Muscarinic And Nicotinic Blockers Flashcards by Iseoluwa Ojo

The efferent (motor) division of the PNS is sub-divided into ______ Nervous System and the ______ Nervous System.

Somatic

Autonomic

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The somatic nervous system innervates the ______ muscles.
The ANS supplies motor impulses to ____ muscle, _____ muscles and to the glandular epithelium.

skeletal

cardiac; smooth

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The ANS is divided into ______ and ______ systems.

sympathetic and the parasympathetic

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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

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Cholinergic Transmission: Site Differences

Skeletal Muscle

Neurotransmitter:_______
Receptor type: _______

Acetylcholine

Nicotinic

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Cholinergic Transmission: Site Differences

Autonomic Effectors

Neurotransmitter: _______
Receptor type:_________

effector coupled to receptor by _______

Acetylcholine

Muscarinic

a G protein

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Cholinergic Transmission: Site Differences

Autonomic Ganglia

Neurotransmitter: ______
Receptor type: _____

Acetylcholine

Nicotinic

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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

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Ganglion stimulants

These are drugs which stimulate the ___ receptors in ___________ ganglia.

nicotinic

both sympathetic and parasympathetic

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Ganglion stimulants

The dominant receptors are the _________.

In addition, there are subsidiary ___________________________________ receptors

nicotinic NN

M1, M2, adrenergic, dopaminergic, aminergic and peptidergic

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autonomic ganglion is a one transmitter – one cell junction system

T/F

autonomic ganglion is not merely a one transmitter – one cell junction, but a complex system

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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.

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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.

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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

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ANTICHOLINERGIC DRUGS

Also known as Cholinergic Antagonists, ___________

Parasympatholytics

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ANTICHOLINERGIC DRUGS

If via the nicotinic receptors, they are referred to as “______,” and “________.”

Ganglion blockers

Neuromuscular blockers

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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

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M1 is It is primarily a _____ receptor

neuronal

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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

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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

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M2:

Clinical Effects: ______
Clinically Selective Anticholinergic Drugs: _______,_________

Bradycardia

Tripitamine, Methoctramine

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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

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M3:

Location : ______,_____,_______,_____

Clinical Effects
CNS - Visceral smooth muscle (contraction or relaxation?)
- Iris (pupillary (constriction or dilatation?)

Smooth muscles, endocrine glands, lungs, pancreas

Contraction

Constriction

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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.

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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

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 _______ 2. Agitation may require -____________ -________(Benzodiazepines) 3. If ingested, ____ 4. 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

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)