117 terms

BS IV - Pharmacology of NS (Hersh)

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How many neurons does the somatic nervous system have?
single neuron
the end organ in the somatic NS is always ______
skeletal muscle
the NT for somatic NS is ____
ACh
the end organ receptor for the somatic NS is ____
Nicotinic M cholinergic
How many neurons does the autonomic nervous system have?
two neurons
the end organs for the autonomic neuron system are:
smooth muscle, glandular tissue, or heart
the end organ receptor for the autonomic NS is _____
muscarinic (parasympathetic) and adrenergic (sympathetic)
What end organs are normally dually innervated?
cardiac, glands, and smooth muscles - para and sympa balance
ANS 1st nerve NT is:
Ach
ANS 1st nerve receptor is:
Nicotinic N cholinergic
ANS 2nd nerve parasympathetic NT is:
ACh
ANS 2nd nerve sympathetic NT is:
NE
ANS 2nd nerve parasympathetic receptor is:
muscarinic cholinergic receptor
adrenal medulla?
it's preganglionic neuron causes epinephrine to be released into blood
What does acetylcholineresterase do?
the enzyme that chews up ACh to recycle it, prevents muscle by going into depolarizing muscle paralysis
acetylcholine gets cleaved by acetylcholinesterase into
acetic acid + choline
Agonists do what?
stimulate receptors
Antagonists do what?
block receptor, binds with higher affinity to receptors compared to agonists
Curare (or gallamine)
- blocks skeletal muscle contraction
- for intubation (breathing tubes)
- nicotinic M cholinergic receptor antagonist - neuromuscular blocker
- NOT USED FOR GENERAL ANESTHETICS - muscles don't move, yet pt is awake
- non-depolarizing - muscle doesn't fire before paralyzing
- competitive blocker - enough increased ACh using anticholinesterases will reverse the binding of drug
Physostigmine
an anticholinesterase to reverse curare binding
Succinylcholine
- blocks skeletal muscle contraction
- for intubation
- nicotinic M cholinergic receptor antagonist - neuromuscular blocker
- depolarizing - muscle fibers contract before shutting down = paralyzed
- lasts 4-8 min = must wait for it to be degraded by cholinesterases
- non-competitive blocker - if you use anticholinesterase, nothing happens
- pt with "atypical cholinesterases" - they don't have enough cholinesterases to degrade succ so it lasts 24 hr
Anticholinesterases (neostigmine) to treat myosthenia gravis
- MG - autoimmune disease where nicotinic M cholinergic receptors are being destroyed
- anticholinesterase increases ACh at NMJ to increase interactions but eventually fails due to loss of receptors
- but they also increase ACh all over the body --> creates problems
Anticholinesterases in Alzheimer's pts - physostigmine and donepezil
- cross the blood-brain barrier
- improve memory using ACh
- do you want to increase muscle contraction? NO but there are good benefits
Parasympathetic division
- NT: ACh
- smooth muscle, glandular tissue, and cardiac tissue
- relaxed state
- miosis (pupils constricted)
- salivation
- heart rate slow
- digestion of food
- peristalsis
- good blood flow to skin and stomach
- constricted bronchi
- craniosacral neurons
- 1:1 ratio of pre:post ganglionic
Sympathetic division
- NT: norepinephrine
- fight/flight
- energizing multiple body organs
- mydriasis (pupils dilate)
- dry mouth
- sweating*
- bronchi open
- blood flow to brain and skeletal muscles
- heart rate increases
- thoracolumbar
- 1:20 ratio of pre:post ganglionic
SWEAT GLANDS
ACh is the NT yet it's a sympathetic innervation
parasympathetic NS agonist
more para
parasympathetic NS antagonist
more sympa
sympathetic NS agonist
more sympa
sympathetic NS antagonist
more para
beta blockers
slows heart rate by increasing parasympathetic
atropine
- muscarinic cholinergic receptor antagonist
- blocks parasympathetic side
- side effects - more sympa effects, blocks sweating
what's the "backup generator"?
