Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
336 Cards in this Set
- Front
- Back
|
Arachidonic acid metabolites
|
cyclooxygenase: prostaglandin, thromboxanes, prostacyclin
lipoxins leukotrienes |
|
|
chemical mediators of inflammation
|
vasoactive amines-histamine, 5HT, kinins, clotting factors, fibrinolytic factors, complement and products, eosinophil act factor, arachidonic acid metabolites o2 radicals, and proteases
|
|
|
NSAID Fctl Characteristics
|
analgesia, antipyretic, anti inflammatory
|
|
|
COX1
|
consitutive, gastric mucosa, kidney, coagulation
|
|
|
COX2
|
inducible in response to inflammatory elements, consititutive in some tissues
|
|
|
COX1 constitutive effects
|
GI cytoprotection, platelet aggregation, renal electrolyte homeostasis, renal blood flow maintenance
|
|
|
COX 2 constitutive and inducible effects
|
Const: :renal electrolyte homeostasis and renal blood flow maintenance
Inducible: pain fever inflammation |
|
|
Salicylic acid
|
acetylated: ASA
non acet: magnesium salicylate, diflunisal aspirin PG syn inhibitor |
|
|
Acetic acid
|
indometacin, sulindac, tolmetin, diclofenac, ketorolac, bromfenac
|
|
|
Proprionic acid
|
ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen
|
|
|
fenamic acid
|
mefanamic, meclofenamic
|
|
|
pyrazolone
|
phenylbutazone
|
|
|
oxicam
|
piroxicam
|
|
|
COX2 selective inhibitors
|
celecoxib, meloxicam
|
|
|
Aspirin
|
Abs: stomach and sm int. as non ionized acid in low pH
-alkalinization of gastric contents decreases abs and irritation met: high prot bind, met by liver, first order process analgesic doeses, zero order higher doses renal excretion 5-30% |
|
|
Aspirin pharm effects
|
Analgesic-mild to mod pain COX2 inhibit
Antipyretic: COX2 inhibit, fever, asp blocks PG syn and hypothalamic resp to IL1 **CAution REYES syndrome Anti inflamm: Cox2 inhbit anticoag/antithrombotic: cox1 inhibit asp increase bleeding time and decreases blood clotting fct |
|
|
Aspirin ADR
|
hypersensitivity (med by LT?)
rhinitis, urticaria, bronchocontriction, anaphylactic rxn, assoc with asthma and nasal polyps, pts at risk should avoid all asp cont prods and other PG syn inhbitors GI upset: dyspepsia, epigastric pain, NV cramps Ulceration and GI bleed PGE2 and PGI2 decerase gastric acid secretion adn maintain mucosal resistance/enhance repair usually lessesed with buffered cmpds antacids, propionic acids (ibu) H2 antagonists misprostil |
|
|
ASpirin ADR for Kidney
|
Renal impair: hypovolemia effective renal blood flow maintained by PG, PG syn inhbition can result decrease renal blood flow (tubular necrosis)
NA retention/edema: PGE2 inhibits Na reabsorp and PG syn inhibition may allow for an enhanced Na and water reabsorp, secondary may be hyperkalemia |
|
|
Aspirin ADR head and skin
|
HA: paradoxical effect, med overuse Ha, dizziness
Pruritis: hypersensitivity Tinnitus: some pts more sens, typically toxic Reyes syndrome |
|
|
NSAID interactions
|
Displacement of protein binding PK: increase free fraction drug-warfarin, phenytoin, steroids
Diurectics: attenuates effects of diruections via axn Na transport Anticoagulants: antithrombotic effect, ibup diminishes asa effect GI effects: upset, ulcer, bleed, anticoag, risk of bleed, enhanced effects with alcohol, glucocorticoids etc |
|
|
fenamic acid
|
mefanamic, meclofenamic
|
|
|
pyrazolone
|
phenylbutazone
|
|
|
oxicam
|
piroxicam
|
|
|
COX2 selective inhibitors
|
celecoxib, meloxicam
|
|
|
Aspirin
|
Abs: stomach and sm int. as non ionized acid in low pH
-alkalinization of gastric contents decreases abs and irritation met: high prot bind, met by liver, first order process analgesic doeses, zero order higher doses renal excretion 5-30% |
|
|
Aspirin pharm effects
|
Analgesic-mild to mod pain COX2 inhibit
Antipyretic: COX2 inhibit, fever, asp blocks PG syn and hypothalamic resp to IL1 **CAution REYES syndrome Anti inflamm: Cox2 inhbit anticoag/antithrombotic: cox1 inhibit asp increase bleeding time and decreases blood clotting fct |
|
|
Aspirin ADR
|
hypersensitivity (med by LT?)
rhinitis, urticaria, bronchocontriction, anaphylactic rxn, assoc with asthma and nasal polyps, pts at risk should avoid all asp cont prods and other PG syn inhbitors GI upset: dyspepsia, epigastric pain, NV cramps Ulceration and GI bleed PGE2 and PGI2 decerase gastric acid secretion adn maintain mucosal resistance/enhance repair usually lessesed with buffered cmpds antacids, propionic acids (ibu) H2 antagonists misprostil |
|
|
ASpirin ADR for Kidney
|
Renal impair: hypovolemia effective renal blood flow maintained by PG, PG syn inhbition can result decrease renal blood flow (tubular necrosis)
NA retention/edema: PGE2 inhibits Na reabsorp and PG syn inhibition may allow for an enhanced Na and water reabsorp, secondary may be hyperkalemia |
|
|
Aspirin ADR head and skin
|
HA: paradoxical effect, med overuse Ha, dizziness
Pruritis: hypersensitivity Tinnitus: some pts more sens, typically toxic Reyes syndrome |
|
|
NSAID interactions
|
Displacement of protein binding PK: increase free fraction drug-warfarin, phenytoin, steroids
Diurectics: attenuates effects of diruections via axn Na transport Anticoagulants: antithrombotic effect, ibup diminishes asa effect GI effects: upset, ulcer, bleed, anticoag, risk of bleed, enhanced effects with alcohol, glucocorticoids etc |
|
|
NSAID indictations
|
Pain (mild to mod, alone or in combo with caffeine)
fever (asp and other PG syn inhib not reccommended as fever reducers in kids or viral dz, acetominophen can be used, inflammation (arthritis) antithrombotic misc use: menstrual cramps, closure PDA, mycoradial infarction prevention of CRCancer alzheimer's ds |
|
|
Acetaminophen
|
use: Mild to mod pain
efficacy comparable to most nsaids in many mskl condn, common combo drug with dyrocodone, codeine, with agents of diff mxn safety: few adr, hepatotoxicity at high doses with chronic alcohol abuse, cyp450 inducers, elderly |
|
|
Capsaicin
|
topical analgesic only
mxn: enhances release of subs P with subsequent depletion, use for temp relief of peripheral neuralgia, herpes zoster shingles, and rheumatoid arthritis and osteoarthritis |
|
|
Rheumatoid Arthritis
|
NSAIDS, Dz Modifying anti rheumatic ddrugs (dmards): antimetabolite(methotrexate, leucovorin/folate), sulfaasalazine, antimalarial(chloroquine, hydroxychloroquine), leflunomide, TNFa inhibit(etanercept, infliximab), IL1 antagonists(anakinra), gold salts(aurothioglucose, auranofingold na thomalate), glucocorticoids, cytostatic/cytotoxic(azathioprine, cyclophosphamide), antibiotics(minocycline) penicillamine
|
|
|
NSAID indictations
|
Pain (mild to mod, alone or in combo with caffeine)
fever (asp and other PG syn inhib not reccommended as fever reducers in kids or viral dz, acetominophen can be used, inflammation (arthritis) antithrombotic misc use: menstrual cramps, closure PDA, mycoradial infarction prevention of CRCancer alzheimer's ds |
|
|
antimalarials adr
|
retinopathy
|
|
|
gold salts adr
|
dermatitis, GI upset, proteinuria
|
|
|
Acetaminophen
|
use: Mild to mod pain
efficacy comparable to most nsaids in many mskl condn, common combo drug with dyrocodone, codeine, with agents of diff mxn safety: few adr, hepatotoxicity at high doses with chronic alcohol abuse, cyp450 inducers, elderly |
|
|
penicillamine adr
|
dermatits, GI upset, proteinuria
|
|
|
