Flashcards in Valentovic- Herbs and Metals (2)- Leah :) Deck (74):
Why are metals dangerous?
Are they acutely toxic?
How are they metabolized?
-some metals have t/12 10-30 years, so they accumulate with small doses over a lifetime.
-they aren't metabolized/ biotransformed, instead they bind to S/O/N functional groups on proteins and stay in the body
What is the most common way to remove toxic metals from the body?
What are the requirements for this therapy? (6)
-less toxic than the metal itself
-enhance metal excretion
-active at physiological pH
-not metabolized/ biotransformed
-hydrophilic (like metals)
-more affinity for toxic metals than endogenous
Calcium Disodium EDTA:
How does it work?
How is it administered?
What metals does it bind? (2)
-Ca in center of molecule is displaced by toxic molecule; molecule excreted in urine
-INJECTED (IV, IM)
-Lead or cadmium
"CAL"cium= "CA"dmium + "L"ead
-How does it work ?
-How is it administered?
-Why is compliance poor?
-What metal is it used to remove? (1)
-two sufhydryl groups that bind metals --> metal + chelator excreted in urine
-bad odor/ taste = N/V
(Succimer has a SUCKY taste.)
(SUCKS to eat Lead.)
Dimercaprol/ British Anti-Lewisite (BAL):
How does it work?
How is it administered?
What toxins is it used to remove? (3)
How is it excreted?
-SH groups bind metal
-IM with peanut oil
-Lead, arsenic, INORGANIC mercury
-1/2 bile (CI in liver disease), 1/2 urine excretion
-Dimercaprol had a little LAMB (Lead, Arsenic, Mercury = BAL.) He followed her to school one day where the PEANUTS cannot goooo..... (Mary Had A Little Lamb, with a spin off.)
Contraindications to dimercaprol? (3)
-peanut allergy (IM formula includes peanut oil)
-liver** / renal disease (excreted in bile and urine)
-acidosis (complex disassociates in acidic urine)
-derived from?/ how does it work?
-how is it excreted/ administered?
-What toxins does it remove? (3)
-Drug of choice in?***
-penicillin derivate with sulfhydryl groups that bind metals
-oral administration, urinary excretion
-removes inorganic mercury (HgCl2), arsenic, copper
(Penicillamine treats the big MAC -- mercury, arsenic, copper)
Penicillamine major side effect?
If penicillamine is not tolerated, to which chelator do we switch?
- Agranulocytosis; reason to STOP therapy in Wilson's Disease
- Switch to TRIENTINE
(When you're TRIENG to treat Wilsons w/ penicillamine and it fails use TRIENtine)
Contraindication for Calcium Disodium EDTA, succimer, dimercaprol, and penicillamine use?
- All have urinary excretion
- Not good in RENAL DISEASE
(100% for all except dimercaprol which is 1/2 biliary excretion)
Which chelators are oral?
Which are injected?
oral: succimer and penicillamine
(SUCcimer has a SUCKY TASTE and penicillamine has a COPPER TASTE)
injected: "D"imercaprol + E"D"TA require "D"AMN needles!!!
Which chelators have sulfhydryl groups?
all except calcium disodium EDTA
How is lead taken in by humans?
In what local area is lead poisoning a real problem?
-Inhaled or ingested-->
water, soil, paint chips, pottery, or breweries using radiators
-Ohio (sorry, Melissa *tears*) = 1 of top 4 states for lead
Major source of lead in the 1940's
-Single chip was of paint was toxic (1 chip = 100 mg lead)
-Changed in the industry, still problem in old homes
How toxic is lead in children compared to adults?
Where does the lead acutely distribute (3)?
How do we measure lead levels?
-children absorb 5x more Pb than adults
-goes to liver, kidney, RBC (95% bound to Hb)
= measure BLOOD NOT PLASMA (Pb binds Hb RBC)
Long term, where does lead go in the body?
What is the result?
What is the t 1/2 for lead?
