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Page 478
CHAPTER 29 Lipid-Lowering Drugs 463
TABLE 29-3
Properties of Lipid-Lowering Drugs
LIPOPROTEIN
CONCENTRATIONS
PLASMA
CHOLESTEROL
PLASMA
TRIGLYCERIDE TOXICITY DRUG INTERACTIONS
Clofibrate ↓ VLDL, ↓ IDL ↓ ↓ Nausea, diarrhea, myositis,
abnormal liver function tests,
skin rash, ventricular ectopy,
increased incidence of
noncardiac death
Enhanced effect of coumarin
anticoagulants
Gemfibrozil ↓ VLDL, ↓ IDL,
↑ HDL
↓ ↓ Abdominal pain, epigastric pain,
diarrhea, nausea, vomiting,
flatulence, rash, headache,
dizziness, anemia,
eosinophilia, leukopenia
Enhanced effect of coumarin
anticoagulants; myopathy
with HMG-CoA reductase
inhibitors
Nicotinic acid ↓ Chylomicrons,
↓ VLDL, ↓ IDL,
↓ LDL, ↑ HDL
↓ ↓ Flushing, pruritus, nausea,
diarrhea, glucose intolerance,
hyperuricemia,
hepatotoxicity
Myopathy, rhabdomyolysis,
renal failure with
HMG-CoA reductase
inhibitors
Cholestyramine,
colestipol
↑ VLDL (transient),
↓ LDL
↓ May increase
modestly in
some
patients
Constipation, nausea,
abdominal pain, flatulence,
biliary tract calcification,
steatorrhea, hyperchloremic
acidosis
Decreased absorption of
thiazides, tetracycline,
phenobarbital, thyroxine,
digitalis, coumarin
anticoagulants
HMG-CoA
reductase
inhibitors
↓ IDL, ↓ LDL,
↑ HDL
↓ ↓ Headache, flatulence,
abdominal pain, diarrhea,
rash, increased creatine
kinase and other enzyme
activities, myopathy
Enhanced effect of coumarin
anticoagulants;
myopathy,
rhabdomyolysis, renal
failure with nicotinic acid,
gemfibrozil, erythromycin,
cyclosporine
Ezetimibe ↓ LDL, ↓ HDL ↓ ↓ Headache, sinusitis, pharyngitis Cholestyramine binds
ezetimibe and lowers its
bioavailability; does not
alter bioavailability of
digitalis or coumarin
anticoagulants
↓, Decrease; ↑, increase.
HDLs, High-density lipoproteins; HMG-CoA, 3-hydroxy-3-methylglutaryl–coenzyme A; IDLs, intermediate-density lipoproteins; LDLs, low-density lipoproteins;
VLDLs, very-low-density lipoproteins.
anticoagulants, partly by displacing them from protein-
binding sites, but mostly because fibrates interfere with the
synthesis of several clotting factors (fibrinogen and factor VII).
Gemfibrozil is chemically distinct from other fibrates
because it has a propylene connector between the phenoxy
and isobutyrate ends of the molecule. The drug has been
shown to decrease the concentrations of blood triglycerides,
cholesterol, VLDL, IDL, and sometimes LDL. It also tends
to increase HDL concentrations more reliably than clofibrate.
In contrast to clofibrate, gemfibrozil has been shown to
decrease the incidence of myocardial infarction by 34% over
5 years.16 Principal side effects of gemfibrozil include abdomi-
nal pain, diarrhea, nausea, and vomiting. Less frequent adverse
effects are headache, dizziness, anemia, rash, eosinophilia, and
leukopenia. Similar to clofibrate, gemfibrozil enhances the
action of oral anticoagulants and may cause cholelithiasis.
When combined with an HMG-CoA reductase inhibitor,
muscle damage leading to rhabdomyolysis and myoglobinuria
has been reported.
Fenofibrate is the first of the second-generation fibric acid
derivatives to be tested in the United States. Although the
drug has been available in Europe since the early 1980s, it has
not been studied in a large prevention trial, as have clofibrate
and gemfibrozil. Nevertheless, the basic pharmacologic fea-
tures of fenofibrate are similar to the features of the previous
agents. A potential advantage of the second-generation drugs
is their greater ability to reduce LDL concentrations. Side
effects include the gastrointestinal disturbances common to
all fibrates and the potential for causing cholelithiasis.
Nicotinic Acid
Nicotinic acid, otherwise known as niacin, has been recog-
nized since the late 1930s as a member of the vitamin B
complex whose deficiency results in the disease pellagra. In
1955, it was reported that doses of nicotinic acid greater than
1 g (i.e., >50 times the recommended daily allowance of
niacin as a vitamin) reduce plasma cholesterol concentra-
tions,2 subsequently decreasing triglyceride concentrations.9
The function of niacin in the body, after conversion to nico-
tinamide adenine dinucleotide and nicotinamide adenine
dinucleotide phosphate, is to act as important enzyme cofac-
tors. The action of niacin as a lipid-lowering drug is not related
Page 479
464 PART II Pharmacology of Specific Drug Groups
CH CH2 CH CH2
CH2 CH CH2N
+(CH3)3Cl
–
n
n
HNCH2CH2NCH2CH2NCH2CH2NCH2CH2NH
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2CH2NCH2CH2N HNCH2CH2N HNCH2CH2
FIGURE 29-4 Structural formula of bile acid sequestrants cholestyramine and colestipol.
to its function as a vitamin. Nicotinamide, interchangeable
with nicotinic acid as vitamin B3, has no effect on plasma
lipids and should not be used.
Nicotinic acid is used most often to reduce VLDL and LDL
while increasing HDL levels. It has been used alone or in com-
bination with other lipid-lowering drugs. Its mechanism of
action seems to involve inhibition of VLDL synthesis through
inhibition of adipose tissue lipolysis and inhibition of subse-
quent delivery of fatty acids to the liver to produce triglycerides
for packaging into VLDL particles.19 Increased clearance of
VLDL may also play a role in the mechanism because of ele-
vated lipoprotein lipase activity. Nicotinic acid has the broad-
est spectrum of activity of the lipid-lowering agents and is
potentially useful in most forms of hyperlipidemia.
The major disadvantage of nicotinic acid, which affects
50% or more of the patient population, has been its tendency
to produce adverse effects sufficient to impair patient compli-
ance or force cessation of therapy. Common side effects
include cutaneous flushing, pruritus, and gastrointestinal dis-
tress. An additional side effect in some diabetic patients is
increased insulin resistance and hyperglycemia. If treatment
is instituted slowly, with a gradually increasing dosage, toler-
ance to the cutaneous flushing occurs, and therapy can be
continued. Aspirin or ibuprofen taken beforehand ameliorates
prostaglandin-dependent flushing. Withdrawal of nicotinic
acid is most frequently necessitated by gastric disturbances.
