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Chemistry lectures (Sun) > Exam 5 > Flashcards

Exam 5 Flashcards

1
Q

Routes for administering a drug

A

Oral, Rectal, transcutaneous, subcutaneous, intramuscular, intravenous

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2
Q

Absorption is affected by

A

The formulation of the drug (tablet, capsule etc.) and the chemical natures of the drug (weak acid vs weak base, ionized vs nonionized) May be subjected to first-pass metabolism

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3
Q

Transportation of drugs

A

Transported as a free drug which can interact with its receptor and correlates with both the therapeutic and toxic effects or as a drug-protein complex

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4
Q

Distribution

A

Depends on the lipid solubility of the drug, with volume distribution characteristics of a drug and expressed mathematically

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5
Q

Volume distribution equation

A

Vd = D / Ct

Vd = volume of distribution
D = an injected dose
Ct = concentration of the drug in plasma

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6
Q

Metabolism of drugs

A

Undergo oxidation, reduction, hydroxylation and conjugation in liver, facilitated by microsomal cytochrome P-450 which can be influenced by drugs such as barbiturates, alcohol, smoking and diet, generation of the metabolite or metabolites of the parent drug, which may have significant or comparable therapeutic effects

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7
Q

Excretion

A

With the kidneys as the primary route of excretion which is affected by water solubility and pH of urine, the biliary tract, lungs and sweat glands in the event of severe renal failure

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8
Q

Pharmacokinetics

A

The quantitative study of drug disposition in the body, describe mathematically the fate of a drug after administration of a given dosage form by a given route of admission

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9
Q

The therapeutic window

A

Range between minimum toxic concentration and minimum effective concentration

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10
Q

Decay of serum drug concentration equation

A

Ct = C0e-^kdt for many drugs

Ct = the serum concentration of a drug at time t
C0 = the initial dose divided by the volume of distribution
Kd = a disposition or elimination constant

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11
Q

First order of kinetics of drug elimination

A

A constant fraction is eliminated per unit of time, This causes an exponential decrease in the concentration as a function of time

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12
Q

Decline of plasma concentration versus time for a drug obeying zero-order kinetics

A

Elimination rate is constant, independent of concentration, capacity limited

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13
Q

Zero-order kinetics equation

A

Ct = Co - kt

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14
Q

Half-life of the drug

A

The period of time during which the concentration of a drug decays in half, may be determined for phase II of the dose response curve

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15
Q

Half-life equation

A

Ct = C0e -kdt, T1/2 = 0.693/Kd

T1/2 doesn’t vary with plasma concentration of a drug which follows 1st order

T1/2 changes with plasma concentration of a drug which follows zero order kinetics

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16
Q

Multiple oral dose-response curve

A

The dose interval is T1/2, steady state after 5 half lives

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17
Q

Antiepileptic drugs

A

High protein binding and interindividual variation for the protein binding, liver enzyme induction, active metabolite, various toxic effect with different drugs, use therapeutic ranges, interpret plasma concentration, determined by immunoassays

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18
Q

Valproic acid

A

Used for petite mal, administered orally, GI absorption rapid, highly protein bound, eliminated by hepatic metabolism, toxic >120 ug/ml

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19
Q

Carbamazepine

A

Used for variety of seizures, less common, 70-80% protein bound, eliminated by hepatic metabolism, toxic >120 ug/ml

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20
Q

Phenytoin

A

Used for variety of seizures, orally, highly protein bound, zero-order kinetics

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21
Q

Phenobarbital

A

active form of primidone, used in several types, 50% bound to protein, eliminated by liver metabolism and kidney excretion, dosage adjustment required

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22
Q

Tricyclic antidepressants

A

imipramine, amitriptyline, doxepin and fluoxetine. first-pass effect, high protein binding, half-life varies

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23
Q

Therapeutic drug monitoring of antidepressants

A

No improvement after 4 weeks of therapy, question on noncompliance, measured by HPLC

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24
Q

Immunosuppressants

A

Used to prevent rejection of transplants, require establishment of individual dosage regimens to optimize therapeutic outcomes and minimize toxicity

