Cholinergic Neurotransmission, Cholinergic Drugs, Adrenergic Drugs Flashcards

Question

What are catecholamines derived from What NTs are catecholamines

Answer 1

Derived from tyrosine Include NA, dopamine and adrenaline

Answer 2

Tyrosine via carrier-mediated transport Tyrosine is an aromatic AA that is present in body fluids

Answer 3

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

Answer 4

Hydroxylation of Tyrosine - tyrosine hydroxylase

Answer 5

Tyrosine Hydroxylase

Answer 6

DOPA decarboxylase

Answer 7

Dopamine Beta-hydroxylase

Answer 8

Phenylethanolamine N-methyltransferase (found in the medulla)

Answer 9

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

Answer 10

VG Ca2+ are opened Ca2+ enters the nerve terminal

Answer 11

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

Answer 12

Alpha-adrenoreceptors - α1 and α2 Beta-adrenoreceptors - β1 β2 β3

Answer 13

SM contraction

Answer 14

Increase rate and force of cardiac contraction

Answer 15

Found on visceral SM - relax it Bronchus, uterine

Answer 16

Free source of energy from adipocytes

Answer 17

UPTAKE 1 By reuptake in noradrenergic nerve terminals UPTAKE 2 Uptake into non-neuronal cells e.g. SM, cardiac muscle, endothelium

Answer 18

Uptake 1 (into NAergic nerve terminals)

Answer 19

Stops reuptake of NA by blocking Uptake 1 (also transporter protein for dopamine in our brains)

Answer 20

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

Answer 21

MAO - monoamine oxidase COMT - Catechol-O-methyl transferase ADH - Aldehyde dehydrogenase

Answer 22

DOMA - 3,2-dihydroxymandelic acid NM - normetanephrine VMA - Vanillylmandelic acid

Answer 23

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

Answer 24

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

Answer 25

* Inhibit choline uptake transporter * Inhibit ACh storage transporter * Inhibit ACh release process

Answer 26

Mimic action of ACh - cholinergic agonists Block action of ACh - cholinergic antagonists

Answer 27

Inhibit AChesterase - anticholinesterases

Answer 28

Hemicholinium Triethylcholine

Answer 29

Botulinum toxin β-bungarotoxin

Answer 30

Edrophonium

Answer 31

Neostigmine Physostigmine Pyridostigmine

Answer 32

Dyflos Parathion Ecothiopate

Answer 33

Bethanacol Pilocarpine

Answer 34

Suxamethonium

Answer 35

Atropine Hyoscine Ipratropium Pirenzepine

Answer 36

Tubocurarine Pancuronium Atacurium Vecuronium Trimethaphan

Answer 37

Competitive inhibitor of choline uptake Competes with choline for binding to choline transporter Not taken up itself

Answer 38

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**

Answer 39

Inhibits the vesicular acetylcholine transporter Therefore **prevents ACh transport into vesicles**

Answer 40

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

Answer 41

Protein in venom of certain cobras Contains a phospholipase that also prevents exocytosis of ACh

Answer 42

Hemicholinium Triethylcholine

Answer 43

Botulinum toxin β-bungarotoxin

Answer 44

Neuromuscular-blocking drugs

Answer 45

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

Answer 46

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)

Answer 47

Catalyses hydrolysis of ACh into choline & acetic acid

Answer 48

Acetylcholinesterase - synaptic AChE - located in basement membrane of synaptic cleft Butyrlcholinesterase - plasma BChE - widespread distribution including plasam (suxamethonium)

Answer 49

Cholinesterase is inhibited ACh accumulates Cholinergic transmission is enhanced

Answer 50

Ionic bond formed is readily reversible only effective for short durations

Answer 51

By binding to cholinesterase's active site Duration of action is dependent on STRUCTURE

Answer 52

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

Answer 53

Cause the enzyme to become phosphorylated Phosphorylated enzyme is inactive Recovery depends on synthesis of new enzyme

Answer 54

Used to clinically diagnose Myasthenia Gravis

Answer 55

* 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

Answer 56

Medium duration anticholinesterases Used to treat myasthenia gravis

Answer 57

Medium duration anticholinesterases Used to treat glaucoma

Answer 58

Intraocular pressure rises due to accumulation of aqueous humour Due to iris folding over drainage pathway when the pupil is dilated - damages optic nerve

Answer 59

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

Answer 60

Dyflos Parathion Ecothiopate

Answer 61

Irreversible anticholinesterase Organophosphate Used in nerve gases and insecticides Formerly used to treat glaucoma

Answer 62

Irreversible anticholinesterase Organophosphate Used in nerve gases and insecticides Used to treat glaucoma

Answer 63

Organophosphate Used in nerve gases and insecticides Used to treat glaucoma

Answer 64

Contains organophosphates Acts as an irreversible cholinesterase inhibitor

Answer 65

Contains organophosphates Irreversible cholinesterase inhibitor

Answer 66

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)

Answer 67

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

Answer 68

Drugs that mimic the effects of ACh Can be muscarinic and/or nicotinic

Answer 69

Activate both nicotinic and muscarinic receptors like ACh itself

Answer 70

Block effects of ACh Like the agonists, they can be muscarinic and/or nicotinic

Answer 71

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

Answer 72

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

Answer 73

M2 receptors Reduce rate/force of contraction

Answer 74

M3 receptors Visceral SM contracts Pupil, bronchi, stomach, gut, bladder, uterus contract