Other side effects include hyperuricemia, decreased glucose
tolerance, and abnormal liver function tests. Extended-release
preparations of nicotinic acid marketed in the past few years
have made this drug more tolerable to many patients, but do
not eliminate flushing in all patients.
Nicotinic acid is absorbed rapidly, usually reaching a peak
plasma concentration in less than 1 hour. The short half-life
is primarily due to rapid excretion of unmetabolized nicotinic
acid by the kidneys; this necessitates frequent administration
of the drug, usually three times a day with meals. Because of
the frequent lack of tolerance, doses are started at 100 mg
three times per day and are gradually increased at 100-mg
intervals until a dose of 1 to 1.5 g is reached. The usual thera-
peutic dose is 2 to 6 g/day. Extended-release preparations are
taken once each day, in the evening, and can be started at a
higher dose. These preparations have been shown to have less
incidence of side effects even in patients with diabetes.
Bile Acid Sequestrants
Bile acid sequestrants are nonabsorbable anion exchange
resins that bind bile acids in the intestinal lumen, prevent
their reabsorption, and promote their excretion in the feces.
Enterohepatic cycling of cholesterol is markedly reduced by
this mechanism, which blocks reabsorption of bile acids
from the jejunum and ileum, 95% of which are normally
reabsorbed, and increases bile acid excretion rate by 10-fold.
Bile acids are synthesized in the liver from cholesterol by
7α-hydroxylase, which is regulated through negative feedback
by bile acids. Hepatic cholesterol conversion to bile acids is
accelerated, and plasma cholesterol and LDL concentrations
are decreased. LDL concentrations are also reduced by these
drugs because of upregulation of LDL receptors and hepatic
uptake, whereas the VLDL concentration may be unchanged
or increased.26 These resins have no effect in patients with
homozygous familial hypercholesterolemia who have no func-
tioning LDL receptors.
Cholestyramine and colestipol are the two clinically avail-
able drugs in this category (Figure 29-4). They are very large
resins that are insoluble in water. The dry resin is mixed with
a liquid such as fruit juice and drunk as a slurry. Cl− is released
from the resin as bile acids bind to it, and the released Cl− is
absorbed, but the resin itself is not absorbed. Because it is not
absorbed, it has a high safety factor and absence of serious
side effects, but the annoying gastrointestinal side effects
(nausea, vomiting, abdominal distention, and constipation)
limit the use of these drugs. An unpleasant taste adds to the
problem of patient compliance with these agents. Because
cholestyramine and the hydrochloride salt of colestipol clini-
cally exchange Cl− for other anions, hyperchloremic acidosis
may develop when large doses are given to small patients.
Both resins decrease the absorption and the therapeutic effect
of other drugs, such as warfarin, thyroxine, digitalis, pro-
pranolol, and thiazides. This interaction can be partially over-
come by proper timing of the dosage.
Bile acid–binding resins are used alone or in combination
with nicotinic acid and cholesterol synthesis inhibitors. Cho-
lestyramine was used in the Lipid Research Clinics Program
Primary Prevention Trial.27 In this trial of almost 4000 healthy
men with hypercholesterolemia, there was a 20% decrease in
LDL cholesterol with the resin and a 24% reduction in deaths
from myocardial infarction.
The newest bile acid sequestrant to be approved for use
in the United States is colesevelam hydrochloride, which is
available in tablet form. Colesevelam has been found to lower
LDL cholesterol as effectively as cholestyramine,11 but has less
danger of interaction with other drugs such as warfarin
through adsorption.12 There are also somewhat fewer gastro-
intestinal side effects, and, because of the tablet form, compli-
ance is greater.
3-Hydroxy-3-Methylglutaryl–Coenzyme A
Reductase Inhibitors
The development of drugs that specifically inhibit the biosyn-
thesis of cholesterol has been the most important aspect of
hypolipidemic drug development. This class of drugs, called
the statins, currently includes lovastatin, pravastatin, simvas-
tatin, fluvastatin, cerivastatin, atorvastatin, and rosuvastatin.
These agents structurally resemble an intermediate in the
HMG-CoA reductase reaction (Figure 29-5) and are potent
competitive antagonists of HMG-CoA binding.20 (Lovastatin
and simvastatin are actually prodrugs in that they require
cleavage of their lactone ring to become active.) Numerous
clinical studies have now shown these drugs to be the best
tolerated and most effective drugs for lowering LDL choles-
terol and for reducing stroke, coronary heart disease, and
overall mortality. In addition to lowering LDL cholesterol,
Page 956
L1
Index 941
in dentistry, 182
development and use of, 165
inhibition of reuptake of 5-HT by, 376
for migraine prophylaxis, 383
for Parkinson’s disease, 236t
pharmacologic effects of, 175-176
therapeutic uses of, 181
Trifluoperazine, side effects of, 171t
Triflupromazine, side effects of, 171t
Trifluridine, for herpes virus infections, 651
Trigeminal nerve, in pain transmission, 300
Trigeminal neuralgia, 386
diagnostic criteria for, 387b
topical agents for, 389-390
Trigeminothalamic tract, in pain perception,
300f, 301, 303
Triglycerides, in lipoprotein metabolism,
459-460
Trihexyphenidyl, for Parkinson’s disease, 236t,
240
Triiodothyronine, structural formula of, 540f
Trimeprazine tartrate, structural formula and
dosages of, 363t-364t
Trimetazidine, for angina, mechanism of action
of, 423-424
Trimethadione
as anticonvulsant, 221
mechanisms of action and therapeutic uses
of, 216t
Trimethaphan
structural formula of, 138f
uses of, 139-140
Trimethobenzamide
as antiemetic, 531
for migraine, 381-382
Trimethoprim. See also Sulfonamides.
herbal product interactions with, 872t
mechanism of action of, 583
synergism of, with sulfonamides, 631
therapeutic uses of, 632, 633t
Trimethoprim-sulfamethoxazole, for traveler’s
diarrhea prevention, 535
Trimipramine, adverse effects of, 176t
Tripelennamine citrate, structural formula and
dosages of, 363t-364t
Tripolidine hydrochloride, structural formula
and dosages of, 363t-364t
Triptans
adverse reactions to, 381b
contraindications to, 381, 381b
for migraine, 380-381, 380t
names of, 391t
Trizivir, for human immunodeficiency virus
infection, 655
Troleandomycin, 618. See also Macrolide
antibiotics.
