Chapter 20: Drugs & Drug

interactions
Introduction to Drug Interactions
Antibiotic Drug Interactions
Anticoagulant Drug Interactions
Antidiabetic Drug Interactions
Antihypertensive Drug Interactions
Antipsychotic Drug Interactions
Cardiac Drug Interactions
Diuretic Drug Interactions
NonSteroidal anti-inflammatory Drug Interactions
Oral Contraceptive Drug Interactions
Mechanisms of Drug Interactions Drugs
 DRUGS & DRUG INTERACTIONS
Introduction to Drug Interactions
1. Types of drug interactions:
a. Addition (1 + 1 = 2): The response elicited by combined drugs is equal to
the combined responses of the individual drugs
b. Synergism (1 + 1 = 3): The response elicited by combined drugs is greater
than the combined responses of the individual drugs:
c. Potentiation (0 + 1 = 2): A drug which has no effect enhances the effect
of a second drug
d. Antagonism (1 + 1 = 0): A drug inhibits the effect of another drug

2. Mechanisms of drug interactions:

a. Altered absorption
b. Altered metabolism
c. Plasma protein displacement
d. Altered excretion

3. Top 10 interaction drug problem list:

a. Antibiotics
b. Anticoagulants
c. Antidiabetic agents
d. Antipsychotics
e. Beta blockers
f. Digoxin
g. NSAIDS
h. Oral contraceptives

Antibiotic Drug interactions

1. Aminoglycosides with:
a. Cephalosporins (parenteral): Effect is increased nephrotoxicity, mechanism
unknown
b. Penicillins (parenteral): Effect is inactivation of certain aminoglycosides,
mechanism is unknown
c. Loop diuretics: Effect is increased 8th cranial nerve damage with possible
irreversible hearing loss, mechanism is synergistic auditory toxicity

2. Imidazole antifungals (ketoconazole and Itraconazole) with:

a. Seldane: Effect is Cardiotoxicity, arrhythmia, death, mechanism is that
imidazoles exert a quinidine-like effect with prolongation of Q wave on the
EKG
b. Hismanal : Same as with Seldane
c. H2 antagonists: Effect is inactivation of the imidazoles, mechanism is
alteration of the pH by the H2 antagonists and antacids
d. Phenytoin: Effect is decreased action of imidazoles, mechanism is
increased metabolism by hydantoin induction of hepatic enzymes
3. Macrolide antibiotics (erythromycin, clarithromycin and
clindamycin) with:
a. Seldane (with erythromycin and clarithromycin): Effect is cardiotoxicity,
arrhythmia, death, mechanism is macrolides exert a quinidine-like effect with
prolongation of Q wave on the EKG
b. Hismanal: Same as with Seldane
c. Theophylline (with erythromycin and clarithromycin): Effect is increased
theophylline toxicity, mechanism is decreased theophylline renal clearance
d. Oral anticoagulants (with erythromycin only): Effect is increased
anticoagulant activity with hemorrhage, mechanism is unknown
e. Kaopectate (with clindamycin only): Effect is decreased absorption of
clindamycin, mechanism is binding absorption of the antibiotic

4. Quinolones with:
a. Multivalent cations (antacids): Effect is decreased effects of the
quinolones, mechanism is chelation binding decreases the GI absorption
b. Theophylline: Effect is increased theophylline toxicity, mechanism is
inhibition of hepatic metabolism of theophylline
c. Carafate: Effect is decreased effects of quinolones, mechanism is chelation
binding decreases GI absorption
d. Caffeine: Effect is increased effect of caffeine

5. Miscellaneous antibiotics:
a. Penicillins (ampicillin) with allopurinol: Effect is markedly increased rate of
ampicillin retention and induced skin rash, mechanism is unknown
b. Metronidazole with alcohol: Effect is a disulfiram-like reaction, mechanism
is metronidazole inhibits aldehyde dehydrogenase

NOTE Disulfiram reaction (with OH) is nausea, vomiting, hypotension, and

possible coma later on

c. Tetracyclines with multivalent cations: Effect is decreased effects of

tetracyclines, mechanism is chelation binding decreases GI absorption
d. Ampicillin with oral anticoagulants: Effect is increased anticoagulant
activity