Capsaicin
|
topical analgesic only
mxn: enhances release of subs P with subsequent depletion, use for temp relief of peripheral neuralgia, herpes zoster shingles, and rheumatoid arthritis and osteoarthritis |
|
|
methotrexate adr
|
myelosuppression, pneumonitis, ulcerations, hepatotoxicity
|
|
|
sulfasalazine adr
|
dermatitis, GI upset, hepatitis
|
|
|
Rheumatoid Arthritis
|
NSAIDS, Dz Modifying anti rheumatic ddrugs (dmards): antimetabolite(methotrexate, leucovorin/folate), sulfaasalazine, antimalarial(chloroquine, hydroxychloroquine), leflunomide, TNFa inhibit(etanercept, infliximab), IL1 antagonists(anakinra), gold salts(aurothioglucose, auranofingold na thomalate), glucocorticoids, cytostatic/cytotoxic(azathioprine, cyclophosphamide), antibiotics(minocycline) penicillamine
|
|
|
azathioprine adr
|
myelosuppresion, GI upset, hepatotoxicity
|
|
|
antimalarials adr
|
retinopathy
|
|
|
gold salts adr
|
dermatitis, GI upset, proteinuria
|
|
|
penicillamine adr
|
dermatits, GI upset, proteinuria
|
|
|
methotrexate adr
|
myelosuppression, pneumonitis, ulcerations, hepatotoxicity
|
|
|
sulfasalazine adr
|
dermatitis, GI upset, hepatitis
|
|
|
azathioprine adr
|
myelosuppresion, GI upset, hepatotoxicity
|
|
|
cyclophosphamide adr
|
myelosuprression, alopecia, GI upset, infertility, bleeding, cycstitis, malignancy
|
|
|
ciclosporin adr
|
HTN, nephrotoxicity, neurotoxicity, hepatotoxicity
|
|
|
cyclophosphamide adr
|
myelosuprression, alopecia, GI upset, infertility, bleeding, cycstitis, malignancy
|
|
|
glucocorticoids adr
|
cushing's syndrome, osteoporosis, cataracts, ulcers
|
|
|
leflunomide adr
|
myelosuppression, GI upset, hepatotoxicity
|
|
|
etanercept adr
|
rash, infection
|
|
|
ciclosporin adr
|
HTN, nephrotoxicity, neurotoxicity, hepatotoxicity
|
|
|
cyclophosphamide adr
|
myelosuprression, alopecia, GI upset, infertility, bleeding, cycstitis, malignancy
|
|
|
glucocorticoids adr
|
cushing's syndrome, osteoporosis, cataracts, ulcers
|
|
|
leflunomide adr
|
myelosuppression, GI upset, hepatotoxicity
|
|
|
ciclosporin adr
|
HTN, nephrotoxicity, neurotoxicity, hepatotoxicity
|
|
|
glucocorticoids adr
|
cushing's syndrome, osteoporosis, cataracts, ulcers
|
|
|
etanercept adr
|
rash, infection
|
|
|
leflunomide adr
|
myelosuppression, GI upset, hepatotoxicity
|
|
|
etanercept adr
|
rash, infection
|
|
|
infliximab adr
|
rash infection hypersensitivy rxn
|
|
|
anakinra adr
|
injection site rxn
|
|
|
infliximab adr
|
rash infection hypersensitivy rxn
|
|
|
anakinra adr
|
injection site rxn
|
|
|
Gout
|
inflamm resp, deposition urate crystals in jt tissue, prod purine met, granulocytic phagocyt cyrstals, low pH prod by leukocytes lead to inc uric acid crystallization
hyperuricemia: inc prod, met imbal, inc diet consump purine rich foods, inc tissue destr, dec excretion by kidney therapeutic: uricosuric agents-inc excrete uric acid, counter inflamm process NSAIDs no salicylates, prevent uric acid prod=preferred if renal stones or tophi present or renal fail, low purine foods and limit alchohol consumption |
|
|
Gout
|
Inflamm resp to dep of urate crystals in jt tissue
prod purine met inflamm results granulocytic phago crystals, low pH prod by leukocytes lead to incr uric acid crystal |
|
|
Hyperuricemia
|
inc prod, met imbalance, inc dietary consumptoin purine rich foods, inc tissue dest ca chemo, dec excrete by kid
|
|
|
therapeutic strat for Gout
|
uricosuric agents-inc excrete uric acid, counter inflamm process-nsaids not salicylates, prevent uric acid prod-pref if renal stones or tophi pres or renal fail, low purine rish foods and limit alc cosumption
|
|
|
Probenecid
|
uricosuric agent, indic: gouty arthritis, hyperuricemia, prevents renal tub reabsorp, aspirin or other salicylates antag effects, maintain good hydration, shoudln't be used during acute gout attack, may preicipate an attack, use in conjection with colchicine
|
|
|
sulfinpyrazone
|
uricosuric agent, indic: gout and gouty arthritis, prvents renal tub reabsorp, aspirin or other salicylates antag effects, maintain good hydration, shoudn't be used during acute gout attack, may preciipate attack-use with colchicine, other adrs: inhibits platelet aggreg, blood dyscrasias
|
|
|
colchicine
|
anti inflamm agent effective only in gout, used in acute attack or prophylactically, dec granulocyte phago and prevents leukocyte migration, prev spindle form, adr: leukopenia, GI upset, vit b12 def
|
|
|
Allopurinol
|
magmt gout, inhibits xanthine oxidase, syn of urate from xanthine and hypoxanthine, start at low doeses and titrated up to avoid precip gouty attack, keep well hydrated, useful in renal impair when uricosuric agents effective, febuxostat
|
|
|
rasburicase
|
urate oxidase analog, urica acid->allanotoin
|
|
|
Acute mgmt gout
|
nsaids, colchicine
|
|
|
uricosuric agents
|
probenecid and sulfinpyrazone
|
|
|
reduced urate form
|
allopurinol, febuxostat
|
|
|
promote allantoin form
|
rasburicase, tumor lysis syndrome
|
|
|
reduced urate form
|
allopurinol, febuxostat
|
|
|
patho of migraine attack
|
cerebral vasoconstrict-cerebral hypoxia-aura or ractive vasodilation-creberal circ or extracranial circ or neurogenic inflamm--headache--symp activation-cenral or peripheral-central-sensory or peripheral autonomic sxms
|
|
|
promote allantoin form
|
rasburicase, tumor lysis syndrome
|
|
|
symptomatic acute mgmt migraine
|
nsaids or opiods-rarely
|
|
|
patho of migraine attack
|
cerebral vasoconstrict-cerebral hypoxia-aura or ractive vasodilation-creberal circ or extracranial circ or neurogenic inflamm--headache--symp activation-cenral or peripheral-central-sensory or peripheral autonomic sxms
|
|
|
abortive migraine agents
|
triptans: sumatriptan and zolmitriptan
ergot alkaloids: dihydroergotamine, ergotamine, methysergide, methylergonovine |
|
|
symptomatic acute mgmt migraine
|
nsaids or opiods-rarely
|
|
|
preventative migraine agents
|
tricyclic antidepressants: amitriptylline
B blockers: propranolol Anticonvulsants: topiramate, valproic acid |
|
|
abortive migraine agents
|
triptans: sumatriptan and zolmitriptan
ergot alkaloids: dihydroergotamine, ergotamine, methysergide, methylergonovine |
|
|
Triptans
|
5HT1db agonists, cranial vasodilation, neuronal inhibition, diminished central trigeminal transmission
|
|
|
preventative migraine agents
|
tricyclic antidepressants: amitriptylline
B blockers: propranolol Anticonvulsants: topiramate, valproic acid |
|
|
Toxicology
|
subtopic of pharm refers to toxic subs and their: detection, effects, properties and regulation
|
|
|
Triptans
|
5HT1db agonists, cranial vasodilation, neuronal inhibition, diminished central trigeminal transmission
|
|
|
Toxicology
|
subtopic of pharm refers to toxic subs and their: detection, effects, properties and regulation
|
|
|
what is a poison?
|
any chemical that is physio harmful when admined to a living org.
poisoning is situational and quantitative in nature |
|
|
what is a poison?
|
any chemical that is physio harmful when admined to a living org.
poisoning is situational and quantitative in nature |
|
|
primary determinant of toxicity?
|
drug dose
|
|
|
primary determinant of toxicity?
|
drug dose
|
|
|
blood plasma level toxicity
|
toxic effects of chemicals in physio systems are also dependent on duration of time that these chemicals are present
|
|
|
Why study toxicology?