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25
Q

Cyclosporine

A

Antirejection therapy in organ transplants, 5-50% absorption, distributed through RBCs and plasma, 98% protein bound, toxic >400 ng/mL, measured by FPIA or EMIT

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26
Q

Toxic effects of cyclosporine

A

Renal dysfunction, hypertension, hirsutism, tremors

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27
Q

Tacrolimus (FK-506)

A

Immunosuppressive drug, orally, more potent than cyclo, eliminated by hepatic metabolism, whole blood correlation, measured by immunoassays or HPLC/MS

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28
Q

Toxic effects of tacrolimus

A

Similar to cyclo in renal toxicity, thrombus formation

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29
Q

Aminoglycosides

A

Gentamicin, tobramycin, amikacin, streptomycin, neomycin and kanamycin, used in combination with beta-lactam antibiotics, require IV, IM, or intrathecal administration

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30
Q

Toxic effects of aminoglycosides

A

Nephrotoxicity and ototocixity

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31
Q

Therapeutic monitoring of aminoglycosides

A

Serum drug level upon initiation, serum drug level and serum creatinine level during therapy, measured by FPIA or EMIT

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32
Q

Vancomycin

A

Used for infection with staph epi and staph aureus, IV administration, eliminated by renal filtration and excretion, no established relationship between serum level and toxic effect

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33
Q

Toxic effects of vancomycin

A

Phlebitis, neutropenia, nephrotoxicity, nephritis and ototoxicity, measured by FPIA or EMIT

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34
Q

Cardioactive drugs

A

Significant toxic side effects, narrow therapeutic windows, active metabolites

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35
Q

Digoxin

A

improve cardiac contraction in CHF and correct supraventricular tachycardia, orally administered, highly bound to skeletal muscle and myocardial muscle, long half-time, eliminated through kidney

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36
Q

Toxic effects of cardioactive drugs

A

Cardiac dysfunction, CNS toxicity, GI toxicity, measured by FPLA or EMIT

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37
Q

Procainamide

A

Used to correct atrial and ventricular arrhythmias, orally, liver metabolized, kidney eliminated, active metabolite NAPA generated

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38
Q

Toxic effects of procainamide

A

Hypotension, bradycardia, prolongation of ECG intervals, SLE

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39
Q

Lidocaine

A

Used for ventricular arrhythmias and prevention of ventricular fibrillation, considerable overlap of therapeutic and toxic ranges, IV and IM administration, eliminated by hepatic metabolism

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40
Q

Toxic effects of lidocaine

A

CNS toxicity, atrioventricular node blockage

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41
Q

Lidocaine drug monitoring

A

Initial serum drug concentration, every 12 hours in patient with CHF, every 24 hours on prophylaxis after MI, measured by FPIA or EMIT

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42
Q

Salicylates

A

Used as analgesic, antipyretic and anti-inflammatory drug, function by decreasing thromboxane and prostaglandin formation through inhibiting cyclooxygenase

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43
Q

Toxic effects of salicylates

A

Stimulation of the respiratory system which causes an initial respiratory alkalosis, gastric irritation, conversion of pyruvate to lactate and stimulation of mobilization of free fatty acid, resulting in excess ketone body formation which can cause metabolic acidosis

44
Q

Salicylates detection and treatment

A

Trinder method or forced alkaline diuresis

45
Q

Trinder method

A

Salicylate is combined with an acidic ferric chloride to form a blue complex, which can be measured colormetrically

46
Q

Acetaminophen

A

Analgesic drug, eliminated by hepatic uptake, biotransformation, conjugation and excretion, involve the formation of reactive intermediates that are then conjugated with reduced glutathione, which can be depleted in overdoses

47
Q

Toxic effects of acetaminophen

A

Delayed hepatocytic necrosis due to the accumulation of reactive intermediates

48
Q

Detection and treatment of acetaminophen

A

Immunoassays, HPLC, treated with N-acetylcysteine which may function as glutathione substitute

49
Q

Ethanol

A

Most often used and abused substance

50
Q

Ethanol toxic effect

A

Dose-dependent gradient in CNS depression

51
Q

Ethanol absorption

A

Poor absorption by stomach affected by fullness of stomach, rapid absorption from small intestine