Goes to the BONE and the BRAIN:
- Replaces calcium in bones = tertiary lead phosphate
- Interferes w/ calcium mediated processes in the brain
- t 1/2 ~ 10 years
Effects of lead poisoning in:
What is the most serious condition that dan result from lead poisoning?
Which system is MOST sensitive indicator of toxicity? (i.e. where do FIRST symptoms arise)
-Microcytic anemia + *basophilic stippling = RNA precipitation* (hemolysis if acute)
**MOST SENSITIVE INDICATOR OF TOXICITY; prevents heme synthesis
-Lead "colic" -- GI spasm w/ chronic exposure
- Peripheral neuropathy (foot drop/ lead poisoning) --> MY FOOT IS AS HEAVY AS LEAD SO IT DROPS.
- Memory loss (adults)
- MR + **LEAD ENCEPHALOPATHY** in kids (fatal, most serious problem)
What two heme synthesis reactions are inhibited by lead?
Where do these two reactions take place?
(I have had uworld q's on these reactions AND their LOCATIONS!!!)
- Delta-aminolevulinate --> prophobilinogen
**delta-ALA dehydratase in CYTOSOL**
(A young LAD named CYTO= ALAD in the CYTOSOL)
- Protoporphyrin IX --> heme
***ferrochelotase in the mitochondria**
(PROTO the MIGHTY FERRET! =protoporphyrin breakdown, in the mitochdonria, by ferrochelotase)
How is lead poisoning diagnosed (2)?
What must we sample?
-^^ levels of deltaaminolevulinic acid and coporphyrin II (precursor to protoporphyrin) in urine
-WHOLE BLOOD lead levels
How do we treat asymptomatic lead tox?
-oral succimer or penicillamine (off label) for asx patients
-injected EDTA (IV) / dimercaprol (IM) for sx patients
What are the three mercury forms?
When is each toxic?
-elemental (Hg): only toxic when inhaled, not ingested
-inorganic mercury (Hg 2+): toxic if inhaled or ingested
-organicmercurial (C-Hg): MOST TOXIC, ANY ROUTE
Cellular mechanism of mercury toxicity?
Binds sulfhydryl groups --> inactivates enzymes/ proteins
Which mercury was in thermometers?
What are its toxic effects?
-crosses BBB if inhaled
-Hg --> Hg 2+ by catalase in RBC of brain = mercury TRAPPED in brain (charged molecule doesnt cross BBB)
-irreversible neuro (tremor, delirium) and respiratory changes
- effects of oral exposure (GI, renal, eyes/face)
- Is this form of mercury neurotoxic?
- one source of exposure?
- grey esophagus/ mouth/ vomiting/ hematochezia
- proximal tubular necrosis. glomerular damage
- photophobia, acrodynia (red face)
-NO NEURO TOX (2+ charge cannot cross BBB)
-CERTAIN FISH! NO FISH FOR PREGGOS!
*Mercury* the poor beta *fish* lives in the basement & never sees the *light*. He has a *grey mouth, red face, and he never pees* (because
-what type of mercury are these?
-which is most toxic?
-which body system is its main target?
-dimethyl more toxic (^^ carbons in chain = ^^ toxicity)
.... two drops on skin are LETHAL.
-No charge, enters skin --> BRAIN
= ataxia, tremor, blindness --> death
-How did it occur?
-INORGANIC mercury released to environment in Japan
-algae converts inorganic --> METHYLMERCURY
-algae eaten by fish --> humans eat fish and mercury
-HUMANS GOT IRREVERSIBLE NEURO DAMAGE FROM *METHYL*MERCURY
-MiniMata (MM)= Methyl Mercury (MM)
How is asymptomatic/ symptomatic elemental or inorganic mercury toxicity diagnosed? treated?
-measure organic + inorganic Hg in blood
What is the only chelator that can be used for organomercurials?
moderate success with *penecillamine*; NO DIMERCAPROL BECAUSE CAUSES ^^^ BRAIN LEVELS
DIMERCAPROL MAKES YOU DIE IN THIS SITUATION!!!