adrenal medulla
norepinephrine stimulates
alpha1 and beta1
epinephrine stimulates
alpha1 beta1 and beta2
Which system has longer preganglionic fibers - sympa or parasympa?
parasympathetic
Pilocarpine (Salagen)
- muscarinic cholinergic receptor agonist --> increases salivation
- treats xerostomia from Sjogren's syndrome or radiation treatment
- it also increases other parasympathetic symptoms but salivation is most sensitive so you can avoid the other effects
If you use muscarinic cholinergic receptor agonist, do you see skeletal contraction?
no! because those use nicotinic M cholinergic receptors
Why wouldn't you want to use anticholinersterase to treat dry mouth?
it works to decrease xerostomia but it would also increase muscle contraction which you don't want.
mydriasis?
pupil dilation
miosis?
pupils constricting
4 antimuscarinics
1) Propantheline (Pro-banthine)
2) Glycopyrollate (Robinal)
3) Scopolamine (Transderm scop)
4) Diphenhydramine
Propantheline (Pro-banthine)
- antimuscarinics
- permanently charged so they stay out of the brain - minimal sedation
- dry the mouth and other peripheral anticholinergic effects
Glycopyrollate (Robinal)
- antimuscarinics
- permanently charged so they stay out of the brain - minimal sedation
- dry the mouth and other peripheral anticholinergic effects
Scopolamine (Transderm scop)
- patch behind ear
- antihistamine
- readily penetrate CNS therefore highly sedating
- good for motion sickness
Diphenhydramine
- patch behind ear
- antihistamine
- readily penetrate CNS therefore highly sedating
- good for motion sickness
How do diphenhydramine and scopolamine prevent motion sickness?
they block muscarinic cholinergic receptors in CNS (ACh receptors)
Why wouldn't antimuscarinics prevent motion sickness related to radiation or opioids?
that requires blocking receptors for seratonin and dopamine
3 irreversible anti-cholinesterases
1) neostigmine
2) donepezil
3) nerve gases (Soman, Sarin, and Tabun)
Neostigmine
- anti-cholinesterase
- used to treat myassthenia gravis by increasing ACh
- reversible, THEY LET GO
Donepezil
- anti-cholinesterase
- get into brain
- treats Alzheimer's
- reversible, THEY LET GO
Nerve gases
- irreversible binders
- anti-cholinesterases
- extremely lipid soluble - long effects
- penetrate body through skin and mucous - can be problem
- increases ACh and parasympathetic NS
- depolarizing blockade --> muscles keep firing
If you want to stop sweating, which receptors would you block?
muscarinic receptors
alpha 1 receptor of sympathetic division
- stimulation causes constriction of blood vessels under skin and mucous membranes
lidocaine + epinephrine
causes increased duration, increase efficacy, decreased local bleeding, slows systematic absorption of lidocaine
Prazosin (Mini-pres)
- blocks alpha 1 receptors
- alpha1 adrenergic antagonist
- causes vasodilation
- lowers blood pressure
- side effect: postural hypotension - when you stand, blood goes to legs due to dilation and you get low BP
"azosin" indicates
alpha1 blocker
Phentolamine
- alpha1 blocker and alpha2 blocker
- non-selective
- see more reflex tachycardia - heart trying to compensate for low BP
- available as Oraverse - which speeds recovery from numbness
Doxazosin (Cardura) and Terazosin (Hytrin)
- alpha1 blocker
- treat hypertension and congestive heart failure
- they vasodilate
- side effect: postural hypotension
Tamsulosin (Flomax)
- alpha1A* receptor blocker
- treats benign prostatic hypertrophy - enlarged prostate gland. This drug dilates the urethra and bladder neck for better urine flow.