52
Q

Ethanol distribution

A

Readily penetrate cell membrane, distribute to all tissues

53
Q

Ethanol metabolism

A

2-10% excreted by lung and kidney, 90-98% metabolized by ADH and ALDH

54
Q

Ethanol elimination

A

if BAC <20 mg/dL, elimination is first order, between 20-300 mg/dL, kinetics are zero order, BAC decreases at 18 mg/dL/hr, chronic alcoholics can eliminate at rates of 30-40 mg/dL/hr

55
Q

Ethanol detection

A

Enzymatic analysis and GC (headspace analysis)

56
Q

Enzymatic analysis

A

ADH
Eth. + NAD+ -> Ald. + NADH+ + H+

The reaction is driven almost completely to the right by use of excess NAD+ and ADH, and the amount of NADH+, measured at 340 nm is proportional to the amount of ethanol in specimen

57
Q

GC (headspace analysis)

A

Utilize the principle that alcohols and acetone are sufficiently volatile to be present in easily measurable concentrations in the air space in a closed system, inject a portion of this headspace into a gas chromatograph for analysis

58
Q

Methanol metabolism

A

Converted to formaldehyde by liver alcohol dehydrogenase, which is then rapidly oxidized by aldehyde dehydrogenase to formic acid

59
Q

Methanol toxic effects

A

Less severe CNS than ethanol, serious acidosis (formic acid), optic neuropathy and blindness (formic acid)

60
Q

Detection and treatment of methanol

A

Gas chromatography, treated by administration of ethanol to competitively inhibit metabolism, sodium bicarb to alleviate metabolic acidosis, folate administration to enhance folate-mediated metabolism of formate, hemolysis

61
Q

Ethylene glycol

A

Antifreeze, short half life (3 hours)

62
Q

Ethylene glycol toxic effects

A

Neurological abnormalities, severe metabolic acidosis, acute renal failure, cardiopulmonary failure

63
Q

Detection and treatment of ethylene glycol

A

Gas chromatography, treated by ethanol to saturate alcohol dehydrogenase, forced diuresis

64
Q

Isopropanol

A

Converted by alcohol dehydrogenase to acetone which is eliminated slowly

65
Q

Isopropanol toxic effects

A

CNS depression, coma

66
Q

Detection and treatment of isopropanol

A

Gas chromatography, not treated by ethanol

67
Q

Lead

A

From industrial waste, lead-based paint, lead pipes, mainly from ingestion, absorption rate varies with age

68
Q

Lead toxicity

A

Inhibit enzymes for the heme synthesis which often leads to anemia and accumulation of zinc protoporphyrin in RBC and ALA in urine, forms bonds with the sulfhydryl group of cysteine in proteins

69
Q

Toxic effects of lead

A

Neurological, gastrointestinal, renal, hematopoietic, calcium metabolism

70
Q

Lead measurement

A

Whole blood lead, hair and urine levels, 10 ug/dL as cut off in children and 30 ug/dL in adults, chelation therapy required if level is above 60 ug/dL, measured by graphite furnace atomic absorption analysis

71
Q

Lead treatment

A

Avoidance of continued exposure, chelation therapy to allow removal of lead from soft tissue and bone by forming LMW complexes that can be cleared by renal filtration

72
Q

Mercury

A

Major sources are industrial uses, fungicide, dental amalgams, fish

73
Q

Mercury toxic effects

A

Exposed by inhalation or ingestion, mostly from contaminated foods, inhalation and accidental ingestion, nontoxic in elemental form, moderately toxic in ionized form, highly toxic in organic form

74
Q

Basis for toxicity of mercury

A

React with sulphydryl groups of protein, causing a change in tertiary structure of the protein with subsequent loss of the biological activity, binds to proteins in lipid0rich tissues, such as neurons, eliminated primarily through renal filtration

75
Q

Toxic effects of mercury

A

CNS abnormalities: tremors, incoordination, irritability, depression
Renal disorder: disputation of renal function
GI: salivation, diarrhea, stomatitis
Other: increase in congenital abnormalities

76
Q

Mercury measurement

A

Blood, urine and hair mercury measurement, 50 ug/dL is significant exposure in blood, 200 ug/dL is significant in hair, 50 ug/dL is significant exposure in urine, measured by cold vapor atomic absorption spectrophotometry

