Cholinoreceptor Blocking Agents Flashcards by Tyler Soulek

PNS Blocking agents: Pharmacokinetics

Absorption and Distribution
   - Rapidly absorbed
   - Crosses BBB
   - Given topically or injected
Metabolism and excretion
   - Eliminated via hepatic metabolism and urinary excretion 
   - 2-3 hour half life

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Parasympathetic Blocking agents: Belladonna poisoning

Mad as a hatter (delirium)
Red as a beet (vasodilation)
Blind as a bat (can’t accommodate for near vision), mydriasis (maximal pupillary dilation)
Hot as hell (block sweating)

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Atropine: mechanism

Competitive antagonist of Ach at muscarinic sites

Doesn’t distinguish between different subgroups of muscarinic receptors

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Atropine: Action

GIT
Glandular secretions decreased
Bronchial smooth muscle and secretory glands
Heart
- Varies with dose and with vagal tone of individual
- Small doses
- May produce an initial temporary bradycardia
Peripheral action causes progressively increasing tachycardia by blocking muscarinic receptors on the SA node pacemaker
Blood vessels
- Most don’t have PNS innervation
- Cholinergic sympathetic vasodilator fibers to blood vessels are blocked
- Blocks generalized vasodilation caused by direct-acting muscarinic agonists
Eye
- Mydriasis (dilation)
- Relaxation of ciliary muscle
- Can precipitate acute glaucoma in patients with narrow anterior chamber angle
- Decreased lacrimal secretions

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Atropine: Flush

Dilation of cutaneous vessels

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Atropine: Adverse effects

Xerostomia (dry mouth)
Blurred vision
Increase IOP
Urinary retention
Constipation
Anhidrosis
Tachycardia
Asthma ( bronchoconstriction)
CNS
"Can't pee, can't see, Can't spit, can't shit"

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Atropine: Treatment of overdose

Gastric lavage (if oral)
Supportive measures for maintenance of circulation and respiration
Lowering body temperature
Physostigmine
- Once was used (increases Ach)
Diazepam, lorazepam, barbiturates to control CNS excitation

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Atropine: Therapeutic Uses

Inhibition of secretions
Preanesthetic med
Bradycardia
Intestinal hypertonicity
Muscarinic agonist poisoning
Peptic ulcer disease
asthma and respiratory disorders
Renal and biliary colic
CNS
   - Parkinsons
   - Motion sickness
Overactive bladder
   - Tolterodine [ Detrol]
       - Offers no advantage over long acting anticholinergics

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Scopolamine (cholinergic blocker) (TransdermScop, Inopto-Hyoscine)

Topical 
Motion sickness
Opthomology 
Midwives
   - Produced amnesia
Crosses BBB

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Homatropine: USe

Opthamology

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Ipratropium: USe

Respiratory diseases

Inhalers

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Ganglionic stimulants and blockers

Nicotine

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Nicotine (ganglionic stimulant): Mechanism

Stimulates ganglion cells by depolarizing the postsynaptic membrane, resulting in stimulation like Ach
Larger doses of nicotine stimulation followed by block of the ganglia
- Nicotine stays on receptors preventing stimulation by Ach
Addictive

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Nicotine: Actions

NMJ
- Stimulation followed by depression (depolarizing block)
CNS
- Stimulation of CV, Respiratory, and vomiting centers in medulla
- Tremors
- After quitting can have a hard time concentrating sometimes

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Nicotine: agents

Nicorette
Transdermals
Chantix

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Nicotine: Toxicity

Depends on age
Fatal dose
- 1 drop of liquid (amount in 2 cigarettes)
- Ingest of nicotine by kids especially vomiting usually, limiting exposure

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Ganglionic Blocking agents: Mechanism

Competitive inhibition of Ach of autonomic ganglionic sites

Ganglionic Blocking Agents: Pharmacokinetic action

Can be predicted with knowledge of the autonomic innervation of effector organs

Ganglionic Blocking Agents: Adverse Effects

orthostatic hypertension, dilation of pupils and blurred vision, dry mouth, urinary
Hesitancy constipation, impotence in males, numerous other side effects

