Week 1 Notes

NO IMMUNOLOGY

Afferent means?

IN

CNS to periphery

“Sensory”

Efferent means

OUT / away

Periphery to CNS

“motor”

Dendrites

receive information coming onto the cell

Axon

transfers information from the cell to other cells

Cranial nevers carrying parasympathetic fibers?

3, 7, 9, 10

CN 3?

Oculomotor

CN 7?

Facial

CN 9?

Glossopharyngeal

CN 10?

Vagus

3 exceptions to the coinnervation* principle?

*where organs receive both sympathetic and parasympathetic supply

1. Peripheral blood vessels

2. Sweat glands

3. Adrenal medulla

all are only sympathetic

What neurotransmitter is released by ALL preganglionic neurons?

Acetylcholine (ACh)

What neurotransmitter is released by postganglionic parasympathetic neurons?

Acetylcholine (ACh)

What neurotransmitter is released by postganglionic sympathetic neurons?

Norepinephrine (NE)

EXCEPT sweat glands (ACh) and adrenal medulla (no postganglionic)

Main adrenal medulla quirk?

Modified sympathetic ganglion with no postganglionic neuron

What does the adrenal medulla release?

80% Epinephrine, 20% Norepinephrine into bloodstream

Choline acetyltransferase (ChAT)?

the enzyme that makes acetylcholine by catalyzing the reaction between choline and acetyl-CoA

Inhibiting this enzyme would prevent ACh production, thereby reducing parasympathetic neurotransmission.

Acetylcholinesterase (AChE)

the enzyme that breaks down acetylcholine in the synaptic cleft after it has transmitted its signal, splitting ACh into choline and acetate for recycling

Nicotinic Nm (neuromuscular or muscle-type, also called N1)?

Found in Neuromuscular junction (NMJ) and

When ACh from the motor neuron binds Nm receptors on the muscle motor end plate (the specialized postsynaptic membrane), it triggers an end-plate potential (EPP), which depolarizes the muscle membrane and causes muscle contraction (voluntary movement).

Nicotinic Nn (neuronal or ganglionic-type, also called N2)?

Found in Autonomic ganglia (both sympathetic and parasympathetic), adrenal medulla (chromaffin cells that release catecholamines), and CNS

In autonomic ganglia, preganglionic neurons (from spinal cord or brainstem) release ACh, which binds Nn receptors on postganglionic neurons, generating an excitatory postsynaptic potential (EPSP) that propagates the autonomic signal onward. In the CNS,

Nn receptors modulate release of dopamine and other transmitters.

Myasthenia gravis?

autoimmune attack on Nm receptors at the NMJ → muscle weakness (ptosis, diplopia, bulbar weakness).

Myasthenia gravis treatment?

acetylcholinesterase inhibitors (e.g., pyridostigmine) to increase ACh or immunosuppression

Muscarinic M1 location?

TLDR - Brain

Sympathetic postganglionic neurons, some presynaptic sites; CNS neurons

M1 Result of Ligand bInding?

Formation of IP3 and DAG, increased intracellular calcium

Contraction in smooth muscle and neuronal excitement in brain

Muscarinic M2 location?

Heart

Myocardium, smooth muscle, some presynaptic sites; CNS neurons

M2 Result of Ligand bInding?

Opening of K+ channels, inhibition of adenylyl cyclase, reduces cAMP, lower pKa

Reduced exciteability and lower heart rate

Muscarinic M3 location?

Exocrine glands, vessels (smooth muscle and endothelium); CNS neurons,

Smooth muscle is the most common

M3 Result of Ligand bInding?

Formation of IP3 and DAG, increased intracellular calcium

Contraction in smooth muscle and glandular secretion in lungs or GI tract

Carbachol?

cholinergic agonist. 

It stimulates both muscarinic and nicotinic cholinergic receptors, mimicking the effects of acetylcholine.

It's often used to treat conditions like glaucoma or to induce miosis during eye surgeries.

Muscarine?

Agonist for muscarinic receptors

It binds to these receptors and mimics the action of acetylcholine, leading to effects like smooth muscle contraction, gland secretion, and slowing of the heart rate. This is why muscarine-containing substances can have strong parasympathetic effects on the body.

Atropine?

Antagonist for muscarinic receptors

It prevents acetylcholine from binding, reducing parasympathetic activity, which leads to effects like increased heart rate and decreased glandular secretions. Used to treat bradycardia.

Atropine targets what?

It’s non-selective, affecting all muscarinic subtypes

Scopolamine?

