Flashcards in 2Pharm III Deck (313):
Adaptive immunity, Cell mediated:
Where does the body learn to recognize "self" antigens?
What are the 3 specialized forms of T lymphocytes?
*which do we believe is involved in autoimmunes?
Suppressor T cells regulate/dampen helper and cytotoxic T cells, preventing immune rxns from damaging the self
*this is Self Tolerance
When the immune system properly recognizes self/non-self antigens:
When this fails:
Autoimmunity is in 2% of the pop and the majority are women (and elderly, genetically susceptible)
Hypothesis of Autoimmunity is that T and B lymphocytes escape central tolerance mechanisms in the ______ gland
What 2 major factors are necessary to develop autoimmmune disease?
Inherited susceptibility genes
What genes predispose to autoimmune disease?
MHC - major histocompatibility complex
What is the function of MHC genes?
are recognized by T-lymphocytes for antigen processing
What are 3 common environmental triggers for autoimmune disease?
Possessing an autoimmune gene doesn't mean an individual will always develop the disease, but what are 5 diseases that show familial autoimmunity?
Type I diabetes
Foreign antigens release cytokines that can activate T-lymphocytes and _______ T-lymphocytes
*infection as a trigger
What self-antigens can deposit in various places of the body, causing vasculitis, joint damage, and kidney damage?
What autoimmune disease is initiated by the alteration/inhibition of receptor function without tissue damage?
What receptor is inhibited?
acetylcholine (results in paralysis)
What autoimmune disease is initiated by autoantibodies that stimulate receptors that would normally only be stimulated by a hormone?
Organ specific autoimmune disease is mediated by what?
What is the Tx?
reduce inflammation with coriticosteroids, anticytokines
What is the effect of a large dose of corticosteroids when targeting organ specific autoimmune disease?
lymph tissue atrophy
*this decreases T/B cell production, increases susceptibility to infection
Immunosuppressive drugs target what cells?
T cell responses
The goals for Pharmacologic interventions in autoimmune disease are generally what?
*address inflammation with Aspirin/NSAIDS
What is a sign of toxicity to aspirin?
GI, kidney, resp system, tinnitus are all adverse effects of Aspirin use
What are 2 oral complications of Aspirin/NSAID use?
What is used to Tx RA when Aspirin/NSAIDS aren't working?
sulfasalazine (used for RA) has what (4) side effects?
Do not use celebrex with low dose aspirin
*ok to use
If a pt is using celebrex and antihypertensives, what should we do?
*celebrex decreases BP med efficacy
2 side effects of celebrex:
CV (Increased risk for stroke/heart attack)
2 Contraindications for celebrex:
if aspirin/NSAID allergic
if allergic to sulfonamides
Disease-modifying anti-rheumatic drugs
RA and if pts don't respond to COX-2 inhibitor (celebrex)
What intervention can slow the course of RA disease progression, may induce remission, and prevents further destruction of joints/tissues?
DMARDS have fast onset
*takes 3-4 months to see effects
4 classes of DMARDS:
Immune modulators (...mab)
What DMARD is also a heavy metal antidote?
2 DMARD immune modulating drugs:
What is the drug of choice for severe RA or psoriatic arthritis that is unresponsive to NSAIDS?
methotrexate, being a DMARD, takes 3 to 4 months to kick in
3-6 weeks, faster than other DMARDS
What are the 2 uses of methotrexate?
High dose - chemo
Low dose - immune modulator for autoimmune (RA)
What is the (2) most common side effects of methotrexate?
mucosal ulcerations, nausea
cytopenias, cirrhosis, acute pneumonia-like syndrome
What DMARD inhibits pyrimidine synthesis, reduces pain/inflammation, and slows structural damage?
Since leflunomide messes with the immune system by blocking pyrimidine synth, it has a whole lot of side effects (including teratogenicity)
What are 2 proinflammitory cytokines involved in RA?
What secretes IL-1b and TNF-alpha involved in RA?