Ganglionic Blocking Agents: Agents

Trimethaphan
Mecamylamine
Hexamethonium
- First two used in treatment of hypertensive emergencies

Agents that Inhibit Cholinergic Transmission: Main drug

Botulinum Toxin Type A (Botox)

Botulinum Toxin: Mechanism

Inhibits release of Ach at the neuromuscular junction and in cholinergic neurons in the ANS

Botulinum Toxin: Uses

Ophthalmological disorders
Movement disorders
Cosmetic uses
Can cause a decrease in sweating

Botox in strabismus

Can help straighten out the eyes

Neuromuscular blocking agents: Effects

Control of muscle contraction | Interfere with transmission at the neuromuscular end plate causing paralysis

Classification of neuromuscular blockers

Nondepolarizing neuromuscular blockers I (tubocurarine) Nondepolarizing neuromuscular blockers II: (other) Depolarizing neuromuscular blockers (succinylcholine)

Neuromuscular pharmacological categories

Competitive antagonists of Ach at the NMJ - Tubocurarine Depolarizing agonists - Produce a depolarizing block at the NMJ (succinylcholine)

Competitive Antagonist Agents

Curare, d-tubocurarine

Curare alkaloids, d-tubocurarine: Mechanism

At NMJ curare like agents compete with Ach for cholinergic receptors at the motor end-plate of skeletal muscle Curare has little intrinsic activity but competitively blocks the action of Ach Is reversible - Increase Ach to reverse effect of curare by using CHE inhibitors

Curare: Absorption, Distribution and fate of Tubocurarine

Not absorbed orally Can't cross BBB or placenta Rapid initial distribution followed by slower elimination phase - Onset within 4-6 minutes after IV administered - Lasts 1 hour after single dose - Second dose as late as 24 hours after first dose - Less drug is needed to produce same degree of paralysis Excreted in urine

Curare, d-tubocurarine: Pharmacological Actions

Fairly selective at NMJ - Produce paralysis Order of symptoms - Skeletal muscles become weak/ flaccid - small rapid moving muscles, then limbs, neck, and trunk - intercostals and lastly diaphragm paralyzed Histamine release - Flushing - Hypotension - Excessive bronchial and salivary secretions and bronchospasms - Mass cells - Pouring out of mass cells - Degranulation of mass cells

Curare: Adverse effects

Hypotension Bronchospasms and excessive secretions Respiratory failure Patients with myasthenia gravis extremely sensitive

Curare: Drug interactions

General anesthetics Quinidine, lidocaine and other local anesthetics and antiarrhythmics Aminoglycoside antibiotics CCB

Curare: Clinical uses

Adjunct to surgical anasthesia to induce skeletal muscle relaxation and facilitate manipulations during surgery Orthopedic procedures Facilitate intubation with an endotracheal tube Decrease intensity in electroshock therapy Diagnostic for myasthenia gravis

Depolarizing blocking agents

succinylcholine

Succinylcholine: Mechanism

Produces a depolarization of the motor end-plate like Ach which produces a transient muscle activation Persistent depolarization and blocks NMJ Can't be antagonized by cholinesterase inhibitors

Succinylcholine: Action

Before paralysis, depolarizing agents evoke transient muscular fasciculations Has intrinsic activity Ultra-short duration and rapid onset Brief duration due to rapid hydrolysis by cholinesterase enzymes of liver and plasma If prolonged depolarization, muscle cells may loose significant quantities of K - Accompanies skeletal muscle contraction - If you have a leaky membrane (trauma membrane) showing hyperkalemia - Could stop the heart

Succinylcholine: CV Effects

Stimulate all cholinoreceptors including nicotinic receptors in both SNS and PNS and the adrenal medulla, and muscarinic receptors in the heart Low doses can produce bradycardia Larger doses can produce hypertension and tachycardia

Cholinesterase inhibitors: Action

Accentuate the neuromuscular blockade

Succinylcholine:Myasthenia gravis

Resistant, going to need a higher dose

Succinylcholine: Adverse effects

Cardiovascular effects from stimulation of parasympathetic of sympathetic ganglia Respiratory failure Malignant hyperthermia