Trophoblasts, placental transfer of drugs and,
27-28
Tropicamide, for mydriasis and cycloplegia,
132
Tropomyosin, in cardiac muscle contraction,
410
Troponin, in cardiac muscle contraction,
410
TRP (transient receptor potential) channels, on
nociceptive neurons, 301
Tryptamine derivatives, abuse of, 807-808
Tryptophan, antidepressant action and, 173
Tryptophan hydroxylase, in serotonin
synthesis, 374f, 375
Tuberculosis, drugs used for, 615
names of, 636b-637b
Tubocurarine, 136
action and structural formula of, 140,
141f
historical use of, 141
pharmacologic properties of, 142t
Tubular reabsorption, in renal excretion of
drugs, 40
Tumor killing, cytokines in, functional
relationships of, 663t
Tumor resistance, chemotherapeutic
approaches to, 708
Tumor suppressor genes, in chemical
carcinogenesis, 58
Tyramine
monoamine oxidase inhibitors and, 114-115,
177
structure-activity relationships of, 92t
tachyphylaxis and, 52-53
Tyrosine
biosynthesis of, 85f
enzyme-linked receptor action and, 4
Tyrosine hydroxylase, in catecholamine
synthesis, 82
Tyrosine kinase inhibitors, for cancer, 704-706,
704f, 705t
U
Ubiquitin, in antigen processing, 665
Ulcer(s)
oral, glucocorticoids for, 553
peptic. See also Peptic ulcer disease (PUD).
treatment of, 525-530
Ulcerative gingivitis, acute recrotizing,
microbiology of, 602
Unconsciousness, definition of, 267
Unified Parkinson’s Disease Rating Scale
(UPDRS), 233-234
scores on, effects of anti-Parkinson drugs on,
235t
United States Pharmacopeia (USP), 65-66, 862
Unresponsiveness, definition of, 267
Uracil, structural formula of, 694f
Urea, volume of distribution of, 28t
Ureidopenicillins, 606t-607t
Uric acid, in gout, 352
Uridine diphosphate glucuronosyltransferase
polymorphism, 73
Urinary antiseptics, 634-635
Urinary bladder, endogenous catecholamine
effects on, 94-95
Urinary tract
antimuscarinic drug effects on, 132-133
cholinergic drug effects on, 120
ganglionic blocking drug effects on, 139
Urine
alkalinization of, for toxicity treatment, 40
mercury concentrations in, 821, 821f
pH of, in renal excretion, 40
Urofollitropin, 576
Urokinase, for emergency use, 849
Urokinase plasminogen activator, in
fibrinolysis, 498-500, 499f
Urticaria, H1 antihistamines for, 366
Use-dependent block, by local anesthetics,
250-252
USP Dispensing Information, drug information
in, 66
Uterus
endogenous catecholamine effects on,
94-95
relaxation of, adrenergic agonists for, 100
V
Vaccination, 671
Vaccine(s)
caries, 672
herpes zoster, 652-653
human immunodeficiency virus, 656
human papillomavirus, 648t
influenza, 648t, 649
subunit, 663
Vagus nerve
in pain transmission, 300
Valacyclovir
for herpes virus infections, 648t, 651-652
for oral HSVons, 787
Valdecoxib
COX inhibitory activity of, 331f
for inflammatory conditions, 345
structural formula of, 343f
Valerian, pharmacologic profile of, 870t-871t
Valganciclovir, for CMV infections, 652
Valproic acid, 220-221
absorption, fate, and excretion of, 221
adverse effects of, 219t, 221
discovery of, 214-215
drug interactions with, 227
interactions of, with barbiturates, 195t
for mania, 185
mechanisms of action and therapeutic uses
of, 216t
pharmacologic effects of, 221
side effects of, 56t
structural formula of, 217f
for trigeminal neuralgia, 387-388
Valsartan, for chronic heart failure, 413
Van der Waals forces, in drug-receptor
interactions, 5f, 6
Vancomycin, 630
adverse effects of, 630
antibacterial spectrum of, 630
for C. difficile diarrhea, 596
drug interactions with, 630
mechanism of action of, 630
microbial resistance to, 586-587, 630
therapeutic uses of, 630
Vanilloid receptor channels, on nociceptive
neurons, 301
Vapor, elemental mercury, 821
Vaporizer, temperature-compensated,
variable-bypass, for inhalation anesthetics,
278, 278f
Variant angina, 422
Varicella-zoster virus, drugs active against,
652-653
famciclovir as, 652
herpes zoster vaccine as, 652-653
Varicella-zoster virus infection, in cancer
patients, 787
Varnish, fluoride, 726
Vascular effects
of anticholinesterases, 123
of endogenous catecholamines, 93-94
of isoproterenol, 97
Vascular smooth muscle
cholinergic drug effects on, 119-120
relaxation of, by nitrovasodilators, 424
Vasculature
peripheral, local anesthetic action and,
255
systemic, digoxin administration and, 416
Vasoconstriction
endogenous catecholamine-induced, 93-94
in hemostasis, 487
histamine effects on, 361
Vasoconstrictor(s)
adrenergic, 99
for bleeding control, 495
in dentistry, 101-103, 101t
names of, 103b-104b
for emergency use, 849
ergotamine as, 379
in local anesthetics
drug interactions with, 258, 455-456
effects of, 255-256
local tissue responses to, 257
names of, 103b-104b, 509t
Vasodilation
calcium channel blockers and, 427
cerebral, morphine administration and, 313
histamine effects on, 361-362
muscarinic receptor stimulation and, 118,
119f
nitrites/nitrates in, 424
Vasodilator(s)
direct
for hypertension, 452-454
names of, 456b-457b
directly acting, for congestive heart failure,
420
for emergency use, 846t, 849
Vasopressin, 431, 538. See also Antidiuretic
hormone (ADH).