Antagonist for muscarinic receptors

It blocks the effects of acetylcholine on muscarinic receptors, helping to reduce motion sickness, nausea, and vomiting by acting on the central nervous system.

This is commonly used for motion sickness that is contraindicated (NOT recommended) in patients with narrow-angle glaucoma because it causes mydriasis (pupil dilation), which can precipitate acute angle-closure glaucoma.

scopolamine targets what?

Non selective but mainly has strong central nervous system effects.

Ipratropium?

Antagonist for muscarinic receptors

It blocks muscarinic receptors in the airways, leading to bronchodilation and is commonly used for conditions like chronic obstructive pulmonary disease (COPD) and asthma.

Ipratropium targets what?

mainly targets M3 receptors in the lungs to reduce bronchoconstriction.

Epibatidine?

Nn / N2 agonist

extremely strong pain relief

However, because it affects multiple nicotinic receptors, it can also cause serious side effects like hypertension, muscle paralysis, and respiratory depression, making it too dangerous for common therapeutic use.

Trimethaphan?

Nn / N2 antagonist

Targets the autonomic ganglia, which reduces both sympathetic and parasympathetic output

It's used to rapidly lower blood pressure in emergencies, such as during hypertensive crises or controlled hypotension in surgery.

Succinylcholine?

Nm / N1 agonist THEN antagonist!

• Used primarily for short-term paralysis during procedures, then becomes a rapid muscle relaxer (antagonist).

It acts as an agonist by binding to acetylcholine receptors at the neuromuscular junction, causing initial depolarization and muscle contraction.

However, it quickly remains bound, preventing further depolarization, which leads to paralysis and no further muscle contreaction, functioning as an antagonist by blocking normal receptor activity.

Atracurium?

Nm / N1 antagonist

It is non-depolarizing

It binds to the nicotinic acetylcholine receptors but doesn’t activate them, blocking acetylcholine from binding and preventing muscle contraction. This results in muscle relaxation without the initial depolarization phase.

Used for skeletal muscle relaxation during surgery and mechanical ventilation

Pancuronium?

Nm / N1 antagonist

another non-depolarizing neuromuscular antagonist

Used for Longer-duration muscle relaxation for surgery and mechanical ventilation because it is a lot more potent

Talsaclidine?

Selective M1 agonist

Potential treatment for Alzheimer's disease (cognitive enhancement via M1 stimulation in the brain)

Pirenzepine?

M1 antagonist

It reduces gastric acid secretion by blocking M1 receptors in the stomach, which helps treat peptic and gastric ulcers.

This action reduces acid production and aids in ulcer healing while minimizing typical anticholinergic side effects.

Pilocarpine?

M2 agonist

Can be used as:

• topical eye drops to lower intraocular pressure in glaucoma by increasing aqueous humor outflow and causing miosis (pupil constriction)

• oral form to treat dry mouth (xerostomia) in Sjögren's syndrome or after radiation therapy by stimulating salivary gland secretion.

Effective, Not necessarily Selective bc it can affect M3

Gallamine?

M2 antagonist

leads to increased heart rate and reduced secretions, and it can counteract the effects of acetylcholine on the heart and glands.

rarely used today because it causes tachycardia (from M2 blockade in the heart).

Oxotremorine?

M3 agonist

• stimulates smooth muscle contraction,

• increases glandular secretions,

• can cause tremor by activating the central nervous system.

Effective, Not necessarily Selective bc can affect M1

Darifenacin?

Selective M3 antagonist

Helps reduce bladder contractions and is commonly used to treat overactive bladder, reducing urgency and frequency of urination

Acetylcholinesterase Inhibitors (AChEI)?

Increase AChE in brain or wherever by blocking AChE

Can be used to treat alzheimers

Reversible AChE Inhibitor Purpose?

Allows ACh levels to rise then return to normal

This can can improve memory, alertness, and muscle control, especially in conditions like Alzheimer's or myasthenia gravis.

Once the effect wears off, normal neurotransmission resumes, reducing the risk of overstimulation or toxicity.

Organophosphate/ Irrevrsible AChEI Purpose?

binds permanently or for a very long time, leading to a prolonged increase in acetylcholine, which can have stronger and sometimes more dangerous effects, leading to which can lead to severe symptoms like muscle paralysis or respiratory failure

Mostly potent chemicals used in pesticidesand nerve agents. 

