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Pharma > Cholinergic System > Flashcards

Cholinergic System Flashcards

1
Q

What are the classes of drugs acting on the PNS and the neuromuscular junction?

A
  • Direct acting receptor agonists
  • Direct acting receptor antagonists
  • Indirectly-acting receptor mimetics
  • Indirectly-acting receptor lytics
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2
Q

What does acetylcholine composed of ?

A

Acetyl + choline

1• Quaternary ammonium group
• Strongly basic
• Cationic

2• Ester group —> make it susp to hydrolysis—> very rapid by AchE
• Partially anionic
• Renders susceptible to hydrolysis

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3
Q

Where can we find Ach ?

A

In junctions:
Parasympathetic
Ganglionic
Neuromuscular

Ach can be syn in the CNS

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4
Q

What is the effect of the + charge of quaternary ammonium group ?

A

Makes acetylcholine water soluble so it can’t pass the BBB

IMP to know if the drug acting on the cholenergic system is to know if it can cross the CNS bcz if it crosses —> CNS side effects

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5
Q

How to know if the drug is water soluble or lipid soluble ?

A

By looking at the structure

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6
Q

How can we syn Ach?

A

Require the acetylation of the dietary choline ( water soluble essential nutrient of the Vitmin B-complex)

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7
Q

How is the Ach transmitted?

A
  1. After taking choline, it enters the neuron through a carrier —> high affinity choline transporter which is Na+ dependent —> so for choline to enter Na+ enters too
  2. High affinity choline transporter is on neurons but low affinity is in other tissues
  3. After entering, acetylation happens by acting with Acetyl-CoA by acetyltransferase —> transfer acetyl group from acetyl-CoA to choline = Ach
  4. Stored inside a vesicles by another transporter which is VAchT ( vesicular acetylcholine transporter ) —> from cytoplasm to inside to prevent degradation —> depend on H+ influx —> H+ out Ach in
  5. Stimulus —> voltage gated Ca+ channels opened by AP ( depolarization ) —> Ca+2 —> trigger for Ach release —> Ca2+ mediated exocytosis
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8
Q

What happens after releasing Ach ?

A

A. Go to the postsynaptic

  1. Organ
  2. Postganglionic
  3. Muscles

B. Terminate the action by hydrolysis by AchE that cleaves the ester bond —> can’t be uptaken

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9
Q

What are the receptors for Ach?

A
  1. Muscarinic in PNS
  2. Nicotinic Ach ionotropic receptor in
    A. ganglia
    B. Neuromuscular junction
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10
Q

What is AchE?

A
  • Specific for Ach
  • Membrane-bound
  • Cholinergic synapses: each one have many AchE —> duration of action really short but enough!
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11
Q

What is BChE ?

A
  • pseudocholineesterase / plasmacholinesterase
  • Unspecific
  • Soluble in plasma, liver, GIT ..etc
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12
Q

What is the importance of BchE?

A

Can hydrolyze Ach but not as effector the and not specific to Ach —> Very imp for the metabolism of a certain drug

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13
Q

How does the AchE hydrolyze Ach?

A

Have 2 binging sides:
1. Esteric site —> serine (AA) —> bind to ester group and form a covalent bond —> choline can be uptaken but Ach no

  1. Anionic site —> take + charged ammonium

choline was go first but ester group after bcz it was covalently bound

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14
Q

What is the diff between nicotinic and muscarinic ?

A

MUSCARINIC
• 7TM G protein coupled receptors (Metabotropic —> 2nd messenger )
• Found in parasympathetic
• synapses in heart, smooth muscle and glands
• Also found in sweat glands innervated by sympathetic
• Transmission is slow (msecs)
• Action is blocked by Atropine ( non selective muscarinic antagonist )
• G protein has Alfa, beta, and Gama
• Alfa ( I , S , Q ) G protein determines which pathway is activated
• has 5 types —> 3 main subtypes —> M1,2,3

