Cholinergics Flashcards Preview

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Flashcards in Cholinergics Deck (86):
1

Hemicholinium receptor/mechnism

Blocks *choline transporter CHT1* preventing uptake and synthesis of acetylcholine

Used for research

2

Vesamicol receptor/mechanism

Blocks the *vesicular ACh-H+ antiporter VAChT* preventing storage of ACh

Used for research

3

Botulinum Toxin receptor/mechanism

Prevents *synaptic vesicle fusion* inhibiting ACh release (synaptobrevin)

Used in local injection; conditions with excess muscle tone (blepharospasm); wrinkles, HA and pain

4

Neuromuscular blockers drugs

Tubocurarine and Succinylcholine

5

Tubocurarine receptor/mechanism

**Non depolarizing**
Binds to Nm->competitive inhibition
Prevents depolarization

6

Tubocurarine indication/effect

Anesthesia->muscle weakness and flaccid paralysis

Action can be overcome by AChE inhibitors such as neostigmine or edrophonium

7

Tubocurarine PK

Minimal oral absorption so need to be IV
Poor membrane penetration
Doesn't cross BBB

8

Tubocurarine adverse

May cause *histamine release*
May bind *M receptors*

9

Succinylcholine receptor/mechanism

**Depolarizing**
Activates Nm causing depolarization -> transient disorganized contraction -> desensitization followed by flaccid paralysis

10

Succinylcholine indication/effect

Useful for ET intubation

Electroconvulsive therapy

11

Succinylcholine PK

continuous IV infusion

Rapid hydrolysis by plasma cholinesterase
Rapid onset (1m) and brief duration (5-10m)
Not metabolized effectively at the synapse

12

Succinylcholine adverse

**Malignant hyperthermia** an autosomal dominant disorder -> excess release of calcium from the SR; usually when combined with a halogenated anesthetic (Tx dantrolene)

13

Mecamylamine, Trimethaphan, Hexamethonium receptor/mechanism

Antagonize nicotinic receptors in both parasympathetic and sympathetic autonomic ganglia

14

Mecamylamine, Trimethaphan, Hexamethonium effects

Arterioles and veins are under predominant sympathetic control (adrenergic) -> *dilation, hypotension, etc alpha 1*

Block parasympathetics at the heart, iris and ciliaris muscle -> *tachycardia, mydriasis, and cycloplegia (far vision)*

GI, urinary bladder and salivary gland lose parasympathetics -> *reduced motility, secretions; urinary retention, xerostomia (dry mouth)*

Sweat glands lose sympathetics -> *anhydrosis*

15

Mecamylamine, Trimethaphan, Hexamethonium adverse

Vasodilation
Venodilation
Hypotension
Tachycardia
Mydriasis
Decreased GI/urinary motility
Xerostomia
Anhydrosis

16

Mecamylamine, Trimethaphan, Hexamethonium other

Historically used to treat HTN, but have been replaced due to many undesirable effect

Dirty drugs

17

Pralidoxime effect

Regenerate cholinesterase after organophosphate poisoning (before aging)

18

Pralidoxime indication

not used for carbamate poisoning which is reversible and short lived

19

Pralidoxime other

Positively charged; it does not enter the CNS -> not effect on central sx

20

Tolterodine effect

Tertiary amine
Relaxes smooth muscle

21

Tolterodine indication

overactive bladder

22

Muscarinic antagonists

Atropine
Scopolamine
Ipratropium and Tiotropium
Homatropine, Cyclopentolate, Tropicamide
Benztropine, Trihexyphenidyl
Glycopyrrolate
Tolterodine

23

Glycopyrrolate indication

Oral: inhibition of GI motility
Parenteral: prevent bradycardia during surgery

24

Benztropine and Trihexyphenidyl Effects

Restore balance of input after loss of dopaminergic neurons in the nigrostriatal pathway

25

Benztropine and Trihexyphenidyl Indication

Parkinsonism
Extrapyramidal effects ( i.e. drug induced movement disorders) of antipsychotic drugs (D2)

26

Benztropine and Trihexyphenidyl PK

tertiary amines are able to enter the CNS

27

Homatropine, Cyclopentolate, Tropicamide effects

*Mydriasis and cycloplegia* - preferred over atropine because of shorter duration of action

