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Pharmacology 3001 > ANS Pharmacology - Kelly 1 > Flashcards

ANS Pharmacology - Kelly 1 Flashcards

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1
Q

ANS Pharmacology

A

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

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2
Q

Somatic NS

A

Controls voluntary movement of skeletal muscle

One efferent motor neuron that is cholinergic and releases ACh in the NMJ

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3
Q

Autonomic NS

A

Controls involuntary actions of internal organs and glands

Parasympathetic and sympathetic

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4
Q

Enteric NS

A

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

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5
Q

Parasympathetic NS

A

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

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6
Q

Sympathetic NS

A 
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
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7
Q

Organization of efferent ANS

A

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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8
Q

Pupil regulation

A

Acetylcholine causes sphincter pupillae to contracts (PNS)

NE causes dilator pupille to contract (SNS)

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9
Q

ACh

A

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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10
Q

Adrenal medulla cells

A

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

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11
Q

Exceptions to Sympathetic NTs

A

Sweat glands: nicotinic, then muscarinic

Renal vascular smooth muscle: nicotinic then dopamine

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12
Q

Presynaptic modulation

A

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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13
Q

G protein coupled receptors

A

Gq coupled
Gi coupled
Gs coupled

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14
Q

Gq

A

Increase 2nd messengers IP3, DAG, increase Ca

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15
Q

Gi

A

Decrease cAMP, open K channel, decrease Ca influx

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16
Q

Gs

A

Increases cAMP

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17
Q

Ligand-gated ion channels

A

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

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18
Q

Cholinergic Agonists

A

Cholinomimetics, parasympatomimetic

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

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19
Q

Cholinergic Antagonists

A

Cholinolytic, parasympatholytics

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

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20
Q

Cholinergic Nerve

A

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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21
Q

