Antifreeze tx
Alcohol IV
not after 4 hrs or if
after 30 min since ingestion of a corrosive metal
Hydrocarbon solvents ingested
Coma, stupor, delirium or convultions are present
Lavage
Double vision, paralysis
Botox
wrist drop
lead
RBC stippling
lead
anemia and irritable
lead
Keizer… ring around cornea
copper
jaundice
copper
lung cancer
Asbestos
cherry red blood
CO
almond smell
cyanide
SOB
O2 is tx for
cyanide
Do not use lavage
Bleaches
Strong acids
metabolized by CYP450 to free radicals
CCl4 chloroform Carbon tetrachloride
carcinogenic
cirrhosis of liver
Arsenic
CO mechanism
greater affinity for Hb than O2
impares ability of Hb to transport O2
Carboxyhemoglobin is CHERRY RED
isoniazid is example of
PhII before Ph1
Phase 1
Modification of mol thru OXIDATION Rxns
hydroxylation or demethylation (+OH, -CH3)
enzymes attack fx’l groups
can be excreted or to PhII
Phase II
Conjugation: adds Ionized, charged group to PhI to make it more water soluble
Drugs with toxic metabolites
diazepam - nordiazepam - oxazepam
acetaminophen - N -acetyl-benzo - quinone imine
codein – morphine
Cyt P450s
Ph1
microsomal and inducable
oxidation fx (form OH)
acts as HANDLE (OH) for Ph2
inducer is ethanol,
substrate tylenol, ethanol
2E1
Inducer is smoking and charcoal foods
substrate: tylenol, warfarin
1A2 cyp450
inducer” barbituates, St. John’s wort
substrate: tylenol, advil diazepam, lidocaine
All 2… enzymes + 3A4
which impairs codeine metabolism
condeine to morphine
2D6
which metabolizes and induces by alcohol
2E1
which metabolizes > 50% drugs and has high drug interactions?
3A4
Glucoronyl transferase is
only Ph2 inducible and microsomal
inhibitor: grapefruit juice
sub: tylenol, diazepam, lidocaine
3A4
Inhibitor: quinidine
sub: codeine, (oxycodone)
2D6
Phase 2 rxns:
conjugate (bind) a protein to a Ph1 drug with handle (OH, SH, NH2)
Most by glucoronidation and UGTs
End result:
lower lipid solubility, make polar and inactive, increase MW
fast elimination
conjugation of drug with handle with glucorinic acid
UGT (transferase) catalyzes the tranferring of glucoronic acid to substrate drug
Bilirubin and adrenal conticosteroids are conjugated like this
Rule of thumb: the smaller the Vd
The more effective the dialysis bc high plasma [ ], high binding to plasma proteins
Higher dose, bioavail, and half life predict
higher Css
Higher CL or higher Vd
Lower Css
High Vd
High [ ] in body and bound to peripheral tissues
Low Vd
High plasma [ ] and binding to plasma proteins
Warfarin
92% bound to plasma proteins, 8% free
add drug that displaces warfarin from proteint, increase free warfarine and increase effect
example of low Vd and high t1/2
warfarin
if increase binding to albumine
accumulates in plasma
Vd is
drug in body/drug in plasma
can make assumption ab drug in body by measuring plasma [ ]
decreased liver fx
increased bioavail of drug
2D6 enz metabolizes what?
condeine to morphine
tylenol and warfarin are metabolized by
1A2
tylenol and alcohol are metabolized by
2E1
Tylenol, DIAZEPAM, advil, lidocaine are met d by
all 2 and 3A4
tylenol DIAZEPAM and lidocain met d by
3A4
grapefruit juice
codeine is met d into morphine by
2D6