- as _______ medication, especially when irritant general anaethetics (ether) are used to check increase salivary and bronchial secretions.
- in ________, they decrease gastric secretion. Histamine H2 receptor antagonists are however preferred.
- to check excessive sweating and salivation in _______
- in ________, they reduce reflex secretions
pre-anaesthetic
Peptic ulcer
Parkinsonism
pulmonary embolism
Clinical uses of Anticholinergic drugs
Mydriatic and Cyclopegic:
- For _____: since in testing error of refraction, both mydriasis and cyclopegia are needed
For Therapy: used for ____,______,____,_____
Diagnosis
Iritis, choroiditis, keratitis and corneal ulcer
Clinical uses of Anticholinergic drugs
As cardiac Vagolytic: it counteracts _______ and ________ where increased vagal tone is responsible
bradycardia and partial heart block
Clinical uses of Anticholinergic drugs
For Central Action:
Motion Sickness: _____ is most effective. Drug should be administered ______.
Hyoscine
prophylactically
In Parkinsonism: which is more useful, Anticholinergic drugs or L-DOPA
L-DOPA
Anticholinergic drugs are Less effective than L-Dopa, only useful in mild cases
Hyoscine is used to produce _____ and ______ during labour and in maniacal states.
sedation and amnesia
Clinical uses of Anticholinergic drugs
To antagonize muscarinic effects of drugs and poisons: _______ is the specific antidote for Anti ChE and early mushroom poisoning.
Atropine
_______ interfere with absorption of anticholinergics
Antacids
Antinicotinic Drugs
Antinicotinic drugs sub-divided as:
-________ e.g. Hexamethonium, Trimethaphan, Mecamylamine
-___________ e.g. Suxamethonium, Decamethonium, Tubocurarine, Atracurium,
Ganglion blockers
Neuromuscular blockers
Ganglion blockers
All ganglion-blocking drugs of interest are (synthetic or semi synthetic ?) amines.
Synthetic
__________, the first to be recognized as being a ganglion blocker, has a very (short or long ? duration of action.
Tetraethylammonium (TEA)
Short
Effect of ganglion blockers on veins
-Vaso_____
-_____ of blood
- ____eased venous return
Dilation
Pooling
Decr
Effect of ganglion blockers on Arterioles
-Vaso_____
-_____eased peripheral blood flow
-____tension
Vasodilation
Incr
Hypo
Why are ganglion blockers not frequently used??
Ganglion blockers are not too frequently used because more selective autonomic blocking agents are available.
Clinical Applications:
__________ blocks central nicotinic receptors and has been advocated as a possible adjunct with the transdermal nicotine patch to reduce nicotine craving in patients attempting to quit smoking.
Mecamylamine
_______ is occasionally used in the treatment of hypertensive emergencies.
And is a ____ blocker
Trimethaphan
Ganglionic
Neuromuscular Blockers
They block neuromuscular transmission at the ______, causing ____ of the affected skeletal muscles.
neuromuscular junction
paralysis
Neuromuscular Blockers
This action is accomplished either by acting presynaptically via ____________(e.g. _______ and _____); or by acting postsynaptically at the _____________(NMJ blocking agents).
inhibition of ACh synthesis or release
botulinum toxin and tetanus toxin
Ach receptors of the motor end-plate
Two different kinds of functional blockade may occur at the neuromuscular end plate, therefore clinically used drugs fall into two categories:
________ Blocking Agents
________ blocking agents .
Non-Depolarizing
Depolarizing
Non-Depolarizing Blocking Agents: Act by (competitively or non-competitively?) blocking ACh at NM receptor
Blockade could be reversed through administration of ________
competitively
cholinesterase inhibitor.
Depolarizing ( _________ Blockers): agonists at NM receptors.
They act by _________ the receptors
-_________ (Suxamethonium)
- __________
Non-Competitive
over-stimulating
Succinylcholine; Decamethonium
Depolarizing agonists at NM receptors.
Initial stimulation is accompanied by ______ of skeletal muscle (______)
With continued agonist effect, _______ cannot be maintained, and therefore, the continuous depolarization results in a ___________(____) .
Muscles are ____ and have _____ tone.
initial twitching; fasciculations
skeletal muscle tone
functional muscle paralysis (flaccid paralysis)
weak; little or no
Depolarizing agonists at NM receptors.
Prototype is ______ (ultra-___ acting). Must be given by continuous i.v. infusion if prolonged paralysis is required.
succinylcholine
Short
NEOSTIGMINE or any cholinergic agent can be used TO REVERSE DEPOLARIZING BLOCK
T/F
With reason
F
DO NOT USE NEOSTIGMINE (or any cholinergic agent) TO REVERSE DEPOLARIZING BLOCK. It will make it worse, one, since adding acetylcholine will only help contribute to depolarization, and two, because neostigmine also binds to and blocks the action of pseudocholinesterase, which is needed to break down SCh.