Anticoagulant Drug Interactions

1. Anticoagulants (oral) with:
a. Aspirin: Effect is increased bleeding and hypoprothrombinemic effects of
Warfarin, mechanism is protein binding displacement combined with anti
platelet effects
b. Erythromycin: Effect is increased anticoagulant activity with hemorrhage,
mechanism is unknown
c. Cephalosporins: Effect is augmented Warfarin effects, mechanism is
antiplatelet effects of certain parenteral cephalosporins
d. H2 antagonists:: Effect is increased bleeding with possible hemorrhage,
mechanism is inhibition of hepatic metabolism of Warfarin
e. Phenytoin: Effect is increase in both bleeding and phenytoin activity,
mechanism is unknown
f. Sulfonylureas: Effect is hypoglycemia, mechanism is the hepatic
metabolism of the sulfonylureas is inhibited
g. Barbiturates: Effect is decreased effect of Warfarin, mechanism is
barbiturate induced heptic metbolism of Warfarin
h. Griseofulvin: Effect Is decreased effect of Warfarin, mechanism is unknown

Antidiabetic Drug Interactions

1. Insulin with:
a. Alcohol: Effect is hypoglycemia, mechanism is inhibition of
gluconeogenesis
b. Beta Blockers: Effect is hypoglycemia with the masking of hypoglycemic
symptoms, mechanism is that beta blockers blunt sympathetic mediated
responses to hypoglycemia
c. MAO inhibitors: Effect is hypoglycemia, mechanism is inhibition of
gluconeogenesis
d. Salicylates: Effect is hypoglycemia, mechanism is increased circulating
concentration of insulin
e. Steroids/Estrogen/Thyroxin: Effect is increased hypoglycemia

2. Sulfonylureas with:
a. Alcohol: Effect is hypoglycemia and disulfiram-like reactions, mechanism is
decrease elimination and altered metabolism involving aldehyde
dehydrogenase
b. Anticoagulants: Effect is hypoglycemia, mechanism is inhibition of hepatic
metabolism of sulfonylureas
c. MAO inhibitors: Effect is hypoglycemia, mechanism is unknown
d. NSAIDS: Effect is hypoglycemia, mechanism is protein binding
displacement
e. Sulfinpyrazone: Effect is hypoglycemia, mechanism is inhibition of hepatic
metabolysm of sulfonylureas
f. Thiazide diuretics: Effect is hyperglycemia, mechanism is thiazide diuretics
decrease insulin secretion

Antihypertensive Drug Interactions

1. ACE Inhibitors with:
a. Indomethacin: Effect is decreased hypotensive effect of ACE inhibitor,
mechanism is interference with plasma renin activity and vasopressor
response
b. Potassium supplements: Effect is hyperkalemia, mechanism is unknown
c. Capsaicin (Zostrix): Effect is exacerbation of coughing associated with ACE
inhibitor, mechanism is unknown

2. Calcium Channel Blockers (Verapamil and Nifedipine) with:

a. Calcium salts (with Verapamil): Clinical effect of Verapamil is reversed,
mechanism is pharmacologic antagonism
b. Quinidine (with Verapamil): Effect is hypotension
c. H2 antagonists (with Nifedipine): Effect is hypotension, mechanism is
inhibition of hepatic metabolism of nifedipine

Antipsychotic Drug Interactions

1. MAO Inhibitors with:
a. Meperidine: Effect is seizures coma apnea, and death, mechanism is
unknown
b. Tricyclic antidepressants: Effect is seizures, hypotension, coma, and death,
mechanism is unknown
c. Amine containing foods: Effect is hypertensive crisis or stroke, mechanism
is impaired metabolism of tyramine by inhibition of monoamine oxidase

2. Lithium with:
a. Iodide salts: Effect is hypothyroidism or goiter, mechanism is
pharmacologic synergism
b. Thiazide diuretics: Effect is increased lithium toxicity, mechanism is
decreased lithium renal clearance
c. NSAIDS: Effect is increased lithium toxicity, mechanism is decreased
lithium renal clearance

3. Phenothiazines with:
a. Meperidine: Effect is excessive hypotension and sedation, mechanism is
pharmacologic synergism
b. Anticholinergics: Effect is decreased effect of phenothiazines, mechanism
is accelerated metabolism of phenothiazines