Alpha 2 receptor of sympathetic division
- post synaptic
- similar to alpha1 but it has nerve terminals
- decreases NT release when stimulated*
Clonidine
- alpha2 stimulator
- decreases norepi release
- lowers BP
- mainly works in CNS
beta 1 receptor of sympathetic division
- found in the heart
- stimulation --> increased heart rate and contraction force*
too much epinephrine stimulates what receptors?
alpha 1 and beta 1
propranolol (Inderal)
- blocks beta1 receptors
- slows heart rate
- slows contraction force
- used to treat high blood pressure, angina, and rapid heart beats (tachy-arrhythmias)
the heart is _____ innervated by these two receptors
dually
beta1 (sympa) and muscarinic cholinergic (para) receptors . If one is blocked, the other works more.
what happens to heart when...
too much epi?
adding propranolol?
adding pilocarpine?
adding atropine?
- epi --> more beta1 --> increases heart rate (more sympa)
- propranolol --> beta antagonist --> slows heart (more para)
- pilocarpine --> muscarinic cholinergic agonist --> slows heart (more para)
- atropine --> muscarini cholinergic antagonist --> raises heart rate
beta2 adrenergic receptor of sympathetic division
- found in blood vessels in muscle and brain and bronchial tree
- vasoDILATION
albuterol (proventil)
- beta-2 adrenergic agonist
- used for acute attack
- leads to dilation of bronchial tree
ipatropium (atrovent)
- muscarinic cholinergic antagonist
- also useful in asthma along with albuterol
- more breathing
pathway of dopamine
tyrosine --> DOPA (amino acid) --> dopamine (catecholamine) --> norepinephrine --> epinephrine
Parkinsons
- too little DOPAMINE in the brain = too little dopaminergic stimulation in CNS
- too much ACh = too much muscarinic stimulation in CNS
treating Parkinsons
- give DOPA to get into brain then become dopamine
- problems with this - either DOPA turns into dopamine in periphery OR DOPA can get inactivated in the blood
What two drugs can block the nicotinic M cholinergic receptors leading to muscle paralysis?
curare and succinylcholine
Nicotine
- an agonist at nicotinic M and nicotinic N receptors on autonomic ganglia and the brain
- through cigarettes
What are harmful things included in cigarette smoke?
- carbon monoxide
- benzpyrene (carcinogen)
- 90% of lung diseases
effects of nicotine on cardiovascular system
- like sympathetic symptoms - increased bp, tachycardia
effects of nicotine on GI and urinary tracts
- like para symptoms - increased acid secretion, nausea, diarrhea, increasing urine
what two diseases can nicotine contribute to?
- recurrent peptic ulcer disease
- cardiovascular disease
what is physical dependence related to?
withdrawal symptoms
what is psychological dependence related to?
addiction
Nicotrol Patch (McNeil Consumer)
- nicotine transdermal system
- for more than 10 cigs a day
- also includes behavior modification (psych therapy)
NicoDerm CQ Patch (Smith Kline Beecham)
- nicotine transdermal system
- if more and less than 10 cigs a day, use diff dosages
- includes behavior modification too
Nicotine Polacrilex
- nicotine chewing gum
- dosage depends on more or less than 25 cigs a day
- buccal mucosal absorption
Nicorette Gum (smith kline beecham)
- nicotine chewing gum
- depends on more or less than 25 cigs a day
- buccal mucosal absorption
Bupropion
- atypical antidepressant
- weak inhibitor of dopamine, serotonin, and NE reuptake
- works as ANTIDEPRESSANT and SMOKING CESSATION drug and some people overdosed
Varenicline (Chantix)
- partial agonist of nicotinic receptors
- diminishes pleasure of smoking and prevents RELAPSE of smoking
- might induce depression or suicide or seizures
- popular
Mecamylamine (inversine)
- ganglionic blocker
- blocks nicotinic N cholinergic receptors on both sympathetic and parasympathetic autonomic GANGLIA
- mainly used in hypertensive crisis
- lots of para and sympa blockade side effects (resulting in xerostomia, constipation and hypotension)
Trimethaphan (afronad)
- ganglionic blocker
- blocks nicotinic N cholinergic receptors on both sympathetic and parasympathetic autonomic GANGLIA
