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Pharmacology > Cholinergic Neurotransmission, Cholinergic Drugs, Adrenergic Drugs > Flashcards

Cholinergic Neurotransmission, Cholinergic Drugs, Adrenergic Drugs Flashcards

1
Q

MOA of skeletal muscle contraction

A

ACh binds to NICOTINIC receptors

ACh is degraded fast => suitable for NMJ

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2
Q

MOA of fight or flight response

A

HR and force increases

Vascular SM contracts => increase in BP

Visceral SM relaxes

Glandular secretions reduce

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3
Q

MOA of parasympathetic/rest & digest response

A

HR and force decreases

Visceral SM contracts

Glandular secretions increase

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4
Q

Which division of ANS has longer preganglionic axons

A

Parasympathetic

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5
Q

Physiological effects caused by symapthetic vs PS ANS

A
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6
Q

8 steps in neurotransmission

A
  1. Neuron takes up precursor
  2. Synthesis of transmitter
  3. Transmitter stored in vesicles
  4. Depolarisation by AP
  5. Ca2+ influx
  6. Transmitter released by exocytosis (Ca2+ mediated)
  7. Binds to postsynaptic receptors, although not always postsynaptic
  8. Transmitter action terminated by enzymatic metabolism/reuptake
  9. Reuptake of choline
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7
Q

How is choline taken up

A

Choline is taken into the cholinergic neuron via carrier-mediated transport

The rate limiting step for ACh production

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8
Q

What is the rate limiting step for ACh production

A

Choline being taken up by cholinergic neuron via carrier-mediated transport

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9
Q

How is ACh synthesised

A

Choline is acetylated using Acetyl CoA as a source of acetyl groups

This is catalysed by choline acetyltransferase

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10
Q

How is ACh packaged into vesicles

A

Actively packaged into vesicles by an amine transporter

Conc of ACh is very high in vesicles - 100mmol/L

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11
Q

Conc of ACh in vesicles

A

100 mmol/L

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12
Q

Depolarisation of cholinergic neuron

A

nerve terminal depolarises and VG Ca2+ channels open

Ca2+ enters the nerve terminal

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13
Q

How is ACh released by exocytosis

A

Due to Ca2+ entry, synaptobrevin on the VESICLES forms a complex with syntaxin on the inner surface of the plasma membrane thereby causing membrane fusion and exocytosis

ACh is released from nerve terminal into the synapse

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14
Q

What are syntaxin and synaptobrevin a target of

A

BOTOX

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15
Q

Name the 2 types of ACh receptors

A

Nicotinic

Muscarinic

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16
Q

At what receptor is ACh more potent

A

Muscarinic receptors

i.e. larger doses are required to activate nicotinic receptors

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17
Q

What are the subtypes of nicotinic receptors

A

Muscle - skeletal

Ganglion - ANS

CNS - brain

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18
Q

5 subtypes of muscarinic receptors

A

M1 - acid (gastric parietal cells)

M2 - heart

M3 - glandular/SM

M4

M5

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19
Q

M1

A

Acid - gastric parietal cells

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20
Q

M2

A

Heart

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21
Q

M3

A

Glandular/SM

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22
Q

How is ACh action terminated

A

By enzymatic breakdown in the synapse

This is catalysed by acetylcholinesterase

ACh is broken down into choline and acetate

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23
Q

How is choline taken back up

A
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24
Q

Noradrenergic neurotransmission - 8 steps

A
  1. Neuron takes up precursor
  2. Synthesis of transmitter
  3. Transmitter stored in vesicles
  4. Depolarisation by AP
  5. Ca2+ influx
  6. Transmitter released by exocytosis
  7. Binds to (postsynaptic) receptors
  8. Transmitter action is terminated by enzymatic metabolism/reuptake
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25
Q