|
servves humankinds in:
to protect humans and other org from adverse effects of toxicants and to serve as a means to develop improved toxicants |
|
|
LD50 legal poison
|
LD50 of less than or equal to 50mg/kg bwt
|
|
|
ALD
|
average lethal dose, estimated from accdiental deaths in humans
|
|
|
clinical mgmt poisoning
|
rapid measures called for:1)support pat vitals 2) r/o other diff
3) reduce/remove drug in from body, dec dose/dec time of exp 4) tx uncouncious pt: several genearl antidotes avil to tx pt upon pres at hosp, glucose/insulin /diabetic shock/hypoglycemia, naloxone(narcotic overdoes)-use drugs to tx emergent conditions: seizures, cardiac dysrhthmias, and severe agitation |
|
|
ID poison
|
pat Hx, lab test-time!, urine blood, gI contents, ** comparison of drug or chemical responses of the pt with known toxicology standards (toxidromes) and known adrs
|
|
|
Drug removal via emesis
|
mechanical, apomorphine, syrup of ipecac
CI's: petroleum hydrocarbon solvent-chem pneumonitis, caustic acid or alkali agent (rupture), seizing or comatose pt |
|
|
Act charcoal
|
admin orally in water, very lge surface area allows for bdining of organic toxicants which prevents absorption, often induces emesis-CI with caustic agents, lack of absorption and petroleum distillates, pneumonitis
|
|
|
cathartics
|
promotes rapid movement and elim of poison thru GI tract, sorbitol, magnesium citrate, magnesium sulfate
|
|
|
dosing for charcoal
|
for max effect admin within 30 min of ingesting poison,: adult dose 1g/kg po: ped dose 1g/kg po
CI doc hypersensistivity, poisoning or overdosage of mineral acids and alkalis asp risk, consider nG tube and endotracheal intubation |
|
|
Act Charcoal indicatinos:
|
emergency tx in poisoning caused by certain ingested drugs and chemicals
|
|
|
act charcoal moa:
|
network of pores present in act charcoal adsorbs 100-1000-mg of drug per g of charc doesn't dissolve in water
|
|
|
Interactions with act charcoal
|
may inactivate ipecac syrup if used concomitantly: effectiveness of other meds decreases with co admin, dont mix with shertbet, milk, or ice cream, dec absorptive properties
|
|
|
charcoal precautions
|
not very effective in poisoning of ethanol, methanol, and iron salts: can admin in early stages of gastric lavage, without sorbitol, gastric lavage returns are black, protect airway in pts with depressed level of consciouness, if using multiple doses of charcoal, monitor for pres of bowel sounds to minimize risk charoal ileus and vomit with subsequent pulm asp
|
|
|
Other toxicant removal methods
|
diuresis adn alteration of urinary pH-enhances renal excretion of toxicant, water dilution for tx skin or eye esp, demulcents soothes mucous membranes and coats the stomach, hemodialysis drugs or toxins diffuse across a semi permeable membrane and become trapped in dialysate
|
|
|
organophosphates (acetylcholinesterase inhibitors)
|
pralidoxime is a nucleophilic reagent that covalently binds ot organophosophates and permits rapid excretion
|
|
|
pralidoxime
|
used to tx poisoning by insecticides, tabun, sarin, soman, vx, GF-usually admined with atropine to block muscarinic effects of pns nervous system
|
|
|
cyanide
|
binds to and deact cytochrome c oxidase, final transport of electrons from aa to O2 can not be completed, as result e transfport chain is disrupted and cell can't produce atp for energy, CNS And CARDIAC tissue particularly affected
|
|
|
cyanide LD50 and tx
|
LD50=2mg/kg prod death in 1-15 mins
admin amyl nitrite, sodium nitrite and sodium thiosulfate with O2 and whole blood to convert hb to methb, this combines with cn to form non toxic cyanmethb and thiocyanate LD 50 inc 5 fold |
|
|
Toxins
|
botulinum toxin ald<.5ug, LD5010ng/kg, most potent poison known, rapidly absorbed and prevents ach release from nerve terminals most common: resp depression
Tx: ABCs, lavage, emesis, charcoal, trivalent anti toxin, equine derived abs, mortality of 70% reduced to 10% with tx |
|
|
Heavy metals
|
chelators: BAL, EDTA, DMSA, DMPS, cal EDTA deferoxamine complex with Hg, Pb, As, Fe and or Ag making them inert aned inc renal excretion
BAL: british antilewisite, dimercaprol) |
|
|
DMSA Succimer (chemet)
|
indic: tx of arsenic, mercury, lead poisoning
adrs: chills fever diarrhea loss appetite N/V skin rash, will cause urine, sweat and feces to have unpleasant odor Dosage: PO z8h for 5 days adults and children>12 for kidsPO q8hfor 5 days same dose then q12 h for next 14 days for total of 19 days therapy |
|
|
Trivalent Antitoxin for Botulism A,B and E
|
botulinum antitoxin-equine is available from CDC via state and local health dept
indic: licensed trivalent antitoxin contains neutralizing abs x A,B and E, the most common causes of human botulism, heptavalent, soon to be avail |
|
|
Doses for Antitoxin
|
single 10ml vial per pt, diluted 1:10 in .9% saline soln, admin by slow IV infuse
one vial provides bw 5500 and 8500 IU of each type spec antitoxin, the amt of neutralizing ab in licensed antitoxin far exceeds highest serum toxin levels found in food borne botulism pts and additional doses are usualy not required |
|
|
CN antidote
|
kit-has 1)small inhaled dose amyl nitrite, 2) IV sodium nitrite moa:oxidize protion of hb iron from ferrous to ferric state converting hb to methb, cn pref binds to methb adr:methbinemia, hypotension, 3)sodium thosulfate admin IV racts with cyanmethb to give thocyanate and sulfite and hb, then renally excreted
|
|
|
alcohol antidote
|
ethylene glycol/metghanol/isopropyl alc
methanol converted into formaldehyde and formic acid by alc dehydrogenase, ethanol admin competitiively prevents alc dehydrogenase from converting these subs into toxic forms, hemodialysis as adjunct can be lifesaving for methanol and ethylene glycol poisoning |
|
|
ethylene glycol/methanol toxicity
|
met of ethylene glycol by alc dehydrogease prod four toxic metabolites: glycoadlehyde, glycolate, glycolic acid and clyocxylate-prod abnormalities, met acidosis, anion gap, lactic acidemia,hypocalcemia
-oxalic acid combines with ca to form ca oxalate crystals-dep kidneys, hematuria, proteinuria, inc creatinine and renal fail |
|
|
antitodal therapy for ethylene glycol/meth toxicity
|
ethanol comp inhibits alc dehydrogenase
fomepizole also blocks alc dehydrogenase, has few SEs and considered drug of choice for antidotal therapy for ehtylene glycol or methanol toxicity -hemodialysys should be considered in pts who are symptomatic |
|
|
CO intox therapy
|
colorless, odorless, tasteless gas
found prim cig smoke, auto exhaust and industrial emissiosns-early sxms drowsniness and HA-uncons, resp fail CO has 210x greater affinity for hb than does O2, carboxyhb TX: artificial resp with pure O2 to promote displace CO hyper baric O2 chamber if sxmtomatic |
|
|
40-60% coHB
|
severe HA, weakness, dizziness, confusions, dimness of vision, some have cherry red appearance
|
|
|
alcohol antidote
|
ethylene glycol/metghanol/isopropyl alc
