7. Somatic/Autonomic Pharmacology Flashcards
Divisions of Efferent Nervous System
• Voluntary or somatic nervous system
– End organ of single nerve from CNS is always ____ muscle
– Typically must think about it before it is activated
– Neurotransmitter = ____
– End Organ Receptor = ____
• Autonomic nervous system
– Totally “automatic” – is always working
– ____ neuron outflow from CNS to smooth muscle, glandular tissue or heart
– End Organ Receptors = ____ and ____
• Acetylcholine ○ Permanently \_\_\_\_ molecule - do not move throughout the body § Does not have good \_\_\_\_ solubility • Nicotinic M (muscle) receptor on skeletal muscle ○ \_\_\_\_ can cause skeletal muscle contraction, in addition to ACh • Two neuron outflow: one neuron out of CNS, synapses with another neuron, which then synapses with an end organ (smooth muscle, glandular tissue or cardiac tissue) • Autonomic: \_\_\_\_ (keeps us more in a relaxed stage), and \_\_\_\_ (fight or flight) ○ Cholinergic receptor, but not the same as the one on skeletal ○ \_\_\_\_ can stimulate both, but different drugs activate each • Adrenergic - \_\_\_\_
skeletal
acetylcholine
nicotinic M cholinergic
two
muscarinic cholinergic
adrenergic
charged lipid nicotine parasympathetic sympathetic
Ach
adrenaline/epinephrine
• Voluntary: single nerve fiber out of CNS (spinal cord here)
○ ____ - nodes of Ranvier (where most Na+ are located)
○ Release of Ach, muscle contraction
• Autonomic (para or symp)
○ Two neuron outflow
○ ____ released onto post-ganglion from pre-ganglion
§ ____ receptor, but different from skeletal
§ ____ (nerve) receptor
□ Exists in both para and symp divisions - why it becomes messy when playing around with this site
○ Releases onto bronchi, glandular tissue (sweat gland, salivary gland), or smooth muscle
§ Depends on what NT/drug is released, and whether it stimlulates or blocks the receptor
• Most organs are ____ innervated (both symp and para) - can block and/or stimulate specific divisions
○ Propranolol - antagonist on ____ receptor on heart - heart is also innervated by parasymp, so now this predominates thereby slowing HR and contraction force
myelinated
Ach
nicotinic
nicotinic N
dually
B1 adrenergic receptor
The Neuromuscular Junction
• Muscle will fatigue if this process continues on for a while and will enter \_\_\_\_ ○ Excitation following by blockage • Nerve gas - permanently binds \_\_\_\_
depolarizing block
acetylcholinesterase
Acetylcholine
• Chemical can move in and out of synapse, but cannot travel throughout the \_\_\_\_ ○ Permanent \_\_\_\_ • Reuptakes \_\_\_\_ and used to make more acetylcholine ○ \_\_\_\_ - blocks the reuptake of choline back into the nerve terminal - creates paralysis
body
charge
choline
hemicollineum
Some Pharmacological Manipulations of Voluntary Nervous Systems
- Blocking skeletal muscle contraction with ____ or ____ for intubation - a nicotinic M cholinergic receptor antagonist (neuromuscular blocker). Non-depolarizing ____ blocker. Can be reversed by increasing ____. Drugs called ____ (physostigmine) can do this.
- Blocking skeletal muscle contraction with succinylcholiine for intubation - a ____ receptor antagonist (neuromuscular blocker). Depolarizing ____ blocker. No ____. Must ____ for drug to be enzymatically degraded by cholinesterases. Issue in patients with ____.
- Using anticholinesterases (neostigmine) to symptomatically treat myasthenia gravis, an autoimmune disease where ____ receptors are being destroyed. ____ again increase ACH at neuromuscular junction. However they also do it all over the ____ where there are other neurons releasing ACH.