Very high risk treatment for glaucoma

pralidoxime (PAM, 2-PAM)?

reactivates acetylcholinesterase (AChE) that has been inactivated by organophosphate poisoning

Must be given before the organophosphate–AChE bond becomes irreversible, typically within 24–48 hours of exposure depending on the specific organophosphate.

Its primary benefit is at nicotinic sites (especially the neuromuscular junction), so it reverses muscle weakness, fasciculations (muscle twitches), and respiratory paralysis, while atropine is given simultaneously to block muscarinic effects like secretions and bronchoconstriction

Botulinum toxin (botox)?

inhibits acetylcholine release

Botulinum toxin blocks the release of acetylcholine from presynaptic nerve terminals, which prevents muscle contraction and produces therapeutic paralysis in conditions like blepharospasm. (involuntary spasms)

Tropicamide?

most commonly used medication for dilating pupils during routine eye examinations*

It’s an anticholinergic (muscarinic receptor antagonist) that produces mydriasis (pupil dilation) and cycloplegia (paralysis of the focusing muscles of the eye).

*unless you can’t afford it

a1 receptor locations?

1. Vascular smooth muscle

2. Genitourinary smooth muscle

3. Intestinal smooth muscle

4. Heart

5. Liver

a1 receptor functions? fill in

1. Vascular smooth muscle

2. Genitourinary smooth muscle

3. Intestinal smooth muscle

4. Heart

5. Liver

1. Vascular smooth muscle CONTRACTION

2. Genitourinary smooth muscle CONTRACTION

3. Intestinal smooth muscle RELAXATION

4. Heart - EXCITEMENT

5. Liver - GLYCOGENOLYSIS AND GLUCONEOGENESIS

also activates Gq/Go

a2 receptor locations?

1. Nerve presynaptic terminal

2. Platelets

3. Pancreatic B-cells

4. Vascular smooth muscle

a2 receptor functions? fill in

1. Nerve presynaptic terminal

2. Platelets

3. Pancreatic B-cells

4. Vascular smooth muscle

1. Nerve presynaptic terminal - release NE

2. Platelets - aggregate (do)

3. Pancreatic B-cells - secrete insulin

4. Vascular smooth muscle - contract

also activates Gi/Go

b1 receptor locations?

1. Heart

2. Renal juxtaglomerular cells

b1 receptor functions? fill in

1. Heart

2. Renal juxtaglomerular cells

1. Heart - more excitability (Chronotropy, inotropy, and AV node velocity)

2. Renal juxtaglomerular cells - secrete renin (first step in raising BP)

also activates Gs

b2 receptor locations?

1. Pancreas

2. Smooth muscle (+vascular)

3. Liver

4. Skeletal muscle

b2 receptor functions? fill in

1. Pancreas

2. Smooth muscle (+vascular)

3. Liver

4. Skeletal muscle

1. Pancreas - releases insulin

2. Smooth muscle (+vascular) - relaxation

3. Liver - Glycogenolysis and gluconeogenesis (makin suga)

4. Skeletal muscle - Glycogenolysis and K+ uptake for muscle contraction

also activates Gs

b3 location and function?

adipose and used for lipolysis

also activates Gs

Labetalol and carvedilol?

Both block beta and alpha adrenergic receptors. 

This leads to lower heart rate and reduced blood pressure by  relaxing blood vessels. They’re often used for treating high blood pressure and heart conditions.

Oxymetazoline?

Alpha receptor agonist

causes vasoconstriction, reducing nasal congestion by narrowing blood vessels in the nasal passages.

Phentolamine?

nonselective alpha-adrenergic antagonist

causes vasodilation and lower blood pressure

• used for conditions like pheochromocytoma to manage blood pressure

• causes b1 & b2 antagonism causing lowered diastolic pressure

• If there is hypertension from epinephrine, give a1 antagonist

Phenoxybenzamine?

nonselective alpha blocker

binds irreversibly, causing long-lasting effects

Isoproterenol?

nonselective beta-adrenergic agonist

increasing heart rate and causing bronchodilation and vasodilation

Propranolol and Timolol?

both nonselective beta blockers

reducing heart rate, blood pressure, and intraocular pressure.

They're often used for hypertension, heart conditions, and glaucoma.

Beta antagonists decrease blood flow to all tissues except brain

Phenylephrine and Methoxamine?

alpha-1 adrenergic agonists

They stimulate alpha-1 receptors, causing vasoconstriction and increasing blood pressure.

This makes them useful as nasal decongestants and for treating hypotension.