-what are the four types that can cause toxicity?
-how do they each induce toxicity?
-which has no antidote?
-As3+: binds sulfhydryls
-As5+: replaces P in ATP --> uncouples oxphos
-Arsine gas/ AsH3: spontaneous hemolysis
-Organoarsenial: she didnt say (not this year either...)
-AsH3= no antidote
ACUTE Arsenic Tox:
How does it effect...
- Cardio: vasodilator/ arrhythmias
- Skin: hyperkeratosis --> skin cancer
- GI: ^^ capillary perm = RICE WATER diarrhea
- Renal: proximal tubular/ glomerular damage
- Blood: spontaneous hemolysis in AsH3 (GAS ONLY!!)
ARSENIC is a pain in my ARS:
A=arrhythmia, R= renal damage/ rice diarrhea, S= skin cancer/ spontaneous hemolysis
Where is arsenic found in high levels?
-^^ levels of arsenic in ground water --> well water
(esp. common in western US)
-**Recently in babies' rice cereal!!!
RICE cereal --> WATERY RICE diarrhea comes right out of the baby's diaper and onto the GROUND.
(Rice water diarrhea, rice cereal, ground water)
CHRONIC Arsenic Toxi:
How does it effect....
-hyperkeratosis/ Mee's lines on fingernails (horizontal)
-garlic odor to sweat and breath
Options for arsenic tox treatment?
-NO OPTION for arsine gas
-targets which organ if ingested?
-targets which organs if inhaled?
-how does it cause toxicity?
- oral: kidney- proximal tubular damage
- inhaled: same kidney damage + lung: pulm edema/ emphysema if chronic
-induces metallothionein--> binds sulfhydryl groups
Which metals are capable of inducing metallothionein?
Where does the Cd- Metallothionein complex accumulate?
(THE BIG "MAC" except in this case C= CADMIUM, not COPPER.)
-liver and kidney --> high levels of metals in these organs
Treatment for cadmium tox:
+WHAT SHOULDNT BE USED?
How can cadmium levels be measured?
-No dimercaprol/ **BAL**, or sulfhydryls, causes ^^ renal tox
CAlcium EDTA =CAdmium tx
-measure B2microglobulin in urine
Itai Itai Disease:
Means "ouch ouch!"
1. Cadmium in food/ water
2. Low calcium in diet
-Promotes replacement of Ca with cadmium in bones
-Premenopausal women + men got osteoporosis
-What are the defect? (2)
-What is the treatment (1st line)? Must monitor for?
-2nd line treatment?
-Defect in ATP7B --> no biliary copper excretion
(Wilson is "7 year old BOY --> 7B= ATP type)
-low ceruloplasmin --> copper not taken up into blood
-penicillamine, monitor for agranulocytosis
-trientine = alternative in the event of agranulocytosis
Which antidotes are used to treat:
-lead: any of the four chelators, choose oral if asx
-mercury + arsenic: penicillamine --> dimercaprol depending on severity
-copper: 1st line penicillamine, 2nd line trientine
What do each of the following substances contain?
-deep sea sponge
-willow bark: aspirin (ASPen willow bark)
-fox glove: digitalis (DIGITAL fox glove)
-opium poppies: morphine
-pacific yew: paclitaxel (PACLITAXEL YEW)
-deep sea sponge: eribuline for breast cx mets
(ERIB has SPONGY BREASTS)
How does the FDA handle drugs vs herbs?
-drugs assumed to be unsafe unless proven otherwise
-herbs assumed to be SAFE unless otherwise (treats herbs like food vs. meds)
What marker on herb supplement labels guarantees the amount of herb/ capsule?
"NF" or "USP certified"
= STANDARDIZED for purity/ strength; guarantees there is "at least x amount" of herb in a capsule
(could be MORE than the amount guaranteed)
Herbals cannot claim to _____?