____ is the only truly safe reversal agent for succinylcholine.
Time
Actions of neuromuscular blockers
1. Skeletal muscle –
Intravenous injection of non-depolarizing blockers rapidly produces muscle _____ followed by ___ paralysis.
_________ muscles (fingers, extraocular) are affected first; paralysis spreads to hands, feet, arm, leg, neck, face, trunk, intercostal muscle then _____, and _____ stops.
Recovery occurs in the _____ sequence.
weakness; flaccid
Small fast response
diaphragm
Respiration
reverse
Actions of neuromuscular blockers
1. Skeletal muscle
Depolarizing blockers produce initial _____ a few seconds before inducing ____.
____ occurs within 45-90 sec, but lasts only 2-5 min; recovery is (slow or rapid?) .
fasciculation
paralysis
Apnoea
rapid
Actions of neuromuscular blockers
Autonomic ganglia – the cholinergic receptors in autonomic ganglia being nicotinic, ________ NMJ blockers (especially the [newer or older?] drugs, d-TC) produce some degree of ganglionic blockade.
competitive; older
Actions of neuromuscular blockers
Histamine release –____ releases histamine from mast cells, which produces ___tension, broncho___, ___eased respiratory secretions and ____.
_____ may also be simultaneously released from mast cells.
dTC
Hypo; spasm; incr; flushing
Heparin
Actions of neuromuscular blockers
CVS – dTC produces significant (rise or fall?) in BP, due to
i._______
ii. _____ release
iii. ( Enhanced or Reduced?) venous return, resulting from paralysis of limb and respiratory muscles. Heart rate may ___ease, due to vagal ganglionic blockade.
Fall
ganglionic blockade
Histamine
Reduced
Incr
All newer non-depolarizing drugs have negligible effects on BP and HR.
T/F
T
Actions of neuromuscular blockers
GIT – The ganglion blocking activity of competitive blockers may enhance ______ after abdominal operations.
CNS – All NMJ blockers are _______ compounds, and ( do or do not?) cross the BBB. However, dTC when injected in the cerebral ventricles or when applied to the brain cortex, produces ______- like effect.
paralytic ileus
quaternary
Do not
strychnine
NM BLOCKERS
mode of administration
Ability to cross cell membrane
Volumes of distribution
BBB
IV or IM
can’t
Low
Can’t penetrate
When given NM blockers, which gets affected first?
Muscles with high or low blood supply
High
NM blockers’ effect on drugs metabolized by the liver and drugs excreted by the kidney
Increases the half life of those excreted by the kidney
Shortens the half life of those metabolized by the liver
Succinylcholine is rapidly _____ by plasma _______ to ______ and then to __________
hydrolysed
pseudocholinesterase
succinyl monocholine
succinic acid and choline
Pseudocholinesterase deficient patients suffer from _____ and ______ lasting for _____
muscle paralysis and apnoea
Hours
The main difference between the two classes of NMJ blockers is in the ________
reversal of blockade.
Non-depolarizing blockers are reversed by _______ drugs, since they are _______ antagonists of ACh.
acetylcholinesterase inhibitor
competitive
_______ NM blockers cause the tetanic fade
non depolarizing
Phase I Block
Perijunctional ____-Channel cannot reopen until the end plate ______ which cannot happen as long as the __________
Na
repolarizes
depolarizing muscle relaxant continues to bind to ACh receptors.
Phase II Block:
After a period of time, prolonged end-plate depolarization can cause (well or poorly?) understood changes in the ________ that result in a Phase II block.
Poorly
ACh receptor
Tetanic Fade refers to the diminishing ______ response under the effect of either a ________ agent, or a muscle that is under a _____________ agent.
muscle twitch
non- depolarizing neuromuscular blocking
phase II depolarizing neuromuscular blocking
Neuromuscular Junction Disease:
Autoimmune disorders, in the case of neuromuscular diseases, tend to be ____ mediated, __ cell mediated, and result in an antibody improperly created against a motor neuron or muscle fiber protein that interferes with synaptic transmission or signalling.
humoral; B
Myasthenia gravis
-comes from the Greek and Latin words meaning “_________________.”
The most common form of MG is a (acute or chronic?) autoimmune neuromuscular disorder that is characterized by _________ of the (voluntary or involuntary ?) muscle groups.
grave muscular weakness
Chronic; fluctuating weakness
Voluntary
Myasthenia gravis occurs in all races
MG occurs in only females
MG occurs only at adulthood
MG is not thought to be directly inherited nor is it contagious.