- Anticholinesterases that cross the blood brain barrier also shown to improve memory in ____ patients. Drugs like ____ and ____ (Aricept®). DO YOU WANT INCREASED MUSCLE CONTRACTION IN THESE PATIENTS????
curare gallamine competitive Ach anticholinesterases
nicotinic M cholinergic non-competitive reversal agent wait "atypical cholinesterases"
nicotinic M cholinergic
anticholinesterases
body
alzheimers
physostigmine
donepezil
Some Pharmacological Manipulations of Voluntary Nervous Systems
• Drugs that work on nicotinic M cholinergic receptors are all \_\_\_\_ ○ Blockers have higher \_\_\_\_ for receptors, and slowly comes off; \_\_\_\_ have the opposite effect (on-off-on-off constantly) • Breathing machine for 24-48 hours - \_\_\_\_ • Neostigmine ○ Used in myasthenia gravis, where nicotinic M cholinergic receptors are being destroyed ○ Eventually, the receptors get \_\_\_\_ and these drugs will have no effect • Neostigmine won't work for Alzheimer's patients - it is permanently \_\_\_\_ and it cannot cross the BBB ○ Amyloid leads to destruction of cholinergic receptors ○ Doesn't slow down progression, but it improves symptoms (physostigmine and donepezil [Aricept]) § Affects Ach wherever it is: unwanted muscular contraction (\_\_\_\_), diarrhea and increased salivation (affecting the \_\_\_\_ also)
blockers/antagonists affinity agonists "atypical cholinesterases" destroyed charged symp parasymp
Competitive and Non-Competitive Blockade of NMJ
• With \_\_\_\_, because its competitive antagonist, effects of curare can be reversed by increasing acetylcholine at the site ○ Muscle is flaccid and paralyzed • With succ (non-competitive), with \_\_\_\_, cannot reverse the effect
curare
atypical cholinesterases
Other Drugs in Treatment of Alzheimer’s Disease
• Anticholinesterases: ____ (Aricept®), ____ (Exelon®), ____ (Razadyne®)
– Adverse Events predictable by mechanism of actions: muscle ____ and contracting, bradycardia, ____, diarrhea, increased ____, tremors/seizures
• Excitatory amino acid antagonist (i.e. ____, n-methyl-d-aspartate) ____ (Namenda®)
• All 3 can cross the \_\_\_\_ • Can increase response at \_\_\_\_ (nicotinic and cholinergic), and at \_\_\_\_ receptor effects (end organs innervated by parasymp nervous system) ○ \_\_\_\_ are exception (sweating is symp); but anatomically, innervated by sympathetic outflow (first is short, second is long), the NT is acetylcholine • Add-on to anticholinesterase - memantine ○ Too much excitatory AA - \_\_\_\_, and alzheimer's - destroy neurons ○ Blocks the action of \_\_\_\_ (glutamate, aspartate)
donepezil rivastigmine galantamine twitching drooling sweating glutamate memantine
BBB NMJ muscarinic cholinergic sweat glands stroke excitatory NT
Divisions of Autonomic Nervous System 1
• Parasympathetic Division
– Fine control of ____ body systems
– End organs again are ____ muscle, ____ tissue and ____ tissue
– Body is kind of in ____ state
– Pupils constricted (____), salivation is copious, heart rate ____, digestion of food (stomach acid secretion) and ____ turned on, good blood flow to skin and stomach, ____somewhat constricted
• \_\_\_\_ neuron outflow • \_\_\_\_ relationship between first neuron and synapsing on the second neuron ○ \_\_\_\_: first neuron (pre-gang) can synapse on 20 post-gang nerve fibers
individual smooth glandular cardiac relaxed miosis slow peristalsis bronchi
two
1:1
sympathetic
Divisions of Autonomic Nervous System 2
• Sympathetic Division
– Fight, fright, flight system.
– Simultaneous energizing of ____ body organs
– pupils dilate (____), mouth becomes dry, ____, bronchi open, blood flow to brain and skeletal muscle increases, blood flow to skin/stomach ____, heart rate and contraction force ____.
