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Flashcards in Exam #1 Deck (129):
1

pharmacology

interaction of drugs (chemicals) with biological systems

2

pharmacotherapy

selection of right drug in right dose to interact with right target to produce desired therapeutic results (prevention, diagnosis, treatment, cure)

3

drug target

organ or system that is affected by a drug; drug either over-activates or under-activates the target to produce therapeutic result

4

If approved by the FDA, a drug has 1 of 4 therapeutic results...

prevention, diagnosis, treatment, cure

Note: dietary supplements (herbals and vitamins) are not approved drugs under FDA

5

dosing regimen - definition

prescription - incorporates both pharmacokinetics and pharmacodynamics

designed to ensure that the desired steady state drug level [Cpss (avg)] is maintained within the therapeutic window by balancing the rate of drug elimination with the prescribed rate of drug administration

6

dosing regimen - steps

Select Drug and Dose (based on Pharmacodynamics, Disease Targets, & Drug Regulation)

Select Route of Administration (based on Pharmacokinetics → Absorption & Distribution)

Select Dosage Frequency (interval) (based on Pharmacokinetics → Metabolism & Excretion)

Select Duration (based on Disease Pathophysiology)

7

prescription - elements of dosing regimen

Drug (hydrocodone 5 mg – Acetaminophen 500 mg (Vicodin®) - include formulation and spell out # dispensed (# 10 (ten) tablets)

Dose (1-2 tablets)

Route (by mouth - po)

Frequency (every 4-6 hours)

Duration (as needed for pain)

8

what is directly correlated to drug effect / response

plasma concentration of drug (Cp)

note: graphs of Cp vs. time determine drug pharmacokinetics

9

pharmacokinetics

concerned with effects of biological systems on drugs - based on absorption, distribution, and elimination (metabolism, excretion)

what body does to the drug

process of turning dose of drug (mg) into plasma conc. (Cp)

graphs of Cp vs. time determine drug pharmacokinetics

10

pharmacodynamics

relationship between drug conc. in target organ and mechanisms and magnitude of drug effect - based on receptor binding, signal transduction, and physiological effect

what drug does to body

includes concepts of drug potency (related to drug dose) and drug efficiency (related to max effect)

11

MEC (minimun effective concentration)

can be determined for the desired (therapeutic) and undesired (adverse) responses

12

Important concepts for single or first dose administration

onset of effect: time to reach MEC

duration of action: time above MEC

Therapeutic window (aka therapeutic index): difference in Cp b/t desired and adverse response MEC

13

Important concepts for multiple or maintenance dose administration

steady state: rate in = rate out

time to steady state: attainted in 4-5 1/2 lives when maintenance doses are administered at constant interval

steady state concentrations: average Cp after steady state is achieved

fluctuations in steady state Cp: related to # of 1/2 lives in the dosing interval (time b/t doses)

14

goal of pharmacotherapy when multiple doses are administered

to reach and maintain Cp at steady state within the therapeutic window to produce desired response with minimum toxicity

15

drugs doses - LD and MD

loading dose (LD): single dose designed to reach a specified plasma level (Cp)

maintenance doses (MD): multiple doses designed to maintain specified average plasma level at steady state (Cpss (avg))

16

absorption

movement of drug from site of administration to plasma compartment (systemic circulation)
- route of administration will effect rate (Tmax and Cp max) and extent of absorption (F - bioavailability)

17

what is used to estimate rate of absorption

time to peak (T max) and peak plasma conc. (Cp max)

18

bioavailability (F)

fraction of unchanged drug reaching the systemic circulation following administration by any route; extent of absorption of a drug from non-intravenous site of administration

Also, used to convert oral doses to intravenous doses and vice-versa

19

distribution

moment of drug from plasma compartment to site of action (target)

20

volume of distribution (Vd)

describes extent of movement of drug throughout various body compartments

used to convert a drug dose into a plasma conc. (Cp)
- aka dilution factor

LD (mg) = Cp (mg/L) x Vd (L)

21

elimination

removal of parent drug or drug activity from plasma compartment
- includes metabolism (liver) and excretion (kidney)

22

clearance (CL)

measure of ability of body to remove drug from plasma compartment
- related to the elimination rate constant [ke], which is related to the more clinically useful half-life [t1/2]
- used to determine interval between doses [τ] necessary to maintain the desired steady state plasma level [Cpss (avg)]