methanol converted into formaldehyde and formic acid by alc dehydrogenase, ethanol admin competitiively prevents alc dehydrogenase from converting these subs into toxic forms, hemodialysis as adjunct can be lifesaving for methanol and ethylene glycol poisoning |
|
|
Rec competitior therapy
|
warfarin, coumadin, others:
-aticoag that interferes with syn of vit K dep coag factors 2,7,9,10 -ADR include hemoptysis, excessve brusing, bleeding from nose or gums or blood in urine or stool -Frank bleed or high INR requres reversal by injection of vit K A(phytonadione) or in case of severe bleed: prothrombin complex or fresh frozen plasma infusion to replace coag proteines |
|
|
Comp rec antagonistis
|
naloxone: acts at u,k,d rec to comp block/reverse effects of opiates, duration of axn is 45 mins
-naltrexone acts ukd rec to comp block/reverse effects opiates, longer duration of axn, 24-72 hours than naloxone |
|
|
ethylene glycol/methanol toxicity
|
met of ethylene glycol by alc dehydrogease prod four toxic metabolites: glycoadlehyde, glycolate, glycolic acid and clyocxylate-prod abnormalities, met acidosis, anion gap, lactic acidemia,hypocalcemia
-oxalic acid combines with ca to form ca oxalate crystals-dep kidneys, hematuria, proteinuria, inc creatinine and renal fail |
|
|
antitodal therapy for ethylene glycol/meth toxicity
|
ethanol comp inhibits alc dehydrogenase
fomepizole also blocks alc dehydrogenase, has few SEs and considered drug of choice for antidotal therapy for ehtylene glycol or methanol toxicity -hemodialysys should be considered in pts who are symptomatic |
|
|
Metheylene blue chem reducer
|
methbemia-state where heme FE in ferric and not ferrous state-methb unab le to transport O2, cuase by exp to various chemicals, nitrites, sulfa drugs, many others(hypersnsitivity can cause)
cyanosis at 10-15% methb -methylene blue moa: causes direct chem reduction of methb back to hb, toxicity can prod 2x inc central 5ht, use greaet care wtih pts using ssri, tca, maoi, to avoid serotonin syndrome |
|
|
Toxidromes
|
common and often well characterized clinical syndromes that provide symptomatic fingerprint allow for sucessful recognition of patterns of poisoning assoc with spec intoxicants
|
|
|
CO intox therapy
|
colorless, odorless, tasteless gas
found prim cig smoke, auto exhaust and industrial emissiosns-early sxms drowsniness and HA-uncons, resp fail CO has 210x greater affinity for hb than does O2, carboxyhb TX: artificial resp with pure O2 to promote displace CO hyper baric O2 chamber if sxmtomatic |
|
|
Sympathomimetic toxidrome
|
CNS: agitation, halluc, paranoisa
Resp:-- Pupils-mydriasis*dilation |
|
|
40-60% coHB
|
severe HA, weakness, dizziness, confusions, dimness of vision, some have cherry red appearance
|
|
|
Rec competitior therapy
|
warfarin, coumadin, others:
-aticoag that interferes with syn of vit K dep coag factors 2,7,9,10 -ADR include hemoptysis, excessve brusing, bleeding from nose or gums or blood in urine or stool -Frank bleed or high INR requres reversal by injection of vit K A(phytonadione) or in case of severe bleed: prothrombin complex or fresh frozen plasma infusion to replace coag proteines |
|
|
Comp rec antagonistis
|
naloxone: acts at u,k,d rec to comp block/reverse effects of opiates, duration of axn is 45 mins
-naltrexone acts ukd rec to comp block/reverse effects opiates, longer duration of axn, 24-72 hours than naloxone |
|
|
Metheylene blue chem reducer
|
methbemia-state where heme FE in ferric and not ferrous state-methb unab le to transport O2, cuase by exp to various chemicals, nitrites, sulfa drugs, many others(hypersnsitivity can cause)
cyanosis at 10-15% methb -methylene blue moa: causes direct chem reduction of methb back to hb, toxicity can prod 2x inc central 5ht, use greaet care wtih pts using ssri, tca, maoi, to avoid serotonin syndrome |
|
|
Toxidromes
|
common and often well characterized clinical syndromes that provide symptomatic fingerprint allow for sucessful recognition of patterns of poisoning assoc with spec intoxicants
|
|
|
Sympathomimetic toxidrome
|
CNS: agitation, halluc, paranoisa
Resp:-- Pupils-mydriasis*dilation other: sizure, hpertension, tremer, hyper reflexia, hyperthermia drugs: cocaine, amphetamines, PCP |
|
|
Sed/hypnotic toxidrome
|
CNS: coma
Resp: dec Pupils: miosis or mydriasis other: hypothermia, dec reflexes, hypotension Drugs: alc, barbs, benzodiazepines |
|
|
Opiod/opiate toxidrome
|
CNS: coma (dec conscious ness)
ResP: Depression Pupils: pinpoint (miosis) Other: hypothermia, hypotension, opiate triad (dep resp, dec cons) histamine release Drugs: opiates, morphine, codeine, propoxyphene, oxycodone, hydrocodone |
|
|
Anticholinergic toxidrome
|
CNS: agitation
resp:-- pupils: mydriasis other: fever dry skin, flushing, urinary retention, hot dry, red blind Drugs: anticholinergics/antideprssants |
|
|
cholinergic toxidrome
|
CNS: coma not quaternary
resp-- pupils: PPP other: fasiculation, incontinence, salivation, wheezing, lacrimation, bradycardia, SLUDE drugs: organophosphates/carbamates and othe rinsecticides, nicotine |
|
|
Tricyclic antidep toxidrome
|
cns: coma, agitation
resp: --- pupils: mydriasis other: dysrhythmia, convulsions, hypotension, due to alpha block, myoclonus, hyperthermia Drugs: tca's, amitriptyline, imipramine, desipramine |
|
|
Sed/hypnotic toxidrome
|
CNS: coma
Resp: dec Pupils: miosis or mydriasis other: hypothermia, dec reflexes, hypotension Drugs: alc, barbs, benzodiazepines |
|
|
Opiod/opiate toxidrome
|
CNS: coma (dec conscious ness)
ResP: Depression Pupils: pinpoint (miosis) Other: hypothermia, hypotension, opiate triad (dep resp, dec cons) histamine release Drugs: opiates, morphine, codeine, propoxyphene, oxycodone, hydrocodone |
|
|
Anticholinergic toxidrome
|
CNS: agitation
resp:-- pupils: mydriasis other: fever dry skin, flushing, urinary retention, hot dry, red blind Drugs: anticholinergics/antideprssants |
|
|
cholinergic toxidrome
|
CNS: coma not quaternary
resp-- pupils: PPP other: fasiculation, incontinence, salivation, wheezing, lacrimation, bradycardia, SLUDE drugs: organophosphates/carbamates and othe rinsecticides, nicotine |
|
|
Tricyclic antidep toxidrome
|
cns: coma, agitation
resp: --- pupils: mydriasis other: dysrhythmia, convulsions, hypotension, due to alpha block, myoclonus, hyperthermia Drugs: tca's, amitriptyline, imipramine, desipramine |
|
|
Sed/hypnotic toxidrome
|
CNS: coma
Resp: dec Pupils: miosis or mydriasis other: hypothermia, dec reflexes, hypotension Drugs: alc, barbs, benzodiazepines |
|
|
Opiod/opiate toxidrome
|
CNS: coma (dec conscious ness)
ResP: Depression Pupils: pinpoint (miosis) Other: hypothermia, hypotension, opiate triad (dep resp, dec cons) histamine release Drugs: opiates, morphine, codeine, propoxyphene, oxycodone, hydrocodone |
|
|
Anticholinergic toxidrome
|
CNS: agitation
resp:-- pupils: mydriasis other: fever dry skin, flushing, urinary retention, hot dry, red blind Drugs: anticholinergics/antideprssants |
|
|
cholinergic toxidrome
|
CNS: coma not quaternary
