Lec 20_Nicotinic Agonists and Antagonists

All autonomic ganglia have _______ receptors

All receptors at the neuromuscular junction are _____ receptors

Activation of _____ receptors results in muscle contraction

Nicotinic

_______ stimulates and desensitizes receptors

nicotine

Describe the dose dependent responses of nicotine

• low dose stimulates

• high doses induce tachyphylaxis

What are the CV effects of nicotine?

Increase HR and BP d/t adrenal release of ACh

• increase HR

• increase force of contraction

• increase CO

• elevate systolic and diastolic pressures

What are the GI effects of nicotine?

• increased tone and motility

• N/V/D

What are the CNS effects of nicotine?

Dose dependent

• low dose, generalized stimulation

• higher doses, excessive stimulation including seizures

• still higher doses, depression and can be life-threatening

• N/V

What is the pharmokinetics of Nicotine as a drug

• good absorption from skin, resp tract and buccal membranes

• extensive biotransformation before renal elimination

Describe nicotine replacement therapy

• relieve psychological cravings

• relieve physiological withdrawal sx

In nicotine use there can be nicotine toxicity occurring in 2 phases. Describe phase 1

Occurs within 15-60 minutes of exposure

• GI: N/V, salivation, abd pain

• Skin: sweating, pallor

• CV: HTN, tachycardia

• Resp: rapid breathing

• CNS: HA, tremor, dizzy, muscle twitching, seizures

In nicotine use there can be nicotine toxicity occurring in 2 phases. Describe phase 2

Occurs within 30 min-4 hours after exposure

• GI: diarrhea

• CV: Hypotension, bradycardia, arrythmia, shock

• Resp: depression

• CNS: coma, muscle weakness/paralysis

Describe Varencline

1. Class

2. MOA

3. therapeutic use

4. ADE

1. Class - nicotine

2. MOA - partial nicotinic agonist

3. therapeutic use - smoking cessation

4. ADE - negative mood and behavioral changes

   1. had a BBW, now removed

   2. Do no mix with alcohol

   3. increase incidence of seizures

   4. vivid dreams

Describe neuromuscular blockers

Can be non-depolarizing: antagonist action at the neuromuscular junction preventing ACh from activating the receptor and prevents depolarization

• D-tubocurarine (poison dart frog)

• Rocuronium, vecuronium, atracurium, cisatracurium

Can be depolarizing: excess of a depolarizing agonist occupies the receptor and blocks the channel

• Succinylcholine

• Acetylcholine excess

Where would neuromuscular blockers be used?

Rapid Intubation

Surgery

• intubation

• muscle relaxation at lower anesthetic dose

Facilitate mechanical intubation in critically ill

What are the non-depolarizing neuromuscular blocker options?

Rocuronium, vecuronium, atracurium, cisatracurium

Describe what can be expected of non-depolarizing neuromuscular blockers at low and high doses

Low doses: bind to nicotinic receptors and block ACh from binding

• can be reversed by AChE inhibitors (neostigmine)

• can be stimulated with direct electrical stimulation

High doses: blocks the ion channel

• not reversed with AChE inhibitors

• not stimulated by direct electrical stimulation

______ cause a brief progressive flaccid paralysis

non-depolarizing neuromuscular blockers

What are the drug interactions with non-depolarizing neuromuscular blockers?

• aminoglycoside abx

• AChE inhibitors

Describe depolarizing neuromuscular blockers

• option: succinycholine

• acts like ACh

• Produced in two phases

  • Contraction phase - not broken down by AChE

  • relaxation phase - membrane repolarizes but can’t be stimulated again (drug is still in there)

What are the uses for depolarizing neuromuscular blockers?

• rapid intubation

• electroconvulsive therapy

What are the kinetics of depolarizing neuromuscular blockers?

• rapid onset, short duration

• metabolized by plasma enzymes

What are the ADEs for depolarizing neuromuscular blockers?

• muscle soreness

• malignant hyperthermia

• hyperkalemia

• apnea

Describe botulinum toxin

• blocks the release of ACh at ALL cholinergic synapses

• theraputically used as Botox - muscle paralysis (tx for prolonged muscle spasm) and skin to block stimulation of sweat glands

What is botulinum toxin used cosmetically?

inhibits ACh release

What makes Botox toxic?

• neuromuscular paralysis

  • primary tx is supportive

  • BBW: potential life threatening distant spread of toxin from injection site after local injection