28

Homatropine, Cyclopentolate, Tropicamide PK

tertiary amines are able to enter the CNS

29

Ipratropium, Tiotropium effects

Bronchodilation (M3)

30

Ipratropium, Tiotropium indication

Inhalation Tx of ***COPD and adjuvant therapy in asthma**

31

Scopolamine effects/indication

***DOC for motion sickness***
Blocks short term memory (anesthetic procedures)

32

Scopolamine other

Belladonna Alkaloids-Tertiary amines
Greater and longer duration of action in the CNS than atropine

33

Atropine effects

Eye: mydriasis, unreactive to light, cycloplegia (paralysis of ciliaris muscle causing loss of accommodation and adaptation)
GI: antispasmodic; decreases motility (HCl production not affected)
Urinary: *decreases hypermotility*
CVS: low dose -> bradycardia (presynaptic M2)
moderate to high dose-> tachycardia (atrial M2)

Secretions from salivary, sweat and lacrimal glands are blocked (may increase body temperature)

34

Atropine indication

Antisialagogue prior to surgery decreases respiratory secretions
Increased HR or Decrease AV block due to excessive vagal tone
*OD of cholinergic drugs (farmer spraying parathion)*
Death cap mushroom poisoning
Alleviate the muscarinic side effects of AChE drugs

35

Atropine PK

readily absorbed, partially metabolized by the liver, eliminated primarily in the urine

36

Muscarinic antagonists contraindications/adverse effects

"Atropine flush" due to cutaneous vasodilation (especially in upper body)

Anti-PS ->dry mouth, blurred vision, sandy eyes, tachycardia, constipation

CNS: restlessness, confusion, *hallucinations, delirium, depression* -> shock and death

Elderly patients with angle closure glaucoma -> exacerbation and blindness

Use with caution in patients with BPH ->decrease detrusor contraction can cause urinary retention

Low levels may cause bradycardia and sedation

High levels may cause tachycardia and CNS hyper excitation (delirium, hallucinations, and seizures)

37

AChE Inhibitor drugs

Edrophonium (Tensilon)
Physostigmine
Neostigmine
Pyridostigmine
Echothiophate (obsolete)
Malathion, Parathion
Tabun, Sarin, Soman
Tacrine, Donepezil, Rivastigmine, Galantamine

38

Tacrine, Donepezil, Rivastigmine, Galantamine indication

Orally used
Alzheimer's disease

39

Tabun, Sarin, Soman mechanism

Phosphorylate active site (extremely stable)

Ageing-strengthening of the bond making it much more difficult to reverse

40

Malathion, Parathion mechanism

Phosphorylate active site (extremely stable)

Ageing-strengthening of the bond making it much more difficult to reverse

41

Echothiophate mechanism

Phosphorylate active site (extremely stable)

Ageing-strengthening of the bond making it much more difficult to reverse

42

Echothiphate indication

Chronic angle glaucoma
NOT liposoluble-> doesn't enter CNS

43

Malathion, Parathion effects

Activated by conversion to oxygen analogs in the body

44

Malathion, Parathion indications

insecticides (farmer spraying his field...)

45

Malathion, Parathion PK

Fully distributed (including CNS)

46

Malathion, parathion adverse

Organophosphate overdose treated with atropine or Pralidoxime **have to give before ageing**

CNS toxicity

47

Tabun, Sarin, Soman adverse

Organophosphate overdose treated with atropine or Pralidoxime **have to give before ageing**

CNS toxicity

48

Tabun, Sarin, Soman effects

Nerve agents - most potent synthetic toxic agents known
Used for terrorism

49

Pyridostigmine indication

Treatment of Myasthenia gravis (most common)

50

Pyridostigmine adverse

CNS toxicity

51

Neostigmine mechnism

Covalent bond with AChE and ButyrylChE

52

Pyridostigmine mechanism

Covalent bond with AChE and ButyrylChE

53

Physostigmine mechanism

Covalent bond with AChE and ButyrylChE

54

Physostigmine chemical

carbamate - tertiary amine
Crosses BBB

55

Neostigmine and Pyridostigmine chemical

Carbamates - QAC - does not enter CNS

56

Edrophonium (Tensilon) chemical

simple alcohol QAC

57

Edrophonium (Tensilon) mechanism

*Reversible* binding to active site of AChE and butyrylcholinesterase

58

Neostigmine indications

*Reversal of NMJ block* produced by non depolarizing muscular blockers i.e. tubocurarine