What does this further stimulate?
synovial cells secrete collagenase
3 TNF-alpha blockers:
1 IL-1b receptor antagonist:
What TNF alpha blocker binds TNF molecules, risks activation of hepatitis and TB in carriers, and has Upper Respiratory infections as side effects?
What TNF alpha blocker is associated with developing antibodies against the Drug w/ long term use?
*side effects: pneumonia, cellulitis, dyscrasias
What TNF alpha blocker is a recombinant monoclonal antibody that binds to receptor sites?
(used if inadequate response to other DMARDS)
What drug is typically used if other cytokine drugs fail?
*IL-1b receptor antagonist
anakinra (IL-1b receptor antagonist) mechanism:
slows degradation of cartilage/bone loss
2 Antimalarials that treat RA unresponsive to NSAIDS:
How do antimalarials help with RA?
2 severe side effects:
slows erosive bone lesions, may induce remission
eye damage, blue/black intraoral pigmentation
(kind of Kaposi's sarcoma looking)
What chelating agent slows the progression of bone destruction and RA?
2 mechanisms for Penicillamine:
depresses IgM rheumatoid factor
What drug for RA is used after gold, but before corticosteroids?
4 oral complications to Penicillamine:
Gold compounds used to treat RA decrease inflammation and slows bone/articular destruction via multiple....
Why does gold require intensive monitoring?
4 side effects of gold compounds:
Dermatitis w/ mucosal ulcerations
There are all kinds of complications with Gold, including blue-black intraoral pigmentation and _____
What 2 drugs cause blue-black intraoral pigmentation as a side effect to combating RA?
What are 3 immunosuppressive drugs used for Refractory RA
*refractory = doesn't respond to normal Tx
What immune suppressant used for Refractory RA is also used in Dentistry for severe erosive lichen planus (and 3 other mouth diseases)?
What drug is it used in combination with?
4 oral diseases azathiprine + prednisone is used for:
severe erosive lichen planus
major aphthous stomatitis
benign mucous membrane pemphigoid
What immunosuppressant used for severe RA is also an antineoplastic?
*side effects: alopecia, infertility, GI, dyscrasias
What immunosuppressant for RA is primarily used to prevent organ rejection in transplants?
When is cyclosporine used to treat RA?
if methotrexate doesn't work
What drug combats RA by inhibiting production/release of IL-II (and IL-II induced T cells)?
cyclosporine is contraindicated for RA in what 3 cases?
abnormal renal function
16% of cyclosporine users will have what?
3 used for Synthetic Glucocorticoid meds
Immunosuppressive transplant therapy
Glucocorticoids (steroids) have anti-inflammatory effects and profound effects on number, distribution, and function of ________
What do they inhibit that decreases production of prostaglandins and leukotrienes from arachidonic acid?
Steroids increase what peripheral leukocyte?
Decrease what peripheral leukocytes?
decrease T/B cells, monocytes, eosinophils, basophils
Steroid suppress the immune system and the adverse rxns are proportional to the _____.
Tx is considered ______
With Sjogren's Syndrome _____ % of the glandular cells remain intact, allowing for ______
salivary stimulating meds
An elevated BP can always be due to what?
What does natural cortisol regulate?
cortisol also has _____ effects
metabolism of carb, fat, and protein
What is the most potent activator of cortisol?
Excessive production of cortisol:
Insufficient production of cortisol:
A medication induced adrenal insufficiency (taking steroids will suppress own production) is what kind of disorder?
What adrenal insufficiency is more common than Addison's disease?
*associated with chronic steroid use
What is a RARE, life-threatening emergency that exacerbates symptoms like sweating, hypotension, weak pulse, dyspnea, and cyanosis?
6 systemic disease categories for which Steroids can be used?
Collagen diseases (lupus)
Steroids function intracellularly
*bind receptor, come inside, regulate gene expression
How is the potency of a steroid measured?
Corticosteroids are characterized by what?
Duration of action
Prednisone has how much more of an anti-inflammatory effect than hydrocortisone?