NICOTINIC
• Directly coupled to cation channels (ionotropic —> linked to ions so very fast )
• Found at neuromuscular junction ( somatic ) and autonomic ganglia and CNS
• ACh causes rapid depolarization bcz ionotropic
• Action is blocked by decamethonium ( nicotinic receptor antagonist )
•has 2 types : muscle ( in neuromuscular junction ) and neuronal ( in the autonomic ganglia and CNS )

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15
Q

What does Ach do to the following:

A. Eye
B. Lungs
C. Heart 
D. Glands 
E. GI 
F. urinary bladder and rectum
G. Male organs 
H. Autonomic ganglia 
I. Adrenal medulla 
J. Neuromuscular junction
A

A. Pupil constricts —> to look at near objects
B. Bronchoconstriction
C. ⬇️ HR / Contractility / Conduction velocity
D. ⬆️ sec
E. ⬆️ motility
F. Contraction of the bladder, relaxation of the sphincter, and defecation
G. Erection
H. ⬆️ transmission
I. ⬆️ adrenal release
J. Contraction of skeletal muscles

H / I / J —> only NICOTINIC

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16
Q

What are the 3 main types of muscarinic Ach receptors and what are the others?

A

M1
M2
M3

The other types are M4 and M5

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17
Q

What is the role of M receptors?

A

M1, M3, and M5 —> ⬆️ cellular excitability

M2 and M4 —> ⬇️ cellular excitability

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18
Q

What is the 2nd messenger cascade in M receptors?

A

M1 / M3 / M5: IP3 and DAG production by PKC formation

M2 / M4: inhibition of adenylate Cyclase

M2: activation of K+ and inhibition of Ca+2

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19
Q

What is the function of

  1. IP3
  2. DAG
A
  1. releases calcium from endoplasmic and sarcoplasmic reticulum.
  2. opening of smooth muscle calcium channels
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20
Q

What is the effect of cAMP

A

muscarinic agonists attenuate the activation of adenylyl cyclase and modulate the ⬆️ of cAMP levels induced by hormones such as catecholamines —> net action is ⬇️cAMP

These muscarinic effects on cAMP generation reduce the physiologic response of the organ to stimulatory hormones.

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21
Q

What are the M receptor agonists?

A
  1. Ach
  2. Carbachol

NON-SELECTIVE —> agonist to all M receptors

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22
Q

What is the antagonist of M receptors?

A

Atropine

NON-SELECTIVE

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23
Q

What does the muscarinic receptors do ? ( P 113 )

A
  1. regulate the production of intracellular second messengers
  2. modulate certain ion channels via their G proteins
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24
Q

Where is the G proteins and what do they do? (P113)

A

third cytoplasmic loop of the 7 transmembrane domains

They are transducers

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25
Q

Where can we find M1 receptors?

A
  1. Nerves
  2. Autonomic ganglia ( CHECK )
  3. Parietal cells in GI
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26
Q

Where can we find M2 receptors?

A
  1. ❤️ —> first discovered there so it is called cardiac M2
  2. Nerves
  3. Smooth muscles
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27
Q

Where can we find M3 ?

A
  1. glands
  2. Smooth muscle
  3. Endothelium
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28
Q

Where can we find M4 and M5 ?

A

Not known where peripherally

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29
Q

Where can you find muscular nicotinic receptor?

A

Somatic cells —> skeletal muscle neuromuscular junction

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30
Q

Where can we find neuronal nicotinic receptor ?

A
  1. CNS
  2. Autonomic ganglia
  3. Postganglionic cell body
  4. Dendrites
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31
Q

What does nicotinic receptors do?

A

They are ion channels so they modulate the influx and efflux of Na and K

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32
Q

What are the subunits of receptors?

A

Alfa —> bind to Ach

Beta

Gama

Delta

They have to receive 2 Ach to activate the receptor so they need 2 Alfa

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33
Q

what are the ways of selectivity of action on M and N receptors? ( p. 114)

A
  1. Some drugs stimulate either M or N receptors
  2. Some stimulate N receptors at NMJ and less effect on the ganglia
  3. Organ selectivity by choosing the route of administration —> minimize SE
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34
Q

What happens after the binding of Ach to Alfa subunit ?

