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Flashcards in Cholinergic Drugs Deck (44)
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Bethanechol

Synthetic Choline Ester (both CH3=Muscarinic specific and NH2 (amide is poorly degraded by AchE)

Cholinergic Agonist (Lower HR, BP; Activate GI & Mucosal Cells, Empty Bladder/rectum, Constrict Bronchi, Miosis)

Only M receptor no N receptor
Longest DURATION (60-90 min)

Stimulate smooth muscle Post-Op (atony of GI tract following surgery), dysfunction of bladder emptying, and promotion of saliva formation

1

Carbachol

Synthetic Choline Ester (Has a amide group so not easily degraded)

Cholinergic Agonist

Has both M receptor and N receptor action

Long action (60-90 min)

Used by corneal application for therapy of wide-angle glaucoma (constrict ciliary muscle, to open the meshwork of the canal of Schlemm.)

2

Methacholine (Carbastat)

Synthetic Choline Ester (Has a CH3 attached so specific for M receptor)

Cholinergic Agonist

Short acting (10-15 min)

Used to test function of muscarinic receptors, to slow heart in severe Tachycardia

Test for bronchial hyperactivity

3

Edrophonium (Tensilon)

Cholinesterase Inhibitor

Competitive

Simple Alcohol with a quaternary ammonium group (can't pass lipid bilayer)

Used in the diagnosis of MYASTHENIA GRAVIS

Duration of Action: 5-15 min

4

Neostigmine
(Prostigmin)

Cholinesterase inhibitor

Competitive

Carbamate (Carbamic ester of alcohol with quaternary ammonium)

Increases smooth muscle motility and useful for paralytic ileus and atony of the bladder from surgery

Treatment and diagnosis of myasthenia gravis

Reversal of neuromuscular blockade (caused by curare)

Duration of action: .5-2 hr

5

Physostigmine (Antilirium)

Cholinesterase Inhibitor

Competitive

Carbamate (carbamic acid ester of alcohols with tertiary amine group=can cross lipid bilayer)

Used TOPICALLY to treat wide-angle glaucoma

Duration of action: .5-2 hr

6

Pyridostigmine (Mestinon)

Cholinesterase Inhibitor

Competitive

Carbamate

Used in treatment of myasthenia gravis

PRETREATMENT to reduce mortality after exposure to nerve gas, reversal of neuromuscular blockade

Duration of Action: 3-6 hour

7

Ambenonium (Mytelase)

Cholinesterase Inhibitor

Competitive

Treatment for Myasthenia Gravis

Duration of action (4-8 hr)

8

Muscarine

Natural Alkaloid

Cholinergic Agonist

(Amanita muscaria)

Selective for muscarinic receptor

9

Pilocarpine

Natural alkaloid

Cholinergic agonist

Pilocarpus leaves

Anomalous cardiovascular responses, sweat glands particularly sensitive

10

Nicotine

Natural Alkaloid

Cholinergic agonist

Solanceae nightshade

Tobacco

Selectivity for nicotinic receptors

11

Vareniciline

Natural alkaloid
Nicotinic Selective

Cholinergic agonist

12

Diisopropylfluorophosphate (DFP)

Cholinesterase Inhibitor

Noncompetitive

Insecticide

Organophosphate derivative

Irreversible, long lasting

13

Echothiophate

Cholinesterase Inhibitor

Noncompetitive

Organophosphate derivative

Clinically relevant

Treatment of Glaucoma

Duration of Action: 100 hr

14

Carbaryl (Sevin)

Cholinesterase Inhibitor

Non Competitive

Insecticide

15

Malathion

Cholinesterase Inhibitor

Non Competitive

Insecticide

16

Parathion

Cholinesterase Inhibitor

Non Competitive

Insecticide

17

Tetraethylpyrophosphate (TEPP)

Cholinesterase Inhibitor

Non Competitive

Insecticide

18

Sarin

Cholinesterase inhibitor

Non Competitive

Nerve Gas

19

Soman

Cholinesterase inhibitor

Non Competitive

Nerve Gas

20

Atropine

Cholinergic Antagonist

Muscarinic Selective
- Very low potency for nicotinic sites, but no selectivity amongst M subtypes

STEP 1 THERAPY against O-P intoxication
- Administer Large DOSE >5mg w/ following smaller doses (1-2mg)
- Competitively binds M receptor
- Does not alleviate NEUROMUSCULAR HYPERACTIVITY and resulting paralysis

Quick Distribution to CNS= limits use due to side effects
- Therapeutic dose only minor vagal stim
- Toxic dose= central excitation w/restlessness, irritability, disorientation, hallucinations, delirium

- Useful adjunct therapy for PARKINSONs disease

- Salivary, bronchial, sweat glands are most sensitive to atropine

- Relieves urinary incontinence



21

Pralidoxime (2-PAM)

AChE (Cholinesterase Reactivator)

Step 2 Therapy following O-P intoxication
- Releases the phosphoryl moiety to restore AchE activity of esteratic site
- Must be administered before AchE aging occurs
- Nerve Gas: within min
- Insecticide: within 24 hrs

Therapeutic dose: 1-2 g iv,
- Restores skeletal muscle responsiveness, little effects in CNS

22

Drugs to treat Acute closed angle glaucoma?

Pilocarpine (muscarinic agonist) and

Physostigmine (AChE inhibitor)

Medical emergency not long term treatment

23

Drugs to treat GI and Urinary Tract problems?