Equivalent doses of steroids are based on the amount normally secreted in an adult w/o stress, which is...
3 short acting steroids:
hydrocortisone (cortisol), prednisone, methylprednisone
Steroids are usually taken what time of day?
When is steroid use taken at alternate days?
if taking longer than 1 month
What type of steroid therapy increases the risk for adrenal suppression?
*that's why alternate
Any medication that exceeds _____ mg hydrocortisone equivalent may cause adrenal suppression
*normal daily output
Normal cortisol output is 20 mg/day. What is max during stress?
What happens if combine Chronic Steroid use w/ aspirin/NSAIDS?
What are 3 major adverse events with Chronic Steroid use?
4 oral side effects of Steroids:
Poor wound healing
Mask oral infections
4 contraindications to using steroids:
Systemic fungal infections
2 ways steroids are used in Dentistry:
Tx inflammatory pathologies oral mucosa
What is the most common delivery route of Steroids in Dentistry?
High potency topical steroids should only be used for how long?
2 weeks only
Using high potency topical steroids for longer than 2 weeks requires what?
What is the risk?
What oral topical steroid is mixed with tissue adhesive?
What oral topical steroid is a 0.5% gel for mild lichen planus and recurrent aphthous stomatitis?
What oral topical steroid is a 0.5% gel for oral inflammation?
What oral topical steroid is 0.1%?
What are the 2 topical steroid rinses used in dentistry?
used 2-4x/day, rinse 30 secs, spit
What are the 2 types of injected steroid uses?
Intra-articular (3 week intervals)
What are the 2 Oral preparations of steroids used before, during, after oral surgery?
What 3 populations require special consideration when using steroids?
*but there are many more (glaucoma, hypertension, peptic ulcer, osteoporosis, diabetes, TB)
geriatric (liver/kidney function = lower dose)
What type of dental procedures require steroid used before/during/after?
*routine procedures won't stimulate cortisol production
When do cortisol levels increase in dental pts?
1-5 hrs post procedure
(pain response, loss of local anesthesia)
What BP levels are hypotensive?
Systolic: less than 100 mm Hg
Diastolic: less than 60 mm Hg
For a routine dental procedure, if the pt has a past history of steroid use, supplementation is necessary
*no supplementation necessary
3 types of lab tests to determine if pt needs steroids:
ACTH in plasma
For a pt currently taking steroids, the protocol for diagnostic/minimally invasive procedures:
Pt takes usual dose
Schedule in morning
Stress reduce (pain/anxiety)
For major invasive procedures like oral surgery a physician consult, lab testing, and steroid supplementation as needed is protocol
Pts either currently taking steroids (topically or orally) or with a history of taking steroids should be given no additional steroids with routine Tx
Schedule in morning, monitor BP - What are 2 anxiety control interventions for pts on steroids?
Target dose of hydrocortisone for Minor oral/perio surgery:
Target dose of hydrocortisone for major oral surgery involving general anesthesia:
3 mechanisms used by Antivirals:
Alter uncoating of virus
Inhibit viral protein synth
2 drugs used for Influenza A?
*blocks viral uncoating
Drug for either Influenza A or B:
This is a classic example of what?
This drug inhibits what enzyme
Neuraminidase does what?
Cuts viral progeny from cellular envelope prior to release
*inhibiting prevents viral release
What drug is used for respiratory syncytial virus?
ribavirin (Rebetol, Virazole)
Mechanism of ribavirin (drug used for respiratory syncytial virus):
Prevents synth of viral proteins encoded by viral mRNA
3 side effects to using ribavirin (messes with mRNA)
What drug is indicated for herpes simplex keratitis
(In the eye)
*mechanism involves incorporating into viral DNA in place of what?
What drug is used for Herpes zoster, genital HSV, immunocompromosed primary and recurrent herpes, and is the IV drug of choice for HSV encephalitis?
Acyclovir must be used every ____ hours
(Consistent with cycle phases of virus)
CMV - human cytomegalovirus (and CMV retinitis) is treated with what drug?
