Step 1: pharmacology: autonomic drugs

What components of the sympathetic nervous system are innervated by cholinergic fibers?
adrenal medulla and sweat glands

ACh acts are 2 types of receptors: nicotinic and muscarinic. What types of receptors are these?
nicotinic ACh receptors are Na+/K+ channels
muscarinic ACh receptors are G-protein-coupled receptors (more detail in another card)

What G-protein class are the alpha-1, alpha-2, beta-1, and beta-2 receptors? (acronym) All of these receptors act to engage the sympathetic response except…?
q, i, s, s, respectively (like KISS)
alpha-2 receptor decreases sympathetic outflow and decreases insulin release

What G-protein class are the M1, M2, and M3 receptors? (acronym) All of these receptors engage the parasympathetic response. Where are they found?
q, i, q, respectively (like KICK)
M1 is in the CNS and ENS
M2: heart
M3: everywhere else

What G-protein class are the D1 and D2 receptors?
D1: s
D2: i
(dopamine receptor? – SI, it is)

What G-protein class are the H1 and H2 receptors? What are the roles of these receptors?
H1: q
H2: s
H1: all of the classic ‘histamine things’- mucus, contraction of bronchioles
H2: parietal cell, H+ secretion

Vasopressin/AVP/ADH acts to both contract arterioles and increase H2O absorption in the kidney. What receptors are involved and what are the G-protein classes of these receptors
V1: arterioles, q
V2: kidneys, s
(histamine and vaspopressin receptors follow the same pattern)

Some G proteins are q. Some are s. Some are i. What is the significance? What are the cellular pathways that these G protein receptors are activating/inhibiting?
G(q) –> stimulates phospholipase C –> DAG, IP3 –> protein kinase C and increased Ca2+ into the cell
G(s)/G(i) –> stimulates/inhibits adenylyl cyclase –> cAMP –> protein kinase A –> more Ca2+ in the heart, relaxation of smooth muscle

Describe the negative feedback mechanism associated with NE release from the noradrenergic nerve terminal?
NE activates the alpha-2 receptor on the pre-synaptic terminal, thus inhibiting further release of NE

Discuss the actions of hemicholinium, vesamicol, and botulinum on the release of ACh from the cholinergic nerve terminal.
hemicholinium: blocks uptake of choline –> decreases [ACh]
vesamicol: (looks like vesicle) –> blocks accumulation of ACh in vesicles
botulinum: cleaves SNAP-25, part of the dock + release apparatus for ACh vesicles on the cell surface

Discuss the actions of metyrosine, reserpine, cocaine, and amphetamines on the release of NE from the noradrenergic nerve terminal.
metyrosine: blocks tyrosine –> DOPA
reserpine: blocks vesicular monoamine transport channel
cocaine: blocks NE re-uptake
amphetamines: stimulates release and blocks reuptake

What does bethanechol do? When is it used?
Direct cholinergic agonist (resistant to AChE)
used to wake up bowel and bladder smooth muscle after surgery

What does carbachol do? When is it used?
Direct cholinergic agonist (just like ACh)
used for glaucoma, constricts pupils

What does pilocarpine do? When is it used?
Direct cholinergic (M3) agonist (resistant to AChE)
potent stimulator of secretions, used for narrow-angle glaucoma

What does metacholine do? When is it used?
Direct cholinergic agonist
Challenge test for diagonsis fo asthma

What is the main difference between neostigmine, pyridostigmine and physostigmine? When are they used? (AChE inhibitors)
Neo- and pyrido- do not penetrate the CNS; used for myasthenia gravis (pyrido-) and post-operatively (neo-)
Physo- does penetrate the CNS, used for atropine overdose

What is unique about edrophonium and what is it used for?
Very short acting AChE inhibitor for myasthenia gravis diagnosis

What do echothiophate and donepezil do? What are they used for?
They are AChE inhibitors
Echothiophate is used for glaucoma
Donepezil is used for Alzheimer’s disease

A patient presents with diarrhea, urination, miosis, bronchospasm lacrimation, and other parasympathetic signs? What is going on here?
Probably AChE inhibitor poisoning, possibly from an organophosphate (insecticides)

What do atropine, homatropine, tropicamide do? For what organ system are they used?
Antagonize muscarinic receptors, causing a sympathetic response
All of these are used for the eye: mydriasis and cycloplegia (atropine is also used to treat bradycardia)

What does benztropine do? When is it used?
Antagonizes muscarinic receptors in the CNS
used to treat Parkinson’s disease

What does scopolamine do? When is it used?
Antagonizes muscarinic receptors in the CNS
used for motion sickness

What does ipratropium do? When is it used?
Antagonizes muscarinic receptors in the lungs
used for COPD and asthma

What do oxybutynin and glycopyrrolate do? When are they used?
Antagonize muscarinic receptors in the bladder
used to reduce urgency in mild cystitis

What do methscopolamine, prienzepine, and propantheline do? When are they used?
Antagonize muscarinic receptors in the gut
used to treat peptic ulcers

What are the 5 classic side effects of atropine toxicity?
hot as a hare
dry as a bone
red as a beet
blind as a bat
mad as a hatter

Describe the effect of epinephrine on alpha-1, alpha-2, beta-1, and beta-2 receptors.
Potent agonist for all, a little stronger effect on beta receptors (for the purposes of boards…)

Describe the effect of NE on alpha-1, alpha-2, beta-1 and beta-2 receptors.
Potent agonist for alpha-1, alpha-2, weak agonist for beta-1, no effect on beta-2 receptors

