Constitutive expression in tissues

Protein levels are constant

Synthesized prostanoids for housekeeping

Purposes: gastric protection, kidney function, blood clotting

Inhibition leads to GI related side effects

Express induced by stress, growth factors, cytokines, and inflammatory mediators

Sources involve cancer and inflammation

Tissue specific effects

Inhibition leads to anti-pyretic, analgesic, and anti-inflammatory actions of the NSAIDs

Selective inhibition can cause less GI toxicity

Mild analgesia (MSK pain)

Effective where inflammation has sensitized pain receptors

Can be additive to opioids

Elevates set point of fever in hypothalamus

Inflammation, particularly MSK disorders (RA, OA)

Symptomatic relief

Closure of PDA

Chemoprevention

GI pain, nausea, diarrhea, hemorrhage, ulcers, perforation

Renal insufficiency, failure, hyperkalemia, proteinuria

Decreased effecs of anti-hypertensives

Decreased excretion due to effect on arterioles (esp ASA)

Analgesic nephropathy

Selective inhibition of PGI2 (and not TXA) can lead to platelet aggregation

Increased gestation and inhibition of labor

Post-partum hemorrhage

Vasomotor rhinitis

Angioneuritic edema

Asthma

Urticaria, flushing

ACE + NSAID + hyperkalemia = bradycardia and syncope

Attenuates effects of ACE inhibitors

Warfarin - CYP enzymes

NSAIDs inhibit metabolism of warfarin - increased propensity for bleeding

Often occurs in children

Coma, convulsions, cardiovascular collapse

Mild headache, dizziness, tinnitus, drowsiness, sweating, thirst, hyperventilation, nausea, vomiting

High doses: CNS stimulation and depression, hyperthermia

Respiratory alkalosis and eventual acidosis

Reactive metabolite benzoquinone imine

Occurs when gluthione is depleted

Single doses 10-15 g

Nausea, ab pain, anorexia

Serum transaminases can be elevated

Hepatic damage occurs at 2-4 days

Exacerbated by alcohol and malnutrition

Tx: activated charcoal, Mucomyst, supportive care

Willowbark

Competitive and irreversible inhibitor of COX1 and COX2

Analgesia, Antipyretic at low doses, Anti-inflammatory at high doses, blood thinner, keratolytic, uricosuric

Indicated for pain, fever, inflammation, CV disease, UC, gout, RA, cancer

Can get Reye's syndrome if given with viral infection

First pass metabolism --> salicylate

Excreted renally

NSAID with no effects on respiratory, CV, GI tract, platelets, coagulation, acid-base status, or uric acid

Used for analgesia and fever, but not inflammation

Can be combined with opioids

Well absored

Metabolized by glucuronic acid

Most commonly used NSAID

2400 mg for inflammation

2 hour half life

Indications: PDA closure, topical relief of OA

May co-admin with ASA for cardioprotective effects

GI effects in 15%

Single enantiomer NSAID

14 hour half life

Used in RA

Older NSAID that is a stronger analgesic than aspirin

Indications: PDA closure, gout, ankylosing spondylitis

Opthalmic prep and oral rinse

Adverse effects can be more severe

NSAID that inhibits leukocyte migration in high doses

Absorbed completely

Food delays absorption

50 hour half life allows for once daily dosing

Indicated for RA

A pro-drug NSAID that undergoes enterohepatic cycling

Indications: familial polyps, cancers

Side effects: Stevens-Johnson syndrome, thrombocytopenia, agranulocytosis, nephrotic syndrome, and liver damage

A selective COX2 inhibitor

11 hour half life

Has less GI side effects than non-selective NSAIDs

Side effects: thrombosis, hypertension, atherogenesis

Metabolizes SSRIs

Metabolized by microsomal enzymes

Aldosterone (only)

Cortisol

Prednisolone

Methylprednisolone

Fludrocortisone

Cortisol

Prednisolone (mostly)

Methylprednisolone (mostly)

Dexamethasone (only)