A

channel opens forming an ion pore in the post-synaptic membrane

  • Influx of Na+
  • Efflux of K+ ( CHECK )

Leading to: propagation of action potential into cell, Ca2+ release from intracellular stores and activation of contractile machinery

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35
Q

What is the diff btwn the nicotinic receptor in the CNS and in any other place?

A

has a receptor that has only Alfa subunits

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36
Q

Dale’s experiment

A

Look at it 💀

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37
Q

How do the drugs that affect the cholinergic system work / MoA of drugs ?

A
  1. Acting on the receptor itself ( directly bind )
  2. Affect the ganglia
  3. Block neuromuscular transmission / nicotinic receptors
  4. Enhance cholinergic transmission ( indirect )
  5. Modulate the synthesis, release, and storage of Ach
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38
Q

What is the pharmacological act of M Ach receptors ?

A

Mimics the action of Ach

  • Vasodilation
  • Bradycardia (decrease in heart rate)
  • Decreased blood pressure
  • Contraction of gut smooth muscle ( ⬆️ motility and secretion )
  • Exocrine secretions
  • Contraction of ciliary muscle ( myosis ) allows adjustment and focus and accommodation of near vision
  • Regulation of intraoccular pressure —> imp for patients with glaucoma
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39
Q

What are the M receptor agonists?

A

• Ach —> endogenous ligand —> non-selective
—> hydrolyzed

  • Carbachol —> 1st synthetic —> non-selective
  • Metacholine —> nonselective ( but more selective to M )—> hydrolyzed
  • Bethanechol
  • Muscarine —> 2nd natural product —> isolated from poisonous mushroom —> reason for the naming of the receptor
  • Pilocarpine
  • oxotremorine

AcCar Meta ya Bet Muscar pilox

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39
Q

What are the drugs that mimed the action of Ach?

A

Cholinoceptor stimulants are classified to
A. Muscarinic
B. Nicotinic

Depending on their MoA:

  1. Bind directly to cholinoceptors
  2. Indirectly by inhibiting the hydrolysis of endogenous Ach
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41
Q

What do the M receptor agonists differ in?

A
  1. Selectivity on the receptor ( ⬆️ selective —> ⬇️ side effect )
  2. Rate of hydrolysis by AchE
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42
Q

What are the agonists that resist hydrolysis and what does this indicate?

A
  1. Carbechol
  2. Benthanchol
  3. Muscarine
  4. Pilocarpine
  5. Oxotremorine

They all have ⬆️ duration of action

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42
Q

What are the drugs specific for muscarinic receptors?

A
  1. Bethanchol ( bcz of the beta-methyl group)
  2. Muscarine ( bcz of the beta-methyl group)
  3. Pilocarpine
  4. Oxotremorine
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44
Q

Why Ach is hard to be used clinically but carbachol not?

A

Bcz Ach is highly hydrolyzed so must give as IV infusion —> brief effect but if IM or subC —> local effects

while carbechol is not hydrolyzed

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45
Q

What are the drugs that does not cross the CNS ?

Should give us the structure 🙄

A
  1. Ach
  2. Carbechol
  3. Methacholine
  4. Bethanchol
  5. Muscarine
46
Q

What are the drugs that can cause CNS side effects / cross the CNS ?

A
  1. Pilocarpine: may produce hypertension after a brief hypotension effect

2 oxotremonine

46
Q

Can Muscarine be toxic?

A

less completely absorbed from the gastrointestinal tract than the
tertiary amines but is nevertheless toxic when ingested—eg, in
certain mushrooms and it even enters the brain.

47
Q

What is the clinical use of Ach ?

A

Eye drop as miotic in cataract surgery

49
Q

What is the clinical use of Carbechol? ( has car so IOP )

A

Eye drop to ⬇️ IOP in glaucoma ( ايوب عربي كل )

50
Q

What is the clinical use of bethanchol ( بطن كل ) ?

A

Used orally ( امال هناكل بإيه؟ )

⬆️ GI motility during period of GIT paralysis ( e.g. paralytic ileus )

Relieve urinary retention in depressed bladder muscle activity

51
Q

What is the clinical use of Methacholine ?