77
Q

Mercury treatment

A

Chelation therapy

78
Q

Arsenic

A

Major sources from air and water in industrialized areas, agriculture and smelting industries, homicide and suicide agent, absorbed rapidly by passive diffusion, eliminated by renal filtration

79
Q

Arsenic measurement

A

Atomic absorption spectrophotometry

80
Q

Arsenic toxic effects

A

Many organ systems affected due to high-affinity binding to the thiol groups in proteins
GI distress, renal failure, hemopoietic effects, vascular disease, CNS system

81
Q

Cadmium

A

Major sources: paints and plastics, nickel-cadmium batteries, exposed by inhalation of cadmium particulates in industry and by ingestion of contaminated food

82
Q

Cadmium detection

A

Atomic absorption spectrophotometry

83
Q

Cadmium toxic effects

A

Binds to proteins and other cellular components, renal toxicity

84
Q

Amphetamine

A

CNS stimulation due to enhancement of neurotransmitter release, can be used to treat narcolepsy, obesity and ADHD

85
Q

Amphetamines abuse potential

A

The initial euphoria, restlessness, irritability and paranoid psychosis

86
Q

Amphetamines metabolism

A

Unchanged (30%) or go through oxidative deamination in liver

87
Q

Amphetamines overdose effects

A

Dizziness, tremor, hypertension, cardiac arrhythmia, convulsion and coma

88
Q

Amphetamines immunoassays

A

Variable cross-reactivities with other sympathomimetic amines, GC/MS

89
Q

Cannabinoids

A

Can treat anorexia and nausea, abuse potential to feel high

90
Q

Cannabinoids absorption and metabolism

A

Consumed by smoking marijuana, absorbed through the lungs, reach peak blood concentration within minutes followed by rapid declines in THC concentration due to rapid tissue distribution, metabolized to a large number of compounds with THC-COOH as the major urinary metabolites

91
Q

Cannabinoids method of detection

A

Immunoassays calibrated with THC-COOH, GC/MS

92
Q

Cocaine

A

Alkaloid present in the leaves of the coca plant, stimulate CNS system by blocking uptake of dopamine and norepinephrine, can be used as local anesthetic for nasal surgery

93
Q

Cocaine abuse potential

A

increased alertness and euphoria

94
Q

Cocaine absorption and metabolism

A

Administered by nasal insufflation or smoking, metabolized to ecgonine methyl ester and benzoylecgonine, excreted as parent compound or metabolites

95
Q

Cocaine effects of overdose

A

Seizure, arrhythmias, MI, hypertension, hyperthermia, sudden death

96
Q

Cocaine method of detection

A

Immunoassays designed for the detection of its metabolites, GC/MS

97
Q

Opiates

A

Naturally occurring or semisynthetic analgesic alkaloids derived from opium, used clinically due to their analgesic properties

98
Q

Semisynthetic derivatives or morphine

A

Heroin, oxycodone, hydromorphone

99
Q

Opiates absorption and metabolism

A

Administered by IV injection or subcutaneous injection, smoking or nasal insufflation less frequent, converted to 6-acetalmorphine which is hydrolyzed to morphine, inactivated by glucuronide conjugation

100
Q

Codeine

A

combined with non-opiate analgesic agents for clinical use, have 10% of the analgesic potency of morphine, can be converted to morphine

101
Q

Opiates and codeine abuse potential and overdose

A

Sedation, euphoria, respiratory depression, orthostatic hypotension, diminished intestinal motility, nausea and vomiting, coma, pulmonary edema

102
Q

Codeine and opiates methods of detection

A

Immunoassays designed primarily for the detection of morphine and codeine, variable cross-reactivity with morphine-3-glucuronide and with other opiates among the immunoassays, GC/MS

103
Q

Frequency histogram

A

Frequency (y) vs the values of the clinical results (x), bell shaped, described by mean, median, mode, standard deviation, and coefficient of variable

104
Q

Mode

A

Most frequent observation

105
Q

Standard deviation

A

Dispersion of single observations

106
Q

Coefficient of cariation

A

CV (100%) = (SD/mean) x 100

Chemistry lectures (Sun) (5 decks)

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