Topic 4: Peripheral Pain, Inflammation, Dermatology Flashcards
Erythroxylum Coca
Common name: Cocaine
Geography: Andes in S. America
Ethnomedical Use: leaves are chewed with alkaline substance by Quechua people today (Incan people in the past)
Active compounds: Cocaine Alkaloid
Chemical derivatives: Procaine HCl, tetracaine, lidocaine, tocainide & procainamide
Cocaine Mechanism of Action as an Analgesic
inhibition of local norepinephrine reuptake.
Causes local vasoconstriction
Local anesthetic by blocking nerve impulses
Tetracaine Mech of Action & Use
local anesthetic –> nerve impulse blockage (long duration action)
Used topically as an anesthetic for cornea of the eye
Procaine HCl Mechanism of Action & Use
local anesthetic –> nerve impulse blockage (short duration of action)
Used as an infiltrative anesthetic by dentists
Lidocaine mechanism of action & Use
local anesthetic –> nerve impulse blockage (intermediate duration of action)
Blocks both open and inactivated cardiac Na+ channels–> slows conduction of heart
Used as a local anesthetic by dentists and to suture lacerations. Also used to treat ventricular arrhythmias
Tocainide & procainamide mechanism of action
blocks both open and inactivated cardiac Na+ channels –> slows conduction of heart
Cocaine Therapeutic Uses
applied topically by dentists and nose and throat experts
- local anesthetic
- local vasoconstrictor that shrinks mucosal cells
Filipendula ulmaria
Common name: meadowsweet
Geography: Eurasia , small tree in meadows & swamps
Ethnomedical Use: bark used for inflammation, pain, fever
Chemical Class: glycoside
Chemical derivatives: salicylic acid –> ASPIRIN
Salicin (Salix)
Salix alba
Common name: willow
Geography: Mediterranean Europe
Ethnomedical Use: bark used as an analagesic for headaches, antiinflammatory and fever
Active compounds: salicin (metabolizes into salicyclic acid)
Chemical derivatives: saligenin (analgesic)
Aspirin Mechanism of Action
blocks cyclooxygenase (prostaglandin synthase) which:
- decreased the conversion of arachidonic acid to endoperoxide which:
- decreases the formation of thromboxane A2
- decreases prostaglandin synthesis/inflammation &inhibits platelet hemostasis (makes them less sticky)
COX-1 Enzyme
cyclooxygenase
-enzyme involved in prostaglandin synthesis
makes prostaglandins that are responsible for maintenance and protection of the GI tract
-blocked by aspirin
COX-2 Enzyme
cyclooxygenase
- enzyme involved in prostaglandin synthesis
- makes prostaglandins that are responsible for inflammation and pain.
- blocked by aspirin
COX-2 selective inhibition
COX 2 selective inhibitor is a form of a non-steroidal anti-inflammatory drug (NSAID). It selectively targets COX-2. Provides pain relief without irritating the stomach lining.
Aspirin and COX enzymes
inhibits both (equipotent).
Ibuprofen and COX enzymes
has a 7x greater inhibition of COX-2 in comparison to COX-1
Aspirin Therapeutic Uses
taken orally analgesic anti inflammatory antipyretic (fever) antiplatelet
Salicyclic acid, salicin, & saligenin Topical therapeutic uses
Salicyclic acid:
- warts, acne, eczema
- pain caused by: rheumatism, myalgia, nerualgia, headaches
salicin: antiheumatic (joint pain/inflammation)
saligenin: applied topically as analgesic
Disogenin
Dioscorea Mexicana
Common name: wild yam
Geography: Mexico
Ethnomedical Use:anti inflammatory, fish poisons
Active compounds: diosogenin
Chemical Class:steroid
Chemical derivatives: precursor to glucocorticoids
Glucocorticoids/corticosteroids
hydrocortisone cortisone prednisone prednisolone methylpredisolone
Glucocorticoid Mechanism of Action
Down regulates cytokine production which reduces inflammation:
- steroid binding to glucocorticoid receptor (GR) in cell cytoplasm results in activation of receptor and translocation to the nucleus where regulatory regions of certain genes are effected including negative regulation for genes that code for cytokines
Reduces prostaglandin production which reduces inflammation:
-blocks the conversion of phospholipid to arachidonic acid which blocks the formation of protasglandins.