Cholinergic Receptors

A

Muscarinic and nicotinic receptors

ACh binds equally with both receptor types

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22
Q

Muscarinic Receptors

A

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

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23
Q

M1

A

CNS, Gq

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24
Q

M2

A

Heart, decrease HR

Gi

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25
M3
Smooth muscle contraction, exocrine gland increased secretion Gq
26
Nicotinic receptors
Nn: autonomic ganglia stimulation of SNS and PNS, Adrenal medulla release of NE, EN Nm: skeletal muscle contraction
27
Muscarinic agonists
Agents that activate muscarinic receptor directly: post-synaptic receptors Glaucoma, dry mouth, stimulate tone in bladder, increase gut motility
28
Non-selective muscarinic agonist
ACh
29
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
31
Glaucoma: use of direct muscarinic agonist
Constricts ciliary muscle of eye and increase aqueous humour drainage Uses as eyedrops Activate M3 receptors
32
Side effects of muscarinic agonists
``` Stimulates all muscarinic receptors GI disturbances CNS effects Effects on HR Salivation and bronchoconstriction ```
33
Muscarinic competitive antagonists
Bind to muscarinic receptors preventing ACh from binding Naturally occurring alkaloids: atropine Synthetic analogue: ipratropium bromide
34
Atropine
``` Naturally occurring alkaloid Muscarinic competitive antagonist Dilates eye pupil for ophthalmic exam (relaxes iris sphincter and ciliary muscle) Treats bradycardia Reduces secretion during surgery ```
35
Ipratoprium bromide
Synthetic analogue Muscarinic competitive antagonist Treats asthma, COPD
36
Pilocarpine
Muscarinic agonist Constricts iris sphincter muscle and constricts pupil Contracts ciliary muscle to relax suspensory ligaments to increase lens thickness and refractory power
37
Cycloplegia
Paralysis of ciliary muscle of the eye
38
Bethanechol
Selective muscarinic agonist used to increase GI motility and bladder tone after surgery
39
Nicotinic receptor agonists
Nn and Nm
40
Selective Nicotinic receptor agonists
Nicotine Used in nicotine addiction Side effects tend to be CNS: tremor, concussions, coma
41
Non-selective Nicotinic receptor agonists
ACh
42
Nicotinic receptor antagonists
Ganglionic blockers: block Nn receptors at autonomic ganglia Antagonists at NMJ: Nm at NJM Depolarizing and non-depolarizing
43
Non-depolarizing nicotinic antagonists
Competitive Can overcome by increase [ACh] ie. Curare
44
Curare
Non-depolarizing nicotinic antagonists | Used to produce skeletal muscle paralysis during surgery and ICU
45
Depolarizing nicotinic antagonists
Non-competitive Cannot overcome blockage by increase [ACh] ie. Succinylcholine
46
Succinylcholine
Used to produce skeletal muscle paralysis during surgery and ICU
47
Cholinesterase Inhibitors
Inhibit metabolism of ACh in synapse: enhance duration of action Mimics affect of PNS stimulation
48
Reversible Cholinesterase Inhibitors
Weakly bind to AChE ie. Neostigmine, physostigmine Loss of tone in bladder and gut, glaucoma (lowers intraocular pressure), myasthenia gravis
49
Myasthenia gravis
Autoimmune disease Body makes antibodies to Nm Want to prolong ACh at functional synapses
50
Irreversible Cholinesterase Inhibitors
Covalent bond with AChE - irreversible Insecticides, nerve gasses Effects on both N and M receptors Initial signs muscarinic followed by central and peripheral nicotinic signs Organophosphates Treatment: support respiration, decontamination, muscarinic antagonist, compound that can break covalent bond with enzyme inhibitor
51
Adrenergic pharmacology
Antagonists and agonists
52
Adrenergic Agonists
Sympathomimetics, adrenergic | Mimic action of EN and NE at adrenergic receptors and increase sympathetic nervous system responses
53
Adrenergic Antagonists
Sympatholytics, anti-adrenergic | Inhibit action of NE at adrenergic receptors and decrease SNS responses
54
beta1
Predominant receptor in heart
55
alpha1
Important in controlling peripheral blood vessel resistance
56
Adrenergic nerves
Tyrosine is taken into the nerve and converted to L-DOPA by tyrosine hydroxyls L-DOPA is converted to DA by dopadecarboxylase DA is taken into vesicle by VMAT and converted into NE MAO metabolizes NE in nerve that isn't taken up AP triggered release of NE and co-transmitter into synapse NE/co-NT bind to pre-post synaptic receptors NE taken up by reuptake transporter
57
alpha2
Presynaptic transporter
58
Adrenergic agonists
Drugs that mimic actions of NE by: 1. Direct acting 2. Indirect acting
59
Direct acting adrenergic agonists
Bind to pre or postsynaptic receptors
60
alpha1 direct acting agonists
Prototype: phenylephrine | To treat: nasal congestion, dilate pupils, combine with local anesthetics
61
alpha2 direct acting agonists
Presynaptic nerve terminal Decrease NE release via inhibition of AC and cAMP signalling ie. clonidine
62
Clonidine
alpha2 direct acting agonist Used to treat hypertension, reduces SNS outflow from brain to periphery CNS side effect: sedation
63
beta1 direct acting agonist
In heart Increase force of contraction of cardiac muscle ie. dobutamine
64
Dobutamine
beta1 agonist Used to treat heart failure Increases ability of the heart to contract: phosphorylation of Ca channels and increase Ca influx Increase Ca can cause arrhythmias
65
beta2 direct acting agonist
In airway smooth muscle Decreased contraction of smooth muscle ie. salbutamol
66
Salbutamol
beta2 agonist Used to treat asthma (relax airway smooth muscle via inhibition of MLCK phosphorylation) Used to prevent premature labor Side effect: increases heart rate
67
Indirect acting adrenergic agonists
1. Inhibit NE uptake (cocaine) | 2. Cause NE release (amphetamine, ephedrine)
68
Cocaine
Indirect acting adrenergic agonist Used as anesthetic (blocks Na channels in nerve) Drug of abuse Used as topical anesthetic in nasopharyngeal surgery Powerful CNS stimulant, increased HR, BP and force of contraction, arrhythmias
69
Amphetamine, ephedrine
Used to treat narcolepsy, ADHD, used as an appetite suppressant Powerful CNS stimulant, increased HR, BP and force of contraction, arrhymias
70
Mechanism for amphetamine
Enters nerve terminal via NET Competes with NE for uptake in synaptic vesicles via ventricular monoamine transporter and causes NE to accumulate in cytosol NE is degraded by MAO and some escapes via reversal of NET transport Competes for uptake with NE and prolongs action of released NE
71
Tyramine
By product of tyrosine metabolism, can be produced in high concentrations in protein-rich foods by decarboxylation of tyrosine Metabolized by MAO in liver Indirect sympathomimetic causing release of stored NE Inhibition of MAO produces increased tyramine levels and release of NE Patients taking MAO inhibitor should avoid tyramine-rich food
72
Direct alpha adrenergic antagonists
Block alpha receptors in the SNS | ie. Phenoxybenzamine, prazosin
73
Phenoxybenzamine
Direct alpha adrenergic antagonists Non selective for alpha1 and alpha2 Decrease BP
74
Prazosin
Direct alpha adrenergic antagonists | Selective for alpha1 and used to treat high BP
75
Direct beta adrenergic antagonists
Drugs that block beta receptors in the SNS Used to treat high BP, angina, arrhythmias, glaucoma Side effects: exercise tolerance, asthma ie. Proproanolol, metoprolol
76
Propranolol
Non selective direct beta adrenergic antagonists | Hypertension, glaucoma
77
Metoprolol
Cardioselective beta 1 direct beta adrenergic antagonists | Angina, hypertension
78
Beta-AR blockers and glaucoma
Aqueous humour is secreted by ciliary epithelium 1. Passive spaces between ciliary muscle via the trabecular meshwork tissue 2. Act on beta-AR receptors on epithelium and decrease aqueous humour secretion decreasing pressure in the eye

Pharmacology 3001 (19 decks)

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