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Pharmacology 3001 > ANS Pharmacology - Kelly 1 > Flashcards

ANS Pharmacology - Kelly 1 Flashcards

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
Q

M3

A

Smooth muscle contraction, exocrine gland increased secretion
Gq

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26
Q

Nicotinic receptors

A

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

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27
Q

Muscarinic agonists

A

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

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28
Q

Non-selective muscarinic agonist

A

ACh

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29
Q

Selective muscarinic agonist

A

Naturally occurring alkaloids: muscarine, pilocarpine

Synthetic analogues of ACh: bethanechol

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30
Q

Muscarine

A

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

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31
Q

Glaucoma: use of direct muscarinic agonist

A

Constricts ciliary muscle of eye and increase aqueous humour drainage
Uses as eyedrops
Activate M3 receptors

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32
Q

Side effects of muscarinic agonists

A 
Stimulates all muscarinic receptors
GI disturbances
CNS effects
Effects on HR
Salivation and bronchoconstriction
33
Q

Muscarinic competitive antagonists

A

Bind to muscarinic receptors preventing ACh from binding
Naturally occurring alkaloids: atropine
Synthetic analogue: ipratropium bromide

34
Q

Atropine

A 
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
Q

Ipratoprium bromide

A

Synthetic analogue
Muscarinic competitive antagonist
Treats asthma, COPD

36
Q

Pilocarpine

A

Muscarinic agonist
Constricts iris sphincter muscle and constricts pupil
Contracts ciliary muscle to relax suspensory ligaments to increase lens thickness and refractory power

37
Q

Cycloplegia

A

Paralysis of ciliary muscle of the eye

38
Q

Bethanechol

A

Selective muscarinic agonist used to increase GI motility and bladder tone after surgery

39
Q

Nicotinic receptor agonists

A

Nn and Nm

40
Q

Selective Nicotinic receptor agonists

A

Nicotine
Used in nicotine addiction
Side effects tend to be CNS: tremor, concussions, coma

41
Q

Non-selective Nicotinic receptor agonists

A

ACh

42
Q

Nicotinic receptor antagonists

A

Ganglionic blockers: block Nn receptors at autonomic ganglia
Antagonists at NMJ: Nm at NJM
Depolarizing and non-depolarizing

43
Q

Non-depolarizing nicotinic antagonists

A

Competitive
Can overcome by increase [ACh]
ie. Curare

44
Q

Curare

A

Non-depolarizing nicotinic antagonists

Used to produce skeletal muscle paralysis during surgery and ICU

45
Q

Depolarizing nicotinic antagonists

A

Non-competitive
Cannot overcome blockage by increase [ACh]
ie. Succinylcholine

46
Q

Succinylcholine

A

Used to produce skeletal muscle paralysis during surgery and ICU

47
Q

Cholinesterase Inhibitors

A

Inhibit metabolism of ACh in synapse: enhance duration of action
Mimics affect of PNS stimulation

48
Q

Reversible Cholinesterase Inhibitors

A

Weakly bind to AChE
ie. Neostigmine, physostigmine
Loss of tone in bladder and gut, glaucoma (lowers intraocular pressure), myasthenia gravis

49
Q

Myasthenia gravis

A

Autoimmune disease
Body makes antibodies to Nm
Want to prolong ACh at functional synapses

50
Q

Irreversible Cholinesterase Inhibitors

A

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
Q

Adrenergic pharmacology

A

Antagonists and agonists

52
Q

Adrenergic Agonists

A

Sympathomimetics, adrenergic

Mimic action of EN and NE at adrenergic receptors and increase sympathetic nervous system responses

53
Q

Adrenergic Antagonists

A

Sympatholytics, anti-adrenergic

Inhibit action of NE at adrenergic receptors and decrease SNS responses

54
Q

beta1

A

Predominant receptor in heart

55
Q

alpha1

A

Important in controlling peripheral blood vessel resistance

56
Q

Adrenergic nerves

A

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
Q

alpha2

A

Presynaptic transporter

58
Q

Adrenergic agonists

A

Drugs that mimic actions of NE by:

  1. Direct acting
  2. Indirect acting
59
Q

Direct acting adrenergic agonists

A

Bind to pre or postsynaptic receptors

60
Q

alpha1 direct acting agonists

A

Prototype: phenylephrine

To treat: nasal congestion, dilate pupils, combine with local anesthetics

61
Q

alpha2 direct acting agonists

A

Presynaptic nerve terminal
Decrease NE release via inhibition of AC and cAMP signalling
ie. clonidine

62
Q

Clonidine

A

alpha2 direct acting agonist
Used to treat hypertension, reduces SNS outflow from brain to periphery
CNS side effect: sedation

63
Q

beta1 direct acting agonist

A

In heart
Increase force of contraction of cardiac muscle
ie. dobutamine

64
Q

Dobutamine

A

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
Q

beta2 direct acting agonist

A

In airway smooth muscle
Decreased contraction of smooth muscle
ie. salbutamol

66
Q

Salbutamol

A

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
Q

Indirect acting adrenergic agonists

A
  1. Inhibit NE uptake (cocaine)

2. Cause NE release (amphetamine, ephedrine)

68
Q

Cocaine

A

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
Q

Amphetamine, ephedrine

A

Used to treat narcolepsy, ADHD, used as an appetite suppressant
Powerful CNS stimulant, increased HR, BP and force of contraction, arrhymias

70
Q

Mechanism for amphetamine

A

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
Q

Tyramine

A

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
Q

Direct alpha adrenergic antagonists

A

Block alpha receptors in the SNS

ie. Phenoxybenzamine, prazosin

73
Q

Phenoxybenzamine

A

Direct alpha adrenergic antagonists
Non selective for alpha1 and alpha2
Decrease BP

74
Q

Prazosin

A

Direct alpha adrenergic antagonists

Selective for alpha1 and used to treat high BP

75
Q

Direct beta adrenergic antagonists

A

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
Q

Propranolol

A

Non selective direct beta adrenergic antagonists

Hypertension, glaucoma

77
Q

Metoprolol

A

Cardioselective beta 1 direct beta adrenergic antagonists

Angina, hypertension

78
Q

Beta-AR blockers and glaucoma

A

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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