FM0 Ultimate (All Learning Outcomes)

Missing Learning Outcomes for Pharmacodynamics + Pharmacokinetics, as they are not posted yet

Passive diffusion

Movement of molecules from high to low concentration across a membrane, no energy or carrier protein needed (e.g., O2, CO2 crossing the cell membrane)

Carrier-mediated transport

Movement of molecules across a membrane using a specific protein carrier; includes facilitated diffusion, active transport, and secondary active transport

Facilitated diffusion

Carrier-mediated transport down the concentration gradient, no ATP required (e.g., glucose entering cells via GLUT transporters)

Active transport

Carrier-mediated transport against the concentration gradient, requires ATP directly (e.g., Na+/K+ ATPase pump)

Secondary active transport

Carrier-mediated transport that uses the energy stored in an ion gradient (created by active transport) to move another molecule, no direct ATP use (e.g., Na+/glucose cotransporter)

Symport

Secondary active transport where both molecules move in the same direction across the membrane

Antiport

Secondary active transport where molecules move in opposite directions across the membrane

Phagocytosis

Type of endocytosis where the cell engulfs large particles or whole cells ("cell eating")

Pinocytosis

Type of endocytosis where the cell takes in small amounts of extracellular fluid and dissolved solutes ("cell drinking")

Receptor-mediated endocytosis

Type of endocytosis where specific molecules bind receptors on the membrane, triggering uptake into the cell (e.g., LDL cholesterol uptake)

Exocytosis

Process where a vesicle inside the cell fuses with the cell membrane to release its contents outside the cell (e.g., hormone or neurotransmitter release)

Transcytosis

Process where a substance is taken into a cell by endocytosis on one side, transported across the cell, and released by exocytosis on the other side (used to move substances across a cell layer, e.g., capillary endothelium)

Intracellular fluid (ICF)

Fluid inside cells; makes up about 2/3 of total body water; high in potassium, low in sodium

Extracellular fluid (ECF)

Fluid outside cells, includes plasma and interstitial fluid; makes up about 1/3 of total body water; high in sodium, low in potassium

Plasma

The fluid portion of blood; part of the ECF, contains more protein than interstitial fluid

Interstitial fluid

Fluid surrounding cells in tissues, outside blood vessels; part of the ECF

Starling forces

The balance of hydrostatic and oncotic pressures that determine fluid movement between plasma and interstitial space

Hydrostatic pressure

The physical pushing force of fluid against a vessel wall, tends to push fluid out of capillaries

Oncotic pressure

The osmotic pressure created specifically by plasma proteins (mainly albumin), tends to pull fluid into capillaries

Osmotic pressure

The pressure created by solute concentration differences that draws water across a semipermeable membrane

Osmolality

The concentration of solute particles per kilogram of water, expressed as mOsm/kg

Tonicity

The effect a solution has on cell volume, based only on solutes that cannot cross the membrane (effective osmoles)

Calculating plasma osmolality

Estimated as 2 x [Na+] + [glucose]/18 + [BUN]/2.8

Effect of increased ECF sodium

Increases ECF osmolality, drawing water out of cells into the ECF, and stimulates thirst and ADH release, increasing total body water

Effect of decreased ECF sodium

Decreases ECF osmolality, causing water to move into cells and reducing effective circulating volume signals

Sodium's role in ECF volume

Sodium is the major determinant of ECF volume because water follows sodium osmotically; total body sodium roughly determines ECF volume

Osmolal gap

The difference between measured and calculated osmolality; a large gap suggests presence of an unmeasured osmotically active substance (e.g., toxic alcohol ingestion)

Anion gap

The difference between measured cations and anions in plasma, calculated as [Na+] − ([Cl−] + [HCO3−]); a raised gap suggests accumulation of unmeasured acids (e.g., lactic acidosis, ketoacidosis)

Homeostasis

The maintenance of a stable internal environment despite external changes

Sensor

A component of a feedback system that detects a change in a controlled variable

Control center

A component of a feedback system that receives input from the sensor and determines the appropriate response

Effector

A component of a feedback system that carries out the response to restore balance

Negative feedback

A control loop where the response counteracts the original change to bring the variable back toward normal (e.g., thermoregulation

Positive feedback

A control loop where the response amplifies the original change rather than reversing it (e.g., labour and delivery

Feedforward control

A mechanism that anticipates a change and initiates a response before the change actually occurs (e.g., the digestive system

Endocrine signalling

Cell communication where a hormone is released into the bloodstream to act on distant target cells

Autocrine signalling

Cell communication where a cell releases a signal that acts on itself

Paracrine signalling

Cell communication where a signal acts on nearby neighbouring cells, not the cell that released it