Cannot claim to cure disease, can only "treat symptoms"
-i.e. ginkgo and bilboa:
"improves memory, not for treatment of alzheimers"
i.e. St. John's Wart
"improves mood, not for treatment of depression"
Describe the complexity of herbal compounds:
Are they uniform?
What is one factor that may cause active ingredients to change?
How do we determine the active ingredient?
-active ingredients vary with climate,
-contain a "complex" of ingredients"
(Hard to isolate one "active" ingredient--dependent on 'family' of compounds)
-what are its two touted effects?
-what is the active ingredient?
-why is this not effective when it is cooked?
-one of the top 5 supplements in US, 20 million dollar market
-lowers cholesterol and prevents MI
-when chopped: garlic --> **allicin** via allinase
-heat causes loss of sulfur compunds/ active ingredient
ALLINASE: IT ALLwilltASTE better with GARLIC.
-How effective is it at lowering cholesterol?
-What is its mechanism of action to lower cholesterol
-How effective is it at inhibiting platelets ?
- 1 clove garlic lowers cholesterol ~12%
(comparable to cholestiramine!)
- Allicin + diallyl sulfides = HMG CoA reductase inhibition
- More effective than cholesterol reduction
- Allicin (ajoene) causes platelet COX inhibition --> DECREASE TXA2
- important drug-herb interaction
- where should it be stored and why?
- Shouldnt combine high dose garlic + antiplatelet drugs because ^^^ chance of bleeding
- Shouldn't take garlic before surgery = ^^ bleeding
- Must store in the refrigerator, room temperature = clostridium infection when ingested
-2 active ingredients/ effects?
(mproves varicose veins + decrease leg pain
Active ingredients = saponins
- Escin (good for leg pain/ swelling)-- good
- Aesculin (bleeding)--Danger!
-The two CANNOT be separated)
**ESCIN/AESCULIN kind of sound like "EQUESTRIAN" and are saponins --> think SAPPY EQUESTRIANS*
Escin: Decreases venous vascular permeability = less leg edema
Aesculin: coumadin like; ^^ bleeding
Contraindications for horse chesnut? (2)
- Coadmin w anticoags/ NSAIDs
- Pregnancy X/ breastfeeding
(THINK: shouldn't ride "HORSES" when "PREGNANT".)
-^^ peripheral and cerebral circulation = ^^ mental focus
-#5 best selling herb in US
What are the proven effects of ginkgo bilboa?
Which two active ingredients are responsible for its effects?
^^ skin/ peripheral blood flow (but not proven in brain)
-kaempferol: anti-oxidant, raises ATP levels
-kaempferol and apigenin: weak MAO-A/Bi
Gingkgo helps you put on your thinking KAP.
-ADRs with leaves? seeds?
-Avoid with what drugs?
- bleeding can slightly ^^
- DOUBLES bleeding time
- anti- B6 effect (aa metabolism issues)
- Seizures + DEATH with small amount of seeds (2/150 lb person)
-DO NOT take with ANY anticoagulants/ antiplatelets
St. Johns Wart:
-marketed for (3)?
-active components (2)?
-mood, sleep, weight loss
-hypericin and hyperforin
-Hyperforin: SSRI, MAO-i, ^ GABA
-Hypericin: MAO-i, ^ GABA
SSRI effect stronger than MAO
^ GABA inhibited by flumazinil
St. John's Warts:
-which formula has higher hypericin/ hyperforin amounts: water or alcohol extracts?
-effective to treat?
-alcohol extract ^^ dose
-helps with MILD depression, moderate --> severe should get the real drugs.
ADRs for St Johns Warts?
Is this a CYP inducer or inhibitor; which drugs are affected?
-H/A and loss of appetite
-DO NOT coadmin w/ MAO-i's, SSRi's
-CYP3A4 inducer --> must ^^ doses of theophylline, OCPs, warfarin
-stop before surgery
Be careful not to get TOWed on St. Johns Street.