resp-- pupils: PPP other: fasiculation, incontinence, salivation, wheezing, lacrimation, bradycardia, SLUDE drugs: organophosphates/carbamates and othe rinsecticides, nicotine |
|
|
Tricyclic antidep toxidrome
|
cns: coma, agitation
resp: --- pupils: mydriasis other: dysrhythmia, convulsions, hypotension, due to alpha block, myoclonus, hyperthermia Drugs: tca's, amitriptyline, imipramine, desipramine |
|
|
salicylate toxidrome
|
cns: variable up or down
resp: can inc or normal pupils-- other: diaphoresis, tinnitus, agitation, alkalosis early, acidosis, late, hyperpyrexia Drugs: ASA, aspirin, other salicylates |
|
|
Freq encount opiate toxins
|
codeine, heroin, hydrocodone, morphine, oxycodone: bilateral miosis PPP, cns depression, apnea, dec body temp, HR and resp dep/arrest
tx: abc's, naloxone, gastric lavage, and supportive care |
|
|
Meperidine toxicant
|
demerol:signs: dilated pupils due to antimuscarinic effects, inc HR, convulvions due to metabolite, resp dep,/arrest coma, tx: abcs, gastric lavage, diazepam for seizures and naloxone for dep effects
|
|
|
benzodiazepines toxicant
|
diazepam, alprazolam, tiazolam signs: rarely fatal unless taken with ethanol or other cns depressant due to synergistic cns depression, tx abs, emesis, gastric lavage, receptor antagonist: flumazenil***
|
|
|
ethanol toxicant
|
alchohol, odor, impaired motor coord, slurred speech, dehyd, gastritis, hypothermia, coma and death due to resp dep, tx abs, gastric lavage with bicarb, caffeine, hemodialysis
|
|
|
acetaminophen
|
tylenol: after depletion of glutahione, NV, elevated SGOT, SGPT, bilirubin, hep necrosis, death due to hepatic fail
tx: abcs, emetics, gastric lavage, charcoal, LFT, nacetylcysteine to restore gluthione |
|
|
cocaine
|
coca plant, cocaine crack signs: cns stim, euphoria, halo lights, seizures, hallucinations, CARDIAC DYSRYTHMIA leadign to cardiac arrest
tx: abs, charcoal, dizepam seizures, LIDOCAINe dysrthmia, no dialysis or lavage reccomended |
|
|
soaps
|
metallic salts of fa's and alkaline in nature
|
|
|
detergents
|
agents taht purify or clean by reducing surface tension-so dirt and debris more easily washed away
|
|
|
soaps derived three sources
|
animal fat: rendering lard, very drying to skin harsh
vegetable oil base: potassium sopas of saponified veg oils super fatted soap: less drying but also less effective in cleansing |
|
|
Detergent soaps:
|
anionic wetting agetns: saops and saop substitutes:only mildly defatting (drying) prod less skin irritation, hav ea very mild bacteriostatic effect
agents: sodium lauryl sulfate (duponol C) *** lauryl sulfoacetate (lowila)** |
|
|
Cationic wetting agents properties
|
quaternary ammonium cmpds
properties: detergent effect removes dirt, bacterial and dead cells, denatures lipoproteins in cell wall/memb-det effect disrupts mem, good emulsifiers, keratolytic action (breaks down skin) antimicrobial against gram +and some gram neg microbes but not spores |
|
|
cationic wetting agents:
|
benzalkonium chloride (zephiran, cetylcide, bactine, mercurochrome II)
BENZALKONIUM CHLORIDE and methylbenzethonium chloride |
|
|
benzalkonium chloride
|
USE: preop cleaning of normal skin (tinctures 1:250-1:1000)
cleaning of broken/injured skin, sterilization of instruments, preparation creams dusting powders, aquieous or alcholic solutions key point: cationic agetns are inactivated by anionic cmpds, all traces of anionic agetns like soap should be removed with alcohol to maxiumize use of cat agents |
|
|
antiseptic
|
an agent that kills or prevents the growth of microbes when applied to living tissue
|
|
|
properites of ideal antiseptic
|
lethal to microbes, clinically useful only if broad spec, low surface tension, ability to retain potency in pres of body fluids, exudates, and infection, rapid and sustained action, safe therapeutic index, low potential for sensitization of skin
|
|
|
disinfectant
|
agent that prevents infection by destruction of pathogenic microbes on NON LIVING SURFACES
|
|
|
properties of ideal disinfectant
|
high efficacy as germicide, wide spec, rapid-dont want to have equip out o fservice too long, lethal in pres of organic matter (blood excudates) compatible with soaps and other subst likely to be used, chemically stable, should have good shelf life, safe for use with instruments and other equip, good aesthetic qualiites such as color, odor staining potential, cost
|
|
|
alcohols
|
effective at dec surface tension, damaages proteins in bact walls, surfactant effect makes them usefful for inc effectiveness of other agents**
Ethyl alchohol and isopropyle alchohol |
|
|
ethyl alcohol
|
props:rel low potency: .6 min for 70% ehOH to kill only 50% bact, conc imp recommend 40-70%, over 70 can lead to spore form. effective against most pathogens, combined with other agents to inc effectiveness
Uses: common agent for skin prep/cleaning or as antiseptic before venipuncture |
|
|
isopropyl alcohol
|
slightly more effective than EtOH, effective at conc >70% not effective against spore form microbes, disadvantage: causes more local vasodilation beneath skin after needle puncture
Use: skin prep, disinfect equip, ingred in solns to sertilize rubber goods or suture material |
|
|
iodine
|
one of most potent and useful germicides, broad spec, axn: oxidize microbial protoplasm
disadvantage: iritating, stains clothing adn skin, effectiveness dec by org matter, rare hypersensitivity, sensitizes skin, rel insol in water use: antiseptic sup to all others, treat wounds and abrasions, disinfect drinking water, avoid use conc >2% ON SKIN |
|
|
Iodophors
|
prop: loose complex of I with carrier to inc sol of I, complex provides sustained release reservoir of iodine, less effective than I alone, less iritating and sensitziing to skin, rel non staining
agents: povidone-iodine**(betadine, isodine, poviderm) poloxamer-iodine) |
|
|
povidone-iodine
|
use: skin prep of pt and surgeon, widespread use as antiseptic on skin, membraines, aqueous or alcohol solns
|
|
|
iodochlorhydroyquin
|
iodochrlohydroxyqin USP prop contains 40% iodine, multiple preparations ointments powders, lotions and uses: spec in tx of coccogenic infections of skin, gen skin infect, wounds ulcers burnes
|
|
|
sodium hypochlorite
|
clorpactin, javex,
prop: irritating, action due to liberation of free Cl use: clean blood soaked clothing or instruments, dissolves clots or delay clotting |
|
|
silver cmpds properties
|
silver salts hav eastringent and caustic action, act on bact cell surfact to drastically alter wall +membrane, highly effective, rapid, sustained action
|
|
|
silver nitrate
|
spec-strongly active against staph and gram neg, topical solutions .01-10%
|
|
|
silver sulfadizine (silvadene)
|
action: reacts with nacl on contact with skin to release sulfadieazene(sulfonamide action) use: burn treatment
|
|
|
thimerosal (organic mercurial)
|
prop: 49% mercury, antiseptic for surgical prep of skin, mucous membranes and open wounds, use: solns for rinsing, sotrage and cold steriliztion of contact lenses, preservative for biologicals (caution) do not bandage a mercury cmpd!