What are catecholamines derived from

What NTs are catecholamines

A

Derived from tyrosine

Include NA, dopamine and adrenaline

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26
Q

What does the NA neuron take up

A

Tyrosine via carrier-mediated transport

Tyrosine is an aromatic AA that is present in body fluids

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27
Q

how do noradrenergic neurons synthesise NA

A

Tyrosine is converted to NA in a number of steps catalysed by different enzymes

The first step - hydroxylation of tyrosine - is the rate-limiting step

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28
Q

Rate limiting step in synthesis of noradrenaline

A

Hydroxylation of Tyrosine - tyrosine hydroxylase

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29
Q

Enzyme responsible for conversion of Tyrosine → DOPA

A

Tyrosine Hydroxylase

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30
Q

Enzyme responsible for conversion of DOPA → dopamine

A

DOPA decarboxylase

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31
Q

Enzyme responsible for conversion of dopamine → NA

A

Dopamine Beta-hydroxylase

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32
Q

Enzyme responsible for conversion of NA to adrenaline

Where is it found

A

Phenylethanolamine N-methyltransferase (found in the medulla)

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33
Q

What sort of substance is adrenaline

A

Hormone

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34
Q

How is NA packaged into vesicles

A

By an amine transporter

The conc of NA is very high in vesicles (0.3-1 mol/L)

ATP is also stored in NA vesicles

ratio of 4 molecules of ATP per molecule of NA

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35
Q

Consequences of depolarisation of nerve terminal

A

VG Ca2+ are opened

Ca2+ enters the nerve terminal

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36
Q

How is NA released

A

Due to Ca2+ entry, synaptobrevin on vesicles forms complex with syntaxin on inner surface of plasma membrane thereby causing membrane fusion and exocytosis

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37
Q

What are the 2 types of NA receptors

A

Alpha-adrenoreceptors - α1 and α2

Beta-adrenoreceptors - β1 β2 β3

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38
Q

What are alpha-adrenoreceptors responsible for

A

SM contraction

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39
Q

β1 receptors

A

Increase rate and force of cardiac contraction

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40
Q

β2 adrenoreceptors

A

Found on visceral SM - relax it

Bronchus, uterine

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41
Q

β3 receptors

A

Free source of energy from adipocytes

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42
Q

How is NA action terminated

A

UPTAKE 1

By reuptake in noradrenergic nerve terminals

UPTAKE 2

Uptake into non-neuronal cells e.g. SM, cardiac muscle, endothelium

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43
Q

Which uptake is most important for termination of NA action

A

Uptake 1 (into NAergic nerve terminals)

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44
Q

What does cocaine do

A

Stops reuptake of NA by blocking Uptake 1

(also transporter protein for dopamine in our brains)

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45
Q

How is NA recycled or broken down

A

Up to 50% of NA taken up by uptake 1 is repackaged into vesicles and recycled by NAergic neuron

The rest (and that taken up by reuptake 2) is metabolised

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46
Q

How is NA metabolised in the periphery

A
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47
Q

Enzymes used in metabolism of NA

A

MAO - monoamine oxidase

COMT - Catechol-O-methyl transferase

ADH - Aldehyde dehydrogenase

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48
Q

Periphery metabolites in metabolism of NA

A

DOMA - 3,2-dihydroxymandelic acid

NM - normetanephrine

VMA - Vanillylmandelic acid

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49
Q

Overview of NAergic neurotransmission

A
  1. Neuron takes up tyrosine
  2. Synthesis of NA
  3. NA stored in vesicles
  4. Depolarisation by AP
  5. Ca2+ influx
  6. NA released by exocytosis
  7. NA binds to postsynaptic adrenoceptors
  8. NA action is terminated by reuptake
  9. NA recycled or metabolised by MAO or COMT
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50
Q

Where is cholinergic NT seen

A

NMJ - muscle nicotinic receptors

ANS/Parasympathetic - muscarinic receptors (M1, M2, M3)

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51
Q

MOA of presynaptic cholinergic drugs

A
  • Inhibit choline uptake transporter
  • Inhibit ACh storage transporter
  • Inhibit ACh release process
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52
Q