23

pharmacokinetics of elimination - half-life (t1/2) allows quick rule-of-thumb estimates of following:

time to reach steady state plasma drug levels following multiple doses (4-5 half-lives)

fluctuations in plasma levels between doses (proportional to number of half-lives in dosing interval)

time for elimination of drug from plasma (4-5 half-lives)

24

absorption - physiology

pharmacokinetic process involving the passage of drugs across membranes

25

factors influencing movment of drugs across membranes

Molecular size → can be affected by drug binding to plasma proteins

Lipid solubility → estimated by oil:water partition coefficient

Degree of ionization → affected by tissue pH, will influence lipid solubility (unionized move)

Concentration gradient → created at site of administration

26

factors that increase absorption

smaller molecular size

higher oil:water partition coefficient

higher % unionized (uncharged binds better with lipids)

27

PKA

pH of a solution in which the acidic form of a molecule is equal to the basic form of the molecule

28

factors that increase elimination

larger molecular size (phase I)

higher % ionized (charged binds better with water / not as well with lipids) (phase I)

lower oil:water partition coefficient (higher water solubility) (phase and II)

29

mechanisms for membrane passage of drugs

passive diffusion: driven by conc. gradient
- aqueous diffusion: smaller, hydrophilic molecules
- lipid diffusion: most common for majority of larger-sized drugs

carrier-mediated diffusion: transporters regulate passage of drugs (not as common)

endocytosis / exocytosis: (not as important for drug passage)
- vitamin B12 and iron (endocytosis), P-glycoproteins (exocytosis)

30

determining bioavailability (F)

determine by comparing area under the curve (AUC) (from Cp v. time) following 1 dose of drug by any route to the AUC obtained following single dose by IV route

F = AUC - route of interest / AUC - IV

31

bioavailability for different routes of administration

IV: F = 100%
Oral: F varies from 0-100%
Other routes (IM, SC, inhalation, sublingual, IN): F ~100%
- but, rate of absorption differs

32

oral route - factors effecting bioavailability (F)

survival of drug in GI environment (acidity, digestive enzymes)

ability of drug to cross GI membranes (lipid solubility, size (mol wt), % unionized)

efficacy of drug metabolism by gut wall or liver (first-pass effect)

Note: pt compliance is issue with this route

33

rate of absorption

Estimated value - time to obtain peak Cp plasma levels (units per time - mg/hr)

Influenced by drug formation (liquid v. enteric coated tablet v. sustained release)

Note: bioavailability is not affected (only rate, Tmax, to reach peak, Cpmax)

34

rate of absorption - compare different routes of administration

IV = inhalation > IM > SQ > oral

Note: this is for soluble formations; suspensions (insoluble formulations) are designed to slow rate of absorption

35

factors affecting drug absorption

Drug solubility in biological fluid (aqueous environment)
- drug formulation must have hydrophilicity to dissolve
- drug molecule itself must also be lipophilic to cross membranes and distribute to site of action

Rate of dissolution of solid (oral formulations) or suspended particles (parenteral formations)

Conc. of drug at site of administration (conc. gradient created)

Circulation at site of absorption (varies with disease and exercise)

Area of absorbing surface (stomach v. SI v. lungs)

36

bioequivalence - definition (formal)

FDA required manufacturers of generic drugs to prove formation is bioequivalent to brand name formation

Definition: rate (T max and Cpmax) and extent (F) that the active ingredient drug is absorbed and becomes available at the site of action is "similar" to the brand name product

Similar: drugs considered bio-equivalent if the 90% confidence interval of the mean AUC and mean Cpmax of the generic product is within 80-125% of brand product

37

bioequivalence - formula

Bio Equ = AUC po-gen / AUC po-brand

note: 1 drug, 2 formulations

38

bioequivalence - definition (general)

generic drug product is bioequivalent to brand if:
- rate of absorptions (estimated by Tmax and Cpmax) AND extent of absorption (bioavailability - F) of active drug in generic formation is within set limits of those parameters for brand drug

Note: bio equivalent products are considered therapeutic equivalent products

39

p-glycoproteins

located on inner cell membranes of renal brush border, bile canaliculi, astrocyte foot processes in brain microvessels, GI tract

pump drugs out of cell (key in drug elimination):

GI tract: decrease oral absorption of drugs

Liver-Kidney: enhance biliary and renal excretion of drugs

Blood-brain barrier: limits distribution of drugs to the brain

40

relationship b/t first pass metabolism and bioavailability (F)

inverse - as first pass metabolism increases, bioavailability decreases

41

bypass effect

drug bypasses first pass metabolisms (e.g. liver)
- usually get to peak faster (Tmax) and actual peak (Cpmax) is higher