Neural signalling

Cell communication where a neuron releases a neurotransmitter across a synapse to act rapidly on a specific target cell

Na+ concentration gradient

High extracellular (~140 mM), low intracellular (~10-15 mM) — driving force is into the cell

K+ concentration gradient

High intracellular (~140 mM), low extracellular (~4-5 mM) — driving force is out of the cell

Ca2+ concentration gradient

Much higher extracellular than intracellular (intracellular kept very low, ~10,000-fold gradient) — driving force is strongly into the cell

Equilibrium potential

The membrane voltage at which the electrical force balances the chemical (concentration) force for a specific ion, so there is no net movement of that ion; calculated using the Nernst equation

Resting membrane potential

The stable voltage across the membrane of a non-stimulated cell, typically around -70 mV, mainly set by K+ permeability

Why K+ dominates resting potential

The resting membrane is much more permeable to K+ than other ions (via leak channels), so resting potential lies close to the K+ equilibrium potential

Action potential generation

A rapid, transient reversal of membrane potential triggered when depolarization reaches threshold, opening voltage-gated Na+ channels

Depolarization phase of action potential

Caused by rapid opening of voltage-gated Na+ channels, Na+ rushes into the cell

Repolarization phase of action potential

Caused by inactivation of Na+ channels and opening of voltage-gated K+ channels, K+ flows out of the cell

Threshold

The minimum depolarization needed to trigger enough voltage-gated Na+ channels to open and produce an action potential

All-or-none principle

Once threshold is reached, an action potential fires at full amplitude; if threshold is not reached, no action potential occurs

Absolute refractory period

Period after an action potential when Na+ channels are inactivated and no new action potential can be generated, regardless of stimulus strength

Relative refractory period

Period after the absolute refractory period when a stronger-than-normal stimulus can trigger another action potential, due to ongoing K+ efflux hyperpolarizing the membrane

Propagation of action potential

Local depolarization spreads to adjacent membrane regions, sequentially opening voltage-gated Na+ channels along the axon

Myelination

Insulation of the axon by Schwann cells/oligodendrocytes that prevents current leak and speeds conduction

Saltatory conduction

Action potentials "jump" between nodes of Ranvier in myelinated axons, greatly increasing conduction velocity

7 steps of chemical synaptic transmission

1) Action potential arrives at axon terminal, 2) Voltage-gated Ca2+ channels open, 3) Ca2+ influx triggers vesicle fusion, 4) Neurotransmitter released into synaptic cleft, 5) Neurotransmitter binds postsynaptic receptors, 6) Postsynaptic response (excitatory or inhibitory) generated, 7) Neurotransmitter is removed (reuptake, degradation, or diffusion), ending the signal

Ionotropic receptor

A receptor that is itself an ion channel; neurotransmitter binding directly and rapidly opens the channel, producing fast synaptic effects

Metabotropic receptor

A receptor coupled to a G-protein and second messenger system; produces slower, longer-lasting, and more diverse synaptic effects than ionotropic receptors

Excitatory postsynaptic potential (EPSP)

A depolarizing ionotropic effect, usually from Na+ influx, making the postsynaptic cell more likely to fire an action potential

Inhibitory postsynaptic potential (IPSP)

A hyperpolarizing (or stabilizing) ionotropic effect, usually from Cl− influx or K+ efflux, making the postsynaptic cell less likely to fire

Pharmacological targeting of synaptic transmission

Each step (synthesis, storage, release, receptor binding, termination) can be a drug target — e.g., blocking reuptake (SSRIs), blocking release (botulinum toxin), or blocking/mimicking receptor binding (agonists/antagonists)

Sympathetic nervous system (SNS)

The "fight or flight" branch of the ANS; generally increases heart rate, dilates airways, redirects blood flow to muscles, and inhibits non-essential functions like digestion

Parasympathetic nervous system (PNS)

The "rest and digest" branch of the ANS; generally decreases heart rate, promotes digestion, and conserves energy

Neurotransmitter

A chemical messenger released by a neuron to communicate with a target cell across a synapse

Adrenergic receptor (α or β)

A receptor activated by norepinephrine/epinephrine; α receptors typically cause vasoconstriction, β receptors typically cause effects like increased heart rate or bronchodilation depending on subtype

Muscarinic receptor

A metabotropic acetylcholine receptor found at parasympathetic target organs, mediating most PNS effects

Nicotinic receptor

An ionotropic acetylcholine receptor found at autonomic ganglia and the neuromuscular junction, mediating fast synaptic transmission

Sympathomimetic

A drug that mimics the effects of the sympathetic nervous system

Atropinic (anticholinergic)

