Cholinoreceptor Blocking Agents Flashcards
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
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)
Atropine: mechanism
Competitive antagonist of Ach at muscarinic sites
Doesn’t distinguish between different subgroups of muscarinic receptors
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
Atropine: Flush
Dilation of cutaneous vessels
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"
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
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 anticholinergicsScopolamine (cholinergic blocker) (TransdermScop, Inopto-Hyoscine)
Topical Motion sickness Opthomology Midwives - Produced amnesia Crosses BBB
Homatropine: USe
Opthamology
Ipratropium: USe
Respiratory diseases
Inhalers
Ganglionic stimulants and blockers
Nicotine
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
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
Nicotine: agents
Nicorette
Transdermals
Chantix
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
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