A

In the lab to test bronchial hyperactivity ( متى البريك )

52
Q

What is the clinical use of Pilocarpine? ( has car so IOP )

A

⬇️ IOP in glaucoma

Sjögren’s syndrome

( أيوب خس من صجج؟ )

53
Q

What is the clinical use of Cevimeline?

A

Sjögren’s syndrome (سيڤي الإيميل من صجج )

54
Q

What is Sjögren’s syndrome ? لا لا من صجج ما تعرفين ؟ 😂😱

A

An auto immune disease where antibodies attack self antigens —> attack the salivary gland —> destroy it —> very very dry mouth

55
Q

What are the side effects of M receptor agonists ?

A
  1. Diarrhea
  2. Cardiovascular (Bradycardia / hypoT)
  3. GI —> e.g. ulcers
  4. Bronchoconstriction so should take care in patients with asthma
  5. nausea
  6. vomiting
  7. urinary urgency
  8. salivation
  9. sweating
  10. cutaneous vasodilation
56
Q

What are the contraindications of M agonists ?

A
  1. Asthma
  2. glaucoma ( CHECK the diff btwn it and closed angle )
  3. Ulcers
  4. Hyperthyroidism
  5. Cardiovascular disease

Bcz condition will be exacerbated

57
Q

What does the M antagonists do?

A
  1. ⬆️ HR —> tachycardia
  2. Block all the secretions
  3. Eye:
    A. Dilate the pupils by relaxing the SPHINCTER muscle ( mydriasis ) —> adjusting for far vision
    B. Relax the CILIARY muscle —> cycloplegia ( lens fixed for far vision )
  4. GI —> ⬇️ motility
  5. Lungs —> bronchodilation
  6. Paralysis of the bladder
  7. if lipid soluble bcz it can enter CNS
    A. Low dose —> mild CNS SE
    B. high dose —> Restlessness ( very active) / disorientation / hallucinations (at high doses)
  8. Sedation, drowsiness and amnesia —> esp hyoscine
58
Q

Examples of M antagonists? ( يعني نحفظ؟ )

A
  • Atropine
  • Benztropine
  • Hyoscine
  • Pirenzepine
  • Darifenacin
  • Ipratropium & Tiotropium
  • Tropicamide
  • Cyclopentolate
  • Homatropine
  • Glycopyrrolate
  • Dicycloamine
  • Clidinium

AB HPDITC HGDC

59
Q

What do you know about atropine?

A
  1. Non selective
  2. Competitive
  3. Potent anti-cholinergic
  4. Alkaloid
  5. Isolated atropa belladonna
  6. Now can be synthesized
60
Q

What is hyoscine ( scopolamine / buscoban )

A
  1. Alkaloid

2. Isolated from datura stramonium

61
Q

What are Ipratropium & Tiotropium

A
  1. Selective M3 antagonist
  2. Used to facilitate Bronchodilation —> relaxation and may ⬇️ sec in the lungs
  3. It is administered by inhalation Ipratropium is also combined with salbutamol for the management of chronic obstructive pulmonary disease (COPD) and asthma.
  4. Ipratropium can reduce rhinorrhoea (runny nose) but will not help nasal
    congestion
  5. Usually given by nebulizers —> targeting the lungs
  6. Tiotropium has LONGER duration of action than ipratropium
62
Q

What is darifenacin?

A
  1. M3-selective antagonist
  2. Used in the treatment of urinary incontinence: lack of voluntary control —> so we block the bladder activity —> ⬇️ urination
63
Q

What is pirenzepine?

A
  1. M1 receptor antagonist —> present one parietal cells in GI
  2. used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm.
  3. Pirenzepine is being investigated for use in myopia* ( قصر نظر )control.
64
Q

What are Tropicamide & cyclopentolate & Homatropine?

A
  1. Used as eye drops ( topical ) For eye exam

2. Shorter duration of action than atropine

65
Q

What are Glycopyrrolate & Dicyclomine?

A
  1. Selective at M3 receptors
  2. Competitive
  3. Used to treat:
    A. Irritable bowel syndrome
    B. minor diarrhea
66
Q

What is Clidinium?