Answer 75

M3 receptors Glandular secretions stimulated Tears, mucus, saliva, acid, sweat

Answer 76

M2 receptors Blocks ACh induced reduction in HR - therefore HR increases

Answer 77

M3 receptors Blocks ACh induced contraction of visceral SM

Answer 78

M3 receptors Blocks ACh induced stimulation of secretions

Answer 79

Muscarinic agonist Not cleaved by cholinesterase Used clinically to treat bladder and gut hypotonia Beneficial effects are mediated via M3 receptors

Answer 80

Not cleaved by cholinesterase Muscarinic agonist Used to treat GLAUCOMA Beneficial effects mediated by M3 receptors

Answer 81

Contracts constrictor pupillae muscle Iris contracts (M3 receptors) Drainage pathway is unblocked Intraocular pressure is reduced

Answer 82

Muscarinic antagonist Extract from deadly nightshade - Atropa belladonna Naturally occuring

Answer 83

Reduces secretions in anaesthesia GI hypermotility Bradycardia Anticholinesterase poisoning

Answer 84

Urinary retention Dry mouth Blurred vision (no constriction of pupils)

Answer 85

Naturally occuring Extract from thorn apple (datura stramonium)

Answer 86

Reduces secretions in anaesthesia GI hypermotility Bradycardia Anticholinesterase poisoning motion sickness

Answer 87

Dry mouth Urinary retention Blurred vision **Sedation - crosses BBB**

Answer 88

Muscarinic antagonist Used as a bronchodilator for asthma and bronchitis

Answer 89

Selectively blocks M1 receptors (on gastric parietal cells) Used to treat peptic ulcer as it reduces acid secretion, allowing ulcer to heal

Answer 90

Muscle type - skeletal muscle Ganglion type - postganglionic neurons in all autonomic ganglia CNS type - neurons in CNS

Answer 91

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

Answer 92

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

Answer 93

Neuromuscular blockers - block transmission at NMJ Ganglion-blocking drugs - block both sympathetic and PS ganglia

Answer 94

Nicotinic antagonist Neuromuscular blockers Naturally occuring Used rarely as a muscle relaxant during anaesthesia

Answer 95

Synthetic derivatives of tubocurarine Used as muscle relaxants during anaesthesia

Answer 96

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**

Answer 97

Nicotinic antagonist Ganglion blocker Used rarely to lower BP in surgery

Answer 98

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

Answer 99

* 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

Answer 100

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

Answer 101

* Inhibit NA synthesis * Reduce NA availability * Inhibit NA storage * Block NA release * Evoke NA release * Inhibit NA uptake * (Inhibit NA metabolism)

Answer 102

Mimic actions of ACh - NAergic agonists Block action of ACh - NAergic antagonists

Answer 103

α-methyl-para-tyrosine Carbidopa

Answer 104

Methyldopa

Answer 105

Guanethedine

Answer 106

Ephedrine Amphetamine Tyramine

Answer 107

Desipramine Imipramine Cocaine

Answer 108

Moclobemide Selegiline

Answer 109

NA, adrenaline

Answer 110

Dobutamine Salbutomol Salmeterol Terbutaline Clenbuterol

Answer 111

Prazosin Doxazocin Terazosin

Answer 112

Propranalol Alprenalol Oxprenalol Atenolol

Answer 113

Inhibits tyrosine hydroxylase Used to treat pheochromocytoma

Answer 114

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)

Answer 115

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

Answer 116

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

Answer 117

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

Answer 118

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

Answer 119

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

Answer 120

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

Answer 121

Indirectly-acting sympathomimetic amine Used as a nasal decongestant (glandular secretions reduce in fight or flight)

Answer 122

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

Answer 123

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

Answer 124

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

Answer 125

inhibit monoamine oxidase MOCLOBEMIDE - antidepressant SELEGILINE - Parkinsons - inhibits metabolism of dopamine

Answer 126

They show little receptor selectivity

Answer 127

1. Vascular SM & liver 2. VasoC & glycogenolysis

Answer 128

1. Vascular SM & glands 2. VasoC & decreased glandular secretion

Answer 129

1. Heart 2. Increased cardiac rate and force

Answer 130

1. Bronchial SM & visceral SM, skeletal muscle, liver 2. Relaxation/dilation, relaxation, contraction/tremor, glycogenolysis

Answer 131

1. Adipose tissue 2. Lypolysis

Answer 132

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

Answer 133

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

Answer 134

Used to treat cardiac arrest

Answer 135

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

Answer 136

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

Answer 137

Adrenaline relieves breathing difficulties // bronchodilation via β2 adrenoceptors Raises BP // increased cardiac output via β1 adrenoceptors, vasoC via α 1 & 2 adrenoceptors

Answer 138

Selective β2 adrenoceptor agonist treats premature labour Like sympathetic activity, it strongly dilates uterine SM by activation of β2 adrenoceptors

Answer 139

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)

Answer 140

β2 agonist - performance enhancing drug Like sympathetic activity, causes tremor in skeletal muscle thereby increasing muscle strength

Answer 141

Selective α1 adrenoceptor antagonists used to treat hypertension Side effects include postural hypotension

Answer 142

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

Cholinergic Neurotransmission, Cholinergic Drugs, Adrenergic Drugs Flashcards

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