for emergency use, 846t-848t, 848-849
Vasopressors, for emergency use, 849
Vectors, for breaching blood-brain barrier, 27
Vecuronium
pharmacologic properties of, 142t
toxic extension of therapeutic effect of, 55t
Venable, James, 266
Venlafaxine, 180
adverse effects of, 176t
for chronic pain syndromes, 383
structural formula of, 178f
Tricyclic antidepressants (Continued) Valproic acid (Continued)
Page 957
L1
942 Index
Ventilation
mechanical, neuromuscular blocking drugs
in, 144
pulmonary, for acute opioid intoxication,
313
Ventricular fibrillation, electrocardiographic
appearance of, 396-397, 397f
Ventricular tachycardia, electrocardiographic
appearance of, 396-397, 397f
Verapamil
actions of, 400t
benzodiazepine interactions witn, 195
cardiovascular effects of, 427, 428t
for cluster headache, 384
digoxin and, 419
for emergency use, 846t-848t, 848
for hypertension, 447-448
indications for, 407t
pharmacokinetic properties of, 401t
structural formula of, 427f
Vertigo, H1 antihistamines for, 366-367
Vesicles, synaptic, in nerve stimulation, 149
Vestibular function, antimuscarinic drug
effects on, 132
Vidarabine
for herpes virus infections, 648t, 650-651
mechanism of action of, 650f
structural formula of, 650f
Vigabatrin
adverse reactions to, 219t
clinical toxicology of, 215
mechanisms of action and therapeutic uses
of, 216t
for seizures, 223-224
structural formula of, 223f
Vildagliptin, for diabetes, 563-564
Vinblastine
for cancer, 686t-692t, 698
structural formula of, 698f
Vinca alkaloids, for cancer, 686t-692t, 698
Vincent’s infection, microbiology of, 602
Vincristine
for cancer, 686t-692t, 698
structural formula of, 698f
Vinorelbine, for cancer, 686t-692t, 698
Viral hepatitis, in drug-abusing patient, 811
Virulence, microbial, factors affecting, 594
Virus(es)
inactivation of, in therapeutic blood
products, 497
infections due to
antibiotics for, 610t-611t
antiviral agents for, 647-656, 648t
names of, 657b
oral, in immunosuppressed patients,
787-788
transmission of, in hemophiliacs, 508
Vitamin B12, 477-479
deficiency of
megaloblastic anemia from, 476-477
pathophysiologic characteristics of,
478-479
dietary sources of, 477
metabolic pathways of, 481f
physiologic characteristics of, 477-478
preparations of, names of, 485t
Vitamin D, 543-544
effects of, 544t
on bone, gastrointestinal tract, and kidney,
544t
preparations of, names of, 546b-547b
structural formula of, 544f
Vitamin K
coumarin-indandione action and, 502, 504
deficiency of, hemorrhage and, 503
Vitamin K-dependent clotting factors, 490
Vitamin K epoxide reductase, inhibition of, by
coumarin-indandiones, 502, 503f
Volatile solvents, abuse of, 810
Voltage-gated ion channels, 2
anesthetic action and, 270
Volume depletion
loop diuretics and, 437
thiazide diuretic action and, 435
Volume of distribution
of drugs, 28, 28f, 28t
in renal drug excretion, 40
of various agents, 28t
Vomiting. See also Antiemetics.
antihistamines for, 366-367
cancer chemotherapy-induced, 531, 789-790
digoxin administration and, 417
morphine-induced, 312
von Willebrand factor, in platelet adhesion,
487, 488f
von Willebrand’s disease, 496-497
treatment of, 497-498
Voriconazole
for fungal infections, 644
introduction of, 596
structural formula of, 643f
Vorinostat, for cancer, 705t
Warfarin
chloral hydrate with, 202
drug interactions with, 504
interactions of
with barbiturates, 190t
with chloral hydrate, 190t
for myocardial infarction prevention, 429
structural formula of, 503f, 831f
toxicity of, 830
Warren, John C., 267
Water
body, glucocorticoid effects on, 551
renal reabsorption of, 431-432
supplies of, fluoridated, 721-724, 722f
safety of, 722-724
of schools, 724
Water solubility, of drugs
drug access to central nervous system and,
27
membrane penetration and, 17
placental transfer and, 27-28
volume of distribution and, 28, 28f
Waxman-Hatch Act, 863
Wedensky inhibition, by local anesthetics,
250
Weight, body
drug effects and, 49
gain of, with antipsychotic drugs, 170-172,
171t
loss of, sympathomimetic anorexic drugs for,
101
Weights and measures, for drugs, 861-862,
862t
Wells, Horace, 266
Wetting agents, as laxatives, 532, 532f
Wilson’s disease, drugs used for, 242
Withdrawal
from alcohol, benzodiazepine therapy for,
197-198
amphetamine, 805
of antihypertensive drugs, 455
from benzodiazepines, 194, 197
from cocaine, 806
from marijuana, 809
from opioid analgesics, 801-802
from sedative-hypnotics, 803-804
Withdrawal syndrome, definition of, 800
Women, iron stores in, 472
World Health Organization, regulations of, for
occupational mercury exposure, 821-822
Wound healing, phenytoin for, 227
�
Xanthines, for asthma, names of, 522b-523b
Xenogeneic antibodies, oral administration of,
674
Xerostomia
adrenergic agonists and, 115
antidepressant use and, 183
antihypertensive use and, 456
antimuscarinic drugs and, 134-135
from cancer radiation therapy, 793
palliation of, 794
caries and, 794
causes and characteristics of, 125-126
dental practice and, 173
in drug-abusing patients, 811
in elderly, 837
in Parkinson’s disease, 242
xPharm, 67
Xylitol, for salivary gland stimulation, 793
�
Young’s rule, for drug dosage calculations,
861
�
Zafirlukast, for asthma, 517
Zalcitabine
for human immunodeficiency virus infection,
655
structural formula of, 650f
Zaleplon, 198
for oral sedation, 765
Zanamivir, for influenza, 647-649, 648t
Zero-order kinetics, of absorption and
elimination, 41
Zidovudine
for HIV and AIDS, 654
side effects of, 56t
structural formula of, 650f
Zileuton, for asthma, 517-518
Zinc phosphide, toxicity of, 829
Zinc supplements, for taste dysfunction in
cancer radiation therapy, 793
Ziprasidone
antipsychotic activity of, 167
metabolism of, 172t
relative potency of receptor antagonist
affinities in, 166t
side effects of, 171t
Zoledronic acid, 544. See also Bisphosphonates.