42

clinically useful drug levels

rate in (rate of absorptions) at least 10x greater than rate out (rate of elimination)

43

routes of administration - enteral v. parenteral

enteral: oral and rectal (drug places within GI tract)

parenteral: all other routes

44

unionized drug - exception to the rule of rate of absorption

typically, rate of absorption is greater for unionized drug; however, ionized drug in SI will be absorbed faster then unionized form in stomach due to large surface area

surface are has greater influence then ionization

45

influences on rate of absorption - oral route

surface area (faster absorption w/ greater SA)

ionization (unionized absorbed faster)

gastric motility (inc. rate of absorption with inc. motility - drug reached SI faster)

food (delays absorption be delaying gastric emptying)

46

role of enteric coating on pills

prevents dissolution until more basic SI is reached (for drugs that cause GI irritation or those destroyed by gastric secretion)

47

controlled-release drug preparations - advantages and disadvantages

ADVANTAGES:
- dec. frequency of administration (inc. compliance)
- maintain therapeutic effects overnight
- eliminate peaks and troughs of plasma levels

DISADVANTAGES:
- patient variability in systemic levels obtains and "dose-dumping"

48

ion trapping

total conc. of drug is greater on side where ionization is greater (non-protonated weak acid or protonated weak base)
- acid drugs trapped in basic solutions
- basic drugs trapped in acidic solutions

Note: at equilibrium, conc. of non-ionized for will be same on both sides of membrane (move freely)

49

bolus toxicity

can occur with IV route of administration

toxicity when too high of a dose is injected into plasma before able to distribute to other tissues

main issue with "rate" of distribution

how to prevent:
- multiple lower doses
- infusion

50

pharmacologic equivalent

Same active ingredient(s)
Same dosage formulation (capsule, tablet, solution, etc.)

Same route of administration

Identical in strength or concentration

generic and brand drugs are pharmacologic equivalents

51

bioequivalent drug products

Rate of drug absorption (estimated by T max and Cp max) and Extent (AUC-bioavailability) of drug absorption from generic formulation is within set limits of that of brand formulation

- Most generic products are bioequivalent to brand (avg. variation < 4%)
- Assumed that (in the absence of any scientific evidence to the contrary) bioequivalent drugs will be therapeutically equivalent

52

therapeutic equivalents

pharmaceutical equivalents administered to same individual in same dosage regimen provide same efficacy with same safety

drug trials needed = expensive!

53

generic drug

pharmacologic equivalents and bioequivalents
- contain same active ingredient
- have exact same dosage, intended use, therapeutic effects, side effects, route of administration
- Also same risks, safety, and efficacy of brand product (but not specifically tested)

54

convert 1 grain to mg

64.8

55

convert 1 ounce to grains

437.6 grains

56

convert 1 ounce (437.6 grains) to grams

28.35 (30)

57

convert 2.2 pounds to grams

1000 grams (1 kg)

58

convert 1 tsp to ml

5 ml

59

convert 1 tbs to ml

15 ml

60

convert a fluid ounce to ml

29.56 (~30) ml

61

controlled substances

manufacture and distribution (Rx) is overseen by DEA (federal government)

divides drugs into 5 schedules based on medical usefulness and abuse potential

62

routes of administration for systemic effects

oral / rectal
IV
IH (gaseous)
IM
SQ
IN
sublingual / buccal
transdermal

63

routes of administration for local effects

inhalation (aerosolized particles)

dermal (topical to skin or mucous membranes)

64

which route of administration should be used for drugs with narrow TI

IV - most direct route right into circulation

65

which route of administration is good for lipid soluble, potent drugs

sub lingual or buccal (<1mg dose, small SA of mouth)

66

is bioavailability greater for oral or rectal

generally greater for rectal since only 50% undergoes 1st pass metabolism by liver and rest bypasses liver

67

transdermal patches - uses and precautions

drug must be potents (<2mg) and able to permeate the skin

avoids 1st pass metabolism

slowest route for systemic administration

68

drug binding to plasma proteins - which proteins do acid drugs and basic drug bind to

note: only FREE drug is diffusible

acidic drugs bind to albumin; basic drugs bind to alpha-1 acid glycoprotein

69

effects of drug binding to protein

Reduces conc. of active, free drug (can limit fetal exposure)