Bethanechol (cholinergic agonist)

Neostigmine (AChE inhibitor)

Pilocarpine may be used to increase salivary secretions

24

Cevimeline

Used for treating dry mouth in Sjögren's syndrome

25

Drugs to treat Neuromuscular junction problems?
- Myasthenia Gravis, neuromuscular blockade reversal

AChE inhibitors
- Edrophonium, pyridostigmine, neostigmine, ambenonium

26

Homatropine

Cholinergic Antagonist

Muscarinic Selective

Tertiary Semisynthetic derivative of ATROPINE

Elicit Mydriasis (Opening of Pupil) and Cycloplegia (loss of accomodation) TOPICAL TREATMENT

Duration of Action: 2-4 hours

Minor inhibition of Respiratory Tract secretions

Tertiary: Non polar so can cross BBB

27

Scopolamine

Cholinergic antagonist

Muscarinic Selective

Quick distribution after dose makes it limited use due to CNS side effects

- Tertiary ammonium= crosses BBB (central effects)
- CNS depression with drowsiness, amnesia, fatigue, dreamless sleep, euphoria

- Prevents motion sickness

- HIGH AMNESIA effect used before for pre-anesthetic

- Duration: 5-10 hours

28

Methscopoloamine

Cholinergic Antagonist

Muscarinic Selective

Quaternary Derivative of scopolamine
- PNS activity only due to charged N
- USED FOR GI Diseases

- Inhibits secretions of respiratory tract
- Does not have CNS effect so no amnesia or anti-Parkinson effects

Duration of action: 5-10 hours

29

Trihexyphenidyl

Cholinergic Antagonist

Muscarinic Selective

Tertiary amine

Useful adjunct therapy for low uncoordinated movement and excess salivation for parkinsonism
- Extra pyramidal side effects of anti-psychotic drugs

Duration of action: 3-6 hours

30

Tropicamide

Cholinergic Antagonist

Muscarinic Selective

Tertiary amine

Useful for mydriasis and cycloplegia

ONLY TOPICAL OCULAR TREATMENT

Duration of action: .5-1.5 hours

31

Cyclopentolate

Cholinergic Antagonism

Muscarinic specific

Duration of action: 1 day

Used in Opthalmology to elicit mydriasis and cycloplegia

32

Ipratropium

Cholinergic Antagonist

Muscarinic selective

Reduce bronchial secretions as a TOPICAL treatment (target bronchodilation and minimizes mucociliary clearance problems)

Quaternary derivative of Atropine, CANT CROSS BBB
- Bronchodilation, tachycardia, decreased salivation
- Minimize mucociliary clearance effect usually seen so useful for patients with airway problems
- Cannot cross membrane so very specific
- Useful in COPD patients

33

Tiotropium

Cholinergic antagonist

Muscarinic specific

Target Respiratory tract

Longer acting compared to ipratropium

Reduce bronchial secretions, elicits bronchodilation

34

Darifenacin

Cholinergic Antagonist

M3 selective

Greater M3 selectivity makes it longer duration of action

May help alleviate bladder spasm, slows micturition

35

Solifenacin

Cholinergic Antagonist

M3 Specific

Greater M3 selectivity has a longer duration of action at relaxing the smooth muscle wall of genitourinary system (ureters, bladder wall)

Alleviates bladder spasm following urologic surgery

36

Tolterodine

Cholinergic Antagonist

M3 Selective

Greater M3 selectivity allows a longer duration of action

Helps relax smooth muscle of genitourinary system

- Lower micturition speed

37

Mecamylamine

Cholinergic Antagonist

Nicotinic Selective

Ganglionic Blocking Agent

Secondary Amine to improve GI absorption following oral admin

Lasts 12 hours

CNS side effects: Tremor, Confusion, seizures, mania, depression


Nondepolarizing COMPETITIVE antagonist

38

Trimethaphan

Cholinergic Antagonist

Nicotinic Selective

Ganglionic Blocking Agent
- Sulfonium (positive charge sulfur groups) developed for IV infusion (lasts minutes)

NONDEPOLARIZING competitive antagonist

Clinical use: Short acting ganglionic blocker that give through IV during surgery to minimize blood loss in operative area (LOWERS ARTERIAL PRESSURE)

Must monitor excessive hypotension and possible brain anoxia

39

Succinylcholine

Cholinergic Antagonist

Noncompetitive Depolarizing Agent

Depolarize end plate region to inhibit acetylcholine
- Acts NONCOMPETITIVELY as receptor agonist opening Na channels, mimicking ACh action,

NOT A SUBSTRATE FOR AChE, but is hydrolyzed by plasma ChE

ONLY DEPOLARIZING neuromuscular BLOCKER

Phase I block: Membrane remains depolarized and unresponsive to later pulses,
- ChE inhibitors augment response rather than reverse block

Phase II Block: if allowed to stay in system will repolarize membrane but becomes resistant to depolarization

Do not use if patient:
- Plasma ChE mutations (DIBUCAINE TEST)
- Organophosphate intox
- Patients with CHF, burns, trauma, or neuromusc disease, due to excess release of K as a result of this function
- Patients with glaucoma as extraocular muscles will contract

40

Curare (d-tubocurarine)

Cholinergic Antagonist

Non-Depolarizing

Benzylisoquinolines (Devoid of vagolytic and ganglionic blocking activity)
- Elicitis some histamine release

Competes with acetylcholine for N2 receptor site

Induces Muscle RELAXATION

41

Atracurium and cisatracurium

Cholinergic antagonist

Non-depolarizing

Competes with acetylcholine for N2 receptor site

Benzylisoquinolones

Intermediate Acting

42

Mivacurium

Cholinergic antagonist

non-depolarizing

Benzylisoquinolone (some histamine)

Short Acting

43

Pancuronium (long lasting) and vecuronium (intermediate lasting)f

Cholinergic antagonist

Non-depolarizing

Long Acting

AMMONIO STEROID
- NO histamine release, some Muscarinc block eliciting vagal blockade and tachycardia