Fludrocortisone

Influence water and electrolyte balance

Made in Zona glomerulosa

Does not respond to ACTH stimulus

Mineralocorticoid receptors bind aldosterone and glucocorticoids (an enzyme exists to prevent cortisol from binding)

Anti-inflammatory agents that have effects on carbs and protein metabolism

Made in Zona fasciculata

Responds to ACTH and stress

Made in zona reticularis

Responds to ACTH

Carb and protein metabolism to maintain blood glucose levels

Synthesis of glucose, glycogen deposition, protein breakdown, increase of FFA, stimulation of hormones (NE, epi, GH), decrease lymphocytes, eosinophils, monocytes, basophils, decreased lymphoid mass, decrease in TNF

Alter immune response of lymphocytes, cytokine releas

Decreased prostaglandin and leukotrienes

Inhibition of arachidonic acid, leukotrienes, COXs

acute adrenal insufficiency

Fever, myalgias, arthritis, malaise

Weeks to months recovery with slow taper

Mineralocorticoid that is produced in the zona glomerulosa that alters Na and water reabsorption in the kidney.

Indications: nephrogenic DI

Endogenous hormone with glucocorticoid and mineralocorticoid activity that works as an anti-inflammatory and immunosuppressant

Responds to ACTH and has a negative feedback inhibition to the pituitary and hypothalamus

Hormone made in opthalmic prep that has mainly glucocorticoid activity with some mineralocorticoid activity.

Used in eye inflammation

Oral prep hormone that has mostly glucocorticoid activity with some mineralocorticoid activity

Used as an anti-inflammatory

Hormone with glucocorticoid activity that can be given as oral, opthalmic, or topical prep

Used to diagnose hypercorticism, arthritis, systemic disorders, severe allergies, asthma, and cancers

Hormone with mostly mineralocorticoid and some glucocorticoid activity that is used to control fluid and electrolyte imbalance

Used in Addison's disease

1. Relax venous smooth muscle at low doses and arterial smooth muscle at high doses to decrease preload during diastole, increase coronary blood flow

2. Decreases oxygen demand of cardiac muscle by decreasing tension on cardiac walls

3. Dilate epicaridal coronary vessels (preferential to the ones that need oxygen)

Relaxes smooth muscle at lower concentrations than those required to reduce Ca influex into cardiac cells

Generally decreases arterial resistance and BP

Reflex increase in CO

Decrease coronary resistance

Increases coronary blood flow

Decreases oxygen demand of myocytes

Less potent vasodilator

Decreases HR, contractility, and decreases rate of recovery of Ca channels to slow conduction through AV node

Decreases coronary resistance

Increases coronary blood flow

Decreases oxygen demand of myocytes

A non-DHPR Ca Channel blocker

Used for angina (esp in individuals with higher HR), SVT, atrial tachycardia, atrial flutter, and atrial fibrillation

Non-DHPR Ca Channel blocker

Used in Angina, SVT, Atrial tachycardia, atrial fibrillation, and atrial flutter

It is also a non-specific antagnoist for the SNS to reduce the reflex tachycardia produced by vasodilation

A DHPR Ca Channel blocker
Used in angina for people with low HR

Long acting form is much safer

Can cause reflex tachycardia (increase HR and contractility)

A DHPR Ca Channel blocker

Used in variant angina vasospasm

It has a high affinity for cerebral vessesl and may reduce vasospasm after subarachnoid hemorrhage