Prazosin and Tamsulosin?

alpha-1 blockers

They block alpha-1 receptors, leading to relaxation of smooth muscle in blood vessels and the prostate, which helps lower blood pressure and improve urine flow in benign prostatic hyperplasia.

Clonidine and Apraclonidine?

alpha-2 adrenergic agonists

They stimulate alpha-2 receptors, reducing sympathetic outflow (calming), lowering blood pressure, and decreasing intraocular pressure.

Yohimbine?

alpha-2 receptor antagonist

It blocks alpha-2 receptors, increasing sympathetic outflow, which can lead to increased heart rate and blood pressure.

Dobutamine?

beta-1 agonist

increasing heart rate and the force of heart contractions, often used to treat heart failure or during cardiac stress testing.

Atenolol and Metoprolol?

selective beta-1 blockers

They reduce heart rate and lower blood pressure by blocking beta-1 receptors mainly in the heart.

That makes them the safest choice for patients who need beta-blocker therapy for COPD and hypertension.

Albuterol and Ritodrine?

beta-2 agonists.

activate Gs proteins

causing bronchodilation in the lungs (because it increases intracellular cAMP) and relaxation of uterine smooth muscle.

Butoxamine?

selective beta-2 antagonist.

leading to bronchoconstriction and potential vasoconstriction,

and it's mainly used in research.

Mirabegron?

B3 agonist

stimulates beta-3 receptors in the bladder,

leading to relaxation of the bladder muscle and improving urinary storage.

Indirect-Acting Sympathomimetics?

drugs that produce sympathetic nervous system effects not by directly binding to adrenergic receptors (like direct agonists do), but by increasing the amount of endogenous catecholamines (norepinephrine, epinephrine, dopamine) available at synapses, which then activate receptors.

Ephedrine?

mixed-acting sympathomimetic

produces sympathetic effects both directly (by activating adrenergic receptors itself) and indirectly (by increasing norepinephrine release and blocking norepinephrine reuptake at sympathetic nerve terminals)

commonly used as a vasopressor (medication that constricts blood vessels to raise blood pressure) during anesthesia (especially obstetric anesthesia) to treat hypotension, and it is preferred over pure α agonists like phenylephrine in pregnant patients because its combination of modest α and β effects tends to increase blood pressure while preserving or even slightly increasing heart rate, which maintains cardiac output and uteroplacental blood flow better than pure vasoconstriction alone

Amphetamine and tyramine?

release enhancers

act as indirect sympathomimetics by entering sympathetic nerve terminals and causing the displacement and release of stored norepinephrine (and dopamine in the CNS) into the synapse, producing sympathetic effects without directly binding to adrenergic receptors themselves.

Desipramine and cocaine?

uptake inhibitors

• they act as indirect sympathomimetics by blocking the norepinephrine transporter (NET, also called uptake-1), which is the protein on the presynaptic nerve terminal that normally clears norepinephrine from the synapse back into the neuron. By blocking reuptake, these drugs increase the concentration and prolong the presence of norepinephrine in the synaptic cleft, which allows more and longer stimulation of postsynaptic adrenergic receptors (α and β), producing sympathetic effects without directly binding to those receptors themselves.

monoamine oxidase (MAO)?

an enzyme whose job is to chemically inactivate (“break down”) monoamine neurotransmitters such as norepinephrine (NE), dopamine (DA), and serotonin (5‑HT).

essential for maintaining proper neurotransmitter balance in both the central nervous system (brain and spinal cord) and peripheral tissues, because if monoamines accumulate unchecked they can overstimulate receptors and disrupt normal signaling, leading to emotional, cognitive, and autonomic dysregulation.

Clorgyline

selective and irreversible MAO-A inhibitor

• It works by permananetly inactivating MAO-A ("suicide inhibitors"), so the body must synthesize new MAO-A protein to restore activity, which is why the effects last days to weeks

• blocking MAO-A increases serotonin (5-HT), norepinephrine (NE), and to some extent dopamine, which is why MAO-A inhibitors have antidepressant effects.

MAO-A (especially in the gut and liver) normally breaks down tyramine, a dietary monoamine found in aged cheeses, cured meats, fermented foods, and certain alcoholic beverages. When MAO-A is inhibited (by clorgyline or nonselective MAOIs), tyramine is not degraded, so it is absorbed intact, enters sympathetic nerve terminals, displaces norepinephrine, and triggers massive NE release, producing a hypertensive crisis with severe headache, sweating, palpitations, and risk of stroke or MI.