Zollinger-Ellison syndrome, H2 antihistamines
for, 369
Zolmitriptan
dosage forms and Tmax of, 380t
for migraine, 381
Zolpidem, 198, 198f
in dentistry, 207
for oral sedation, 765
toxic extension of therapeutic effect of, 55t
Zona fasciculata, hormones produced by, 549,
550f
Zona glomerulosa, hormones produced by,
549, 550f
Zona reticularis, hormones produced by, 549,
550f
Zonisamide
adverse reactions to, 219t
mechanisms of action and therapeutic uses
of, 216t
for seizures, 225
structural formula of, 223f
Zopiclone, 198
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Page 478
CHAPTER 29 Lipid-Lowering Drugs 463
TABLE 29-3
Properties of Lipid-Lowering Drugs
LIPOPROTEIN
CONCENTRATIONS
PLASMA
CHOLESTEROL
PLASMA
TRIGLYCERIDE TOXICITY DRUG INTERACTIONS
Clofibrate ↓ VLDL, ↓ IDL ↓ ↓ Nausea, diarrhea, myositis,
abnormal liver function tests,
skin rash, ventricular ectopy,
increased incidence of
noncardiac death
Enhanced effect of coumarin
anticoagulants
Gemfibrozil ↓ VLDL, ↓ IDL,
↑ HDL
↓ ↓ Abdominal pain, epigastric pain,
diarrhea, nausea, vomiting,
flatulence, rash, headache,
dizziness, anemia,
eosinophilia, leukopenia
Enhanced effect of coumarin
anticoagulants; myopathy
with HMG-CoA reductase
inhibitors
Nicotinic acid ↓ Chylomicrons,
↓ VLDL, ↓ IDL,
↓ LDL, ↑ HDL
↓ ↓ Flushing, pruritus, nausea,
diarrhea, glucose intolerance,
hyperuricemia,
hepatotoxicity
Myopathy, rhabdomyolysis,
renal failure with
HMG-CoA reductase
inhibitors
Cholestyramine,
colestipol
↑ VLDL (transient),
↓ LDL
↓ May increase
modestly in
some
patients
Constipation, nausea,
abdominal pain, flatulence,
biliary tract calcification,
steatorrhea, hyperchloremic
acidosis
Decreased absorption of
thiazides, tetracycline,
phenobarbital, thyroxine,
digitalis, coumarin
anticoagulants
HMG-CoA
reductase
inhibitors
↓ IDL, ↓ LDL,
↑ HDL
↓ ↓ Headache, flatulence,
abdominal pain, diarrhea,
rash, increased creatine
kinase and other enzyme
activities, myopathy
Enhanced effect of coumarin
anticoagulants;
myopathy,
rhabdomyolysis, renal
failure with nicotinic acid,
gemfibrozil, erythromycin,
cyclosporine
Ezetimibe ↓ LDL, ↓ HDL ↓ ↓ Headache, sinusitis, pharyngitis Cholestyramine binds
ezetimibe and lowers its
bioavailability; does not
alter bioavailability of
digitalis or coumarin
anticoagulants
↓, Decrease; ↑, increase.
HDLs, High-density lipoproteins; HMG-CoA, 3-hydroxy-3-methylglutaryl–coenzyme A; IDLs, intermediate-density lipoproteins; LDLs, low-density lipoproteins;
VLDLs, very-low-density lipoproteins.
anticoagulants, partly by displacing them from protein-
binding sites, but mostly because fibrates interfere with the
synthesis of several clotting factors (fibrinogen and factor VII).
Gemfibrozil is chemically distinct from other fibrates
because it has a propylene connector between the phenoxy
and isobutyrate ends of the molecule. The drug has been
shown to decrease the concentrations of blood triglycerides,
cholesterol, VLDL, IDL, and sometimes LDL. It also tends
to increase HDL concentrations more reliably than clofibrate.
In contrast to clofibrate, gemfibrozil has been shown to
decrease the incidence of myocardial infarction by 34% over
5 years.16 Principal side effects of gemfibrozil include abdomi-
nal pain, diarrhea, nausea, and vomiting. Less frequent adverse
effects are headache, dizziness, anemia, rash, eosinophilia, and
leukopenia. Similar to clofibrate, gemfibrozil enhances the
action of oral anticoagulants and may cause cholelithiasis.
When combined with an HMG-CoA reductase inhibitor,
muscle damage leading to rhabdomyolysis and myoglobinuria
has been reported.
Fenofibrate is the first of the second-generation fibric acid
derivatives to be tested in the United States. Although the
drug has been available in Europe since the early 1980s, it has
not been studied in a large prevention trial, as have clofibrate
and gemfibrozil. Nevertheless, the basic pharmacologic fea-
tures of fenofibrate are similar to the features of the previous
agents. A potential advantage of the second-generation drugs
is their greater ability to reduce LDL concentrations. Side
effects include the gastrointestinal disturbances common to
all fibrates and the potential for causing cholelithiasis.
Nicotinic Acid
Nicotinic acid, otherwise known as niacin, has been recog-
nized since the late 1930s as a member of the vitamin B
complex whose deficiency results in the disease pellagra. In
1955, it was reported that doses of nicotinic acid greater than
1 g (i.e., >50 times the recommended daily allowance of
niacin as a vitamin) reduce plasma cholesterol concentra-
tions,2 subsequently decreasing triglyceride concentrations.9
The function of niacin in the body, after conversion to nico-
tinamide adenine dinucleotide and nicotinamide adenine
dinucleotide phosphate, is to act as important enzyme cofac-
tors. The action of niacin as a lipid-lowering drug is not related
Page 479
464 PART II Pharmacology of Specific Drug Groups
CH CH2 CH CH2
CH2 CH CH2N
+(CH3)3Cl
–
n
n
HNCH2CH2NCH2CH2NCH2CH2NCH2CH2NH
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2
HCOH
CH2
CH2CH2NCH2CH2N HNCH2CH2N HNCH2CH2
FIGURE 29-4 Structural formula of bile acid sequestrants cholestyramine and colestipol.
to its function as a vitamin. Nicotinamide, interchangeable
with nicotinic acid as vitamin B3, has no effect on plasma
lipids and should not be used.
Nicotinic acid is used most often to reduce VLDL and LDL
while increasing HDL levels. It has been used alone or in com-
bination with other lipid-lowering drugs. Its mechanism of
action seems to involve inhibition of VLDL synthesis through
inhibition of adipose tissue lipolysis and inhibition of subse-
quent delivery of fatty acids to the liver to produce triglycerides
for packaging into VLDL particles.19 Increased clearance of
VLDL may also play a role in the mechanism because of ele-
vated lipoprotein lipase activity. Nicotinic acid has the broad-
est spectrum of activity of the lipid-lowering agents and is
potentially useful in most forms of hyperlipidemia.
The major disadvantage of nicotinic acid, which affects
50% or more of the patient population, has been its tendency
to produce adverse effects sufficient to impair patient compli-
ance or force cessation of therapy. Common side effects
include cutaneous flushing, pruritus, and gastrointestinal dis-
tress. An additional side effect in some diabetic patients is
increased insulin resistance and hyperglycemia. If treatment
is instituted slowly, with a gradually increasing dosage, toler-
ance to the cutaneous flushing occurs, and therapy can be
continued. Aspirin or ibuprofen taken beforehand ameliorates
prostaglandin-dependent flushing. Withdrawal of nicotinic
acid is most frequently necessitated by gastric disturbances.
