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1

ANS Pharmacology

Study of drugs that act on receptors and neurotransmitters in the ANS

2

Somatic NS

Controls voluntary movement of skeletal muscle
One efferent motor neuron that is cholinergic and releases ACh in the NMJ

3

Autonomic NS

Controls involuntary actions of internal organs and glands
Parasympathetic and sympathetic

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Enteric NS

3rd division of ANS
Network of ANS neurons in the walls of the gut that regulate gut activities
Motor, secretory

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Parasympathetic NS

Rest and digest
Cranial and sacral regions, ganglion are located close to target area
Slows HR and reduces BP
Simulates digestive tract to process food and eliminate waste
Controls erections

6

Sympathetic NS

Fight or flight
Thoracic and lumber regions, ganglia located close to spinal cord
Increases HR and force of contraction of heart
Increases basal metabolic rate
Increases sweating
Widens airways to make breathing easier
Decreases digestion/urination
Controls ejaculation

7

Organization of efferent ANS

Preganglion neuron is in brain or spinal cord
Synapses on postganglionic neuron in an autonomic ganglion
Axon of postganglionic neutron innervates the target organ

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Pupil regulation

Acetylcholine causes sphincter pupillae to contracts (PNS)
NE causes dilator pupille to contract (SNS)

9

ACh

In PNS and SNS
PNS: Pre (nicotinic) and post (muscarinic) - synaptic ganglia are cholinergic
SNS: only presynaptic ganglia (nicotinic) - post are adrenergic
Somatic: nicotinic receptor in NMJ

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Adrenal medulla cells

Innervated by preganglionic fibres that release ACh and stimulate release of NE and EN

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Exceptions to Sympathetic NTs

Sweat glands: nicotinic, then muscarinic
Renal vascular smooth muscle: nicotinic then dopamine

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Presynaptic modulation

NT release is modulated by receptors on the presynaptic membranes of neurons
Presynaptic receptors respond to primary NT of nerve
Receptors can be positive or negative modulators of NT release

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G protein coupled receptors

Gq coupled
Gi coupled
Gs coupled

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Gq

Increase 2nd messengers IP3, DAG, increase Ca

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Gi

Decrease cAMP, open K channel, decrease Ca influx

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Gs

Increases cAMP

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Ligand-gated ion channels

Nn: ganglionic
Nm: NMJ
Activation by ligand opens a cation channel and allows Na influx, depolarization

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Cholinergic Agonists

Cholinomimetics, parasympatomimetic
Drugs that mimic the action of ACh at cholinergic receptors and increase parasympathetic nervous system responses

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Cholinergic Antagonists

Cholinolytic, parasympatholytics
Drugs that inhibit the action of ACh at cholinergic receptors and decrease parasympathetic nervous system responses

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Cholinergic Nerve

ACh is made from choline and acetyl CoA
In synaptic cleft, ACh is rapidly broken down by AChE
Choline is transported back into the axon terminal and used to make more ACh

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Cholinergic Receptors

Muscarinic and nicotinic receptors
ACh binds equally with both receptor types

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Muscarinic Receptors

Bind muscarine with very high affinity
Do not bind nicotine
M1, M2, M3

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M1

CNS, Gq

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M2

Heart, decrease HR
Gi

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M3

Smooth muscle contraction, exocrine gland increased secretion
Gq

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Nicotinic receptors

Nn: autonomic ganglia stimulation of SNS and PNS, Adrenal medulla release of NE, EN
Nm: skeletal muscle contraction

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Muscarinic agonists

Agents that activate muscarinic receptor directly: post-synaptic receptors
Glaucoma, dry mouth, stimulate tone in bladder, increase gut motility

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Non-selective muscarinic agonist

ACh

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Selective muscarinic agonist

Naturally occurring alkaloids: muscarine, pilocarpine
Synthetic analogues of ACh: bethanechol

30

Muscarine

Can find in mushrooms
Can cross into the CNS
In periphery, mimics effects of parasympathetic nerve stimulation