Hinders metabolic degradation and reduces rate of excretion (will decrease elimination rate and increase half-life), i.e., acts as circulating drug reservoir that can prolong drug action

Decreases volume of distribution by enhancing apparent solubility in blood

Decreases ability to enter CNS across blood brain barrier

70

volume of water compartments in the body

plasma/blood: 3-5L
interstitial: 9L
intracellular: 29L

extracellular water (plasma+IS): 12-15L
total body water: 42L

71

what should you do if you need to reach steady state plasma level quickly

give a loading dose prior to maintenance doses

NOTE: simply increasing the dose will not get to ss faster (always 4-5 halves lives)

72

maintenance dose (MD)

dose to achieve steady state conc. in plasma over time (rate in=rate out)

MD/frequency (tau) = Cpss x clearance

73

characteristics of drugs with high Vd

mainly exist outside plasma

inc. tissue binding, lipid solubility, small size that can enter cells

associated with accumulation of drugs in specific tissues

these drugs have longer 1/2 life since not as much in Cp (which is where elimination occurs)

74

characteristics of drugs with low Vd

mainly exist in plasma

extensive binding to plasma proteins, large size, low lipid solubility, highly water soluble so do not enter cells

75

relationship between Vd and Cp

inverse - the more of the dose that remains in the plasma, they less the distribution volume

76

drug metabolism

enzyme-catalyzed chemical structure transformation of drug following administration
- occurs in liver (phase I and II)

typically changes drug to inactive form

influenced by inducers and inhibitors

77

drug excretion

mainly occurs via kidney; excretion of unchanged drug

78

drug metabolism - pharmacological consequences

detoxification (95% of time)

metabolism ot more active drug
- codeine --> morphine

metabolism of inactive compound (prodrug) to active ingredient (designed)

metabolism to toxic metabolite
- acetaminophen --> NAC (n-acetyl-benzoquinoneimine)

79

type of drugs that do not undergo phase I or phase II metabolism in liver

highly water soluble drugs

80

Phase I and Phase II metabolisms - general rules

Phase I: inserts functional group that makes molecule more water soluble (hydrophilic and less active)

Phase II: forms highly polar conjugate that is readily excreted in urine (highly water soluble, inactive)

81

genetic polymorphisms in drug metabolism

poor metabolisms (PMs) or ultra-rapid metabolisms (UM)

result depends on if metabolism of the drug is a detoxifying process or an activating process

82

what happens with PMs and UMs for drugs that undergo detoxifying process during metabolism

PMs: inc. drug toxicity (antipsychotics)
UMs: non-response to drug (antidepressents)

83

what happens with PMs and UMs for drugs that undergo activating process during metabolism

PMs: dec. efficacy of drug (insufficient analgesia)
UMs: drug intoxication (codeine > morphine)

84

inducers - definition

stimulate enzymatic activity / metabolism; thus, decreased amount of drug available for action

Effect is slow → 48-72 hrs (2-3 d) to see effects
- mechanism: inc. synthesis of enzyme proteins

Note: mainly relevant to phase I reactions in liver

85

inhibitors - definition

inhibit enzymatic activity / metabolism; thus, increasing amount of drug available for action

Effect is fast → seen within hours (as soon as sufficient hepatic conc. is reached)
- many mechanisms: blocking, competitive binding, destruction

Note: mainly relevant to phase I reactions in liver

86

inducers

phenobarbital (epilepsy)
phenytoin (anti-seizure)
carbamazepine (epilepsy)
rifampin (ABX)
ethanol
st. Johns wart
tabacco / marijuana (not nicotine)

87

inhibitors

cimetidine (heart-burn)
erythromycin/clarithromycin (ABX)
antifungal agents
omeprazole (GERD)
grapefruit juice

88

anytime you change rate in (inducers, inhibitors, alter dose), how long will it take to reach steady state

4-5 halve lives

89

enterohepatic recirculation

drugs are excreted into bile along with drug metabolites

bacterial B-glucuronidase (naturally occurring in gut) hydrolyzes drug metabolites in intestine to parent drug (more lipid soluble) so that it can be taken back up through hepatic (portal) vein to liver and re-circulated
- mat be source of DDI (but not clinically significant)
- keeps drugg in body longer (but not in systemic circulation), prolongs half life