nitomersol-other agent |
|
|
peroxides
|
action-release o2 from hydrogen peroxide on contact with blood or tissue fluid, mechanical fizzing release of o2 via catalase which has germicidal action
|
|
|
hydogren peroxide
|
OTC:3% soln
unstable, effective only while gas is released, fizzing, cuation: gas needs to escape, avoid abscesses or bandage, effectiveness dec by organiz debris, questionable use for intact skin |
|
|
benzoyl peroxide
|
clearasil, slow release o2, bactericidal esp to anaerobic flora, acne tx
|
|
|
carbamide peroxide
|
use in removal of ear wax
|
|
|
permanganates
|
potassium permanganate: limited topical use, slow action, oxidized by many other drugs, use: wet dressing in tx of poison ivy or suppress vesicular states of various dermatits conditions
|
|
|
phenol cmpds
|
phenol: bacteriostatic, axn: denatures protein, antisept/disinfectant, antipruritic, local anesthetic effect, keratolytic, prob: systemic toxicity CNS Depression, damages liver
caution: phenols assoc with hepatic dz in neonates, not used or with caution in ped setting |
|
|
hexachlorophene
|
prop: widely used as topical antiseptic and hand cleaner, effectiveness requires repeated daily application, not recommended for single application, effective use requires residual amts to be absorbed-bacteriostatic, axn most effective against gram positive!-a substituted phenol
|
|
|
hexachlorophene use
|
pre op hand and skin scrubbbing surgeon and pt, many forms, cake soap, liquid soap, lotion detergent, doubtful effectiveness as prohylactic scrub for skin infections, effectiveness dec by cleansing with other agents
other agent: tricosan |
|
|
chlorhexidine gluconate
|
prop:versatile broad spec agent used for cleaning of surgical sites, srugeons hands, desirable features: borad spec, residual action, rapid, low sensitization, one of popular and primary scrubs and cleaning agents
|
|
|
chelating agnets: EDTA, EGTA
|
use potentiate act of many antibacterials against gram neg but no gram pos org
|
|
|
emollients
|
fats or oils used for their local axn on skin to lubricarte, soften adn protect skin (trap moisture)
eveg oils: olive, cottonseed, corn, almond and peanut oils, animal fats-anhydrous lanolin, USP wool fat |
|
|
lanolin
|
hydrous wool fat alpha keri, caution : allergy -emollient
|
|
|
hydrocarbons
|
petroleum jelly and mineral oil
waxes: paraffin aquafor, eucerin |
|
|
astringents:
|
agnets applied to skin to prod local and limited prot coag effect, coating serves to protect underlying tissue and create a barrier
axns: cause skin dehydratoin, tightening of skin, shrinking of tissues, contraction of skin pores use: tx of hyperhidrosis (excessive sweating), aluminum chlorhydride, aid in wound healing, reduce weeping from wounds |
|
|
acetic acid
|
astringent home recipe: 1/4 vinegar/pt h20
|
|
|
keratolytic info
|
prod damage to cornified layer of skin adn cause it to separate or slough off, remove keratin
use: enhance emollient effects of a cream, reduce pore occulsion as with acne, remove excess keratin |
|
|
keratolytic agents
|
podophyllum resin, resorcinol, **SALICYLIC ACID, axn: solubilizes cell surface proteins that keep stratum corneum intact, resutling in desquamation, conc effects, adr: systemic salicylate toxicity due to percut absorp
|
|
|
other keratolytic agents:
|
anthralin adr: violet brown stain skin adn clothing, skin sensitive, silver nitrate, sulfur, dichloractetic acid, trichloracetic acid, propylene glycol, urea, cantharidin
|
|
|
Keratolytic agents caustic and escharotic
|
higher does of drugs: caustics and escharotics:
caustic: corrosive-topical agent that cuases destruction of tissues at site of application escharotic (cauterizant)=casutic which precipiates cell protein-inflamm excudate forms scab (eschar) that is later org into a scar---glacial acetic acid, podophyllum, phenol, tichloracitei acid, salicylate |
|
|
keratoplastic
|
stimulate the epidermis but dont prod rapid destruction adn desquamation, agents traumatize the skin to stim basal layer
|
|
|
keratoplastic agents actual
|
COAL TAR**: usually combined with UVB to improve effectiveness of UVB tx, mode of axn unkown, phototoix in UVA range, formualations: solns, gels, shampoos, baths, creams, ADR: follicultis, irritation, allegy, carcinogenic in animals
|
|
|
other keratoplastic agents
|
juniper tar, salicylic acid
reducing agetns: sulfur, chrysarobin, anthralin |
|
|
protectives and absorbents
|
genearlly inert and insol, used to cover and protect normal skin, ulcers or wounds, act by reducing friction, absorbing moisture and discouraging microbes
|
|
|
protectants:
|
agents used to promote occlusive protection from environment and give mechanical support
|
|
|
absorbents:
|
agents that absorb moisture or reduce friction
|
|
|
dusting powders
|
*starch, talc never in open wounds, ca carbonate, zinc and mg stearate
|
|
|
mechanical protectives
|
collodion, zc gelatin, dimethicone
|
|
|
irritants
|
agents that act locally on skin to prod inflammation or inc blood flow (reactive hyperemia) which then contributes to feeling of comfort and warmth
|
|
|
rubefacients
|
heat, camphor
|
|
|
vesicants
|
little therapeutic use: cantharidin
|
|
|
pustulants
|
very little therapeutic use
|
|
|
counterirritants
|
applied topically which help relieve pain in viscera, muscles and joints
agents: methyl salicylate*** camphor, mustard plaster, menthol, capsicum, eucaluptus oil, triethanolamine saliclate, salicylamide, glycol salicylate |
|
|
wound cleaning agents non enzymatic
|
DEXTRANOMER: forms inert matrix that acts lik ea sponge to pull small size particles into slurry, use: nonezymeatic clean of wounds, slurry forms soothing covering of irritated tiessue, limits: slurry must be periodically reapplied due to limited ability to hold particles
|
|
|
common antirpuritic agents
|
antihistamines and local anesthetics:
benzocaine, dibucaine, dyclonine, capsaician, ehtyl chloride, phenazopyridine, pramoxine HCL |
|
|
antipruritic agents misc
|
camphor, mehtnol, phenol, calamine
|
|
|
older pts
|
13% pop but 33% rx drugs
spend 25-30% of total money on drugs 1 in 3 take >3 meds 43% emerg dept admits 48% cit care admits |
|
|
drug rxns in OA's mimi stereotypical expectation of being OLD
|
unstreadiness, dizziness, confusion, drowsiness, falls, depression, incontinence, fatigue, insomnia
|
|
|
Older body
|
houses smaller engine, aging dec lean mass, fewer cells per nunit of body wt, drug doses calc on presumption of X number of cells per unit body wt, conseq: more drug per cell more adrs, more toxicity, more overdose
|
|
|
altered Gi absorption OA
|
inc gastric pH, dec H,achlorhydric, dec absorptive surface, dc splancnic blood flow, dec GI motility, delayed gastric empty
Rate of absorption typic slower delay drug resp, no change passive diff/bioavail, most drugs, dec active transport/bioavail for some, dec first pass effect, inc bioavil for some |
|
|
aging reduces stomach acid
|
rediced bioavil of some tablets/capsules, absorption of some drugs requres acid media ie aspirin, altered rate of stomach empty, reduced drug absorption
|
|
|
Aging reduces GI motility
|
less mixing of contents, less exp drug to int wall for absorb, net effect=delayed absorp, irritating drugs do more damage (ulcerogenic) eg nsaids
|
|
|
aging dec proteins in blood stream
|
role of prot: bind and serve as astore for drug, prevent drug from being metabolized, conc of prot plasma dec 15-15% so failty and concurrent ds will dec albumen-binds acid drugs, no change or inc alpha 1 acid glycoprot binds basic drugs-->consequ:more free drug active adn overdose activity inc: digitalis, asp, warfarin, anticonvulsants, diazepam, concer: illness and poor nutrition worsen problem
|
|
|
aging change dec body water
|
hydrophilic drugs dec Vd like ethanol and lithium
|
|
|
aging change dec lean body mass
|
drugs binding muscle dec Vd like digoxin
|
|
|
aging change inc fat stores
|
lipophilic drugs inc Vd diazepam and trazodone
|
|
|
aging change dec plasma proteins
|
inc per cent unbound drug, dizepam, valproic acid, phenytoin, warfarin
|
|
|
aging change inc plasma proteins alpha 1 acid glycoprotein
|
dec per cent unbound drug like quinidine,propranolol, erythromycin, amitriptyline
|
|
|
liver changes OAs
|
liver primary organ for drug bkdn metabolism agiang dec: numbe rliver cells, blood flow to liver (red first pass) enzymes to break down drug-->better to use phase II glucuronidation conjug or acetylation path drugs where converted to inactive metabolism like lorazepam, oazepam or temazepam bc easier on old liver
|
|
|
summary liver changes
|
begin age 30: 1% decline/yr in liver blood flow plus liver mass: dec metabolic clearance of drugs by liver