Other side effects include hyperuricemia, decreased glucose
tolerance, and abnormal liver function tests. Extended-release
preparations of nicotinic acid marketed in the past few years
have made this drug more tolerable to many patients, but do
not eliminate flushing in all patients.
Nicotinic acid is absorbed rapidly, usually reaching a peak
plasma concentration in less than 1 hour. The short half-life
is primarily due to rapid excretion of unmetabolized nicotinic
acid by the kidneys; this necessitates frequent administration
of the drug, usually three times a day with meals. Because of
the frequent lack of tolerance, doses are started at 100 mg
three times per day and are gradually increased at 100-mg
intervals until a dose of 1 to 1.5 g is reached. The usual thera-
peutic dose is 2 to 6 g/day. Extended-release preparations are
taken once each day, in the evening, and can be started at a
higher dose. These preparations have been shown to have less
incidence of side effects even in patients with diabetes.
Bile Acid Sequestrants
Bile acid sequestrants are nonabsorbable anion exchange
resins that bind bile acids in the intestinal lumen, prevent
their reabsorption, and promote their excretion in the feces.
Enterohepatic cycling of cholesterol is markedly reduced by
this mechanism, which blocks reabsorption of bile acids
from the jejunum and ileum, 95% of which are normally
reabsorbed, and increases bile acid excretion rate by 10-fold.
Bile acids are synthesized in the liver from cholesterol by
7α-hydroxylase, which is regulated through negative feedback
by bile acids. Hepatic cholesterol conversion to bile acids is
accelerated, and plasma cholesterol and LDL concentrations
are decreased. LDL concentrations are also reduced by these
drugs because of upregulation of LDL receptors and hepatic
uptake, whereas the VLDL concentration may be unchanged
or increased.26 These resins have no effect in patients with
homozygous familial hypercholesterolemia who have no func-
tioning LDL receptors.
Cholestyramine and colestipol are the two clinically avail-
able drugs in this category (Figure 29-4). They are very large
resins that are insoluble in water. The dry resin is mixed with
a liquid such as fruit juice and drunk as a slurry. Cl− is released
from the resin as bile acids bind to it, and the released Cl− is
absorbed, but the resin itself is not absorbed. Because it is not
absorbed, it has a high safety factor and absence of serious
side effects, but the annoying gastrointestinal side effects
(nausea, vomiting, abdominal distention, and constipation)
limit the use of these drugs. An unpleasant taste adds to the
problem of patient compliance with these agents. Because
cholestyramine and the hydrochloride salt of colestipol clini-
cally exchange Cl− for other anions, hyperchloremic acidosis
may develop when large doses are given to small patients.
Both resins decrease the absorption and the therapeutic effect
of other drugs, such as warfarin, thyroxine, digitalis, pro-
pranolol, and thiazides. This interaction can be partially over-
come by proper timing of the dosage.
Bile acid–binding resins are used alone or in combination
with nicotinic acid and cholesterol synthesis inhibitors. Cho-
lestyramine was used in the Lipid Research Clinics Program
Primary Prevention Trial.27 In this trial of almost 4000 healthy
men with hypercholesterolemia, there was a 20% decrease in
LDL cholesterol with the resin and a 24% reduction in deaths
from myocardial infarction.
The newest bile acid sequestrant to be approved for use
in the United States is colesevelam hydrochloride, which is
available in tablet form. Colesevelam has been found to lower
LDL cholesterol as effectively as cholestyramine,11 but has less
danger of interaction with other drugs such as warfarin
through adsorption.12 There are also somewhat fewer gastro-
intestinal side effects, and, because of the tablet form, compli-
ance is greater.
3-Hydroxy-3-Methylglutaryl–Coenzyme A
Reductase Inhibitors
The development of drugs that specifically inhibit the biosyn-
thesis of cholesterol has been the most important aspect of
hypolipidemic drug development. This class of drugs, called
the statins, currently includes lovastatin, pravastatin, simvas-
tatin, fluvastatin, cerivastatin, atorvastatin, and rosuvastatin.
These agents structurally resemble an intermediate in the
HMG-CoA reductase reaction (Figure 29-5) and are potent
competitive antagonists of HMG-CoA binding.20 (Lovastatin
and simvastatin are actually prodrugs in that they require
cleavage of their lactone ring to become active.) Numerous
clinical studies have now shown these drugs to be the best
tolerated and most effective drugs for lowering LDL choles-
terol and for reducing stroke, coronary heart disease, and
overall mortality. In addition to lowering LDL cholesterol,
Page 956
L1
Index 941
in dentistry, 182
development and use of, 165
inhibition of reuptake of 5-HT by, 376
for migraine prophylaxis, 383
for Parkinson’s disease, 236t
pharmacologic effects of, 175-176
therapeutic uses of, 181
Trifluoperazine, side effects of, 171t
Triflupromazine, side effects of, 171t
Trifluridine, for herpes virus infections, 651
Trigeminal nerve, in pain transmission, 300
Trigeminal neuralgia, 386
diagnostic criteria for, 387b
topical agents for, 389-390
Trigeminothalamic tract, in pain perception,
300f, 301, 303
Triglycerides, in lipoprotein metabolism,
459-460
Trihexyphenidyl, for Parkinson’s disease, 236t,
240
Triiodothyronine, structural formula of, 540f
Trimeprazine tartrate, structural formula and
dosages of, 363t-364t
Trimetazidine, for angina, mechanism of action
of, 423-424
Trimethadione
as anticonvulsant, 221
mechanisms of action and therapeutic uses
of, 216t
Trimethaphan
structural formula of, 138f
uses of, 139-140
Trimethobenzamide
as antiemetic, 531
for migraine, 381-382
Trimethoprim. See also Sulfonamides.
herbal product interactions with, 872t
mechanism of action of, 583
synergism of, with sulfonamides, 631
therapeutic uses of, 632, 633t
Trimethoprim-sulfamethoxazole, for traveler’s
diarrhea prevention, 535
Trimipramine, adverse effects of, 176t
Tripelennamine citrate, structural formula and
dosages of, 363t-364t
Tripolidine hydrochloride, structural formula
and dosages of, 363t-364t
Triptans
adverse reactions to, 381b
contraindications to, 381, 381b
for migraine, 380-381, 380t
names of, 391t
Trizivir, for human immunodeficiency virus
infection, 655
Troleandomycin, 618. See also Macrolide
antibiotics.
