Readings

• acetylcholinesterase: enzyme that inactivates ACH
• muscarinic receptor: nerves and receptors of the PNS that's on smooth and cardiac muscle
• Nm (nicotinic muscle) receptor: cholinergic receptor located at the neuromuscular junction of skeletal muscle
• Nn (nicotinic neural) receptor: cholinergic receptor located on both sympathetic and parasympathetic ganglia
• Drugs that block muscarinic receptors are anticholinergic
• ACH is synthesized from choline and acetyl CoA
• Acetylcholinesterase inactivates ACH when it is outside a nerve ending and not on a receptor
• Pseudocholinesterase is located in the liver and plasma and can hydrolyze ACH and other similar drugs
• Botulism: toxins from bacteria causing food poisoning
• Some toxins can inhibit the release of ACH from cholinergic nerve endings to produce skeletal muscle paralysis.
• Each cholinergic receptor type accepts ACH as its neurotransmitter but they are each blocked by a different drug class
• Muscarinic receptors are at the parasympathetic postganglionic nerve ending.
• The cholinergic receptors at the ganglionic sites of both parasympathetic and sympathetic nerves are the nicotinic neural receptors
• Nicotine stimulates the autonomic ganglia in low doses and blocks the autonomic ganglia in high doses
• Ganglionic stimulants/blockers refer to the Nn receptors
• Nicotinic muscle receptors are seen at the neuromuscular junction
• Drugs that block the effects ACH at Nm receptors are called neuromuscular blockers or skeletal muscle relaxants
• Cholinergic drugs are either direct acting or indirect acting
• The direct acting drugs bind to cholinergic receptors while indirect acting inhibit acetylcholinesterase
• Indirect acting drugs increase the concentration of ACH at all muscarinic and nicotinic receptors sites
• Direct acting drugs only increase ACH activity at the muscarinic sites
• ACH is not useful as a drug because of its very short duration
• Derivatives of ACH not only have a longer duration, they are also more slowly inactivated by acetylcholinesterase
• Cholinergic drugs are used to constrict the pupils to treat glaucoma
• Indirect acting drugs are known as anticholinesterases
• Anticholinesterase is divided into reversible and irreversible inhibitors of acetylcholinesterase
• Reversible inhibitors are used in the treatment of myasthenia gravis, Alzheimer's and as antidotes for cholinergic/nicotinic blockers
• Myasthenia gravis is an autoimmune disease that causes skeletal muscle weakness/paralysis
• By inhibiting acetylcholinesterase in PTs with myasthenia gravis, ACH concentrations are increased in the Nm receptors which increases the strength of muscular contraction
• Irreversible inhibitors of acetylcholinesterase are derivatives of organophosphate compacts such as insecticides, pesticides and warfare agents. They have very long duration of actions. In large doses, they produce toxicity referred to a cholinergic crisis
• Cholinergic crisis refers to when a high concentration of ACH causes excessive stimulation of muscarinic receptors but a blockage of nicotinic receptors. Can result in respiratory paralysis
• Atropine is a drug that can be administered to block the effects of excessive muscarinic stimulation
• Pralidoxime is a drug that can undo the effects of anticholinesterase
• Reversible anticholinesterase drugs are used more commonly than direct acting cholinergic drugs. They are used to treat glaucoma, myasthenia gravis, urinary retention, intestinal paralysis and Alzheimer's
• Alzheimer's causes a loss of neuronal synapses and reduction of ACH in the brain
• At high doses skeletal muscle blockers can cause respiratory paralysis
• Anticholinergic drugs compete with ACH to bind to muscarinic receptors.
• By blocking effects of ACH, anticholinergic drugs decrease the activity of the vagus nerve in the heart
• Anticholinergic drugs should not be administered when there is an intestinal obstruction as they decrease GI motility
• Anticholinergic drugs are contraindicated for males with hypertrophy of the prostate gland