causing: dec hepatic first pass met and dec due to dec liver size/mass ie morphine, meperidine, metoprolol, propranolol, verapamil, amitriptyline, nortiptyline conseq: inc drug half life, inc blood conc: inc ADR/toxciity, prolonged resp, ie beta blocks, narcotics, nitrates, antidepressants, acetaminophen |
|
|
other pot factors affect drug met in geriatric pt
|
gender, coexist conditions, smoking, diet drug interactions, race, frailty
|
|
|
elimination OA
total clearnance=clrenal+clhepatic++clother; age changes: |
dec GFR, RBF, dec renal mass (size and number nephrons), dec tubular secretion, dec resp fct, dec liver fct, dec elimination=drug accum and toxicity
|
|
|
aging alters renal clearance
|
creatinine cl=est GFR, measures of creat serum not accurate in older adult, dec loss lean body mass+dec GFR= so dec creatinine production , serum creatinine looks normal masking change in CrCl
need to compensate for age effects on renal cl CrClmale=140-age)x(total BWin kg)/(72xserum creat in mg/dl) famales=.85xresult for male |
|
|
drugs with reduced renal clearnance:
|
atenolol, gabapentin, h2 blockers, digoxin, allopurinol, quinolones
|
|
|
pharmacodynamics (time course+intensity of effect) not as much known as should be for OA
changes in drug receptors: |
change in rec density or affinity, altered 2nd messenger (camp, cGMP, etc)
examples age changes: inc sensitivity to sedation/psychomotor impairment (benzos), inc etent /duration pain relief (narcotics), inc drowsiness/sway (alcohol), dec HR resp to beta blockers, inc sensitivity to anticholinergic agents, inc cardiac sensitivity (digoxin) |
|
|
adverse drug rxns or events:
|
drug interaction that results in undesirbale or unexpected event requiring change in pt mgmt
relate to number drugs taken/prescribed, 95% adrs in OAs predictable, 50% adrs in OAs preventable, over 10000 deaths from hosp admit adrs 85 bill dollars |
|
|
most common medications resulting in adrs oas:
|
opiod analgesics, NSAIDS, anticholinergics, benzodiazepines, other : CV agents, CNS agents, Musculoskeletal agents
|
|
|
adrs result of
|
drug drug interactions (cv and psych =confusion, drug dz interactions (constip-narcotics, anticholinergics), drug food interactions grapefruit, drug SE, drug toxciity
|
|
|
Beer's list
|
list of drugs iwth highest potential for ADRS, consult list when prescribe for OA's
|
|
|
Beer's list high adr potential
|
amitriptyline, chlorpropamide, digoxin, antispasmodics, meperidine, methyldopa, pentazocine, ticlopidine
less severe: antihistamines, diphenhudramine, dipyridamole, indomethacin, muscle relaxants |
|
|
risk factors for adrs
|
polypharmacy, multiple path, prior adr, low bw or bmi, 85 yrs, estimated crcl<50ml/min
|
|
|
med compliance
|
presume 50% non compliance in OA's, results in dec drug effectiveness, in adr, major cause iatrogenesis, oa's avg 5-8 meds
|
|
|
intentional noncompliance
|
stoic personality, high cost drugs, denial, dissatifsaction with doc or pharmacist, exp with sE's
|
|
|
unintentional noncompliance
|
complex drug regimens, lack understanding illness, drug regimen, or instructions
|
|
|
common factors contributing to noncompliance
|
inability to afford meds, inabiltiy to adhere to complicated regimen, cognitive, fctal or sensory impairment, lack knowledge or insight about purpose/imp , denial illness, unclear admin instructions, inappropriate dosage form, feel better without med, use of alchohol
|
|
|
gen prescribing principles for Oa's
|
1. avoid drugs ipossible, 2. use spec drug for spec dx, 3. min # drugs, 4. avoid tx SE drug a with drug B, 5. reg review of meds (every 3 mo) 6. avoid drugs with sim axn/same class, 7. good communication with pt/caretakers 8. wtach drug cost
|
|
|
overview nsaids OAs
|
freq use due to incidence arthritis=COX inhibiton-inhibition protective prostaglandins in gastric mucosa-ulceration stomach/int-dec pleately act-bleeding impaired-kidney damage with long term use, loss erythropoietin-anemia, PGE2 and PGI2-vasodilators inc renal blood flow, NSAIDs inhibit them so leads to low flow kidney/kidney fail
|
|
|
herbal med preps percentages used US
|
5-6 billion retail sales, 25% annual growth, only 10% >250000 plant species hav ebeen evaluated for therapeutic potential
|
|
|
pharmacognosy
|
study of natural product medicines mostly herbs
|
|
|
synergism
|
multiple ingredients work together to give better results
|
|
|
case against herbal meds
|
lack of fda regulation, dosage variability, adulteration potential-other subs present in them, potential toxicity: natural not always safe, more effective therapy may be delayed, many herbs not sup to what is already available, synergism of her drug interactions and potentiation or potency /efficacy reduction
|
|
|
patient education herbals
|
you may not know whats wrong with you, your regimen may not be correct, self med may delay more appropriate tx, self med may conflict with other prescribed meds, self tx may help a minor prob at expense of major one
|
|
|
other patient education potential danges with herbal therapy
|
natural, whil often good, not same as safe, plant toxins defensive chemicals include alkaloids, resins, glycosides, oxalates, herbs, like drugs have spec med indications, ci's, se's, and poss interactions with othe rherbs drugs, resp use necessary even if OTC, proper dosage more not better, too much may be toxic, self tx may delay seeking care, abuse potential, coca, marijuana, kava, peyote
|
|
|
herb drug inter that prolong bleed time
|
gingko, garlic, ginger, feverfew, avoid with coumadin stop before surgery!
|
|
|
ginseng
|
reduced INR and BP fluctuation
|
|
|
prolonged anesthesia effects
|
kava, st johns wort, valerian-stop 2 weeks before surgery
|
|
|
lower blood levels of various meds
|
st. johns wort
|
|
|
kava
|
liver toxicity
|
|
|
reg issues herbals
|
herbal products legally food/dietary supps outside of FDA reg, labels may state usage, effect, and safety info but curative/spec health claims not permitted, FDA must prove herbal producst unsafe to take it off market-in europe regulated like prescriptions
|
|
|
herbals claim
|
a usage(st johns wort can claim to enhance mood but must alos state that not eval by FDA, not intended to dx, tx, or cure or prevent any dz
|
|
|
website to direct pts
|
www.consumerlab.com
|
|
|
top 7 herbs
|
echinacea, ginkgo, saw palmetto, milk thistle, st johns wort, valerian, herbal antioxidants
|
|
|
echinacea
|
purple coneflower, immune stim for colds, flu, does short 2 week course, SEs: N, hypersnesistivity, HA, caution avoid in autoimmune states, immunosup drug use or preg, safe promisigng fo ruse during illness but disappointming results for cold prevention
|
|
|
saw palmetto
|
porstatie obstructive sxms, SE ND HA
take with meals avoid with other hormonal therapy, not indicated for other conditions, r/o prostate cancer first,alpha 1 rec antagoneists possibly better |
|
|
ginkgo biloba
|
cerebral insuff, dementia, chronic venous insuff, tinnitus
SE: hypersensitivity bleeding nausea, caution aspirin, avoid with anticoag-promising vasodilator |
|
|
st johns wort
|
mild to moderate depressoin, wound healing, mild analgesis/anesthetic for pain, se: photosens, n, dry mouth, restless ness, caution with SSRI, MAOb interactions serotonin syndrome, prego alc, absense of prof eval, multiple cytochrome p450 med drug interactions, effective for mild depression
|
|
|
kava
|
sedative and anxiety redcuer, SE: dec refelxes and judgement, kava dermatitis, caution hepatic fail, psych dependence avoid with alchohol or benzo levo dopa, effective with some abuse potential limit to 3 mo
|
|
|
valerian
|
sedation anxiety reduction
SE: hypersens, N, rare paradoxical rxn excitability, caution avoid with alchohol CNS depressants, avoid in liver dz unstudied in prego, popular but insuff evidence to recommend |
|
|
st johns wort induces:
|
CYP3A4 most abundant senzyme in cyto P system which in turn in reat elim many drugs, including: antiepileptics, antifungals, benzos, CCBs, fentanyl, hmgcoa reductase inhibitors, macrolide abs, nonsedating antihist, oral contraceptives and protease inhibitors, signif lower blood levels digoxin, indinavir, warfarin, cyclosporin, theophylline, ehtinyl estradiol/desogestrel OCPS
|
|
|
milk thistle
|
liver disorders, hepatotoxic ingetsions, ca? SE:loose stools, inc bile sol, caution prior hypersens, prego, promising fo rmushroom poisoing, may benefit mild cases liver dysfct not not conlucsive evidence acute and chronic viral hep
|
|
|
herbal antioxidants
|
green tea, grapeseen extract, turmeric, milk thistle, cabbage family, misc plant pigemtns: carotenoids, flavenoids
|
|
|
hawthorn
|
heart failure stage II, coronary vasodilator, SE: hypotension, fatigue, N, sweating, sedation, caution follow BP esp, if on antihypertensives, nitrates may also inc digoxin effect, avoidwith seds, should not be self prescribed
|
|
|
evening primrose
|