Second line treatment for myasthenia gravis
Does not enter the CNS
Prevention and Tx of urinary retention

59

Neostigmine adverse

Hypotension
Salivation, flushing
Abdominal pain
Nausea, diarrhea
Bronchospasm

60

Physostigmine indications

Tx for *anticholinergic overdose*

Intestinal or bladder atony

61

Physostigmine adverse

High dose -> convulsions**, skeletal muscle paralysis, bradycardia

**Contraindicated in suspected TCA overdose** -> aggravates depression of cardiac conduction (TCA's block sodium channels)

62

Edrophonium indication

Diagnosis of Myasthenia gravis (rapid increase in muscle strength after dose)

Reverse neuromuscular block produced by non depolarizing muscular blockers (can be used for recovery after surgery)

63

AChE inhibitor effects

CNS: convulsion, coma, respiratory arrest

PS action in the eye, respiratory, GI and urinary tracts

CVS: -ve chronotropic and inotropic effects -> decreased CO and hypotension

NMJ: increased contraction in weak muscles

64

Acetylcholine Receptor

N and M

65

Acetylcholine mechanism

Binding to M receptor induces PS activity

Nicotinic effects once M receptors are blocked by atropine (high dose)

66

Acetylcholine Effects

M: parasympathetic and sympathetic activity, sweat glands

CVS: M3 vasodilation and reflex tachycardia at small doses; hypotension and bradycardia at higher doses

N: stimulate all autonomic ganglia, secretion of Epi from adrenal medulla; skeletal muscle increase HR, BP, etc.

67

Acetylcholine indication/use

Small iv-> drop BP with tachycardia

Virtually no use except
Cataract surgery -> rapid miosis

68

Cholinergic agonist adverse

Muscarinic syndrome
Generalized cholinergic stimulation -> sweating, miosis, flushing, salivation, bradycardia, hypotension, bronchospasm

DUMBBELLSS->
Diarrhea
Urination
Miosis
Bradycardia
Bronchoconstriction
Emesis
Lacrimation
Lethargy
Salivation
Sweating

69

Bethanechol receptor

M

70

Bethanechol mechanism

Parasympathetic

71

Bethanechol effects

Activates bowel and bladder

72

Bethanechol indication/use

Urinary retention (post-surgical postpartum)
Hypotonic, myogenic, neurogenic bladder ... atony

Ileus, gastroparesis, congenital megacolon

Cannot cross BBB

73

Carbachol receptor

M and N

74

Carbachol mechanism

parasympathetic

75

Carbachol effects

Miosis and contraction of ciliaris muscle

76

Carbachol indication/use

Intraocular surgery
Glaucoma - decrease intraocular pressure (use pilocarpine first)

External use only

77

Methacholine receptor

M and little N

78

Methacholine indication/use

*diagnosis of bronchial airway hyperreactivity* in patients without clinically apparent asthma

79

Pilocarpine receptor

Partial M
tertiary amine

80

Pilocarpine effects

Contraction of ciliaris
Secretion from sweat, salivary, lacrimal and bronchial glands

81

Pilocarpine indication/use

Acute close-angle glaucoma
Open angle glaucoma -> 2nd line after timolol
Included in the regimen for close angle glaucoma with: timolol, apraclonidine, acetazolamide, and mannitol or glycerol

82

Pilocarpine adverse

CNS disturbances
Sweating
Salivation

83

Nicotine receptor

Nn>Nm
Tertiary amine

84

Nicotine mechanism/effect

Low dose: ganglion deploarization in both sympathetic and parasympathetic
CVS: sympathomimetic due to catecholamine release
GI and UG: parasympathomimetic -> n/v/d, voiding, salivary and bronchial secretions

High dose: *ganglion blockade due to prolonged depolarization* (desensitization)

85

Nicotine indication/use

smoking cessation therapy

86

Nicotine adverse

Acute nicotine poisoning: nausea, salivation, abdominal pain, vomiting, diarrhea, cold sweat, confusion, etc.
Hypotension with a rapid and weak pulse
Can lead to death respiratory arrest (central or peripheral)