Describe the effect of isoproterenol on alpha-1, alpha-2, beta-1, and beta-2 receptors.
potent beta-1 and beta-2 agonist, no effect on alpha receptors

Describe the affinity of dopamine for D1, alpha and beta receptors
D1 > beta > alpha (with a small dose, only hits dopamine receptors; with a large dose, stimulates alpha-1 and -2 receptors

Describe the effect of dobutamine on alpha-1, alpha-2, beta-1 and beta-2 receptors.
Essentially only agonist for beta-1 receptors

When do you use dopamine vs. dobutamine in the tx of cardiogenic shock?
Key: dopamine will dilate renal beds, so if a patient is in shock and has little urine output, dopamine is OK
use dobutamine if SBP>80

Describe the effect of phenylephrine on alpha-1, alpha-2, beta-1 and beta-2 receptors.
agonist for alpha-1 and alpha-2, no effect on beta receptors
(good for vasoconstriction and decongestion)

What class of drug are metaproterenol, albuterol, salmeterol, and terbutaline? How are each of these drugs used clinically?
Beta agonists, with a greater effect on the beta-2 receptor.
Metaproterenol and albuterol are used for acute asthma control (bronchodilation)
Salmeterol is used for long term asthma control (must be used with steroid tx)
terbutaline is used for premature contractions

What is the drug ritodrine used for?
premature contractions (selective beta-2 agonist)

How do amphetamine, ephedrine, and cocaine work to produce their sympathomimetic effects?
amphetamine: releases stored catecholamines and blocks reuptake
ephedrine: releases stored catecholamines
cocaine: blocks reuptake of catecholamines

How do you expect HR to change if given a dose of NE vs a dose of isoproterenol?
NE favors alpha-1 receptor stimulation, reflex bradycardia = decreased HR
ISO favors beta-1 and beta-2 stimulation = increased HR

What is the action of clonidine and alpha-methyldopa?
centrally acting alpha-2 agonists (decrease central sympathetic outflow)

What is the action of phenoxybenzamine (irreversible) and phentolamine (reversible)?
non-selective alpha-blockers
(associate phenoxybenzamine with pheochromocytoma – tx before removal of tumor)

What is the action of drugs ending in -zosin?
alpha-1 selective blocker (for HTN (not first line) and urinary retention in BPH)

What is the action of mirtazapine? For what is it used?
alpha-2 selective blocker
used for depression (has a sedative effect and causes weight gain)

Patient A receives a dose of epinephrine. Patient B receives a dose of phenylephrine. Both have an increase in MAP. Both patients are then given a dose of phentolamine (hint: what does this do?), and then A gets EPI again and B gets phenylephrine again. How will MAP respond after the second dose in A and B?
A: MAP goes DOWN (EPI response reversal) 2/2 action on beta-2 receptors
B: MAP stays near normal 2/2 action on alpha receptors being completely blocked by phentolamine (non-selective, reversible alpha blocker)

How do beta-blockers affect the RAAS? How do beta-blockers help with glaucoma?
beta-blockers decrease renin secretion 2/2 beta-receptor blockade on JGA cells
Timolol decreases the secretion of aqueous humor

What are 2 groups of patients that must be watched carefully with beta-blockers?
Those with asthma
Those with DM

What is the activity of acebutolol, betoxolol, esmolol, atenolol, and metoprolol?
selective beta-1 blockers (useful in those with asthma, other pulmonary conditions)

What is the activity of propranolol, timolol, nadolol, and pindolol?
non-selective beta blockers

What is the activity of carvedilol and labetalol?
alpha-1, beta-1 and beta-2 blockers

What is significant about pindolol (beta-1,-2 blocker) and acebutolol (beta-1 blocker)?
partial beta agonists (not antagonists)

alpha 1- found where? – vascular smooth muscle in skin and gut alpha 1- effect? – activates vasoconstriction – during flight or fight want reduced blood flow to skin and gut – End result: VASOCONSTRICTION at skin and gut WE …

_________ cholinergic receptors are found on the autonomic ganglia/skeletal muscle NMRs while __________ cholinergic receptors are found on smooth muscle of the heart and glands (muscarinic/nicotinic) nicotinic; muscarinic _____________ cholinergic receptors are GPCRs and ____________ cholinergic receptors are ion channels …

parasympathethic nervous system decrease heart rate, nonvascular smooth muscle contracts (increase mobility of digestive muscles, increased bladder motility) sphincters relax eye ciliary muscles contract increase in exocrine gland secretion Sympathetic nervous system Fight or flight increase in HR increase in …

A-methyl-dopa Use: HTN, Opioid Withdrawal. Mechanism: A2 agonist, decreases sympathetic outflow, inhibits NE release, rebound HT. SE: dry mouth, sedation. Note: A-methyl-dopa is metabolized to A-methyl-NE (A2 agonist) Cocaine Inhibits neuronal uptake, can cross into CNS. I: amphetamines, CA Always …

Two divisions of the Nervous System Central Nervous System (brain and spinal cord) Peripheral Nervous System (outside of brain and spinal cord) Two divisions of the Peripheral NS Efferent Division (consists of the neurons that carry signals AWAY from the …

First-Pass Effect Drug absorbed from GI tract and carried to the liver through portal circulation. Some drugs extensively metablized by liver. Only part of drug reaches systemic circulation for distribution theses types of drugs should not be administered PO (lidocaine/some …

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