exzeme, mastalgia SE: HA N rash, tmpeoral lobe, epilepsy in schizos, caution avoid in seizure pats and schizos, aviod with phenothiazines, conflicting study results, controversial for hyperactivity
|
|
|
bearberry
|
urinary tract antiseptic/mild diurectic, arbutin, SE: greenish urine, Nausea, caustions: avoid in prego, avoid urine acidifiers, needs alkaline urine to work, promising but abs faster
|
|
|
black cohosh
|
phytoestrogen for menopause, suppresses LH, SE hypotension, nausea abortion, CI in prego, follow BP questionably effective in relieveing menopausal sxms-not sup to estrogen and needs further study of benefits and risks
|
|
|
phytoestrogens
|
3 groups naturally occurring plant sterols: isoflavones, genistein, daidzein, lignans and coumestans
favorable impact on lipids and cardiac risk but modest estrogen effect depresses LH, promensil and estroven probably provide minimal vasomotor sxms relief in menopause PRIMARY ACTIONS may be due to sertonergic actions****** |
|
|
aloe vera
|
fresh aloe gel for burns, superficial wounds, soothing, antiinflamm, antipruritic, antibact SE: rare dermatitis, stabilized gel in products less beneficial, avoid internal use: severe diarrhea, avoid injections-death, recomend fresh gel for ext use only
|
|
|
GI herbs
|
cascara sagrada -constipation, psyillium (metamucil)-IBS, constip, senna leaf-contip, peppermint oil-IBS, red respberyleaf-diarrhea
|
|
|
ginger
|
antiemetic, antispasmodic, carminatie, diabetes? dec insulin resp? SE: heartburn, caution: anticoag, prego controversial, safe in food amts, possibly unsafe in lage amts, beneficial fo rmotion sickness
|
|
|
chamomile
|
stomach disorders, antispasmodic, wound healing, SE: allergic rxns, conjunctivities, vomit, avoid use with anticoag, or prego avoid if very allergic to ragweed avoid near eyes, time honored antispasmodic home remedy but limited human data
|
|
|
garlic
|
lipid reduction , antibact, antifungal SE : dermatitis, odor nausea, caution : anticoag, ulcer/reflux prego, status: fresh garlic better for health, modest lipid benefit for some studies some BP dec adn possible plaque reduction
|
|
|
ginseng
|
tonic for dec stamina, fatigue, SE: elevated BP, nervousness, insomnia, estrogenic effect possible, caution: HTN, CV dz, diab, avoid in prego or with steroids, adulteration probs with caffeine, dec INR, useful for improved well being with caution
|
|
|
feverfew
|
migraine tx and prevention, stimulates serotonin release SE: hypersen, mouth ulcers, post feverfew syndrome, caution variable potency, avoid prego taper does, two clinical trials deomonstrate effecgiveness but better regimens for migraines exisit
|
|
|
pschoactive herbs
|
kava, marijuana, peyote, datura or jimson weed, morning glory, opium poppy
|
|
|
pharmacogenetics
|
study of genetic basis for variations in drug resp
|
|
|
pharmacogenomics
|
uses tools for surveying entire genome to assess multigenetic determinants of a drug resp
|
|
|
advantages of a pharm/genomic approach
|
elim trial and error dosing regimen, avoid adrs
2000000cases/yr in US, 100000 deaths/yr in US |
|
|
gene by environment phenotype
|
complex interplay bw environmental and genetic factors
|
|
|
monogenic
|
expression of single gene results in single phenotype
|
|
|
multigenic
|
networks of genes acting together ot create a single phenotype
|
|
|
recessive trait
|
phenotype exhibited when a non fctl allele occurs on btoh maternal and paternal chromosome
|
|
|
dominant trait
|
pehnotype exhibited whe a non fctl allele occurs on eithe rmaternal or paternal chromosome
|
|
|
co dominant trait
|
heterozygotes display an intermediate phenotype as compared to wild type and homozygotes
|
|
|
polymorphism
|
variation in the genetic code present at an allele freq of >eq 1%
|
|
|
single nucleotide polymophisms SNP
|
1 SNP every 300-1000 base pairs
|
|
|
insertions/deletions(indels)
|
less freq than SNPS
|
|
|
nonsynonymous/missense
|
bp change-amino acid substitution, may result in a change in protein structure, stability, substrate affinity, intro of a stop codon
|
|
|
synonymous/sense
|
basepair change-no aa subs, may result in dec transcript stability or alter splicing
|
|
|
SNPS in noncoding region of a gene can be in the :
|
promoter, intron, or regulatory region
|
|
|
variations in noncoding regions may result in alterations in:
|
transcription factor binding, enhancers, splicing, transcript stability
|
|
|
insertions:
|
addition of genetic material, framsshift leading to change in prot structure, alter promoter and result in an inc transcript quantity, gene duplication/multiplication, intro of stop codon
|
|
|
deletions:
|
loss of genetic material, loss of a gene, premature stop codon
|
|
|
cosmopolitan polymorphisms
|
polymorphism common across all ethinic groups
|
|
|
population polymorphisms
|
polymorphisms that differ between groups ethnic or race
|
|
|
phenotype to genotype
|
drug resp outliers are compared to normal responders to ID altered resp to drugs
|
|
|
pharmacogenetic trait:
|
measureable trait assoc with a drug-enzyme activity, drug levels in bodily fluids, drug metabolite in fluids, phsyio resp (bp), gene exp patterns
advantages: sum of all genes giving ris eto an effect disadvantages: non genetic influences giving rise to and unstable result |
|
|
genotype to phenotype
|
genome surveyed to determine if genomic variability results in phenotypic variability
|
|
|
genotyping
|
testing that reveals spec genetic seq of an allele, requres extraction of DNA from somatic cells, often blood or buccal cells, advantages: DNA very stable , testing only once
Disadvantages: dependent upon annealing of an oligonucleotide seq to DNA, may render false positives or false negatives |
|
|
candidate gene
|
known or partially known cell path involved in drug resp, ID polymorphisms which result in a resp (pt screen, data base), test polymorph in a fctl assay
disadvantage: wrong gene may be studied |
|
|
OCT1:
|
hepatic transporter that mediates the uptake of org cations, endogenous cmpds: dopamine, exogenous cmpds: metformin, toxins: 1methyl4phenyl1236tetrahydopyridine MPTP
|
|
|
genome wide approach
|
unbiaseed survey of genoma, compare DNA, RNA or protein of ID tx pts (pt with adr rxn vs normal responders)
disadvantage: ID of a variation that doesn't matter |
|
|
3 phenotype categories
|
1. pharmacokinetic, 2. recptor/target 3. indirect
|
|
|
pharmacokinetic:
|
polymorphism in a gene or genes that reg pharmacokinetics, enzymes or trnasporters, alter drug conc resulting in changes in therapeutic and adr
|
|
|
receptor/target:
|
polymorphism in a gene that codes for drug target, alters drug resp (impaired drug binding)
|
|
|
indirect phenotype category:
|
polymorphism in gene that doesn't interact with drug, not a direct target of drug or not involved with drugs disposition
|
|
|
CYP2D6
|
est taht 25% of all meds are metabilized by 2D6, poor metabolizers 7 variant allels IDed, fast metabolizers, gene duplication
|
|
|
CYP2C9
|
invovled in met of many drugs, well recognized for its role in warfarin met, est that 2-10% population are poo rmetabolizers, result: elevated warfarin levels resulting in bleeding complications: model for use of pharamcogenetics: highly prescribed drug, high rate of adr,current dx tool to monitor drug effects
|
|
|
CYP2C19
|
poor metabolizers primarily in chinese and japanese populations, proton pump inhibitors are inactivated by it
|
|
|
TYMS (thymidylate synthetase)
|
methotrexate (anticancer and immunosup agent) used to inhibit methionine and DNA syn, indel which results 3,28 bp repeats in the enhancer reigion of promoter for TYMS, result is increase in TYMS exp, a dec efficacy of the drug, poorer px
|
|
|
ERa
|
polymorphism in intron between 1st and 2nd exon of ERa gene, homozygotes for less common allele had a greater inc in HDL levels following hormone replacement therapy
|
|
|
APOE
|
lipoprotein found in chylomicrons, VLDL, IDL< and HDL, absense of certain alleles in apoE gene correlate with better therapeutic success for alzheimers dz therapy with tacrine
|
|
|
KCNE2 (pot channel subunit)
|
1.6% population are variants, ab therapy (clarith) can induce prolonged QT interval, result in deadly cardiac arrhythmia
|
|
|
major types of evidence
|
screens of tissue from multiple pts linking polymorphism to trait, preclinical fctl studies, clinical phenotype/genotype studies
|
|
|
acute lymphoblastic leukemia ALL
|
TPMT, 6MP dec
|
|
|
results of pharmacogenomic data can lead to:
|
ID of new drug targets, genomic spec development of new drugs, genotype spec dosing regimens
|
|
|
CYP 3A4
|
major metabolizing enzyme of codeine, therapeutic effect of codeine dpenedson CYP 2D6 metabolism to morphine
|
|
|
CYP 2D6
|
two nonfctl alleles=poor metabolizer, 7-10% whites, one or two fctl allels=rextensive metabolizer, gene duplication=ultrarapid metabolizer, 1-7% whites and 25% ethiopians
|