Antiinflammatory uses of glucocorticoids
skin: eczema, dermatitis, psoriasis
eye: conjunctivitis
joint: arthritis
GI: Inflammatory bowel disease
Respiratory: asthma
Kidney: nepthrotic syndrom
Hydroxychoroquine (Cinchona officinalis)
Geography: S. American rainforest
Ethnomedical Use: bark used for rheumatoid arthritis and lupus:
Colchicum autumnale
Common name: crocus
Geography: Europe & N. America, gardens
Ethnomedical Use: corms used for gout, arthritis,inflammation and pain.
Used today for all of the above and autoimmune arthritis & lupus
Colchicum Mech of Action
causes a doubling of chromosomes by disorganizing the spindle mechanism at mitosis
Harpagophytum procumbens
Common name: devil’s claw
Geography: Southern Africa, Kalahari desert
Ethnomedical Use: root used for lower back, hip, and knee pain
Active compounds: harpagoside
anti inflammatory
Cold and Hot pain receptors
Menthol- cold
capsaicin- heat
wasabi- heat
TRPM8
cold sensitive ion channel associated with the menthol pain receptor
TRVP1
heat sensitive ion channel associated with capsaicin pain receptor
TRPA-1
heat sensitive ion channel associated with wasabi pain receptor.
Wasabi receptors
contains, TRPA-1, an ion channel in sensory nerves under the skin, including mouth and mucus membranes. Detect temperature, mechanical abrasion and irritating chemicals.
Activators of Wasabi Pain receptor (TRPA-1)
wasabi -enhancer horse radish- enhancer hot mustard - enhancer onion - enhancer garlic- enhancer cholorquine endogenous mast cell, BAM8-22, which is released during inflammation
All contain allyl isothiocynate
Wasabi
Eutrema Wasabi Common name: wasabi Geography: Japan Ethnomedical Use: condiment Active compounds: allyl isothiocyanate, stimulates TRPA-1; wasabi pain receptor
Horse Radish (Amoracia rusticana)
Geography: S.E. Europe and W. Asia
Ethnomedical Use: condiment
Active compounds: allyl isothiocyanate, stimulates TRPA-1, wasabi pain receptor
Mustard (Brassica)
Geography: Asia
Ethnomedical Use: condiment
Active compounds: isothiocyanates, stimulate wasbi hot receptors
Brassica Nigra: black mustar
Brassica Juncea: Brown/Indian mustard
Brassica hirta: white/yellow
Onion (allium cepa)
Geography: Central Asia
Ethnomedical Use: food, spice, condiment
Active compounds:allyl isothiocyanate, stimulates wasabi pain receptors
Onion lacrymatory factor
when an onion is cut, cells are broken releasing alliinases to break down amino acid sulphenis acids which are converted into syn-propanethial-S-oxide, a volatile gas known as the onion lacrymatory factor (LF)
Garlic (allium sativum)
Geography: Asia
Ethnomedical Use: food, spice, condiment
Active compounds:ally isothiocyanate, stimulates wasabi pain receptors
Molecules that induce itching by way of wasabi receptor
Cholorquine, BAM8-22, Mucuna prureins
Cholorquine Mechanism as a pain/itch molecule
stimulates wasabi pain receptor, TRPA-1. It also stimulates MrgprC11 itch receptor.
Cholorquine first binds to the wasabi receptor and opens the ion channel, depolarizing the nerve cell which then sends an itch signal to the brain.
BAM8-22
endogenous peptide released during inflammation by immune cells (mast cells).
Stimulates the wasabi receptor & the MrgprC11 itch receptor. It first stimulates the wasabi receptor opening to ion channels and sends an itch signal to the brain
Capsaicin Heat Receptor
Heat sensitive.
TRVP1 is the ion channel associated with this receptor.
Capsicum
capsicum annuum- chile pepper
capicum frutescents- tabasco pepper
Geography: Tropical America
Ethnomedical Use: topically used as an analgesic for: arthritis, inflammation, neuralgia
orally used as a: stimulant, antimicrobial
Active compounds: capsicin
Capsaicin Mechanism of action
The capsaicin receptor is a heat activated ion channel in the pain pathway. Noxious temperature receptors are sensitive to capsaicin. These receptors get excited and result in pain perception.
prolonged perception causes the receptors to become desensitized to the capsaicin and other noxious stimuli..