Inhibits viral DNA synth
What 2 classic Prodrugs are used for genital herpes?
What do they turn into when they pass through the intestinal wall?
famcyclovir - penciclovir
valacyclovir - acyclovir
A family of naturally occurring inducible glycoproteins that interfere with viral ability to infect cells:
3 Interferon actions:
3 types of interferons:
T/F the antiviral mechanism of interferons isn't completely understood
Though not well understood, we know that Interferons inhibit viral ________
(Degrades both mRNA and tRNA)
Interferons appear to have many mechanisms, including affecting gene transcription, cell growth, differentiation, surface antigen expression, increasing phagocytic and cytotoxic activity - and interfering with what particular gene expression?
Interferons are used to combat some cancers, but what are the 2 most common indications?
Heb B and C
What are the adverse effects of Interferons?
*it's really hard to be on
There are new, and VERY expensive, drugs for Hepatitis C
What is the main challenge to Antiretroviral drugs?
Toxic to host cells
When does a viral infection technically begin?
When virus attaches to host cell
*mediated by viral proteins and host membrane receptors
What are 3 general mechanisms Antiretrovirals use to inhibit disease?
Alter viral genome replication
There is a new drug that inhibits HIV from entering host cells - the first of its kind
(Fusion protein inhibitor)
*vaccine could do this too
What type of drug alters retroviral genome expression?
Antiretroviral immunization provides antibodies against what?
Viral envelope proteins
Retroviridae all use what enzyme?
*this is essential for HIV replication
Reverse transcriptase is a ______ polymerase
(RNA to DNA)
The targets of antiretroviral drugs is what?
What happens after a retrovirus undergoes reverse transcription?
*virus incorporates into host DNA
What is the integrated DNA segment of a retrovirus called?
What can it do?
Produce new RNA - protein synth for new viruses
Another name for a compete virus:
What are the 3 Primary classes of Antiretroviral drugs for HIV?
Nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Aside from the 3 primary classes of Antiretroviral drugs for HIV, what are 3 additional classes?
Nucleotide reverse transcriptase inhibitors
Fusion protein inhibitor
Integrase inhibitors block viral integration into host ____.
Protease inhibitors ______ of certain long peptide chains
What is the anti-HIV drug combination therapy called?
HAART - Highly Active AntiRetroviral Therapy
*usually 3 different drugs
A typical anti-HIV antiretroviral cocktail will include what 3 classes of drugs?
nucleoside reverse transcriptase inhibitor
non-nucleoside transcriptase inhibitor
*these are the 3 primary classes
When are antiretrovirals used for HIV-infected pts?
CD4 less than 500
5 side effects to Antiretrovirals:
EBV, Cytomegalovirus, and other Viral infections associated with immunocompromised HIV pts are treated how?
Pneumocystis carinii (pneumonia associated with HIV) is treated with oral trimethoprimsulfamethoxazole (Bactrim), which is a ____ drug
Candidiasis, Cryptococcus, and Histoplasma in HIV pts are treated with the azoles and _______.
*If you see this drug you can pretty much assume the pt is HIV positive
TB from HIV is treated with isoniazid and rifampin
Nucleoside reverse transcriptase inhibitors must be ______ to be integrated into ______
reverse transcriptase (a DNA polymerase
***end result is inhibition of reverse transcriptase
Nucleoside reverse transcriptase inhibitors work because the enzyme reverse trascriptase in HIV is _____ times more susceptible to inhibition than are normal human cells.
What is the downside to these drugs?
NO effect in cells already containing HIV
2 Nucleoside reverse transcriptase inhibitors:
zidovudine (Retrovir) ***(AZT)
AZT, zidovudine, is very toxic - pts are often required to have transfusions why?
Also causes Oral and CNS effects and ______
bone marrow depression
Oral effects of AZT:
4 of them
Acetominophen, aspirin, indomethacin (NSAID) have DDI's that inhibit the metabolism of ______
This potentiates _____ of both agents
AZT - zidovudine
How do non-nucleoside RT inhibitors differ from nucleoside?