Postsynaptic cholinergic drugs - MOA

A

Mimic action of ACh - cholinergic agonists

Block action of ACh - cholinergic antagonists

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53
Q

MOA of synaptic drugs

A

Inhibit AChesterase - anticholinesterases

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54
Q

Overview of drugs affecting cholinergic transmission

A
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55
Q

Drugs that inhibit choline uptake transporter

A

Hemicholinium

Triethylcholine

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56
Q

Drugs that block ACh storage transporter

A

Vesamicol

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57
Q

Drugs that inhibit ACh release

A

Botulinum toxin

β-bungarotoxin

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58
Q

Anticholinesterases - short duration

A

Edrophonium

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59
Q

Anticholinesterases - medium duration

A

Neostigmine

Physostigmine

Pyridostigmine

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60
Q

Anti-cholinesterases - irreversible

A

Dyflos

Parathion

Ecothiopate

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61
Q

Cholinergic agonists - muscarinic

A

Bethanacol

Pilocarpine

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62
Q

Cholinergic agonists - nicotinic

A

Suxamethonium

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63
Q

Cholinergic antagonists - muscarinic

A

Atropine

Hyoscine

Ipratropium

Pirenzepine

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64
Q

Cholinergic antagonists - nicotinic

A

Tubocurarine

Pancuronium

Atacurium

Vecuronium

Trimethaphan

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65
Q

MOA hemicholinium

A

Competitive inhibitor of choline uptake

Competes with choline for binding to choline transporter

Not taken up itself

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66
Q

Triethylcholine

A

Competitive inhibitor of choline uptake

Competes with choline for uptake via the choline transporter taken up itself

acetylated (by ChAT) and stored

Released as a false transmitter

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67
Q

MOA vesamicol

A

Inhibits the vesicular acetylcholine transporter

Therefore prevents ACh transport into vesicles

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68
Q

MOA of botulinum toxin

A

A protein produced by clostridium botulinum

Can cause BOTULISM (rare form of food poisoning that causes resp and musculoskeletal paralysis)

Contains several peptidases that cleave the proteins involved in exocytosis of ACh

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69
Q

MOA of β-bungarotoxin

A

Protein in venom of certain cobras

Contains a phospholipase that also prevents exocytosis of ACh

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70
Q

Blockade of choline uptake

A

Hemicholinium

Triethylcholine

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71
Q

Blockade of vesicular ACh storage

A

Vesamicol

72
Q

Blockade of vesicular ACh release

A

Botulinum toxin

β-bungarotoxin

73
Q

What do cholinergic presynaptically-acting drugs have in common

A

Neuromuscular-blocking drugs

74
Q

Which ACh receptor is more potent

A

Muscarinic receptors

THEREFORE blocking ACh release will affect nicotinic transmission before it affects muscarinic transmission

75
Q

What is botulinum toxin used for

A

Cosmetic purposes related to skeletal muscle contraction

therapeutic purposes related to excessive skeletal muscle contraction/spasm painful neck spasms (cervical dystonia, torticollis)

Crossed eyes (strabismus) and uncontrolled blinking (blepharospasm)

Therapeutic purposes related to excessive autonomic innervation - overactive bladder/incontinence, Excessive sweating

Therapeutic purposes related to excessive neurotransmitter release in the brain (Frequent and severe migraines)

76
Q

Normal function of cholinesterase

A

Catalyses hydrolysis of ACh into choline & acetic acid

77
Q

2 types of cholinesterase

A

Acetylcholinesterase

  • synaptic AChE
  • located in basement membrane of synaptic cleft

Butyrlcholinesterase

  • plasma BChE
  • widespread distribution including plasam (suxamethonium)
78
Q

What happens in the presence of anti-AChE

A

Cholinesterase is inhibited

ACh accumulates

Cholinergic transmission is enhanced

79
Q

short duration anti-AChEs

A

Ionic bond formed is readily reversible

only effective for short durations

80
Q

How do anticholinesterases act

A

By binding to cholinesterase’s active site

Duration of action is dependent on STRUCTURE

81
Q

Medium duration anti-AChEs

A

These drugs take longer to hydrolyse than ACh - mins rather than microseconds (occupy enzymes for longer)