Cardiac Drug Interactions

1. Beta Blockers with:
a. Epinephrine: Effect is initial hypertensive episode, followed by bradycardia,
mechanism is beta blockade allowing alpha receptor stimulation increasing
BP which stimulates baroreceptors causing
bradycardia
b. Verapamil: Effect is that the effects of both drugs are increased,
mechanism is pharmacologic synergism
c. Insulin: Effect is prolonged hypoglycemia with masking of hypoglycemic
symptoms (tachycardia), mechanism is that beta blockers blunt sympathetic
mediated responses to hypoglycemia
d. NSAIDS: Effect is impaired antihypertensive effect of beta blockers,
mechanism is NSAIDS inhibit renal prostaglandin synthesis allowing
unopposed vasopressor activity
e. Theophylline: Effect is antagonistic activity increasing airway resistance,
mechanism is pharmacologic antagonism
f. H2 Antagonists: Effect is increased effects of beta blockers, mechanism is
H2 antagonists can inhibit first pass hepatic metabolism of beta blockers

2. Digoxin with:
a. Diuretics: Effect is electrolyte disturbances predispose to digitalis-induced
arrhythmias, mechanism is increased loss of potassium affects cardiac
muscle action
b. Verapamil: Effect is increased digoxin toxicity, mechanism is additive
effects
c. Erythromycin: Effect is increased digoxin toxicity in about 10% of patients,
mechanism is in about 10% of patients, digoxin is metabolized by GI bacteria
d. Tetracycline: Effect is the same as above, mechanism is the same as
above
e. Quinidine: Effect is increased digoxin toxicity, mechanism is reduced renal
and biliary clearance of digoxin
f. Quinine: Effect is same as above, mechanism is same as above

Diuretic Drug Interactions

1. Loop diuretics with:
a. Aminoglycosides: Effect is increased 8th cranial nerve damage with
possible irreversible hearing loss, mechanism is synergistic auditory toxicity
b. Phenytoin: Effect is decreased effect of the diuretic, mechanism is
decreased absorption and increased metabolism

2. Thiazide diuretics with:

a. Lithium: Effect is increased lithium toxicity, mechanism is decreased
lithium renal clearance

3. Potassium sparing diuretics with:

a. Potassium supplements: Effect is hyperkalemia. mechanism is decreased
elimination of the potassium ion

4. Spironolactone with:
a. Salicylates: Effect is blockage of spironolactone-induced diuresis,
mechanism is blockage of the renal tubular secretion

Non Steroidal Anti-Inflammatory Drug

Interactions
1. NSAIDS with:
a. Anticoagulants: Effect is increased bleeding and hypothrombinemic effects
of Warfarin, mechanism is protein binding displacement combined with anti-
platelet effects
b. Beta Blockers: Effect is impaired antihypertensive effect of beta blockers,
mechanism is NSAIDS inhibit renal prostaglandin synthesis allowing
unopposed vasopressor activity
c. Lithium: Effect is increased lithium toxicity, mechanism is decreased
lithium renal clearance
d. ACE inhibitors (Indomethacin): Effect is decreased hypotensive effect of
ACE inhibitors, mechanism is interference with plasma renin activity and
vasopressor response
e. Methotrexate: Effect is increased methotrexate toxicity, mechanism is
decreased renal clearance of methotrexate

Oral Contraceptive Drug Interactions

1. Oral contraceptives with:
a. Phenytoin: Unintended pregnancy
b. Barbiturates: Unintended pregnancy
c. Griseofulvin: Unintended pregnancy
d. Corticosteroids: Effect is therapeutic and adverse actions of corticosteroids
are enhanced
Mechanisms of Drug Interactions
1. Alteration of Intestinal Absorption:
a. Antacids diminish absorption of: (Antacids contain Ca++, Mg++, or
Al +++)
i. Phenylbutazone
ii. Sulfonamides
iii. Barbiturates
iv. Salicylates
v. Oral anticoagulants
vi. Indomethacin
vii. Ampicillin/penicillin
viii. Tetracycline
ix. Cipro®

b. Antacids increase the absorption of:

i. Talwin®
ii. Antihistamines
iii. Phenergan®
iv. Darvon®

c. Drugs that alter vitamin K levels:

i. antibiotics (penicillin, ampicillin, erythromycin, and tetracycline) reduce
vitamin K production, therefore may increase anticoagulant activity.