Do NOT require bioactivation
inhibits catalytic rxn of RT independent of nucleotide binding
Resistance to non-nucleoside RT inhibitors is uncommon
*happens quickly if used alone
Protease inhibitors affect the enzyme responsible for cleaving viral precursor peptides, thus preventing _____ of HIV infected cells
3 Protease inhibitors:
What prevents a proviral gene inserting into human DNA?
What is a new combo drug containing 3 meds in 3 different classes for HIV?
Linear gingival erythema, NUP, and perio can all result from HIV
The range of responses per dose:
Greater than normal reaction to a drug:
Qualitatively different response to a drug
(stimulant = sleep)
Lower doses for what 2 groups?
In most cases of Liver disease drug metabolism is affected by what system failing?
In cases or renal disease dosing must be modified based on excretory function of renal _______
A rapid development of tolerance:
The study of deleterious effect of phyisical, chemical or biological substances (toxins)
50% of lethal dose
effective dose - shows effect in 50% mice receiving
Margin of Safety
Acceptable margin of safety is _____ or more
Daily dosing to rats/dogs from 3 months to 2 years:
Long-term (chronic) toxicity studies
The range of doses (concentrations) of a drug that elicits a therapeutic response (withouth unacceptable side effects in a population)
toxic response, 50% pop.
therapeutically effective, 50% pop.
Therapeutic Index =
*what does a large therapeutic index suggest?
Large therapeutic window
body doesn't distinguish drugs from toxic foreign substance (xenobiotics) and handles them the same way
pharacokinetics = toxicokinetics
pharmacodynamics = toxicodynamics
The study of the absorption, distribution, metabolism and excretion of toxic compounds and metabolic products used to predict toxin concentration
Acute toxicity usually is visible right away, and occasionally not visible for weeks/months post exposure
The effect of toxic insult that occurs over a prolonged period
Can this manifest long AFTER the individual is no longer exposed to toxin
Toxins must cross at least one epithelial layer to be systemically absorbed - what are the 3 primary sites of absorption?
Benzene, tetrachloroethylene, and asbestor are absorbed into the body through what?
Toxins must diffuse though 7 layers of skin to gain systemic exposure
Toxin distribution to a tissue is directly related to what 2 factors?
Amount of blood flow to the tissue
Affinity of toxin to tissue
Lipid soluble toxins can cross membranes - what toxins have a difficult time crossing the BBB
water-soluble (and therefore polar)
Detoxification usually occurs where and by what enzyme system?
Cytochrome P450 creates what?
Water soluble molecules for elimination
Nontoxic material - toxic metabolite:
Toxins go through what 3 types of changes upon metabolism:
another toxin (active to active)
3 toxins stored in the body for a long time:
Lead - bones
DDE (from DDT) - fat
Inhaled macrophage engulfed particulate in lung
Toxins damage tissue by altering the structure of proteins, lipids, carbs, nucleic acids so severely that _____ is lost
Non-specific sites damaged by environmental tissue damaging agents tend to be skin, eyes, respiratory system and are
Because Reactive Species tend to react chemically with biologic macromolecules the site of action is _______
Example of a site-specific Reactive Species:
*fire extinguishers - not toxic, but metabolized into toxic free radicals that damage liver, kidney
2 types of immune responses triggered by toxins:
What kind of toxicity alters metabolic pathways or interacts with critical receptors?
*this can mess with neurotransmission, cardiac rhythm, oxygen delivery, ATP generation, or intracellular Ca balance.
Enzyme and Receptor-Mediated Toxicity
Nerve gases and pesticides are _______ inhibitors
making them ____ mediated toxin
*ACh amasses in cleft - parasympathetic
Another enzyme mediated toxin: What does Cyanide bind to?
This prevents the generation of what?
heme iron in cytochrome C oxidase
Carbon monoxide is a ____ mediated toxin
Most carcinogenic initiators damage what?