A
  1. is used to treat irritable bowel syndrome
  2. It is commonly prescribed in combination with chlordiazepoxide (a benzodiazepine derivative) using the brand name Librax
67
Q

What are the clinical uses for M antagonists?

A

• Cardiovascular:
- Control bradycardia

• Ophthalmic:

  • to dilate pupil for eye exams
  • To prevent synechia formation

• Respiratory:
- treatment of asthma

• Pre-Anaesthetic: ( usually combine more than one drug )
- control (Block) secretion of saliva & bronchus

• Gastrointestinal:

  • to facilitate endoscopy
  • Slow gut motility
  • treatment of irritable bowel syndrome
  • Control the secretion of gastric acid
  • Prevent vomiting
  • Anti-nausea & anti-motion sickness
  • Parkinson’s Disease —> hypersensitivity of Ach so we block it use benzatropine ( CHECK )

• Treatment of anticholinesterase poisoning & prevent the side effects of
anticholinesterase

68
Q

What are the side effects of M antagonists?

A
  1. Tachycardia
  2. Blurred vision
  3. Constipation
  4. Dry mouth
  5. Urinary retention
  6. CNS side effect
69
Q

What are the contraindications of Mantagonists?

A
  1. Constipation
  2. Closed angle glaucoma
  3. Urinary problem
70
Q

What can nicotine do?

A

At low doses it can stimulate the nicotinic receptors off the autonomic ganglia —> but the receptor is non selective so you activate both PNS and SNS —>

  1. not used now but it is experimental tool
71
Q

What are SE of ganglionic nicotinic AchR?

A

Both sympathetic and parasympathetic ganglia are stimulated, so effects are complex.

  1. Tachycardia
  2. ⬆️ BP
  3. ⬆️ secretions
  4. ⬆️ GI motility ( CHECK )
  5. Miosis —> constrict —> in the book cycloplegia happens but the effect on the ciliary muscle is not known
  6. increased bronchial, salivary and sweat secretions.
  7. sympathetic tachycardia may alternate with a bradycardia mediated by vagal discharge
  8. nausea
  9. vomiting
  10. diarrhea
  11. voiding of urine
72
Q

What are the effects of ganglionic blockers?

A
  1. Mydriasis —> dilation of the pupils —> mainly P
  2. Cycloplegia
  3. ⬇️ arterioler and venomotor tone —> mainly S
  4. ⬇️ BP —> orthostatic/postural hypotension
  5. ⬇️ contractility
  6. Moderate tachycardia —> SA node dominated by P
  7. 🚫Sec
  8. 🚫motility
  9. Hesitancy in urination
  10. ⬇️ Thermoregulatory sweating
  11. high doses of Nicotine cause a Prolonged depolarization, causing a ganglionic blockade
73
Q

What are the SE of ganglionic blockers?

A
  1. Constipation
  2. Mecamylamine can cross the BBB —> leading to tremors / sedation / choreiform movements / mental aberrations
  3. Constipation
  4. Dry mouth
  5. Dry eye
74
Q

What is the use of ganglionic blockers ?

A

Treating hypertension in hypertensive crisis

Paralytic ileus —> paralysis of the GI tract

75
Q

What is the CNS nicotinic agonist?

A

Vareniciline

For smoking cessation

76
Q

What are the SE of vareniciline ?

A
  1. Nausea and vomiting
  2. Exacerbation of psychiatric illness
  3. Suicidal ideation
77
Q

What are the NMJ blockers?

A

Drugs used to cause paralysis during anesthesia:
1. Nondepolarizing

  1. Depolarizing
78
Q

What are the non-depolarizing NM agents?

A
  1. Used as Muscle Relaxants
  2. Competitive antagonist of ACh at N-AChR
  3. Cause relaxation of skeletal muscle
  4. Reversible by anti-AChE drugs
79
Q

What are the SE of nondepolarizing?

A

Side effects:
• a fall in arterial blood pressure due to ganglion block
• Bronchospasm
• Tachycardia

80
Q

What are the types of non-depolarizing?

A

Long acting

Intermediate acting

Short acting

81
Q

What are the long acting ?