82
Q

Irreversible anti-AChEs

A

Cause the enzyme to become phosphorylated

Phosphorylated enzyme is inactive

Recovery depends on synthesis of new enzyme

83
Q

Use of edrophonium

A

Used to clinically diagnose Myasthenia Gravis

84
Q

Myasthenia Gravis

A
  • Autoimmune disease in which antibodies are generated against the muscle-type nicotinic ACh receptors
  • Leads to destruction and loss of nicotinic receptors from the NMJ
  • Failure of neuromuscular transmission causing muscle weakness
  • Muscle weakness improves with administration of anti-AChE
  • Due to accumulation of ACh in NMJ synapse and enhanced NMJ neurotransmission
85
Q

What sort of drugs are neostigmine and pyridostigmine

What are they used to treat

A

Medium duration anticholinesterases

Used to treat myasthenia gravis

86
Q

What sort of drug is physostigmine

What is it used to treat

A

Medium duration anticholinesterases

Used to treat glaucoma

87
Q

Glaucoma

A

Intraocular pressure rises due to accumulation of aqueous humour

Due to iris folding over drainage pathway when the pupil is dilated - damages optic nerve

88
Q

How do anticholinesterases treat glaucoma

A

Enhances PS cholinergic transmission

Increased activation of M3 receptors and contraction of constrictor pupillae muscle

Iris contracts

Drainage pathway is unblocked

Intraocular pressure is reduced

89
Q

Name 3 irreversible anticholineaterases

A

Dyflos

Parathion

Ecothiopate

90
Q

Dyflos

A

Irreversible anticholinesterase

Organophosphate

Used in nerve gases and insecticides

Formerly used to treat glaucoma

91
Q

Parathion

A

Irreversible anticholinesterase

Organophosphate

Used in nerve gases and insecticides

Used to treat glaucoma

92
Q

Ecothiopate

A

Organophosphate

Used in nerve gases and insecticides

Used to treat glaucoma

93
Q

Sarin

A

Contains organophosphates

Acts as an irreversible cholinesterase inhibitor

94
Q

Novichock - A234

A

Contains organophosphates

Irreversible cholinesterase inhibitor

95
Q

Poisoning by a nerve gas leads to

A

Contraction of pupils

Profuse lacrimation (tears)

Runny nose

Profuse salivation/drooling

Severe bradychardia

Tightness in chest

Involuntary defecation

Involuntary urination

Convulsions and eventual death by respiratory depression (due to CNS effects of excessive ACh)

96
Q

Recall where cholinergic transmission is located

A

NMJ (via nicotinic)

ANS/parasympathetic (via muscarinic) - heart, visceral SM, glands

97
Q

Cholinergic agonists

A

Drugs that mimic the effects of ACh

Can be muscarinic and/or nicotinic

98
Q

What are non-selective cholinergic agonists

A

Activate both nicotinic and muscarinic receptors

like ACh itself

99
Q

Cholinergic antagonists

A

Block effects of ACh

Like the agonists, they can be muscarinic and/or nicotinic

100
Q

Synonym for muscarinic agonists

A

Referred to as parasymptomimetics - the effects they produce are similar to the effects of PS stimulation

101
Q

Synonym for muscarinic antagonists

A

Parasymptolytics

Main effects they produce are similar to the effects of PS blockade

102
Q

Agonist effect on heart

A

M2 receptors

Reduce rate/force of contraction

103
Q

Agonist effect on SM

A

M3 receptors

Visceral SM contracts

Pupil, bronchi, stomach, gut, bladder, uterus contract

104
Q

agonist effect on glands

A

M3 receptors

Glandular secretions stimulated

Tears, mucus, saliva, acid, sweat

105
Q

Antagonist effect on the heart

A

M2 receptors

Blocks ACh induced reduction in HR - therefore HR increases

106
Q

Antagonist effect on SM

A

M3 receptors

Blocks ACh induced contraction of visceral SM

107
Q

Antagonist effect on glands

A

M3 receptors

Blocks ACh induced stimulation of secretions

108
Q

Bethanecol

A

Muscarinic agonist

Not cleaved by cholinesterase

Used clinically to treat bladder and gut hypotonia

Beneficial effects are mediated via M3 receptors

109
Q

Pilocarpine

A

Not cleaved by cholinesterase

Muscarinic agonist

Used to treat GLAUCOMA

Beneficial effects mediated by M3 receptors

110
Q

How does pilocarpine work

A

Contracts constrictor pupillae muscle

Iris contracts (M3 receptors)