90

factors that influence drug passage from plasma to breast milk

most drugs do, but in clinically insignificant amounts
- exception: ethanol and lithium

milk more acidic so "traps" basic drugs (opioid analgesic)

lipid-soluble drugs build up in milk

drugs with high protein binding are decreased in milk

91

processes that reduce bioavailability (ability to get into plasma)

first pass metabolism
digestive enzymes in gut
poor solubility
poor absorption of drug

92

processes that effect vol. of distribution (Vd)

getting older and getting fatter (for fat soluble drugs)

93

processes that effect systemic clearance (CL)

systemic clearance: sum of renal and hepatic clearance

renal CL: effected by changes in renal fx (GFR, creatinine)

hepatic fx: effected by inducers and inhibitors

94

how to determine fluctuation in plasma drug levels between doses

fold fluctuation - 2^x

x: # of 1/2 lives in dosing interval

95

half-life of drug - dependent and independent factors

dependent on CL
dependent on Vd

CL = Vd x ke

T1/2 = 0.693/ke

can be used to determine time to reach steady state and time to elimination

independent of dose

96

elimination rate constant (ke)

fraction of drug leaving body per unit time via all elimination processes
- slope of graph of ln Cp. time
- number or constant that allows us to calculate the amount of drug remaining at any time during elimination process
- convert Ke to ½ life to appreciate rate at which drug is eliminated (see equation above)

97

first-order kinetics

rate of elimination (mg/hr) is proportional to the conc. of the drug in the plasma (mg/L)

constant fraction of drug (e.g. ½ life) is eliminated per unit time and is independent of the total amount of drug in system

note: most drugs (since hepatic metabolism and renal excretion are 1st order processes)

98

zero-order kinetics

rate of elimination of drug from body is independent of amount of drug in body
-amount of drug removed per unit time is constant (no half live)

- most commonly occurs for drugs that saturate hepatic metabolic pathways when given in therapeutic doses (phase II saturate) - aspirin, phenytoin, ethanol

99

drug-receptor concept

assumes that the interaction follows simple mass action relationships, binding is reversible, and response is proportional to receptors [R] occupied by drug [D] as follows

R + D ←→ RD
- RD proportional to response

100

receptor

component of the biologic system to which a drug binds to bring about a change in the fx of the system

101

transduction

conformational change in the receptor as a result of binding leads to transduction step (begins and amplifies the response)

102

consequences of drug-receptor theory to drug therapy

receptors are specific for specific drugs

receptors mediate the actions of pharmacologic agonists and antagonists

allows determination of quantitative relation between dose or concentration of drug and its pharmacologic effects via use of dose-response curves

103

graded dose-response curve - hyperbolic shape

y-axis is % max response (e/emax)

curve is relatively linear (straight) at low doses of drug:
• At low doses of drug, the response usually increases in direct proportion to the dose
• Consistent w/ receptor theory → greater the number of receptors occupied by drug, the greater the response produced

curve levels off at high drug doses:
• There is a limit to the inc. in response that can be achieved by increasing the drug dose
• Consistent w/ receptor theory → response obtained by administration of any drug is proportional to the amount of receptors occupied by drug
o High dose → all receptors occupied → no further inc. in response can be obtained

104

graded dose-response curve - log shape

Allows a wide range of doses to be plotted allowing easy comparison of different drugs
- USED TO COMPARE POTENCY AND EFFICACY

Dose-response relationship is nearly a straight line over large range of doses (generally corresponding to the therapeutic range)

105

potency (EC50, Kd, affinity)

concentration (EC50) or dose (ED50) required to produce 50% of that drug’s individual maximal effect

Provides information on how much drug (dose) will be required to produce a given effect

Largely determines the dose necessary to administer to the patient

position of the curve along the dose [x] axis

106

efficacy (power, Emax)

Indicates the relationship between binding to the receptor and the ability to initiate a response at the molecular, cellular, tissue or system level

Efficacy of a drug is the most important determinant of its clinical utility

position of the curve along the dose [y] axis

107

agonist

drug that activates its receptor upon binding and brings about the characteristic tissue response
- full and partial (less efficacy)

108

how are potency and efficacy of a drug related

they can vary independently

109

antagonist

drug that inhibits the action of an agonist but has no effect in the absence of an agonist

110

pharmacologic (receptor) antagonists

bind to the same receptor as the agonist

competitive reversible:
- curve shifts right
- surmountable
- Emax stays same, EC50 inc., potency dec.

non-competitive (irreversible)"
- curve shifts down
- non-surmountable
- Emax dec, EC50 and potency stay same