Trophoblasts, placental transfer of drugs and,
27-28
Tropicamide, for mydriasis and cycloplegia,
132
Tropomyosin, in cardiac muscle contraction,
410
Troponin, in cardiac muscle contraction,
410
TRP (transient receptor potential) channels, on
nociceptive neurons, 301
Tryptamine derivatives, abuse of, 807-808
Tryptophan, antidepressant action and, 173
Tryptophan hydroxylase, in serotonin
synthesis, 374f, 375
Tuberculosis, drugs used for, 615
names of, 636b-637b
Tubocurarine, 136
action and structural formula of, 140,
141f
historical use of, 141
pharmacologic properties of, 142t
Tubular reabsorption, in renal excretion of
drugs, 40
Tumor killing, cytokines in, functional
relationships of, 663t
Tumor resistance, chemotherapeutic
approaches to, 708
Tumor suppressor genes, in chemical
carcinogenesis, 58
Tyramine
monoamine oxidase inhibitors and, 114-115,
177
structure-activity relationships of, 92t
tachyphylaxis and, 52-53
Tyrosine
biosynthesis of, 85f
enzyme-linked receptor action and, 4
Tyrosine hydroxylase, in catecholamine
synthesis, 82
Tyrosine kinase inhibitors, for cancer, 704-706,
704f, 705t
U
Ubiquitin, in antigen processing, 665
Ulcer(s)
oral, glucocorticoids for, 553
peptic. See also Peptic ulcer disease (PUD).
treatment of, 525-530
Ulcerative gingivitis, acute recrotizing,
microbiology of, 602
Unconsciousness, definition of, 267
Unified Parkinson’s Disease Rating Scale
(UPDRS), 233-234
scores on, effects of anti-Parkinson drugs on,
235t
United States Pharmacopeia (USP), 65-66, 862
Unresponsiveness, definition of, 267
Uracil, structural formula of, 694f
Urea, volume of distribution of, 28t
Ureidopenicillins, 606t-607t
Uric acid, in gout, 352
Uridine diphosphate glucuronosyltransferase
polymorphism, 73
Urinary antiseptics, 634-635
Urinary bladder, endogenous catecholamine
effects on, 94-95
Urinary tract
antimuscarinic drug effects on, 132-133
cholinergic drug effects on, 120
ganglionic blocking drug effects on, 139
Urine
alkalinization of, for toxicity treatment, 40
mercury concentrations in, 821, 821f
pH of, in renal excretion, 40
Urofollitropin, 576
Urokinase, for emergency use, 849
Urokinase plasminogen activator, in
fibrinolysis, 498-500, 499f
Urticaria, H1 antihistamines for, 366
Use-dependent block, by local anesthetics,
250-252
USP Dispensing Information, drug information
in, 66
Uterus
endogenous catecholamine effects on,
94-95
relaxation of, adrenergic agonists for, 100
V
Vaccination, 671
Vaccine(s)
caries, 672
herpes zoster, 652-653
human immunodeficiency virus, 656
human papillomavirus, 648t
influenza, 648t, 649
subunit, 663
Vagus nerve
in pain transmission, 300
Valacyclovir
for herpes virus infections, 648t, 651-652
for oral HSVons, 787
Valdecoxib
COX inhibitory activity of, 331f
for inflammatory conditions, 345
structural formula of, 343f
Valerian, pharmacologic profile of, 870t-871t
Valganciclovir, for CMV infections, 652
Valproic acid, 220-221
absorption, fate, and excretion of, 221
adverse effects of, 219t, 221
discovery of, 214-215
drug interactions with, 227
interactions of, with barbiturates, 195t
for mania, 185
mechanisms of action and therapeutic uses
of, 216t
pharmacologic effects of, 221
side effects of, 56t
structural formula of, 217f
for trigeminal neuralgia, 387-388
Valsartan, for chronic heart failure, 413
Van der Waals forces, in drug-receptor
interactions, 5f, 6
Vancomycin, 630
adverse effects of, 630
antibacterial spectrum of, 630
for C. difficile diarrhea, 596
drug interactions with, 630
mechanism of action of, 630
microbial resistance to, 586-587, 630
therapeutic uses of, 630
Vanilloid receptor channels, on nociceptive
neurons, 301
Vapor, elemental mercury, 821
Vaporizer, temperature-compensated,
variable-bypass, for inhalation anesthetics,
278, 278f
Variant angina, 422
Varicella-zoster virus, drugs active against,
652-653
famciclovir as, 652
herpes zoster vaccine as, 652-653
Varicella-zoster virus infection, in cancer
patients, 787
Varnish, fluoride, 726
Vascular effects
of anticholinesterases, 123
of endogenous catecholamines, 93-94
of isoproterenol, 97
Vascular smooth muscle
cholinergic drug effects on, 119-120
relaxation of, by nitrovasodilators, 424
Vasculature
peripheral, local anesthetic action and,
255
systemic, digoxin administration and, 416
Vasoconstriction
endogenous catecholamine-induced, 93-94
in hemostasis, 487
histamine effects on, 361
Vasoconstrictor(s)
adrenergic, 99
for bleeding control, 495
in dentistry, 101-103, 101t
names of, 103b-104b
for emergency use, 849
ergotamine as, 379
in local anesthetics
drug interactions with, 258, 455-456
effects of, 255-256
local tissue responses to, 257
names of, 103b-104b, 509t
Vasodilation
calcium channel blockers and, 427
cerebral, morphine administration and, 313
histamine effects on, 361-362
muscarinic receptor stimulation and, 118,
119f
nitrites/nitrates in, 424
Vasodilator(s)
direct
for hypertension, 452-454
names of, 456b-457b
directly acting, for congestive heart failure,
420
for emergency use, 846t, 849
Vasopressin, 431, 538. See also Antidiuretic
hormone (ADH).