Drainage pathway is unblocked

Intraocular pressure is reduced

111
Q

Atropine

A

Muscarinic antagonist

Extract from deadly nightshade - Atropa belladonna

Naturally occuring

112
Q

Clinical uses for atropine

A

Reduces secretions in anaesthesia

GI hypermotility

Bradycardia

Anticholinesterase poisoning

113
Q

Side effects of atropine

A

Urinary retention

Dry mouth

Blurred vision (no constriction of pupils)

114
Q

Hyoscine (scopolamine)

A

Naturally occuring

Extract from thorn apple (datura stramonium)

115
Q

Clinical uses of hyoscine (scopolamine)

A

Reduces secretions in anaesthesia

GI hypermotility

Bradycardia

Anticholinesterase poisoning

motion sickness

116
Q

Side effects of hyoscine (scopolamine)

A

Dry mouth

Urinary retention

Blurred vision

Sedation - crosses BBB

117
Q

Ipratropium

A

Muscarinic antagonist

Used as a bronchodilator for asthma and bronchitis

118
Q

Pirenzepine

A

Selectively blocks M1 receptors (on gastric parietal cells)

Used to treat peptic ulcer as it reduces acid secretion, allowing ulcer to heal

119
Q

Where are nicotinic receptors located

A

Muscle type - skeletal muscle

Ganglion type - postganglionic neurons in all autonomic ganglia

CNS type - neurons in CNS

120
Q

Suxamethonium

A

Used as a muscle relaxant - during surgery so there are no inadvertent muscle twitches

NMJ blocker

121
Q

MOA of suxamethonium

A

Initially stimulates muscle type nicotinic receptors and causes muscle cell depolarisation, but it then causes depolarisation block

122
Q

2 categories of nicotinic antagonists

A

Neuromuscular blockers - block transmission at NMJ

Ganglion-blocking drugs - block both sympathetic and PS ganglia

123
Q

Normal MOA of nicotinic receptor following binding of ACh

A
124
Q

Tubocurarine

A

Nicotinic antagonist

Neuromuscular blockers

Naturally occuring

Used rarely as a muscle relaxant during anaesthesia

125
Q

Pancuronium/Atacurium/Vecuronium

A

Synthetic derivatives of tubocurarine

Used as muscle relaxants during anaesthesia

126
Q

2 ways in which NM blocking drugs can act

A

PRESYNAPTICALLY

Block choline uptake

Block ACh storage in vesicles

Block ACh release

POSTSYNAPTICALLY

Block nicotinic ACh receptors

non-depolarising drugs - nicotinic antagonists

Depolarising blocking drugs - some nicotinic agonists

127
Q

Trimetaphan

A

Nicotinic antagonist

Ganglion blocker

Used rarely to lower BP in surgery

128
Q

S and PS effects

A

Mostly opposing EXCEPT BVs only have S innervation - contract vascular SM

129
Q

Effects of ganglion blocker drugs

A
  • Marked fall in BP - due to sympathetic ganglion block with consequent arteriolar vasodilation
  • Postural hypotension - reflex vasoconstriction blocked
  • Post-exercise hypotension - vasoconstriction in non-exercising area blocked
130
Q

Effect of sympathetic stimulation on the body

A
131
Q

9 steps in NAergic neurotransmission

A
  1. Neuron takes up tyrosine (2 transporters)
  2. Synthesis of NA
  3. NA stored in vesicles
  4. Depolarisation by AP
  5. Ca2+ influx
  6. NA released by exocytosis
  7. NA binds to postsynaptic adrenoceptors
  8. NA action is terminated by reuptake
  9. NA recycled or metabolised by MAO or COMT

**** no enzyme to break down NA in synapse - unique to ACh

132
Q

MOAs of presynaptic NAergic drugs

A
  • Inhibit NA synthesis
  • Reduce NA availability
  • Inhibit NA storage
  • Block NA release
  • Evoke NA release
  • Inhibit NA uptake
  • (Inhibit NA metabolism)
133
Q