• \_\_\_\_ neuron outflow • Same organs stimulated as para, but the effects are opposite • Drops at eye office - \_\_\_\_, or alpha norepinephrine stimulating receptors - stimulates sympathetic system • Sweat glands - anatomically: sympathetic, but uses \_\_\_\_ ○ Drugs that affect sweating, are the ones that stimulate or block the end organs of the \_\_\_\_ system • Different receptor types: ○ B2 for brain, when stimulated, dilation of BV ○ A1 for skin and stomach, when stimulated, constriction of BV
multiple mydriasis sweating decreases increase
two
alpha adrenergic
acetylcholine
parasymp
IMPORTANT CONCEPT CONCERNING AUTONOMIC NERVOUS SYSTEM 1
• Most organs are dually innervated by both systems so…………
– If u give a drug that stimulates (an agonist) ____ nervous system that system’s effects predominate
– If u give a drug that blocks (an antagonist) the parasympathetic nervous system the ____ nervous system’s effects predominate
parasympathetic
sympathetic
IMPORTANT CONCEPT CONCERNING AUTONOMIC NERVOUS SYSTEM 2
• Most organs are dually innervated by both systems so…………
– If u give a drug that stimulates (an agonist) ____ nervous system that system’s effects predominate
– If u give a drug that blocks (an antagonist) the sympathetic nervous system the ____ nervous systems effects predominate
sympathetic
parasympathetic
Parasympathetic anatomy
end organ receptor = ____
ganglionic receptor = ____
* Parasymp nerve fibers come of \_\_\_\_ and \_\_\_\_ regions of spinal cord * 1:1 (one pregang to one postgang) * Pregang is \_\_\_\_, and postgang is \_\_\_\_ * Not talking about skeletal muscle anymore - smooth muscle in eye, salivary gland, etc. * GI ulcers - nicotine is hitting the \_\_\_\_ receptors on the end of pre-gang - driving acid in the stomach
muscarinic cholinergic
nicotinic N cholinergic
cranial sacral long short nicotinic
Divisions of Autonomic Nervous System 1
• Parasympathetic Division
– Fine control of individual body systems
– Typically one long preganglionic nerves synapses on one very short postganglionic nerve which then synapses on end organ
– Neurotransmitter at both preganglionic and postganglionic sites is ____
– Receptor at ganglionic site = ____
– Receptor at end organ =____ (M1, M2, M3, M4, M5).
• Do not have any drugs that selectively stimulate/block the different \_\_\_\_
acetylcholine
nicotinic N cholinergic
muscarinic cholinergic
muscarinic subtypes
Some Effects of Parasympathetic (Muscarinic) Stimulation
- Increased ____ (watery saliva)
- Pupillary constriction (____)
- Bronchoconstriction and ____ respiratory secretions
- Decreased heart rate (negative ____) and contraction force (negative ____)
- Increased GI peristalsis and acid secretion
- A few blood vessels dilate but most only have ____ innervation
ACTIONS ARE GENERALLY OPPOSITE THE SYMPATHETIC SYSTEM
salivary flow miosis increased chonotropic inotropic sympathetic
Drug strategies effecting muscarinic receptors 1
• Treating dry mouth (xerostomia) from Sjogren’s syndrome or radiation treatment
– Prescribe muscarinic cholinergic receptor agonist like ____ (Salagen®)
– What are potential side effects of pilocarpine??
– Pupillary ____, bradycardia, diarrhea, increased ____, increased sweating – WHY ?? All these organs also contain muscarinic receptors. ____ muscarinic receptors most sensitive to drug.
Why not employ anticholinesterase to treat xerostomia???
pilocarpine
constriction
stomach acid
salivary gland
Drug strategies effecting
muscarinic receptors 2
• Want to dry patient’s mouth before impression for 7 crowns which will make you a lot of money!!
– Prescribe muscarinic cholinergic receptor antagonist like ____.
– What are possible side effects of atropine?
– ____, increased heart rated, decreased ____, constipation, drowsiness. These organs also have muscarinic receptors and now ____ nervous system predominates except for the decreased sweating.
