Basic Science Concepts

Chapter 2 - 2025 Naplex book

What is a substrate/ligand?

Substance that creates a signal or produces an effect by binding to a receptor, enzyme, or transporter

What is the difference between endogenous and exogenous substances?

Endogenous = made by the body; Exogenous = made outside of the body

What is an agonist?

A substance that combines with a receptor to initiate a reaction

What is an antagonist?

A substance that reduces or blocks a reaction

What is the difference between induction and inhibition?

Induction = increases activity of an enzyme; Inhibition = decreases or blocks activity of an enzyme

What structures make up the CNS and what is its function?

brain and spinal cord; controls the functions of the rest of the body by sending signals to the PNS

What are the two main systems of the PNS and what do they control?

Somatic (voluntary) = controls muscle movement;

Autonomic (involuntary) = controls digestion, cardiac output, blood pressure, and other body functions

What are neurotransmitters and how do they work?

Neurotransmitters are the natural messengers/substrates of the body; they are released from presynaptic neurons into the synaptic cleft and travel to postsynaptic neurons or other areas of the body to elicit effects

What are the common neurotransmitters (NTs)?

ACh (acetylcholine), NE (norepinephrine), EPI (epinephrine), DA (dopamine), and 5HT (serotonin)

What is the role of ACh in the somatic nervous system?

ACh is the primary neurotransmitter of the somatic nervous system and controls muscle movement

How does ACh cause skeletal muscle movement?

ACh is released in response to neuron signals and binds to nicotinic receptors in skeletal muscles to cause muscle movement

What are the two main divisions of the autonomic nervous system?

Parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS)

What is the general role of the parasympathetic nervous system (PSNS)?

Rest and digest

How does the PSNS work and what effects does it produce?

Works via release of ACh, which binds to muscarinic receptors in organs such as the GI tract, bladder, and eyes; results in SLUDD (salivation, lacrimation, urination, defecation, and digestion)

What is the general role of the sympathetic nervous system (SNS)?

Fight or flight

How does the SNS work and what effects does it produce?

Works via release of EPI and NE, which act on adrenergic (alpha and beta) receptors in the cardiovascular and respiratory systems; increases BP, HR, and bronchodilation; stimulation of β2 receptors increases glucose production; digestion and urination are minimized

when the SNS is activated it leads to an increase in which of the following

a. HR

b. BP

c. bronchodilation

d. all of the above

d

How do substrates and receptors interact to produce a biological effect?

Substrates bind to receptors on the receiving cell to cause a signal or change; once bound, the receptor-substrate complex causes a change that results in a biological effect

How do antagonists affect receptor activity?

Antagonists block an agonist from binding and inhibit the subsequent reaction

What are the two types of antagonist-receptor interactions?

Competitive inhibition and noncompetitive inhibition

What is competitive inhibition?

The antagonist binds to the same active site of a receptor as the endogenous substrate, preventing it from binding and causing a reaction

What is noncompetitive inhibition?

The antagonist binds to an allosteric site (not the active site), changing the shape of the active site and preventing the endogenous substrate from binding

What are examples of medications that affect multiple receptors?

Isoproterenol = mixed β1 and β2 agonist used for bradycardia and causes bronchodilation

Carvedilol = α1, β1, and β2 antagonist used to decrease BP but can also cause bronchoconstriction

How do some vasopressors affect receptors and physiologic responses?

stimulate α1 and β1 receptors, leading to increased vasoconstriction, heart rate, and blood pressure

How does clonidine lower blood pressure?

centrally acting α2 adrenergic agonist; binding to presynaptic α2 receptors in the brain decreases sympathetic output (NT release), leading to decreased BP (vasodilation) and decreased HR

What is the endogenous substrate for muscarinic receptors?

ACh

What happens when muscarinic receptors are stimulated, and what are examples of agonists?

↑SLUDD; pilocarpine, bethanechol

What happens when muscarinic receptors are blocked, and what are examples of antagonists?

↓SLUDD; atropine, oxybutynin

What is the endogenous substrate for nicotinic receptors?

ACh

What happens when nicotinic receptors are stimulated, and what is an example of an agonist?

↑HR and BP; nicotine

What happens when nicotinic receptors are blocked, and what is an example of an antagonist?

Neuromuscular blockade; rocuronium

What happens when α1 receptors are stimulated, and what are examples of agonists?

Smooth muscle vasoconstriction and ↑BP; phenylephrine, dopamine

What happens when α1 receptors are blocked, and what are examples of antagonists?

Smooth muscle vasodilation and ↓BP; doxazosin, carvedilol, phentolamine

What happens when α2 receptors are stimulated, and what are examples of agonists?

↓EPI and NE release, ↓HR, and ↓BP; clonidine, brimonidine

What happens when α2 receptors are blocked, and what is an example of an antagonist?