A
  1. Tubocurarine
  2. Pancuronium
  3. Gallamine
  4. Doxacurium
  5. Pipecuronium

دة بجد

82
Q

What is tubocurarine?

A

Plant alkaloid from Chondrodendron tomentosum

83
Q

What are the intermediate acting non depolarizing

A
  • Atracurium
  • Cisatracurium
  • Vecuronium
  • Rocuronium
84
Q

What is the short acting non depolarizing?

A

Mivacurium

85
Q

What are the depolarizing NM agents

A
  1. Nicotine ( high dose )
  2. Decamethonium —> Causes twitching of muscle followed by tonic block
  3. Suxamethonium ( succinylcholine )

Used as preanasthetics

86
Q

What is the MoA of depolarizing NM blockers ?

A

Cause initial activation of Nicotinic receptors ( spasm of skeletal muscle ) —> then induce block bcz of sustained depolarization or activation of receptors

Act as an agonist at the beginning. However, when activated for a several amount of time this activation causes deactivation —> so the first SE seen is muscle twitching which is painful

Agonist but if prolonged use antagonist

87
Q

What is suxamethonioum?

A

It has rapid action

Ideal for rapid intubation

Rapidly hydrolyzed by plasma cholinesrerase —> duration very short

88
Q

Why depolarizing agents aren’t reversible by anti AchE?

A

Bcz the drug cannot be displaced by Ach

Bcz already is activated but the activation lead to deactivation

They are not normal antagonist

89
Q

What are the SE of depolarizing NM blockers?

A
  1. Post-operative pain
  2. Hyperkalemia in patients with high K or predisposed to ❤️ disease or severe burns —> bcz we are activating the muscle so Na enters and K comes out —> can lead to arrhythmia
  3. Prolonged paralysis: depends on genetics —> bcz the expression of plasmacholinesterase expression defer from person to person —> if atypical —> prolonged paralysis ( patient won’t walk up ) bcz no metabolism to suxamethonium —> UNPREDICTABLE
  4. Bradycardia & increased IOP
  5. Increased intragastric pressure —> esp in obese —> more pressure in the gastric area
90
Q

Give characteristics of

  1. Atracurium
  2. Cistracurium
  3. Mivacurium
  4. Tubocurarine
  5. Pancuronium
  6. Rocuronium
  7. Vecuronium
  8. Suxamethonium
A
  1. Spontaneous hydrolysis in physiological PH —> no need for enzyme
  2. Mostly spontaneous
  3. Hydrolyzed by plasma ChE
  4. / 5. Renal elimination
  5. / 7. Liver and kidney elimination
  6. Plasma ChE and very short acting
91
Q

What are the drugs that have tendency to cause histamine release ?

A
  1. Atra: slight
  2. Miva: moderate
  3. Tubo: moderate
  4. Suxamethonium: slight
92
Q

What are the drugs that Affect cardiac M receptor from NM agents

A
  1. Pan: moderate
  2. Rock. Slight
  3. Gall: strong block
  4. Suxa: stimulate
93
Q

What are the ones that affect autonomic ganglia ?

A
  1. Tubo: weak block

2. Suxa: stimulation

94
Q

Which NM should have less SE ?

A

Vecuronium bcz it doesn’t stimulate or block ganglia ,M receptors or histamine release

95
Q

What is the MoA of anticholinesterases?

A
  • bind with AChE to prevent ACh hydrolysis
  • Potentiate the action of ACh
  • Classified according to duration of action
96
Q

What are the main uses of anti-AchE ?

A
  1. Glaucoma
  2. Myasthenia Gravis
  3. Reversal of non depolarizing neuromuscular blockage
  4. Alzheimer’s disease
97
Q

What is the short acting anti AchE?

A

Edrophonium —> very rapid action

It is a quaternary ammonium enzyme that will bind ONLY to the anionic site on the enzyme —> electrostatic bond so can hydrolyze very quickly

98
Q

Give ex on medium duration anti-AchE and what are the characteristics?