MOAs of postsynaptic NAergic drugs

A

Mimic actions of ACh - NAergic agonists

Block action of ACh - NAergic antagonists

134
Q

Drugs that inhibit NA synthesis

A

α-methyl-para-tyrosine

Carbidopa

135
Q

Drugs that reduce NA availability

A

Methyldopa

136
Q

Drugs that block NA vesicular storage

A

Reserpine

137
Q

Drugs that block NA release

A

Guanethedine

138
Q

Drugs that evoke NA release

A

Ephedrine

Amphetamine

Tyramine

139
Q

Drugs that inhibit NA uptake

A

Desipramine

Imipramine

Cocaine

140
Q

Drugs that inhibit NA metabolism

A

Moclobemide

Selegiline

141
Q

Non-specific adrenergic agonists

A

NA, adrenaline

142
Q

α-adrenoreceptor agonists

A

Clonidine

143
Q

β-adrenoceptor agonists

A

Dobutamine

Salbutomol

Salmeterol

Terbutaline

Clenbuterol

144
Q

α-adrenoceptor antagonists

A

Prazosin

Doxazocin

Terazosin

145
Q

β-adrenoceptor antagonists

A

Propranalol

Alprenalol

Oxprenalol

Atenolol

146
Q

α-methyltyrosine

A

Inhibits tyrosine hydroxylase

Used to treat pheochromocytoma

147
Q

Phaeochromocytoma

A

Tumour of catecholamine-producing cells of adrenal medulla

Because of the cancerous growth of these cells, excessive amounts of adrenaline & NA are released

Inhibition of tyrosine hydroxylase prevents the synthesis of NA and adrenaline (α-methyltyrosine does this)

148
Q

Carbidopa

A

Inhibits DOPA decarboxylase

Does not cross BBB and thus can be used to prevent the decarboxylation of DOPA in periphery only

149
Q

Treatment for Parkinson’s

A

First line of treatment = dopamine precursor L-DOPA

This is converted to dopamine in the brain

Carbidopa prevents excessive catecholamine production in the periphery and thus prevents the peripheral side effects of L-DOPA treatment

150
Q

Methyldopa

A

REDUCES NA AVAILABILITY

Methyldopa is taken up by noradrenergic neurons

Then converted to a false transmitter = α-methylnoradrenaline

α-methylnoradrenaline is not very effective at adrenergic receptors

Thus it cannot effectively cause sympathetically-mediated cardiac contraction

Used to treat hypertension in pregnancy

151
Q

Reserpine

A

Inhibits the vesicular NA transporter and thus blocks NA transport into vesicles

NA then accumulates in cytoplasm where it is metabolised

Thus, sympathetic neurotransmission is blocked and sympathetically-mediated cardiac contraction and vasoconstriction are reduced

Used to be used to treat hypertension

Serious side effect of depression - due to similar effect in noradrenergic and serotonergic neurons in CNS

152
Q

Guanethidine

A

Inhibits release of NA from sympathetic nerve terminals

MOA is unclear

Impairs AP conduction

Displaces NA from vesicles

Can cause structural damage to NAergic neuron

Used to be used for hypertension

Severe side effects: postural hypotension, diarrhoea, nasal congestion

153
Q

MOA of ephedrine (sudafed), amphetamine, tyramine (dietary amine)

A

These drugs evoke the release of NA from sympathetic nerve terminals and are thus called Indirectly-acting sympathomimetic amines

MOA:

Taken up by Uptake 1

Then enter vesicles in exchange for NA which accumulates in cytoplasm

Some NA is then metabolised but the rest escapes in exchange for drug

154
Q

Ephedrine/pseudoephedrine

A

Indirectly-acting sympathomimetic amine

Used as a nasal decongestant (glandular secretions reduce in fight or flight)

155
Q

Amphetamine

A

Indirectly acting sympathomimetic amine (stim. of NA release)

Psychoactive stimulant (stimulates brain)

Drug of abuse - speed

Used to treat ADHD and narcolepsy

Side effects: increased HR and BP, constipation

156
Q

Tyramine

A

Indirectly acting sympathomimetic amine (stim. of NA release)