↑HR and BP; ergot alkaloids

What happens when β1 receptors are stimulated, and what are examples of agonists?

↑Myocardial contractility, cardiac output, and HR; dobutamine, isoproterenol, dopamine

What happens when β1 receptors are blocked, and what are examples of antagonists?

↓Cardiac output and HR; metoprolol, propranolol, carvedilol

What happens when β2 receptors are stimulated, and what are examples of agonists?

Bronchodilation; albuterol, terbutaline, isoproterenol

What happens when β2 receptors are blocked, and what are examples of antagonists?

Bronchoconstriction; propranolol, carvedilol

What happens when dopamine receptors are stimulated or blocked?

Stimulation = renal, cardiac, and CNS effects (levodopa, pramipexole);

blockade = renal, cardiac, and CNS effects blocked (haloperidol, metoclopramide)

What happens when 5HT receptors are stimulated or blocked?

Stimulation = platelet, GI, and psychiatric effects (triptans);

blockade = platelet, GI, and psychiatric effects blocked (ondansetron, quetiapine)

What is the function of enzymes?

Compounds that speed up reactions

How can substrate-enzyme interactions occur?

Competitive or non-competitive

What does monoamine oxidase (MAO) normally do?

Breaks down catecholamines

What does acetylcholinesterase (AChE) do?

Breaks down ACh

What are examples of AChE inhibitors and what do they do?

Donepezil, rivastigmine, galantamine; block ACh breakdown resulting in ↑ACh; used to treat Alzheimer's disease

What does ACE normally do?

Converts angiotensin I to angiotensin II

What are examples of ACE inhibitors and what do they do?

Lisinopril, ramipril; inhibit production of angiotensin II leading to ↓vasoconstriction and ↓aldosterone secretion; used to treat HTN, HF, and kidney disease

What does COMT normally do?

Breaks down levodopa

What are examples of COMT inhibitors and what do they do?

Entacapone; inhibits levodopa breakdown resulting in increased duration of action; used to treat Parkinson's disease

What does COX normally do?

Converts arachidonic acid to prostaglandins and thromboxane A2

What do NSAIDs do to COX and what are the effects?

Decrease prostaglandins and thromboxane A2; used to treat pain, inflammation, and decrease platelet activation/aggregation

What does MAO normally do?

Breaks down catecholamines

What are examples of MAO inhibitors and what do they do?

Phenelzine, isocarboxazid, tranylcypromine, selegiline, rasagiline; increase catecholamine levels; used for depression; excessive levels can cause toxic effects

What does PDE normally do?

Breaks down cGMP

What are examples of PDE inhibitors and what do they do?

Sildenafil, tadalafil; prevent breakdown of cGMP resulting in prolonged smooth muscle relaxation; used to treat erectile dysfunction

What does vitamin K epoxide reductase normally do?

Converts vitamin K to its active form required to make clotting factors

What does warfarin do?

Blocks vitamin K epoxide reductase resulting in decreased production of clotting factors; used to treat or prevent blood clots

What does xanthine oxidase normally do?

Breaks down hypoxanthine into xanthine and xanthine into uric acid

What does allopurinol do?

Blocks xanthine oxidase to decrease uric acid production; used to treat gout

What does COX normally do?

Converts arachidonic acid to prostaglandins (inflammation) and thromboxane A2 (platelet aggregation)

What does PDE normally do?

Breaks down cGMP, a smooth muscle relaxant

What are examples of PDE inhibitors and what do they do?

Sildenafil, tadalafil; competitively bind PDE5 to prevent breakdown of cGMP resulting in prolonged smooth muscle relaxation; used to treat erectile dysfunction

What can happen when multiple drugs work similarly at the same receptor or enzyme?

Additive effects can occur, which can be detrimental

Why can MAO inhibitors cause hypertensive crisis or serotonin syndrome?

MAO inhibitors block breakdown of catecholamines, causing their accumulation; while beneficial for treating depression, excessive accumulation can lead to hypertensive crisis or serotonin syndrome

How do MAO inhibitors affect catecholamines, what can result, and what symptoms characterize it?

MAO inhibitors inhibit catecholamine breakdown causing ↑ NE and EPI levels; excessive accumulation can cause hypertensive crisis characterized by hypertension, tachycardia, agitation, and death.

Which drugs/foods can cause additive catecholamine excess when combined with MAO inhibitors?

Bupropion, SNRIs, TCAs, stimulants, levodopa, linezolid, methylene blue, and tyramine-containing foods.

How do MAO inhibitors affect serotonin, what can result, and what symptoms characterize it?

MAO inhibitors block 5-HT breakdown which can cause serotonin syndrome characterized by tremors, akathisia, clonus, hyperthermia, and sweating.