A vasodilator

Effects: direct relaxation of arterial smooth muscle to reduce TPR

Used in Hypertension, especially in pregnancy

Contraindicated in patients with HTN and CAD or people > 40 years old

Can lead to ischemia because of increase oxygen demand on the heart

Should co-administer with sympatholytic like a Beta blocker

A vasodilator

Effects: direct arteriole relaxation to reduce TPR

Also helps grow hair

Actives ATP modulated K channels to hyperpolarize the smooth muscle

Contraindicated in HTN with LVH

Should co-administer with sympatholytic drugs like Beta blockers

A vasodilator

Effects: arteriole and venule vasodilatin to reduce TPR

Also reduces preload to decrease O2 demand on heart

Used for hypertensive emergenices and acute MI

A prodrug that activates cGMP to reduce contractile state of smooth muscle

Metabolized by smooth muscle into nitrous oxide

Must be given via IV infusion

An Alpha 1 Antagonist

Inhibits vasoconstriction induced by catecholamines

Effects: Reduces arterial resistance and venous capacitance to reduce TPR

Used in HTN

First dose phenomenon is common

Not effective as a sole treatment for HTN

An adrenergic inhibitor that is concentrated in NE vesicles and depletes NE to inhibit the function of postganglionic adrenergic neurons

Effects: Reduces sympathetic activation to reduce TPR

Adverse effects: postural hypotension, sexual dysfunction, and diarrhea, delayed or retrograde dysfunction

Blocks excitation-secretion coupling

An adrenergic inhibitor that binds to storage vesicles in central and peripheral adrenergic neurons

Inhibits sympathetic effects to reduce TPR

Adverse effects: CNS sedation, inability to concentrate, and depression

An Alpha 2 Agonist

Depletes neuronal stores of NE by blocking feedback mechanisms

Reduces sympathetic activity to reduce TPR

Can be used for HTN in pregnancy

Adverse effects: Hypersensitivity, reduced libido, sedation, depression, blunted sympathetic effects

Very difficult drug to tolerate

An Alpha 2 Agonist

Depletes neuronal stores of NE by blocking feedback mechanisms to reduce TPR

High doses also activate alpha 2 receptors in vascular smooth muscle - vasodilation

Used for HTN

A Beta Blocker

Blocks endogenous sympathetic Beta 1 stimulation of the cardiac SA node and ventricular muscle

Effects: reduces myocarial contractility, reduces cardiac output, and decreases renin and ANG II levels

Used for HTN, angina, and arrhythmias

African Americans can have a lesser response

Side effects: ED, depression, insomnia

Contraindicated in asthma

Decreases mortality after MI

A DHPR Calcium Channel blocker used in HTN

Reduces vascular resistance and BP by decreases influx of Ca into arterial smooth muscle cells and cardiac myocytes

Special population: HTN in low HR and AA

Angina, arrhythmias

Long acting is best

A diuretic that inhibits Na-Cl cotransport in the distal tubule

Decreases blood volume, reduces preload, SV, and CO

Long term use decreases vascular resistance

Used in HTN

Adverse effects: impotence, hypokalemia

Drug interaction: quinidine

A K sparing diuretic that blocks Na channels in the collecting duct

Decreases BV, reduces preload, SV, and CO

Long term use decreases vascular resistance

Used in HTN along with a thiazide diuretic like hydrochlorothiazide

An ACE inhibitor that reduces aldosterone secretion

Reduces vasoconstriction and decreases Na retention

Used in HTN, LVH regression, delay of progression of heart failure and MI, especially good for diabetics

Adverse effects: cough, teratogenic, decreases GFR (do not use in renal failure)