A drug that blocks muscarinic receptors, inhibiting parasympathetic effects

SNS/PNS effect on heart

SNS increases heart rate and contractility (β1 receptors); PNS decreases heart rate (muscarinic receptors via the vagus nerve)

SNS/PNS effect on airways

SNS causes bronchodilation (β2 receptors); PNS causes bronchoconstriction and increased secretions (muscarinic receptors)

SNS/PNS effect on urinary tract

SNS relaxes the bladder detrusor muscle and contracts the internal sphincter (promotes storage, β and α receptors); PNS contracts the detrusor and relaxes the sphincter (promotes voiding, muscarinic receptors)

Phenylephrine

An α-adrenergic agonist; causes vasoconstriction (used as a decongestant or to raise blood pressure)

Salbutamol (albuterol)

A β2-adrenergic agonist; causes bronchodilation (used in asthma)

Atropine

A muscarinic antagonist; blocks PNS effects, e.g., increases heart rate, dries secretions, dilates airways

Ipratropium

A muscarinic antagonist used as an inhaled bronchodilator (limited systemic absorption compared to atropine)

Propranolol

A non-selective β-adrenergic antagonist; blocks β1 and β2 effects, e.g., lowers heart rate, can cause bronchoconstriction

Malathion

An acetylcholinesterase inhibitor (organophosphate); increases acetylcholine at synapses, producing excess PNS-like (muscarinic and nicotinic) effects

5 steps of chemical neurotransmission

1) Synthesis of neurotransmitter, 2) Storage in vesicles, 3) Release into the synapse, 4) Receptor binding on the target cell, 5) Termination of the signal (reuptake, enzymatic breakdown, or diffusion)

Dopamine, norepinephrine, epinephrine synthesis

Synthesized from the amino acid tyrosine through a series of enzymatic steps in the nerve terminal (catecholamine synthesis pathway)

Acetylcholine synthesis

Synthesized from choline and acetyl-CoA by the enzyme choline acetyltransferase

Termination of catecholamine signalling

Ended mainly by reuptake into the presynaptic neuron, with some enzymatic breakdown by MAO and COMT

Termination of acetylcholine signalling

Ended by enzymatic breakdown by acetylcholinesterase in the synaptic cleft

Botulinum toxin

Blocks the release step of neurotransmission (prevents acetylcholine vesicle release at the neuromuscular junction); used therapeutically for muscle spasms/cosmetic use; side effect

Bethanechol

A muscarinic receptor agonist; used to stimulate bladder/GI motility; side effect

Atropine (pharmacology target)

Blocks the receptor step (muscarinic antagonist); used for bradycardia or organophosphate poisoning; side effect

Malathion (pharmacology target)

Blocks the termination step (inhibits acetylcholinesterase, so ACh is not broken down); used as an insecticide/pediculicide; side effect

Amphetamine

Increases the release step (promotes catecholamine release) and blocks reuptake; used for ADHD/narcolepsy; side effect

Phenylephrine (pharmacology target)

Acts at the receptor step (direct α-adrenergic agonist); used as a decongestant/vasopressor; side effect

Salbutamol (pharmacology target)

Acts at the receptor step (direct β2-adrenergic agonist); used for asthma/bronchospasm; side effect

Propranolol (pharmacology target)

Blocks the receptor step (non-selective β-antagonist); used for hypertension, arrhythmias, anxiety; side effect

Prazosin

Blocks the receptor step (α1-antagonist); used for hypertension/BPH; side effect

Amitriptyline

Blocks the termination step (inhibits norepinephrine and serotonin reuptake); used as a tricyclic antidepressant; side effect

Cocaine

Blocks the termination step (blocks reuptake of dopamine, norepinephrine, serotonin); used medically as a local anesthetic/vasoconstrictor; side effect

Effect of increased extracellular K+

Decreases the K+ concentration gradient, causing the resting membrane potential to become less negative (depolarized)

Effect of decreased extracellular K+

Increases the K+ concentration gradient, causing the resting membrane potential to become more negative (hyperpolarized)

Hyperkalemia effect on excitable cells

Mild elevation initially increases excitability (membrane closer to threshold), but severe/prolonged elevation inactivates Na+ channels, ultimately decreasing excitability and impairing conduction

Hypokalemia effect on excitable cells

Hyperpolarizes the membrane, moving it further from threshold, making cells less excitable and slowing electrical conduction

Why altered extravascular ion concentration causes swelling

Changes in solute concentration alter osmotic gradients, drawing water into cells or tissues (e.g., increased intracellular osmoles pull water in, causing cellular swelling/edema)

Why IV concentrated potassium causes death

A sudden spike in extracellular K+ severely depolarizes cardiac cell membranes, inactivating Na+ channels and disrupting normal cardiac action potentials, leading to fatal arrhythmias (cardiac arrest)