(increase doses for Theophylline, OCPs, Warfarin)
three active ingredients?
Don't combine with?
-valtrate, valerenic acid, glutamine
-Augments GABA, opens Cl- channel
-can induce sedation, don't combine with alcohol
-alcohol or water extract more effective?
What are the three echinacea types; what part of the plant do they include?
-reduces cold/ flu symptoms
-alcohol extract = more effective
E. purpura: aerial part only (above root)
E. pallida: aerial + root
E angustigolia: root only
[*Purpura= VISIBLE problem, superficial; PALpable (pallida) things can be superficial OR DEEP; angustiGOLDia= always DEEP, have to DIG for gold]
Two active ingredients in Echinacea?
What are their specific MOAs?
How effective is the formula at preventing colds? In what age groups was it most effective?
-arabinogalactan: releases IL1 + TNFa
-heteroxylan- stimulates PMNs--> ^^ phagocytosis
-Studies= no cold PREVENTION, did have slight improvement of symptoms in those OVER 12yoa
(..... no benefit in kids but my mom gave this to me all of the time when i was a kid... SAMESIES**)
Side effects of echinacea?
Shouldnt combine with what drugs?
-allergic rxn in those allergic to ragweed/ daises
-don't combine with immunosuppressants (reverses their effects)
-mechanism of action? (2)
-improves prostate health + acts as diuretic
-5ARi (like finasteride), prevents testosterone --> DHT
-prevents movement of androgen receptor to nucleus
Saw Palmetto v Finasteride:
-which is more effective?
-which has more ADRs?
-same decrease in symptoms (SOME studies)
-Saw Palmetto = less ADRs (less diminished libido)
**Some studies say could be given in cases of mild BPH; jury still out.
Four marketed uses?
Most active ingredients?
4 Proven MOAs of Ginseng--what are the effects on:
Cholesterol? Platelets? Vasodilation? Stress mediation?
-lowers LDL, raises HDL
-inhibits platelet aggregation
-stimulate NO production
-lower cortisol and NTs during stress (adaptogen)
ACTUAL Effect of ginseng on:
-cancer (which types?)
-lowers stomach and colon cancer; stimulates apoptosis
-stimulates IFN production + chemotaxis
-lowers blood glucose levels 10%
ADRs of ginseng?
Shouldn't be combined with?
-nervousness and insomnia (like caffeine)
"ginseng abuse syndrome"-- think of drinking six starbucks
**Melissa every morning Aug-Dec MS1**
-Don't combine with caffeine
Well documented ADRs (2)?
-beverage-- alcohol alternative (induces relaxation)
-interacts w/ GABA receptors
-assc with HEPATOTOXICITY!
-yellows skin and nails (not jaundice)
-2 active ingredients
-most common use?
-how is it taken?
-sesquiterpene lactones + parthenolide** (most active)
-daily/ prophylactic (not AT headache onset)
Stops your brain from SEQUESTering a MIGRAINE PARTY forafew days.
Stops your brain from sequestering (sesquiterpine) a mirgaine party (parthenolide) forafew (feverfew) days.
How do parthenolides in feverfew work to lower migraine incidence? (2)
-PLA2 inhibitor--> Inhib PG, LT prodxn
-Inhibit platelet serotonin release
**actual alternative to drug therapy, but not MORE effective
Three ADRs assc with feverfew
-Post feverfew sydrome:
muscle aches/ insomnia when stopping the herb
-Uterine Contractions = NOT FOR PREGNANT WOMEN
Five herbs to avoid prior to surgery:
-garlic, horse chesnut, ginko bilboa
(all three ^^ increase bleeding)
-St Johns Wart CYP450 INDUCER--> DECREASE drugs admin during surgery
-Feverfew altered PGs + CYP450 INHIBITOR--> INCREASE drugs admin during surgery
What two herbs should be avoided when taking SSRIs or MAOi's?
-St Johns Warts
What two herbs should you avoid when consuming alcohol?