Carcinogens either damage DNA or promote cancer by what means?
*cirrhosis - liver cancer (causes chronic regeneration of tissues)
Substance that can induce a birth defect
Teratogens can alter DNA or act in what particularly potent manner?
Inhibit intracellular signals
3 types of selective toxicity:
Attack target not present in host
Attack target similar but not identical to those of host
Attack target shared by host, but vary by importance
When is selective toxicity least toxic?
When unique difference between pathogen/cancer and host
target common pathways between pathogen/cancer and host
What is an indication of how selective a drug is?
A narrow therapeutic index tells us what about selectivity?
Drugs less selective - affect host and pathogen/cancer
Antibacterials targeting bacterial cell wall synth (peptidoglycans) is an example of a _____ drug target
*minimal toxicity - safe (penicillin)
Why are antifungals not good at selective targeting?
Fungi are enveloped in lipid bilayer similar to humans
*if attacks membrane, will also affect humans
When would a drug have a therapeutic window smaller than those with a unique target?
similar (pathogen/host) metabolic pathways that target unique enzymes/receptors
bacteria have different ribosomes, RNA, proteins
How do Macrolides work?
How do aminoglycosides work?
prevent protein from coming out of bacterial ribosome
disrupt mRNA decoding
Most drugs with common targets to the host have to do with what?
3 main steps of Carcinogenesis:
The genetic damage involved in the Transformation step of Carcinogenesis can be congenital or later mutations
Cell life cycle, synth DNA:
division of 2 daughter cells:
M phase (mitosis)
Most antineoplastic drugs target what?
What type of cells respond best to chemo?
small, rapidly dividing cells
As cancer gains mutations, responses to chemo may change and metastatic lesions may be less responsive
Chemotherapy works by what 2 mechanisms?
p53 - cell cycle is arrested and repaired
apoptosis - bad cell dies
p53 is a ______ factor
What is its function?
p53's four anticancer mechanisms:
G1/S arrest and repair
Induce growth arrest
3 stressors that induce p53:
DNA damaging drugs
Tumor suppression is severely compromised if what system is damaged?
3 types of cancer that express p53 and are very responsive to chemo?
What are 3 types of cancer that tend to acquire a p53 mutation and aren't very responsive to chemo?
Chemo has what type of kinetics?
First order: constant fraction of tumor cells killed w/ each cycle
Multiple cycles of chemo are given at the highest possible (tolerable) dose
Why do solid tumors not respond well to chemo?
What interventions are used instead?
Why is combo Chemo used?
Chemo that acts on differing targets, phases of cell cycle, and with different dose limiting toxicities:
Some of these therapies have ____ benefits
To be used how often?
What is the current emphasis in chemo?
Drug combination therapy
You can have cell cycle specific or non cell-cycle specific drugs
3 types of normally proliferating cells affected by chemo:
3 ways chemo toxicity manifests:
Alkylating agents transfer alkyl groups to sulfhydryl, carboxyl, and phosphate groups, alkylate DNA (affecting downstream RNA and protein synth) and are Cell cycle specific
5 classes of Chemotherapeutic alkylating agents:
What is a common side effect of chemotherapeutic Alkylating agents?
Susceptibility to infection
3 specific Alkylating Agents:
ifosfamide (nitrogen mustard)
Antimetabolites are specific to what cell cycle phase?
3 classes of Antimetabolites antagonize what?
An Antimetabolite Folic acid antagonist that is specific to S phase (all metabolites specific to S phase):
Antimetabolite Purine antagonist:
*like all antimetabolites, S phase specific
2 Antimetabolite Pyrimidine antagonists:
*like all, S phase specific
2 Platinum Complexes that inhibit DNA synth/repair and are used to fight cancer:
Platinum based chemo is widely used for Tx of many cancers (gyno, bladder, testes, lung, CNS, head/neck)
What is a major toxicity of Platinum derived compounds for cancer? (class emphasized)
What are 4 others?
nephrotoxic, neurotoxic, ototoxic, nausea/vomiting
What, derived from the periwinkle plant, inhibits mitotic division?
