Midterm - Autonomic Pharmacology Flashcards
Autonomic nervous system
- part of peripheral nervous system
- SNS = fight or flight
- PSNS = rest and digest
Where are SNS and PSNS not physiological ANTagonists?
smooth muscle, pilomotor, glands, blood vessels
Preganglionic vs postganglionic fibers
- Preganglionic is closer to CNS (from spinal cord to ganglia)
- Postganglionic is closer to tissue (innervates tissue from ganglia)
Structure of SNS ganglia
- ganglia near the spinal cord
- ONE short pre- to MANY long post- ganglionic fibers
Structuer of PSNS ganglia
- ganglia close to or in target tissue
- ONE long pre- to ONE short post- ganglionic fibers
PSNS neurotransmitters
- cholinergic = release ACh
SNS neurotransmitters
- adrenergic = release NE from postganglionic neurons (& EP from glands)
Balance of neurotransmission in cardiac muscle
- Resting = PSNS = ACh is M2 (less B1 activated from SNS)
- Active = SNS = NE is activating B1 (less M2 activated from PSNS)
ACh
- one step to be synthesized by ChAT or to be degraded by AChE
- activates muscarinic and nicotinic receptors
How do nicotinic receptors act?
Ion influx through Na+/K+ channel = depolarization
Norepinephrine synthesis
1) Tyrosine hydroxylase
2) Dopa decarboxylase
3) Dopamine Beta-hydroxylase
Norepinephrine degredation
1) Re-uptake (by MAO)
2) Diffusion away from synapse (by COMT)
Why is alpha2 different than alpha1, beta1, beta2 and M, N?
It is found on the PREsynaptic cleft (the others are on the POSTsynaptic)
Beta-hydroxylase
Converts dopamine into NE once transported into synaptic vesicles
Receptors of the eye
- Constriction = M3 contracts the sphincter
- Dilation = alpha1 contracts the dilator muscle
- Secretion = beta increases and alpha decreases
- Drainage = M3 contracts the ciliary muscle
Receptors of the heart
Heart rate = M2 decreases, Beta1 increases
Receptors of the blood vessels
- Vasodilation = M3, M5
- Vasoconstriction = Alpha1
- Vasodilation of the BV in skeletal muscle = Beta2
Receptors of most organs & glands
- M3 = contraction and secretion
- Beta2 = relaxation of smooth muscle
- Alpha1 = constriction of sphincters
Why are the two indirect acting cholinergic agonists different?
- Echothiophate = long-acting (irreversible bond to AChE)
- Physostigmine = intermediate-acting (reversible bond to AChE)
Which direct cholinergic agonists do NOT absorb and distribute well?
Acetylcholine, bethanechol
Which direct cholinergic agonists DO absorb and distribute well?
Muscarine, pilocarpine, nicotine
Which cholinergic agonists activate PSNS?
Muscarinic (with the exception of sweat glands which activate SNS)
Which cholinergic agonists activates both PSNS and SNS?
Nicotinic (initially stimulates, then blocks)
What does nicotine do at the ganglia?
- activates both PSNS and SNS
- increases ACh and NE release into tissue
Tissues where SNS dominantes
- blood vessels = no ACh-release (alpha1 = vasoconstriction in organs and skin, beta2 = vasodilation in skeletal muscle)
- heart = rate and force increases
Why does PSNS dominate in tissues that have both PSNS and SNS innervation?
Increased ACh amplifies effects at BOTH ganglia and tissue, unlike in SNS where increased ACh only amplifies at the ganglia (junction with tissue has NE not ACh)
What do drugs that activate N receptors do?
Act at adrenal gland to amplify PSNS AND SNS activity:
- BV = SNS only, so alpha1 vasoconstricts in organs & skin and beta2 vasodilates in skeletal
- heart = increases heart rate
What do indirect cholinergic agonists do to the heart?
- inhibit AChE = increase ACh at ganglia and adrenal gland = activates Nn = stimulates PSNS and SNS
- increased ACh = decreased rate & force of contraction
Symptoms of muscarinic excess
- Diarrhea
- Urination
- Miosis (pupil constriction)
- Bradychardia
- Bronchoconstriction
- Excitation of CNS
- Lacrimation (eye watering)
- Sweating and salivation
Nicotine toxicities
- overexcitement of CNS can cause seizure
- leads to eventual downregulation of N receptors (coma, respiratory depression)
- PSNS activation = muscarinic excess symptoms
- increased BP and heart rate
Why are atropine and pralidoxime used to treat organophosphate poisoning?
- symptoms come from muscarinic excess
- these are muscarinic ANTagonists
Atropine eye drops
- Used to be used for cosmetics because they dilate the pupil
- BUT they block M receptors across the whole body at the same time (causes dry mouth)
Ganglionic blockers
- antinicotinic
- relieves pressure in vessels in emergency situations to decrease SNS activation in BV
- eg. trimethaphan
Neuromuscular blockers
- antinicotinic
- used in surgical procedures to reduce skeletal muscle contraction
-eg. D-tubocurarine
Glaucoma treatment
Pilocarpine, physostigmine, echothiophate
How does the mechanism of action differ between pilocarpine and physostigmine?
- Pilocarpine: direct agonist = binds and activates M3
- Physostigmine: inhibits AChE = increase ACh = increase M3
What cholinergic drug(s) should be avoided in an individual with glaucoma?
Any muscarinic antagonist (atropine, D-tubocurarine, trimethaphan)
Factors influencing heart rate
- cardiac output (CO) = heart rate x stroke volume
- vascular tone = peripheral vascular resistance (PVR)
BP= CO x PVR
Cholinomimetics vs sympathomimetics
- Cholinomimetics = mimic action of
ACh - Sympathomimetics = mimic
action of NE/epinephrine
Baroreceptors
- monitors blood pressure
- BP changes = baroreceptors initiate reflex pathways = moment to moment regulation of BP
How would baroreceptors respond to low blood pressure?
Signal to CNS to decrease PSNS and increase SNS (SNS innervates BV)
How does clonidine prevent diarrhea?
activates alpha2 = ↓ACh release = ↓M3 receptor activation = ↓GI tract motility (more time to absorb fluid)
Toxicities of indirect CNS agonists
Multiple transmitters increased and multiple receptors activated = hyperactivity, tremor, seizures, etc.
Baroreceptor reflex response
- if beta1 is blocked, SNS increases by alpha1 (vasoconstriction)
- if alpha1 is blocked, beta1 increases SNS (increased rate/force of contraction)