111

physiological antagonists

bind to a different receptor that mediates a physiologic response that is opposite to that of activation of the receptor for the agonist

112

chemical antagonist

bind the agonist molecule directly (do not involve any receptor binding)

occurs via inactivation of the agonist itself by modifying it or sequestering it so it is no longer capable of binding to and activating the receptor

113

graded dose response curve

Increasing doses of a drug are given to the same subject and the inc. in response for each dose is measured
- allows determination of the maximal effect of the drug (Emax)
- used as hyperbolic (receptor theory) and log-based (TI)

114

population dose response curve (quantal)

used to characterize pharmacologic responses that are all-or-nothing events (quantal, not graded) in a population of subjects (not an individual);

Provide information about potency

- used to evaluate drug safety through TI and SSM)
- NOT used to obtain Emax

115

therapeutic index

Factor by which the dose that is therapeutically effective in 50% of the population (ED50) must be increased to cause death (or more commonly a selected side effect) in 50% (LD50 or TD50) of the population

TI = LD50 / ED50

116

standard safety margin (SMM)

percent by which the dose effective in 99% of the population (ED99) must be increased to cause death (or a selected side effect) in 1% of the population (LD1 or TD1) [see figure B above]
- more conservative measure than the therapeutic index
- takes into account extremes of population

SMM = [(LD1/ED99) - 1] x 100

117

therapeutic window

safe “opening” between the minimum therapeutic concentration and the minimum toxic concentration of a drug in plasma and dosage regimens are designed to keep plasma levels within this range

selection of values for Cp [minimum effective concentration] and Cp [minimum toxic concentration] is arbitrary but most commonly would correspond to the ED99 and LD1, respectively

118

patients at highest risk for drug-drug interactions

Elderly

Patients in high risk clinical situations (dependent on therapy, acute illness, unstable disease)

Patients w/ renal / hepatic disease

Patients w/ multiple prescribing physicians

119

toxicokinetics

study of absorption, distribution, and elimination of toxic parent compounds and metabolic products that aids in prediction of amount of toxin that reaches site of injury and the resulting damage

Note: a toxic dose of a drug may result in alterations of ”normal” pharmacokinetics
- absorption slowed with large amount of drugs = delay in peak effect
- Vd important for dialysis tx
- CL important to understand to plan tx
- half life can be prolonged in toxic overdose (saturation of elimination mechanisms)

120

pharmacokinetic strategies for toxic drug ingestion

Prevent or decrease absorption of toxin → DECREASE rate in

Inhibition of toxication (prevent conversion to toxic species)

Enhancement of metabolism (detoxification)

Increase elimination of toxin → INCREASE rate out

121

pharmacodynamic strategies for toxic drug ingestion

antidotes - ability to change effect drug has on body

122

single most important determinant of poisoning outcomes

good supportive care!!

123

mechanism of acetaminophen overdose

Saturation of the phase II sulfate and glucuronide conjugation pathways by toxic doses

Excessive formation of hepatotoxic metabolite by unsaturated phase I P450 pathway (enzyme responsible for producing hepatotoxic metabolite = CYP2E1)

Eventual depletion of cellular glutathione stores available for detoxification
- Hepatic cell death

124

acetaminophen overdose and treatment

Activated charcoal and gastric lavage to remove residual drug, best w/in 4 hours

Vigorous supportive therapy

N-acetylcysteine (NAC): w/in 12-36 hours of ingestion
- restores glutathione
- captures and inactivates toxic metabolite

125

methanol and ethylene glycol ingestion

Both form toxic metabolites if ingested:
- ethylene glycol > oxalic acid (acidosis, nephrotoxicity)
- methanol > formic acid (formaldehyde) (severe acidosis, retinal damage)

Enzyme responsible is alcohol dehydrogenase
- inhibit enzyme with ethanol or fomepizole

Additional treatment:
- gastic lavage
- hemodialysis
- correct metabolic acidosis with sodium bicarbonate

126

enzyme in liver that metabolizes local anesthetics, such as lidocaine and bupivacaine

amidases

Lidocane and bupivicaine are amide local anesthetics

127

Phase I metabolisms: types of reactions

oxidations
hydrolysis
reductions

128

Phase II metabolisms: types of reactions

conjugations:
glucuronidation
acetylation
glycine
sulfate conjugation (sulfations)

129

Phase II liver metabolisms - is it the same b/t adults and newborns

no, adult levels of activity occur around age 3-4 years