- mainly used in hypertensive crisis
- lots of para and sympa blockade side effects (resulting in xerostomia/constipation and hypotension/bradycardia)
epinephrine acting on various receptors
- agonist of alpha1, beta1, and beta2 adrenergic receptors
- alpha1 = vasoconstriction
- beta1 = increased heart rate
- beta2 = dilation of bronchi
- THERE IS NO CNS AFFECT BECAUSE EPINEPHRINE IS A CATECHOLAMINE (TQ)
response of alpha1 adrenergic receptor
vasoconstriction skin and mucous membranes
response of beta1 adrenergic receptor
increased heart rate
increased contraction force
response of beta2 adrenergic receptor
bronchodilation
vasodilation skeletal muscle and internal organs
lidocaine vs. lidocaine/epi
lido/epi has a much longer duration
Ephedrine and Pseudophedrine (Pseudophed)
- more epinephrine
- pills for nasal decongestion and asthma
- stimulates alpha1, beta1, and beta2 receptors directly
- stimulates indirectly by releasing NE
- leads to tachyphylaxis (rapid development of tolerance)
- crosses blood brain barrier (not catecholamines)
Oxymetazoline (afrin)
- more epinephrine
- nasal decongestant
- pure alpha agonist --> vasoconstriction and hypertension
- if you push dose --> reflex brachycardia (body tries to compensate)
- studied as a NO NEEDLE tooth anesthesia
- teeth 4-13 numb
Norepinephrine
- alpha1 and beta1 adrenergic agonist
- vasoconstriction and increased heart rate
- no beta2 effects
Dopamine
- dopamine and beta1 adrenergic receptor agonist
- dopamine receptor --> vasodilation
- can't cross blood brain barrier
Isoproterenol (Isuprel)
- anti-asthmatic drug
- stimulates beta1 and beta2 adrenergic receptors
- problem during asthma attack? stimulating beta1 increases myocardial oxygen demand
Albuterol (Proventil)
- beta2 adrenergic agonists
- lacks beta1 activity
- bronchodilation without cardiac stimulation
- a major antiasthamtic inhaler
Terbutaline (Brethaire)
- beta2 adrenergic agonists
- lacks beta1 activity
- bronchodilation without cardiac stimulation
- a major antiasthamtic inhaler
Salmeterol (Servent)
- beta2 adrenergic agonists
- lacks beta1 activity
- bronchodilation without cardiac stimulation
- a major antiasthamtic inhaler
Propranolol (Inderal)
- antagonist to beta1 and beta2 adrenergic receptors
- treats angina, cardiac arrhythmias, and hypertension
- problem with people with high bp and asthma --> bronchoconstriction leads to death due to blockade of beta2
Metoprolol (Lopressor)
- selective antagonist for beta1 receptor
- negative inotropic and negative chronotropic effect without bronchoconstriction!
Atenolol (Tenormin)
- selective antagonist for beta1 receptor
- negative inotropic and negative chronotropic effect without bronchoconstriction!
Haloperidol (Haldol)
- treats Schizophrenia
- dopamine receptor antagonist
- improves some symptoms
- can lead to extrapyramidal effects (Parkinson's-like syndrome)
- also blocks alpha1 receptors --> postural hypotension
Schizophrenia
- brain disorder
- disorganized thoughts, loss of executive function, paranoia, auditory and visual hallucinations
- GRAY MATTER LOSS
- genetic predisposition and certain secondary environmental hits
benztropine
- treats extrapyramidal effects (parkinson's like syndrome)
- block DA receptors, then give this as anticholinergic
What happens when you block alpha1? What does it treat?
- lower BP
- treats benign prostatic hypertrophy
What happens when you stimulate alpha1?
increases local anesthetic duration
What happens when you stimulate alpha2?
lowers BP and decreases NE release
What happens when you block beta1?
- lowers BP
- slows heart in angina and arrythmias
What happens when you stimulate beta2?
treats asthma
What happens when you block MAO?
treats depression and parkinsons
(MAO is an enzyme that degrades NT so blocking this causes more NT, more dopamine)
What happens when you block COMT?
treat parkinsons
What happens when you give L-Dopa?
Treats parkinsons because it's a DA precursor
What happens when you block reuptake 1 (at presynaptic nerve terminal, serotonin and NE)?
treats depression
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