Does not invoke a reflex tachycardia

An ARB that maintains bradykinin levels

Reduces vasoconstriction and decreases Na retention

Used in HTN but is not shown to be particularly helpful in special populations

Contraindicated in pregnancy

An ester local anesthetic that has a shorter duration of action

Used for topical pain, especially eye surgery

Adverse effects: HTN, tachycardia, arrhythmias, and vasoconstriction

Metabolized by plasma and liver pseudocholinesterases

Has a high abuse potential

May produce allergies - PABA

An ester local anesthetic that has shorter duration of action

Used mostly for infiltration and peripheral nerve blocks

Has a low systemic toxicity

Also known as Novocaine

May cause allergies - PABA

An amide local anesthetic that has a rapid onset and longer duration of action

Used for pain and arrhythmias

Combine with epinephrine to prevent vasodilation

Metabolized by microsomal enzymes

Most commonly used local anesthetic

An amide local anesthetic with rapid onset and longer duration of action

Has lower cardiac effects than some other local anesthetics

Exists in S-isoform

Poison that blocks oxygen transport

Route: inhalation

Classic sx: pink flushed skin

Antidote: high partial pressure O2

Poison that blocks oxygen transport systems

Sources: nitrates, aromatics, and nitro compounds

Mechanism: Ferric iron (Fe3) binds to hemoglobin

Classic Sx: chocolate brown blood

Antidote: methylene blue

Poison that alters enzyme activity

Mechanism: blocks cytochrome oxidase

Sx: CNS effects, mydriasis, cyanosis, systemic sx

Antidote:

1. methemoglobin formation with amylnitrate and NaNO, 2. inactivation of poisoning with sodium thiosulfate

Poison that alters enzyme activity

Source: insecticide inhalants (used for lice)

Mechanism: phosphorylates AChesterase

Cholinergic crisis causes vomiting, tremors, lethargy, ab pain, fasisculations, headache, SLUD, and mioisis

Antidote

1. Block ACh with atropine

2. Reactive AChesterase with Pralidoxine

Also renders it inert

Solvent poisoning

(Kerosene, Gasoline, Diesel, Paint Thinner)

Poison that alters membranes

Route: inhalation and ingestion

Causes CNS depression, V-Fib, and at risk for aspiration

Antidote: supportive care and possibly cathartics

Do not induce emesis or lavage

A heavy metal poison that alters membranes

Route: ingestion

Mechanisms: iron sites get saturated, can be corrosive to the GI tract

Can cause hepatic dysfunction and permanent bowel obstruction

Antidote: deferoxamine chelating agent

Heavy metal poisoning that can alter membranes

Routes: elemental via ingestion, ionic/inorganic via inhalation

Mechanisms: targets the CNS, kidneys

Organic version can be bioaccumulated in foods

Can cause erethism (felt hats)

Temporary blindness and red spots

Antidote: BAL (dimercaprol) chelating agent

Heavy metal poison that alters membranes

Routes: ingestion, exposure

Can lead to developmental learning disabilites

Antidote: calcium disodium (EDTA)

Heavy metal poison that alters membranes

Routes: industrial exposure

Can cause lung damage (alpha AT dysfunction), osteomalacia, immunosuppressant, growth retardation, carcinogen

Has a very long half life

Antidote: Calcium disodium (EDTA)

Poison that alters membranes

Routes: inhalation, ingestion, dermal, and ocular

Ex: battery

Free radical poison

Routes: inhalation, percutaneous absorption, ingestion

Effects: nausea, vomiting, dizziness, headache, stupor, convulsions, coma, death, CNS depression, medullary depression, V-Fib

Ingestion can cause ab pain, hematemesis, and hepatic damage

Reactive oxygen species that is used as an herbicide

Effects: lung toxicity, vomiting, burning pain in the mouth, throat, and lethargy

Tx: dialysis

Nerve fiber that releases glutamate into the dorsal horn

Fibers are myelinated

Send a quick propagation of the AP

Produces a fast onset, intense pain that subsides quickly

Nerve fibers that release Substance P into the dorsal horn

The nerve fibers are unmyelinated

Slow propagation of the AP

Produces a later dull pain that lasts a long time

Another effect causes mast cell degranulation and histamine release leading to vasodilation, immune cell release, inflammation, and further pain

Cocaine

Procaine

Tetracaine

Benzocaine

Lidocaine

Mepivacaine

Bupivacaine

Etidocaine

Prilocaine

Ropivacaine

The inherent capacity of a substance to produce injury

Estimated by LD50

Practical certainty that injury will occur when a substance is used in a stated quantity and set of conditions

Also known as proportionate risk

Practical certainty that injury will not occur when a substance is used in a stated quantity and set of conditions

Also known as acceptable risk

Assessment to determine amount and conditions that can be used without appreciable risk of injury.

Affected by route of exposure (inhalation, ingestion), duration of exposure (acute or chronic), and the presence of mixtures (what the chemical is)