Selegiline?

relatively selective irreversible MAO-B inhibitor

permanently inactivates MAO-B ("suicide inhibitors"), but it preferentially targets MAO-B at low doses (5–10 mg/day)

MAO-B preferentially metabolizes dopamine and certain trace amines (like phenylethylamine), so selective MAO-B inhibition increases dopamine availability in the CNS, which is why selegiline is used as adjunctive therapy in Parkinson's disease to enhance the effect of levodopa and prolong dopamine action.

catechol‑O‑methyltransferase (COMT)?

an enzyme that inactivates “catechols,” meaning molecules that contain a catechol ring (a benzene ring with two adjacent hydroxyl groups), which includes the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine.

Tolcapone

catechol-O-methyltransferase (COMT) inhibitor

Tolcapone is more lipophilic and crosses the BBB, so it inhibits COMT both peripherally and centrally (in the brain), which means it can also reduce the breakdown of dopamine itself in the CNS, potentially providing additional benefit by prolonging dopamine action at striatal receptors.

clinical purpose of this drug is to prolong the action of levodopa in Parkinson's disease treatment by preventing its peripheral metabolism, which increases the amount of levodopa that reaches the brain and extends the "on time" (the period when symptoms are well controlled).

Entacapone

catechol-O-methyltransferase (COMT) inhibitor

Entacapone is highly polar and does not cross the BBB, so it acts only peripherally (in the gut, liver, and blood) to block peripheral COMT and reduce peripheral levodopa breakdown.

Also prolongs the action of levodopa in Parkinson's disease treatment by preventing its peripheral metabolism, which increases the amount of levodopa that reaches the brain and extends the "on time" (the period when symptoms are well controlled).

D1 and D5?

dopaminoceptors that couple to Gs and increase cAMP

When dopamine binds to D2 receptors in the brain, it inhibits adenylyl cyclase, reduces intracellular cAMP, and modulates ion channel activity

D2, D3, and D4?

dopaminoceptors that couple to Gi/o and decrease cAMP

Haloperidol?

potent dopamine (more specifically D2 ) receptor antagonist

competitive: haloperidol binds to the D2 receptor with very high affinity (actually tighter than dopamine itself) and occupies the receptor without triggering the normal intracellular signaling cascade

antipsychotic effect, and blocking D2 receptors reduces that pathologic signaling that causes schizophrenia (where hallucinations and delusions are driven by excessive dopamine activity [hyperdopaminergic state])

Fenoldopam?

selective dopamine D1 (and D5?) receptor agonist

used intravenously to rapidly lower blood pressure, especially in hypertensive emergencies, because it produces arterial vasodilation while simultaneously improving renal perfusion

Bromocriptine?

dopamine D2 receptor agonist

used to treat hyperprolactinemia (high prolactin that causes inferility, low libido, low bone density) and prolactin-secreting pituitary adenomas or prolactinomas (pituitary tumors that lead to hypogonadism and has symptoms like headaches or vision loss).

Typical (first‑generation) antipsychotics?

block dopamine D2 receptors and are more likely to cause movement‑related side effects

Sulpiride?

selective dopamine D2/D3 (D4 too?) receptor antagonist

classified as an atypical antipsychotic and is competitive

at low doses (approximately 50–300 mg/day), sulpiride appears to preferentially block presynaptic D2/D3 autoreceptors (the inhibitory feedback receptors on dopamine neurons that normally suppress dopamine release and synthesis), which paradoxically increases dopamine synthesis and release and can produce antidepressant and pro-motivational effects

At higher doses (approximately 400–1600 mg/day), sulpiride's antagonism shifts to dominate at postsynaptic D2/D3 receptors in the striatum, mesolimbic, and mesocortical pathways, producing the antipsychotic effects typical of D2 blockade—reduction of positive symptoms like hallucinations, delusions, and thought disorder.

atypical (second‑generation) antipsychotics?

block both dopamine and serotonin receptors, offering broader symptom control with fewer extrapyramidal (involuntary) symptoms.

More methyls and less O and N means?

easier time to get into brain because the compound is less polar

Adding more N methyl groups (more bulky) to ER can make it more (?)

beta selective

Removing hydroxyl groups from NER can make it more (?)

alpha selective

Most potent a1-receptor–mediated arterial contractor?

Epi

Epi > NE >>> IP (isoproterenol)

Most potent b2-receptor–mediated bronchial smooth muscle relaxator?

IP (isoproterenol)

IP > Epi >>> NE,

Most potent b1-receptor–mediated augmented heart contractor?

IP (isoproterenol)

IP >> Epi ≥ NE