for emergency use, 846t-848t, 848-849
Vasopressors, for emergency use, 849
Vectors, for breaching blood-brain barrier, 27
Vecuronium
pharmacologic properties of, 142t
toxic extension of therapeutic effect of, 55t
Venable, James, 266
Venlafaxine, 180
adverse effects of, 176t
for chronic pain syndromes, 383
structural formula of, 178f
Tricyclic antidepressants (Continued) Valproic acid (Continued)
Page 957
L1
942 Index
Ventilation
mechanical, neuromuscular blocking drugs
in, 144
pulmonary, for acute opioid intoxication,
313
Ventricular fibrillation, electrocardiographic
appearance of, 396-397, 397f
Ventricular tachycardia, electrocardiographic
appearance of, 396-397, 397f
Verapamil
actions of, 400t
benzodiazepine interactions witn, 195
cardiovascular effects of, 427, 428t
for cluster headache, 384
digoxin and, 419
for emergency use, 846t-848t, 848
for hypertension, 447-448
indications for, 407t
pharmacokinetic properties of, 401t
structural formula of, 427f
Vertigo, H1 antihistamines for, 366-367
Vesicles, synaptic, in nerve stimulation, 149
Vestibular function, antimuscarinic drug
effects on, 132
Vidarabine
for herpes virus infections, 648t, 650-651
mechanism of action of, 650f
structural formula of, 650f
Vigabatrin
adverse reactions to, 219t
clinical toxicology of, 215
mechanisms of action and therapeutic uses
of, 216t
for seizures, 223-224
structural formula of, 223f
Vildagliptin, for diabetes, 563-564
Vinblastine
for cancer, 686t-692t, 698
structural formula of, 698f
Vinca alkaloids, for cancer, 686t-692t, 698
Vincent’s infection, microbiology of, 602
Vincristine
for cancer, 686t-692t, 698
structural formula of, 698f
Vinorelbine, for cancer, 686t-692t, 698
Viral hepatitis, in drug-abusing patient, 811
Virulence, microbial, factors affecting, 594
Virus(es)
inactivation of, in therapeutic blood
products, 497
infections due to
antibiotics for, 610t-611t
antiviral agents for, 647-656, 648t
names of, 657b
oral, in immunosuppressed patients,
787-788
transmission of, in hemophiliacs, 508
Vitamin B12, 477-479
deficiency of
megaloblastic anemia from, 476-477
pathophysiologic characteristics of,
478-479
dietary sources of, 477
metabolic pathways of, 481f
physiologic characteristics of, 477-478
preparations of, names of, 485t
Vitamin D, 543-544
effects of, 544t
on bone, gastrointestinal tract, and kidney,
544t
preparations of, names of, 546b-547b
structural formula of, 544f
Vitamin K
coumarin-indandione action and, 502, 504
deficiency of, hemorrhage and, 503
Vitamin K-dependent clotting factors, 490
Vitamin K epoxide reductase, inhibition of, by
coumarin-indandiones, 502, 503f
Volatile solvents, abuse of, 810
Voltage-gated ion channels, 2
anesthetic action and, 270
Volume depletion
loop diuretics and, 437
thiazide diuretic action and, 435
Volume of distribution
of drugs, 28, 28f, 28t
in renal drug excretion, 40
of various agents, 28t
Vomiting. See also Antiemetics.
antihistamines for, 366-367
cancer chemotherapy-induced, 531, 789-790
digoxin administration and, 417
morphine-induced, 312
von Willebrand factor, in platelet adhesion,
487, 488f
von Willebrand’s disease, 496-497
treatment of, 497-498
Voriconazole
for fungal infections, 644
introduction of, 596
structural formula of, 643f
Vorinostat, for cancer, 705t
Warfarin
chloral hydrate with, 202
drug interactions with, 504
interactions of
with barbiturates, 190t
with chloral hydrate, 190t
for myocardial infarction prevention, 429
structural formula of, 503f, 831f
toxicity of, 830
Warren, John C., 267
Water
body, glucocorticoid effects on, 551
renal reabsorption of, 431-432
supplies of, fluoridated, 721-724, 722f
safety of, 722-724
of schools, 724
Water solubility, of drugs
drug access to central nervous system and,
27
membrane penetration and, 17
placental transfer and, 27-28
volume of distribution and, 28, 28f
Waxman-Hatch Act, 863
Wedensky inhibition, by local anesthetics,
250
Weight, body
drug effects and, 49
gain of, with antipsychotic drugs, 170-172,
171t
loss of, sympathomimetic anorexic drugs for,
101
Weights and measures, for drugs, 861-862,
862t
Wells, Horace, 266
Wetting agents, as laxatives, 532, 532f
Wilson’s disease, drugs used for, 242
Withdrawal
from alcohol, benzodiazepine therapy for,
197-198
amphetamine, 805
of antihypertensive drugs, 455
from benzodiazepines, 194, 197
from cocaine, 806
from marijuana, 809
from opioid analgesics, 801-802
from sedative-hypnotics, 803-804
Withdrawal syndrome, definition of, 800
Women, iron stores in, 472
World Health Organization, regulations of, for
occupational mercury exposure, 821-822
Wound healing, phenytoin for, 227
�
Xanthines, for asthma, names of, 522b-523b
Xenogeneic antibodies, oral administration of,
674
Xerostomia
adrenergic agonists and, 115
antidepressant use and, 183
antihypertensive use and, 456
antimuscarinic drugs and, 134-135
from cancer radiation therapy, 793
palliation of, 794
caries and, 794
causes and characteristics of, 125-126
dental practice and, 173
in drug-abusing patients, 811
in elderly, 837
in Parkinson’s disease, 242
xPharm, 67
Xylitol, for salivary gland stimulation, 793
�
Young’s rule, for drug dosage calculations,
861
�
Zafirlukast, for asthma, 517
Zalcitabine
for human immunodeficiency virus infection,
655
structural formula of, 650f
Zaleplon, 198
for oral sedation, 765
Zanamivir, for influenza, 647-649, 648t
Zero-order kinetics, of absorption and
elimination, 41
Zidovudine
for HIV and AIDS, 654
side effects of, 56t
structural formula of, 650f
Zileuton, for asthma, 517-518
Zinc phosphide, toxicity of, 829
Zinc supplements, for taste dysfunction in
cancer radiation therapy, 793
Ziprasidone
antipsychotic activity of, 167
metabolism of, 172t
relative potency of receptor antagonist
affinities in, 166t
side effects of, 171t
Zoledronic acid, 544. See also Bisphosphonates.
Zollinger-Ellison syndrome, H2 antihistamines
for, 369
Zolmitriptan
dosage forms and Tmax of, 380t
for migraine, 381
Zolpidem, 198, 198f
in dentistry, 207
for oral sedation, 765
toxic extension of therapeutic effect of, 55t
Zona fasciculata, hormones produced by, 549,
550f
Zona glomerulosa, hormones produced by,
549, 550f
Zona reticularis, hormones produced by, 549,
550f
Zonisamide
adverse reactions to, 219t
mechanisms of action and therapeutic uses
of, 216t
for seizures, 225
structural formula of, 223f
Zopiclone, 198