Vinca Alyloids go after what phase of the cell cycle?
M and S
*cell cycle specific
2 Vinca Alkyloids
Vinca Alkyloids have a high incidence of toxicity and may cause hearing loss (ototoxic)
What cell cycle phase do hormones interrupt?
Name 4 hormonal agents:
What is an example of a Glucocorticoid used to suppress cancer (antitumor effects)
prednisone's antitumor effects are related to glc transport inhibition, phosphorylation inhibition, or induction of cell death in immature lymphocytes
What is an anti-estrogen drug that competitively binds estrogen receptors?
What cell cycle phases does it target?
G0 and G1
tamoxifen is cytocidal
5 adverse effects of tamoxifen (competitively binds estrogen receptors)
Why are antibiotics used for cancer therapy?
Cytotoxic - bind w/ DNA and inhibit cell division
Cell cycle specificity of antibiotics:
Most effective for what type of tumor?
either non-cell cycle specific or cell cycle specific
solid mass tumors
3 antibiotics used to Tx cancer:
What Antibiotic is used for HIV-associated Kaposi's Sarcoma?
Cancer fighting antibiotic go after cell cycles and inhibit what?
What drug is the Angiogenesis inhibitor to fight cancer?
4 indications for thalidomide:
AIDS aphtous lesions
multiple myeloma (investigational)
What is the classic model drug for teratogenesis?
*morning sickness - birth defects
8 systemic effects of Chemo:
Bone marrow suppression
What is the greatest consequence of the Oral complications to Chemo?
Discomfort interferes w/ eating
(secondary infection risk)
Chemo pts should be manages orally with plaque control, pain control (topical anethesia), salivary replacement, Fluoride, antifungals, antivirals, and antimicrobial mouthrinses/dentrifrices
All metals produce toxicity in animals and humans
Metals form coordination complexes with various ligands that have 4 consequences:
Disrupt enzymatic/transport process
Loss of energy production
Loss of ion regulation
What is the most common arsenic containing mineral?
Everyone has about 3 micrograms of arsenic in the body daily, but can tolerate well
Arsenic effects: dermatological, vasodilation, GI, CNS, headache, coma, teratogenic, carcinogenic, and breath smells like what?
What is given for arsenic poisoning?
How does it work?
sulfhydryl group combines with arsenic - excreted in urine
Antimony is used to flame proof and is highly toxic
What is the antidote to Antimony?
*just like arsenic - sulfhydryl combines and excreted in urine
Silver is germicidal, is used to encapsulate wounds, antiseptic for burns, cauterizes wounds - and used to be placed into newborn eyes to kill gonococcus
What happens when Silver is absorbed into the circ system?
*blue/gray skin pigmentation of skin/mucous membranes
Pure gold is toxic
*salts are toxic
Antidotes to gold toxicity:
Exposure to mercury leads to what 3 things?
Chest pain, dyspnea, cough, hemoptysis, impairment of pulmonary function, interstitial pneumonia:
Acute mercury exposure
Continuous exposure to what leads to fine tremor, initally in the hands but moving to the eyelids, lips, and tongue
elemental mercury - neurotoxic
inorganic mercury - corrosive to what?
Enzyme inhibitor in the production of heme (inhibits protoporphyrin IX and accumulates aminolevulonic acid)
Antidotes to Lead:
What inhibits the same process as Lead and was historically used to treat enlarged joints/glands?
2 Antidotes to Cadmium:
The treatment to Cadmium poisoning mobilized the metal to the ______
*possible renal toxicity
What is the antidote to Iron poisoning?
What is the antidote to Aluminum?
Antidote to Nickel:
4 requirements to heavy metal antogonists (antidotes)
chelate is stable/less toxic at physiological pH
can't bind Ca++
The antidote for Arsenic, Antimony, Gold, and Mercury:
The antidote for Lead, Cadmium:
Calcium disodium edetate (EDTA)
Antidote for Gold, mercury: