Autonomic nervous system Flashcards
What is the study of drugs that influence the ANS which controls involuntary physiological functions like heart rate, digestion, and RR?
autonomic pharmacology
What does the ANS control that drugs target?
cardiovascular, resp, GI, other systemic disorders
What does the sympathetic nervous system do to the eyes?
contracts radial muscle to dilate the eye (mydriasis)
What does the parasympathetic nervous system do to the eyes?
contraction of the circular muscle to constrict the eye (miosis)
How are nore/epi terminated?
reuptake, inactivated by COMT or MAO-Is
Review: receptors
sympathetic - adrenergic
parasympathetic - muscarinic, nicotinic
What does muscarinic M1 act on?
CNS neurons; sympathetic postganglionic neurons
What does muscarinic M2 act on?
myocardium, smooth muscle, CNS neurons
What does muscarinic M3 act on?
exocrine gland, vessels, CNS neurons
What does muscarinic M4 act on?
CNS neurons (cholinergic)
What does muscarinic M5 act on?
vascular endothelium, CNS neurons (cholinergic)
What does alpha 1 work on?
vascular smooth muscle (cholinergic)
What does alpha 2 work on?
presynaptic adrenergic nerve terminals (cholinergic)
What does beta 1 work on?
heart (cholinergic)
What does beta 2 work on?
vascular smooth muscle and cardiac muscle (cholinergic)
What does beta 3 work on?
lipocytes and bladder (cholinergic)
What are cholinergic agonists?
parasympathetiomimetics –> mimic effects of PNS
What type of drug is bethanechol, pilocarpine?
cholinergic agonists
What are cholinergic antagonists/anticholinergic drugs?
parasympatholytics –> block effects of PNS
What type of drug is atropine, scopolamine?
cholinergic antagonists
What are adrenergic agonists?
sympathomimetics –> mimic effect of SNS
What type of drugs are epinephrine, norepinephrine, albuterol?
adrenergic agonists
What are adrenergic antagonists?
sympatholytics –> blocking effect of SNS
What type of drugs are beta blockers and alpha blockers?
adrenergic antagonists
What’s the MOA of cholinergic agonists?
stimulate cholinergic receptors, mimicking PS effects
can be direct (at a muscarinic or nicotinic receptor)
or indirect (block metabolism of acetycholine and increase concentration)
What would these effects be from?
- miosis
- decreased heart rate
- bronchoconstriction/increased secretions
- increased GI motility and sphincter relaxation
- bladder wall contraction and sphincter relaxation
- increased sweat secretion?
cholinergic agonists
What are these drugs an example of?
esters -> bethanechol
alkaloids (pilocarpine, muscarine, nicotine)?
direct muscarinic agonists
What can bethanechol be used for?
urinary retention –> increased bladder contraction, non-obstructive post-op ileus
What can alkaloids be used to treat?
acute-angle closure glaucoma
What can pilocarpine and nicotine cause (separate effects)?
pilocarpine - stimulates salvation, used in dry mouth (xerostomia)
nicotine - stimulates nicotinic receptors, increasing HR and BP
What are contraindications for direct muscarinic agonists?
asthma, GI obstruction, PUD, pronounced bradycardia, HOTN
What MOA are these drugs:
- neostigmine
-pyridostigmine
-donepezil
-galantamine
-rivastigmine
reversible cholinesterase inhibitors (compete w Ach for a site on the enzyme)
What MOA are these drugs:
- malthion
- parathion
-sarin
-insecticides/nerve gas
-phosphorylate AchE and inactivate
-highly lipophilic
irreversible cholinesterase inhibitors (phosphorylate AchE and inactivate it)
What are clinical uses for cholinesterase inhibitors?
Myasthenia gravis, Alzheimer’s disease, open angle glaucoma, reversal of neuromuscular blockade after surgery
What are adverse effects of cholinesterase inhibitors?
SLUDGEM + low HR and bronchorrhea
Salivating/sweating
Lacrimation
Urination
Diarrhea
GI upset
Emesis
Miosis
What is toxicity from cholinesterase inhibitors from?
organophosphate/pesticide exposure, nerve agents which can lead to AMS, coma, seizures
treat w/ atropine and pralidoxime, benzos for seizures
What’s the MOA of cholinergic antagonists?
block cholinergic receptors, reducing PNS effects , competing for binding with Ach on muscarinic receptor
What are these effects from:
- mydriasis
- high HR
- bronchodilation, less secretion
- reduced motility
- urinary retention
- decreased secretions of glands
- potentially drowsiness, hallucinations, coma?
cholinergic antagonists/anticholinergics
What can you use atropine for?
anticholinergic = reversal agent, pre-op for drying secretions
What can you use scopolamine for?
anticholinergic = motion sickness, drying secretions
What can you use dicyclomine (bentyl) for?
anticholinergic = GI antispasmodic (IBS)
What can you use oxybutynin (ditropan XL) for?
anticholinergic = urinary frequency, urgency, incontinence
What can you use benztropine (cogentin) for?
anticholinergic = drug induced extra pyramidal symptoms; parkinsonism
What can you use glycopyrrolate for?
anticholinergic = reduction of secretions (death rattle), PUD
What can you use trihexyphenidyl for?
anticholinergic = drug-induced extra pyramidal symptoms; parkinsonism
What can you use trotropium (spirivia) / ipatropium (nasal) for?
anticholinergic = COPD
What anticholinergics are muscarinic antagonists?
atropine (increases HR) and scopolamine (used for N/V)
What anticholinergics are nicotinic antagonists?
curare (muscle relaxant by blocking nicotonic receptors at neuromuscular junctions)
What typical antipsychotics are anticholinergics?
haloperidol (haldol)
What antidepressants are anticholinergics?
amitriptyline (TCAs)
What are ADRs of anticholinergics?
ANTI-SLUDGE (opp of salivation/sweating, lacirmation, urination, defecation, GI upset, emesis, +CNS effects)
ABCDs
Agitation
Blurred vision
Constipation/confusion
Dry mouth
Stasis of urine
What are anticholinergic contraindications?
untreated narrow angle glaucoma, GI obstruction or constipation, bladder obstruction, BPH
What is characterized by psychosis/delirium, hot/flushed skin, dry mucous membranes, constipation, urinary retention, pupil dilation, inability to focus close, hyperthermia?
anticholinergic syndrome
reverse w/ physostigmine
What do anticholinergic NMBs do?
bind to all nicotinic receptors (at junction, autonomic ganglia –> muscle relaxation)
depolarizing binds to receptor, opening channel (succinylcholine)
non depolarizing = binds to receptor does NOT open channel (rocuronium, vecuronium)
What is the adrenergic agonists MOA?
stimulate adrenergic receptors
a1 = vasoconstriction, GI/urinary sphincter
a2 = lower BP/lowers sympathetic nervous system
b1=high HR and CO
b2 = bronchodilation, vasodilation, relax of bladder muscle, low GI motility
What’s a direct alpha 1 agonist?
phenylephrine (decongestant) and can be used in HOTN to increase BP
What’s a direct alpha 2 agonist?
clonidine for HTN
What’s a direct beta 1 agonist?
dobutamine for CHF (increase contractility)
What’s a direct beta 2 agonist?
albuterol for bronchodilation, asthma
What are alpha and beta agonists?
epinephrine and norepinephrine for vasopressors, epi for anaphylaxis
How do indirect acting adrenergic agonists work?
release previously stored norepinephrine into synapse
amphetamines + derivatives
tx ADHD and narcolepsy
CII meds
pseudophedrine also related to this
What are ADRs of adrenergic agonists?
hypertension, tachycardia, increased risk for stroke/HA, arrythmia, mydriasis/photophobia
What are contraindications for adrenergic agonists?
within 14 days of MAO-I
CV disease
increased IOP
BPH
seizure disorder
thyroid dysfunction
What is the MOA of adrenergic antagonists?
block SNS - alpha and beta blockers
How are central alpha 2 agonists used as adrenergic antagonists?
create a negative feedback loop and inhibit sympathetic output from brain and release of norepi from nerve terminals!
What are examples of central alpha 2 agonists used as adrenergic antagonists?
clonidine, methyldopa, guanfacine, tizanidine
What’s the MOA of alpha 1 blockers?
blockade that will produce vasodilation
more effective when it is “Firing” (i.e. when someone is standing –> postural hypotension or first dose syncope)
can also get reflex tachycardia
What are examples of alpha-1 blockers?
prazosin (HTN and BPH), doxazosin, terazosin for BPH and HTN
What are some more selective alpha-1 blockers for 1a receptor in GI tract?
tamsulosin = flomax (kidney stone) also for BPH
can cause lower ejaculation, or absent/retrograde
What are clinical uses for beta blockers?
cardiac arrythmias (atrial fibrillation)
HTN
angina
HF
hyperthyroidism
migraines
What are examples of cardioselective beta blockers?
acebutolol, atenolol, bisoprolol, esmolol, metoprolol
What are examples of nonselective beta blockers?
propranolol, nadolol, penbutolol, pindolol, timolol
What are ADRs of beta blockers?
decreased BP, HR, CO, fatigue, bronchoconstriction, block the effects of hypoglycemia (prevents response), heart block, ED, depression
What type of drug is labetalol, carvedilol?
mixed alpha/beta blockers, used often similar to beta blockers for HTN and heart failure
labetalol for pregnancy
What of these drugs would you use for HTN?
alpha blockers (prazosin)
beta blockers (atenolol)
alpha 2 agonists (clonidine)
What of these drugs would you use for asthma/COPD?
beta-2 agonists (albuterol), anticholinergics (ipratropium)
What of these drugs would you use for heart failure?
beta blockers (carvedilol), ACE inhibitors
What of these drugs would you use for glaucoma?
muscarinic agonists (pilocarpine)
What of these drugs would you use for motion sickness?
muscarinic antagonists (scopolamine)
How can you treat parkinson’s?
anticholinergics (benztropine) to manage tremors and rigidity
How can you treat alzheimers?
acetylcholinesterase inhibitors (donepezil) to increase Ach
How can you treat overactive bladder?
anticholinergics (oxybutynin) to reduce bladder spasms