Diet derived - fermented meats, ripe cheese, marmit, bovril

Ordinarily metabolised by enzymes (monoamine oxidases) in gut so does not reach circulation

but serious drug interaction risk (CHEESE RXN) with such foods and MAO inhibitors (tyramine) enters bloodstream

EFFECTS: potentially fatal hypertensive crisis, severe throbbing headaches, intracranial haemorrhage

157
Q

Drugs that block NA reuptake

MOA

A

Desipramine, imipramine (tricyclic antidepressants block re-uptake of serotonin), cocaine (also blocks re-uptake of dopamine)

Block neuronal reuptake by Uptake 1 thereby enhancing sympathetic nerve activity & levels of circulating NA

158
Q

Moclobemide and selegiline

A

inhibit monoamine oxidase

MOCLOBEMIDE - antidepressant

SELEGILINE - Parkinsons - inhibits metabolism of dopamine

159
Q

Receptor selectivity of noradrenaline and adrenaline

A

They show little receptor selectivity

160
Q

α1

  1. Location
  2. Physiological effect
A
  1. Vascular SM & liver
  2. VasoC & glycogenolysis
161
Q

α2

Location

Physiological effect

A
  1. Vascular SM & glands
  2. VasoC & decreased glandular secretion
162
Q

β1

  1. Location
  2. Physiological effect
A
  1. Heart
  2. Increased cardiac rate and force
163
Q

β2

  1. Location
  2. Physiological effect
A
  1. Bronchial SM & visceral SM, skeletal muscle, liver
  2. Relaxation/dilation, relaxation, contraction/tremor, glycogenolysis
164
Q

β3

  1. Location
  2. Physiological effect
A
  1. Adipose tissue
  2. Lypolysis
165
Q

Main effects of sympathetic stimulation

A

Sympathetic activity exerts a powerful stimulant effect on heart -

β1 adrenoceptors

Overall effect of sympathetic activity is vasoC -

α1 and α2 adrenoceptors

Sympathetic activity strongly dilates bronchial SM - β2-adrenoceptors

166
Q

Salbutamol, salmeterol, terbutaline

A

These selective β2-adrenoceptors agonists are used clinically to treat asthma

Like sympathetic stimulation, these dilate bronchial SM thereby widening the airways and allowing asthmatic to breathe more easily

167
Q

Adrenaline

A

Used to treat cardiac arrest

168
Q

Dobutamine

A

Selective β1-adrenoceptor agonist that is used to treat cardiogenic shock - state of shock induced because the heart is unable to adequately perfuse tissues

169
Q

Anaphylactic shock

A

Sudden, severe allergic rxn characterised by breathing difficulties and a sharp drop in BP

170
Q

First line of treatment for anaphylactic shock

A

Adrenaline

relieves breathing difficulties // bronchodilation via β2 adrenoceptors

Raises BP // increased cardiac output via β1 adrenoceptors, vasoC via α 1 & 2 adrenoceptors

171
Q

Salbutamol

A

Selective β2 adrenoceptor agonist

treats premature labour

Like sympathetic activity, it strongly dilates uterine SM by activation of β2 adrenoceptors

172
Q

SNS and energy metabolism

A

Sympathetic activity encourages the conversion of energy stores (fat and glycogen) to freely available Fuels (free fatty acids and glucose)

GLYCOGEN → glucose // β1 adrenoceptors in liver and muscle

FAT → free FAs // β3 adrenoceptors in adipose tissue

* selective β3 adrenoceptor agonists are being developed to treat obesity (not yet approved)

173
Q

Clenbuterol

A

β2 agonist - performance enhancing drug

Like sympathetic activity, causes tremor in skeletal muscle thereby increasing muscle strength

174
Q

Prazosin, doxazosin, terazosin

A

Selective α1 adrenoceptor antagonists used to treat hypertension

Side effects include postural hypotension

175
Q

Propranolol, alprenolol, oxprenolol, atenolol

A

Non-selective β-adrenoceptor antagonists (Beta blockers) used to treat hypertension, cardiac dysrhythmias and angina pectoris

SIDE EFFECTS:

bronchoconstriction (hence contraindicated in asthmatics)

bradychardia

cold extremities - blood won’t perfuse to fingers and toes

cardiac failure

Pharmacology (23 decks)

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