-potent depletor of the neurotransmitter substance P103
Capsaicin therapeutic uses today
pain in skin, muscles, joints ,rheumatism, & neuralgia
pruristis (itching) caused by psoriasis or other skin disorders
Cloves (syzygium aromaticum)
Geography: Asia
Ethnomedical Use: oil is used topically on skin as analgesic and is applied topically to gums to treat toothaches
stimulates heat sensitive receptors
Zingiber Officinalis (ginger)
Common name: ginger
Geography: Asia
Ethnomedical Use: analgesic, digestive, anti-nausea, flavoring, antipyretic, antibacterial properties. Can also induce salivation
Active compounds: non volatile phenylpropanoid derived compounds (gingerols & shogaols). Contribute to pungent taste
hot varieties enhance heat sensitive receptors
Piper Nigrum (Black Pepper)
Common name: Pepper
Geography: India
Ethnomedical Use: spice
Active compounds:peperine, which may enhance heat receptors
Cold Sensitive Receptors
Menthol Pain receptor which is associated with the ion channel TRPM8.
Molecules that stimulate cold sensitive receptors
peppermint
camphor
eucalyptus
TRPM8 Mechanism
When TRPM8 is activated there is an initial sense of cold which is followed by desensitization and analgesia.
Mentol Piperita
Common name: peppermint
Geography: Europe
Active compounds:menthol
stimulates menthol pain receptor (cold) and TRPM8
Cinnamomum camphora
Geography: Asia
Active compounds:camphora (leaves)
stimulates menthol pain receptor and TRPM8
Eucalyptus globulus
Common name: Eucalyptus
Geography:Australia
Ethnomedical Use: Topically as analgesic
Phytomedicines: oil, cineole (eucalyptol) is 70% of the oil.
Acmella Oleraceae (toothache plant)
Geography: South America
Ethnomedical Use: leaves consumed as a salad vegetable. Used to treat tooth pain, tongue pain, & sore throats. Also helps induce salivation
Active compounds: spilanthol- makes a tingling sensation on the tongue
Chemical Class:
Chemical derivatives:
Wintergreen Oil
Contains Gaultheria procumbens (wintergreen) and Betula Lenta (sweet birch)
Gaultheria procumbems (wintergreen) & Betula Lenta (Sweet Birch)
Geography: Eastern USA
Active compounds: methyl salicylate
They block the production of prostaglandins by blocking cyclooxygenases (prostaglandin synthase) which inhibits conversion of arachidonic acid to endoperoxide.
Acts as an anti-inflammatory
Tiger Balm
topical analgesic.with ingredients that have heat and cold sensitive analgesic effects.
Aloe Vera
Common name: aloe
Geography: Aloe Vera- S.W. Arabia
Ethnomedical Use: applied topically to treat burns and skin infections
Hamamelis virginiana (witch Hazel)
Geography: Easter North America
Mechanism of action: vasoconstriction and astringent effects
Used to topically for: bruises hemorrhoids varicose veins aftershave
Arnica (Arnica montana & arnica fulgans)
Geography: montana- N. &C. Europe, fulgans: N. America Therapeutic uses: applied topically for -skin inflammation -bruises -blunt injuries -Rheumatism
Calendula Officinalis
Common name: Marigold, calendula Geography:Mediterranean Area Therapeutic Uses: topical application for -skin inflammation -skin infections -wound healing
Avena Sativa (oats)
Europe
used as topical applicant for skin itching
Berberis aquafolium
NW USA
Common name: oregon Berry
Bark and root used
Used to treat psoriasis
Hypericum Perforatum
St. John's Wort Eurasia, naturalized in N. America active compounds: hyperforin (antidepressant, antidiabetic), hypericin (wound healing) Taken orally for: depression Type II diabetes Topically for: wound healing
Carica Papaya
Common Name: papaya
Geography: Tropical Americ
Active Molecules: protease enzymes papain, chymopapain A &B from papaya fruit
Mechanism of Action: these enzymes help digest protein and debride necrotic wound tissue and enhance wound healing. Also helps with digestion
Bromelain (Ananas Comosus)
Common name: pineapple, ananas (tupi name)
Geography: S. America
Cultural Origins: Tupi Indians in S. America
Active Molecules: protease enzyme bromelain (from stem)
Pineapple Mechanism of action
The protease enzyme help enzymatically digest protein and debride necrotic wound tissue and enhance wound healing.
Pineapple Therapeutic uses
applied topically to debride necrotic tissue and enhance wound healing.
taken orally to treat diarrhea and enhance digestion