Which drugs can cause additive serotonin toxicity when combined with MAO inhibitors?

SSRIs, SNRIs, TCAs, mirtazapine, trazodone, triptans, opioids, tramadol, buspirone, lithium, dextromethorphan, and St. John's wort.

How can the expected effect of a drug often be predicted from its structure?

By understanding the drug's MOA and chemical structure (structure-activity relationship, SAR).

What structural feature of celecoxib is clinically important and why?

Celecoxib contains a sulfonamide group and is contraindicated in patients with sulfa allergies.

Why can differences in functional groups within the same drug class be important?

They can affect cross-reactivity and allergy considerations.

What naming pattern is noted for amide-type anesthetics in these notes, and what examples are given?

Amide-type anesthetics can be recognized by the "I" in their name;

examples: lidocaine, bupivacaine, and ropivacaine.

What is drug stability?

Drug stability is the extent to which a product retains the same properties and characteristics it had when it was made.

What requirements must be met for a drug to be considered stable?

It must remain within specified limits throughout its shelf life (storage and use period).

What factors can compromise drug stability?

Manufacturing and storage conditions.

How can loss of drug stability be recognized?

Changes in texture, color, smell, shape, etc.

What is drug degradation, what can it cause, and what are the 3 most common degradation reactions?

Drug degradation involves reactions of functional groups that can make a drug ineffective, unpalatable, and/or toxic. The 3 most common degradation reactions are oxidation, hydrolysis, and photolysis.

What happens during oxidation and reduction?

Oxidation = loss of electrons; Reduction = gain of electrons.

What is the relationship between oxidation and reduction in redox reactions?

Redox reactions occur together; when one compound is oxidized, another must be reduced.

How can oxidation of a drug sometimes be recognized visually?

Oxidation may cause color changes. Examples: epinephrine turns amber (yellow/orange) and some medications turn red/pink when oxidized.

What types of molecular structures are most likely to undergo oxidation?

Structures with a hydroxyl group (-OH) directly bonded to an aromatic ring; examples include catecholamines, phenols, and aldehydes.

What factors catalyze oxidation reactions?

Light, heat, and metal ions can catalyze oxidation reactions by producing free radicals.

Why are free radicals important in oxidation reactions?

Free radicals are highly reactive and can cause oxidation chain reactions that damage drugs.

What is autoxidation?

Autoxidation is an oxidation reaction that occurs routinely during drug preparation and storage.

How can oxidation reactions be prevented through packaging and storage?

Light protection (amber glass, UV-blocking containers) and temperature control (store according to package instructions).

What are antioxidants (free radical scavengers) used to prevent oxidation and what are examples?

Antioxidants inhibit free radicals. Examples: ascorbic acid (Vitamin C), tocopherols (Vitamin E), ascorbyl palmitate, sodium ascorbate, sodium sulfoxylate, and sodium thiosulfate.

How do chelating agents prevent oxidation and what are examples?

Chelating agents bind metal ions and occupy the catalyst to prevent oxidation. Examples: EDTA (edetate disodium), edetate calcium disodium, and edetic acid.

How does pH control help prevent oxidation and what are examples?

Buffers are used to maintain pH and help prevent oxidation. Examples: acetic acid and sodium acetate.

What is hydrolysis?

Hydrolysis occurs when water causes the cleavage of a bond in a molecule.

Which functional groups are most commonly hydrolyzed?

Esters, amides, and lactams.

How can esters, amides, and lactams be recognized as hydrolysis-prone functional groups?

Ester: carbonyl on the OR group; Amide: carbonyl bound to nitrogen; Lactam: beta-lactam ring found in some antibiotics.

What is an example of a hydrolysis reaction involving aspirin (ASA)?

The ASA ester group is hydrolyzed to form acetic acid and salicylic acid.

What important drug-related concept is illustrated by the hydrolysis of ASA?

Hydrolysis of ASA forms salicylic acid, making ASA a prodrug.

Why should medications generally not be stored in the bathroom?

Moisture can promote hydrolysis and drug degradation.

How can adsorbents (desiccants) and lyophilized powders help prevent hydrolysis?

Desiccants absorb moisture in the container; lyophilized powders are stored as powders and reconstituted shortly before use.

How can hygroscopic salts help prevent hydrolysis?

A salt form of the drug may be used that is less hygroscopic, so it absorbs less water.

What additional methods can be used to prevent hydrolysis?

Light protection, chelating agents, temperature control, and pH control.

What is photolysis and how can it be prevented?

Photolysis occurs when UV light breaks covalent bonds and degrades a drug; it can be prevented by light protection.

Which compounds are especially sensitive to photolysis?

Ascorbic acid, folic acid, nitroprusside, and phytonadione.