MG does occasionally occur in more than one member of the same family.
T/F
T
F(both genders)
F(any age)
T
T
In myasthenia gravis, the immune system produces ____ that block or destroy many of the individual’s muscles’ ______ for the neurotransmitter called _____.
antibodies; receptor sites
acetylcholine
Myasthenia gravis
This waxing-and-waning weakness of muscles, worsening with use and improving with rest, is a hallmark of this particular disease. There typically are periods when you may notice more symptoms ( _________), interspersed with periods when symptoms decrease or disappear ( _______ ).
called an exacerbation
remission
MG
The disease most commonly affects muscles that control ____ and _____ movement, so the first symptoms you notice may be ______ and/or ______ or ______.
The majority will go on to develop weakness in other muscle groups within _________
eye and eyelid
eyelid drooping
blurred or doubled vision
one or two years.
_________ is also known as a plasma exchange. This process removes ______ from the blood, which may result in an improvement in muscle strength.
It is a (short or long?) -term treatment. The body continues to produce the harmful antibodies and weakness may recur. Plasma exchange is helpful before surgery or during times of extreme MG weakness.
Plasmapheresis
harmful antibodies
Short
Complications of Myasthenia Gravis
One of the most dangerous potential complications of MG is _______. This consists of life- threatening muscle weakness that can include ______
Individuals with MG are at a higher risk of developing other autoimmune disorders such as _______ and _____
myasthenic crisis
breathing problems.
lupus and rheumatoid arthritis.
There are two types of medications used to treat MG.
_________: temporarily relieves the symptoms of MG.
___________: attack the disease at its source.
Anticholinesterases
Immunosuppressants
Anticholinestarases:
These agents include _______,_____,_______
pyridostigmine, neostigmine, and edrophonium.
Anticholinestarases:
Pyridostigmine is used for ______
Neostigmine is generally used only when _________
Edrophonium is primarily used as a _____ to predict the response to _____-acting cholinesterase inhibitors.
maintenance therapy.
pyridostigmine is unavailable.
diagnostic tool
longer
_____ significantly relieves MG symptoms for a large majority of myasthenics.
This drug is not as fast acting as ______, but it is faster than other _______, and it is relatively inexpensive. While prednisone can be very effective in treating myasthenia, it carries the risk of serious side effects
Prednisone
anticholinesterases
immunosuppressants
Monoclonal antibodies.
One of the newer therapies used to treat myasthenia gravis that is resistant to traditional approaches is the ________
This treatment is given as ______ IV infusions repeated every ___ months. A similar __________, also is being investigated.
monoclonal antibody rituximab.
four weekly
six
monoclonal antibody, eculizumab
Competitive NM blockers
Based on Duration of Action
Long-acting: d-______,______,_____,______
Intermediate-acting: _____,____,_____,______,________
Short-acting: ________
Tubocurarine, Pancuronium, Doxacurium, Pipecuronium
Vecuronium, Atracurium, Cisatracurium, Rocuronium, Rapacuronium
Mivacurium
Competitive NM blockers
Based on chemical structure
- ____ Compounds: ( _____ properties)
-________ (BZIQ): (____________ )
Steroidal; vagolytic
Benzylisoquinoline
histamine realease
Competitive NM blockers
Based on chemical structure
- Steroidal Compounds:
It includes ____,_____,———,_____,———-
- Benzylisoquinoline (BZIQ):
It includes d- ____,______,_____ ,______,____,______ - Others: includes _____,_____
Pancuronium,Vecuronium, Pipecuronium, Rocuronium, Rapacuronium.
Tubocurarine, Metocurine, Doxacurium, Atracurium, Mivacurium, Cisatracurium
Gallamine, Alcuronium
List the quaternary indirect choline agonists
List the tertiary indirect choline agonists
Pyrido, neo, edro
Physo, riva, galantamine, donepezil
The steroidal NMJ drugs has _______ at the end
benzisoquinolins drugs has _____ at the end
curonium
curium
________ and _______ were the most potent inducers of CYP2D6 followed by _________ and ______
Dexamethasone and corticosterone
prednisolone and cortisol
Nicotine is gotten from ______
Nicotiana tobacum
Hyoscamine is ???
Atropine
Selective Nicotinic Agonists:
Natural
- ____________
-_____________
Synthetic
-______________
-_____________
Nicotine (small doses)
Lobeline
Dimethyl phenyl piperazinium (DMPP)
Tetramethyl ammonium (TMA)
