ANS (No Drugs)

NO DRUGS

Nervous system

Involved in signal transmission between different body parts and relies on neurotransmitters

Central nervous system (CNS)

Consists of the brain and spinal cord

Peripheral nervous system (PNS)

Consists of nerves and ganglia outside the brain and spinal cord, connects the CNS to limbs and organs

Somatic nervous system

PNS division that innervates skeletal muscles and provides voluntary control

Autonomic nervous system (ANS)

PNS division responsible for involuntary control of smooth muscles, exocrine glands, and cardiac muscles

Sympathetic nervous system location

Thoracic + lumbar spinal cord

Parasympathetic nervous system location

Cranial nerves III, VII, IX, X + sacral S2, S3, S4

Sympathetic preganglionic fiber

Short, releases acetylcholine

Parasympathetic preganglionic fiber

Long, releases acetylcholine

Sympathetic postganglionic fiber

Long, releases norepinephrine

Parasympathetic postganglionic fiber

Short, releases acetylcholine

Sympathetic function

Fight or flight

Parasympathetic function

Rest and digest

DUMBBELLS mnemonic

Mnemonic for parasympathetic responses, Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, Emesis, Lacrimation, Lethargy, Salivation

D — Parasympathetic response

Diarrhea

U — Parasympathetic response

Urination

M — Parasympathetic response

Miosis

B — Parasympathetic response

Bradycardia

B — Parasympathetic response

Bronchoconstriction

E — Parasympathetic response

Emesis

L — Parasympathetic response

Lacrimation

L — Parasympathetic response

Lethargy

S — Parasympathetic response

Salivation

Sympathetic response

Generally the reverse of DUMBBELLS

Enteric nervous system (ENS)

Nerves located in the gut wall, innervated by the sympathetic and parasympathetic nervous systems

Parasympathetic stimulation of ENS

↑ ENS, ↑ GIT motility, ↑ acid secretion, ↑ digestion

Sympathetic stimulation of ENS

↓ ENS activity

Parasympathetic neurotransmitter

Acetylcholine (ACh)

Cholinergic receptors

Receptors activated by acetylcholine, divided into muscarinic and nicotinic receptors

Acetylcholine synthesis and action sequence

Choline uptake → ACh synthesis → vesicular storage → exocytotic release → receptor binding → AChE degradation → choline recycling

Step 1 of ACh handling

Uptake of choline

Step 2 of ACh handling

Synthesis of ACh

Step 3 of ACh handling

Vesicular storage

Step 4 of ACh handling

Release via exocytosis

Step 5 of ACh handling

Receptor binding, produces DUMBBELLS responses

Step 6 of ACh handling

AChE degrades ACh into choline + acetate

Step 7 of ACh handling

Choline recycling

M1 receptor location

CNS, autonomic ganglia, enteric neurons, gastric glands

M1 receptor signaling

Gαq/11 → ↑ IP3/DAG → ↑ intracellular Ca²⁺

M1 receptor effect

Neuronal excitation and ↑ gastric secretion

M2 receptor location

Heart including SA node, AV node, and atria, plus presynaptic nerve terminals

M2 receptor signaling

Gαi/o → ↓ cAMP, ↑ K⁺ efflux

M2 receptor effect

↓ heart rate, ↓ AV conduction, ↓ atrial contractility, ↓ ACh release

M3 receptor location in exocrine glands

Exocrine glands

M3 receptor signaling in exocrine glands

Gαq/11 → ↑ IP3/DAG → ↑ intracellular Ca²⁺

M3 receptor effect in exocrine glands

↑ salivation, ↑ lacrimation, ↑ bronchial/GI secretions

M3 receptor location in smooth muscle

Smooth muscle

M3 receptor signaling in smooth muscle

Gαq/11 → ↑ intracellular Ca²⁺

M3 receptor effect in smooth muscle

Bronchoconstriction, ↑ peristalsis, ↑ urination, miosis, accommodation

M3 receptor location in vascular endothelium

Vascular endothelium

M3 receptor signaling in vascular endothelium

Gαq/11 → ↑ Ca²⁺ → ↑ nitric oxide

M3 receptor effect in vascular endothelium

Vasodilation

M4 receptor location

CNS

M4 receptor signaling

Gαi/o → ↓ cAMP

M4 receptor effect

↓ neurotransmitter release, CNS inhibitory and modulatory effects

M5 receptor location

CNS

M5 receptor signaling

Gαq/11 → ↑ IP3/DAG → ↑ intracellular Ca²⁺

M5 receptor effect

CNS excitation/modulation, may ↑ dopamine release and cause cerebral vasodilation