A

• Neostigmine
• Pyridostigmine
• Physostigmine (eserine) —> Alkaloid isolated from Physostigma venenosum
Others slide 44

Characteristics:

  1. Binds to both sites on AChE
  2. Form an ester group with OH of the esteratic site
  3. Hydrolysis is slow
  4. T1/2: 30 min-1 hr
99
Q

What are the characteristics of neostigmine and pyridostigmine

A
  1. Quaternary compounds

2. Do not cross the CNS

100
Q

What are the characteristics of physostigmine ?

A
  1. Tertiary amine

2. CROSS the CNS

102
Q

Give examples on the irreversible anti AchE?

A
  • Dyflos
  • Parathion
  • malathion
  • Ecothiophate
103
Q

Why are the irreversible antiAchE / dyflos / parathion called organophosphates?

A

because they cause phosphorylation of the serine group at the active site of Acetylcholine esterase
يمسك فيه و ما يهده

104
Q

How is organophosphates developed?

A
  1. War gas

2. Pesticides

105
Q

What are the characteristics of irreversible antiAchE?

A
  1. Have organic phosphate or fluorine
  2. Phosphorylate the estertic site
  3. the hydrolysis is very very slow
  4. the recovery need the synthesis of a new enzyme ( faster to make a new drug than for the drug to leave the enzyme )
  5. Used in insecticides and war gases
106
Q

What is the relation btwn antiAchE drugs and Ach?

A

They inhibit the hydrolysis of the Ach so they mimic there action

107
Q

What are the clinical uses ?

A
  1. Neostigmine is used by anesthetists to reverse the action of non-depolarizing NMJ blockers without entering the CNS —> peripheral
  2. Neostigmine or pyridostigmine in the treatment of MYASTHENIA GRAVIS.
  3. Edrophonium (short acting) used in the diagnosis of MYASTHENIA GRAVIS and to diff btwn it and cholinergic crisis ( toxicity of Ach ) —> give drug —> if improved —> myasthenia gravis
  4. Physostigmine is used in the treatment ofATROPINE POISONING bcz atropine is a competitive antagonist so if ⬆️ACh —> displace the atropine ( atropine can enter the CNS so we must give antiAchE that cross the CNS —>to target the poisoning centrally and peripherally and it is intermediate bcz we can’t give edrophonium bcz it doesn’t cross the CNS and it is short acting )
  5. Rivastigmine & Galantamine used in ALZHEIMER’S disease ( they have ⬇️Ach ) —> give drug that can cross the CNS
  6. Neostigmine is used to Treat PARALYTIC ILEUS and BLADDER ATONY
  7. Echothiophate and demecarium for GLAUCOMA
108
Q

What is myasthenia gravis?

A

Autoimmune disease that forms antibodies against the nicotinic Ach receptor ( loss of receptors )in the skeletal muscles —> muscle becomes weak

The signs

  1. Muscle weakness—> can affect any muscle but the 1st is the eyelid —> eyelid drop
  2. Feel fatigue easily
  3. Can affect the facial/swallowing/speech muscle
  4. Has impact on the quality of life of the patient

So he takes Neostigmine or pyridostigmine depending on the duration of action

109
Q

What are the SE of Anti-AChEs

A

• Salivation • Sweating • Increased GIT motility • Bronchoconstriction • Bradycardia • Pupillary constriction • Agitation, convulsion & respiratory depression

110
Q

What is the antidote for organophosphates ?

A
  1. By blocking the action of ACh using ATROPINE
  2. By forcing the reactivation of the enzyme by displacing the drug from the enzyme using OXIME ( restore the enzyme functionality )
111
Q

What is oxime / obidoxime / pralidoxime ?

A
  • A chemical antagonist of AChE-inhibitors
  • have greater affinity for the organic phosphate residue than the enzyme
  • results in full enzyme recovery and the phosphate-oxime ( bind to phosphate of the drug ) compound is eliminated from the organism via urine
113
Q

Why irreversible Anti AchE are called like that?

A

Bcz when they bind to the enzyme they don’t leave it —> binding bond very stable —> deactivation require synthesis of new enzyme —> failure to remove ACh from synapse after nerve stimulation —> enhances the stimulatory effect —> muscle contractions, muscle depolarization and paralysis.

But the short and medium can leave it again to be reactivated

Pharma (5 decks)

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