• Atropine extremely effective in drying the mouth • \_\_\_\_-soluble - can get into the brain, etc • Unpredictable effects in \_\_\_\_; chemical structure similar to cocaine ○ May end up getting stimulation
atropine
mydriasis
sweating
sympathetic
lipid
brain
Related drugs to atropine
(antimuscarinics)
• \_\_\_\_ (Pro-Banthine®) • \_\_\_\_ (Robinal) – Both can dry the mouth and have other peripheral anticholinegic effects – Permanently \_\_\_\_ so they stay out of the brain, i.e. minimal sedation with these drugs • \_\_\_\_ (Transderm Scop®) • \_\_\_\_ – also an antihistamine – Both readily penetrate \_\_\_\_ – Highly \_\_\_\_
• These drugs are permanently charged - requires a big dose for it to be absorbed • Stays out of eye chamber and away from the brain, minimal side effects like you get from atropine • To get through skin, need a lipophilic vehcile • Diphenyhydramine - benedryl acts only on \_\_\_\_ ○ Most common: H1 antagonists - classic antihistamines, used as an adjunct for anaphylaxis (helps somewhat) - on bronchi ○ (\_\_\_\_ receptors - on parietal cells - acid secreting cells in the stomach) § Used to treat \_\_\_\_ ○ Also blocks muscarinic cholinergic receptors - \_\_\_\_, can be a side effect (from antihistamine) or good effect depending on what you're taking it for
propantheline glycopyrollate charged scopolamine diphenydramine CNS sedating
H1
H2
GI ulcers
dry mouth
Blocking ____ receptors in CNS to prevent motion sickness. Drugs like diphenhydramine
(Benadryl®) or scopolamine patch. Why won’t they work for nausea caused by opioids (narcotics) or cancer chemotherapy????
* \_\_\_\_ drugs (muscarinic cholinergic antagonists) * +++ - NT stimulates the vomiting center * The above drugs block the +++ - why they're good motion sickness drugs * The drug needs to get into the \_\_\_\_ (\_\_\_\_ isn't good) * Drug-induced vomiting (opioids/chemo) involves NT different from motion sickness; need \_\_\_\_ and \_\_\_\_ receptors
muscarinic cholinergic
anticholinergic brain glycopyrollate dopamine serotonin
Geopolitical Concerns With Irreversible Anti Cholinesterases
- Drugs like neostigmine used in myasthenia gravis and donepezil in Alzheimer’s ____ bind cholinesterase –IN OTHER WORDS THEY LET GO
- Certain types of nerve gases with names like ____, Sarin and ____ are irreversible binders and extremely ____ soluble. They will penetrate body right through ____ and mucous membranes.
reversibly Soman Tabun lipid skin
Physiological Effects of Nerve Gases
• SLUDGE SYNDROME Ø S = Excess \_\_\_\_ Ø L = Excess \_\_\_\_ Ø U = Excess \_\_\_\_ Ø D = Excess \_\_\_\_(diarrhea) Ø G = \_\_\_\_ (convulsions) v \_\_\_\_ excitatory neurotransmitter in brain Ø E = \_\_\_\_ (vomiting) v Remember vomiting center schematic Ø \_\_\_\_
salivation lacrimation urination defecation grand mal like seizures Ach emesis depolarizing neuromuscular blockade
Sympathetic System
• \_\_\_\_ preganglion, \_\_\_\_ postganglion • Same \_\_\_\_ end site on the preganglion for both para and symp • Different NT, except for the \_\_\_\_ • Can be \_\_\_\_ (preganglion:postganglion) • The nerve cell bodies are all \_\_\_\_ ○ \_\_\_\_ rami ○ Excite one and you excite them all • \_\_\_\_ glands act as post-ganglionic nerve fibers ○ Right: \_\_\_\_ shape ○ Left: \_\_\_\_ shape ○ End organ: blood, \_\_\_\_ and some \_\_\_\_ and some \_\_\_\_ • Epinephrine/NE/DA can travel far - not highly \_\_\_\_ molecules
short long nicotinic sweat glands 1:20 connected grey adrenal pyramid crescent epinephrine norepinephrine dopamine charged