NM receptor location

Skeletal muscle neuromuscular junction

NM receptor type

Ligand-gated ion channel

NM receptor effect

End-plate depolarization → skeletal muscle contraction

NN receptor location in autonomic ganglia

Autonomic ganglia

NN receptor type

Ligand-gated ion channel

NN receptor effect in autonomic ganglia

Ganglionic depolarization → activation of postganglionic neurons

NN receptor location in adrenal medulla

Adrenal medulla

NN receptor effect in adrenal medulla

↑ epinephrine and norepinephrine release

CNS-type nicotinic receptor location

CNS neurons

CNS-type nicotinic receptor type

Ligand-gated ion channel

CNS-type nicotinic receptor effect

CNS excitation/modulation, affects arousal, learning, memory, and neurotransmitter release

Cholinomimetics

Drugs that mimic acetylcholine, also called parasympathomimetics

Direct-acting cholinomimetics

Drugs that directly activate cholinergic receptors

Indirect-acting cholinomimetics

Anticholinesterase agents or cholinesterase inhibitors that inhibit AChE

Indirect cholinomimetic mechanism

↓ ACh breakdown → ↑ ACh at cholinergic nerve endings

Indirect cholinomimetic effects

↑ muscarinic and nicotinic effects

Reversible anticholinesterase agents

Agents that reversibly inhibit AChE

Irreversible anticholinesterase agents

Agents that cause persistent inhibition of AChE

Organophosphorus mechanism

Covalently bind or phosphorylate AChE, causing persistent AChE inhibition

Organophosphorus effect on ACh

Marked ↑ ACh at muscarinic, nicotinic, and CNS cholinergic sites

Organophosphorus poisoning treatment

Atropine + pralidoxime

Anticholinergic drugs

Also known as cholinergic antagonists or parasympathetic blockers

Anticholinergic MOA

Block cholinergic receptors

Anticholinergic response

Generally the reverse of DUMBBELLS

Non-selective muscarinic receptor antagonists

Antagonists that block multiple muscarinic receptor subtypes

Mydriatic-cycloplegic antimuscarinic agents

Drugs used mainly in the eye to produce mydriasis and cycloplegia, block muscarinic receptors in the iris sphincter and ciliary muscle.

Quaternary ammonium antimuscarinics

More permanently charged, have poor oral absorption and poor CNS penetration, produce fewer CNS and ocular effects than tertiary amines.

Skeletal muscle relaxants

Drugs that produce only skeletal muscle relaxation or paralysis, they are not analgesics or anesthetics

Patient requirements during skeletal muscle paralysis

Requires proper anesthesia, analgesia, oxygenation, and ventilation

Neuromuscular blocking drugs

Peripherally acting drugs that produce skeletal muscle paralysis

Non-depolarizing neuromuscular blockers

Competitive antagonists of ACh at Nm nicotinic receptors

Non-depolarizing blocker mechanism

ACh cannot bind → Na⁺ channels do not open → no depolarization → flaccid skeletal muscle paralysis

Non-depolarizing blocker reversal

Competitively reversed by increasing ACh using anticholinesterase drugs

Non-depolarizing blocker reversal drugs

Neostigmine or edrophonium combined with atropine or glycopyrrolate

Neuromuscular paralysis sequence

Small and fast muscles → limbs and trunk → intercostals → diaphragm

Neuromuscular recovery sequence

Recovery occurs in the reverse order of paralysis

Long-acting non-depolarizing blocker duration

>60 minutes

Intermediate-acting non-depolarizing blocker duration

30–60 minutes

Other intermediate-acting non-depolarizing blockers

Vecuronium, rocuronium, and alcuronium

Short-acting non-depolarizing blocker duration

10–30 minutes

Ultra-short-acting non-depolarizing blocker duration