d. Drugs that alter GI motility:

i. Decrease motility: codeine, morphine, and other opiates
ii. Increase motility: milk of magnesia, cathartics

2. Competition for Plasma binding protein:

a. Oxacillin/cloxacillin/dicloxacillin/nafcillin can displace uric acid which
can precipitate a gouty attack.
b. Dicoumarol can sustain tolbutamide activity (causes severe hypoglycemia)

3. Metabolism or Biotransformation Alteration:

a. Inhibition of metabolism:
i. Anticholinesterases inhibit metabolism of ester-type local anesthetics
resulting in a prolonged effect of the drug.
ii. Oral anticoagulants prolong the effects of tolbutamide and increase the
toxicity of diphenhydramine by inhibiting metabolism.

b. Acceleration of metabolism:
i. Phenobarbital accelerates the metabolism of coumadin, anticoagulants,
steroids, and griseofulvin.
 Note* Patients on anticoagulants and barbiturates must be carefully
monitored when the barbiturate is discontinued, as prolonged 4.
hemorrhage can result.
Alteration of Electrolytes:
a. Hypokalemia may be caused by long term usage of digoxin, thiazide, and
furosemide diuretics, and corticosteroids.
b. Hyperkalemia may result from ACE inhibitors

5. Alteration of Renal Excretion:

a. Probenecid inhibits renal secretion of penicillin and other medications (see
#6, this chapter)
b. Salicylates (in small doses) interfere with the uricoscuric action of
probenecid

6. Drugs With Opposing Actions:

a. Thiazide diuretics elevate blood glucose levels. This may partially
counteract the hypoglycemic action of an antidiabetic drug, necessitating
adjustment of the dose.
b. Many diuretics produce hyperuricemia, requiring dose adjustments

7. Drug Interactions That Can Be Life Threatening:

a. Warfarin + phenobarbital
b. MAO inhibitor + wine and cheese (tyramine)
c. Neomycin + succinylcholine
d. Tolbutamide + dicumarol
e. Digitalis + thiazide diuretic
f. Seldane or Hismanil + macrolide antibiotics
g. Seldane or Hismanil + Imidazole antifungal agents

8. Potential Drug Interactions During the Perioperative Period:

a. Increase anesthetic requirements (Halothane/enflurane/isoflurane) on the
following:
i. Patients on MAO inhibitors
ii. Alcoholism
iii. Cocaine

b. Decrease anesthetic requirements:

i. Alcoholism
ii. Alpha-methyldopa
iii. Clonidine
iv. Verapamil

c. Potentiate neuromuscular blockers:

i. Magnesium
ii. Aminoglycoside antibiotics
iii. Lithium
iv. Lidocaine
v. Quinidine

9. Other Drug Interactions:

a. Tagamet®: Interacts with benzodiazepines: sedation may be enhanced
b. Morphine and meperidine: Interacts with CNS depressants: enhanced
sedation
c. Valium®: Interacts with alcohol, antihistamines, barbiturates, narcotics:
increased CNS depression

10. Possible adverse reactions to antibiotics in the elderly:

a. Pen G potassium: Hyperkalemia in patients with renal insufficiency
b. Pen G sodium: Sodium retention, volume overload
c. Carbenicillin: Pulmonary edema, hypokalemia associated with serious
arrhythmias, postop hemorrhage
d. Ticarcillin: Pulmonary edema, neurotoxicity
e. Tetracyclines: Exacerbation of pre-existing abnormal renal function
f. Minocycline: Vestibular disorders (nausea, vomiting, dizziness, vertigo)
g. Cephalothin: Nephrotoxicity, acute renal failure
h. Aminoglycosides: Nephrotoxicity, ototoxicity
i. Clindamycin: Pseudomembranous colitis
j. Chloramphenicol: Bone marrow suppression, aplastic anemia
k. Trimethoprin-sulfamethoxazole: Blood dyscrasias in patients with
borderline folate stores

Drugs
1. Topical antibacterials:
a. Muprocyn (Bactroban®): Effective against gram (+) cocci
b. Iodochloroquine (1 % cream/ointment): Effective against gram (+) and (-)
organisms
c. Gentamycin (Garamycin®): An aminoglycoside effective against gram (+)
and (-) organisms
d. Chloramphenicol (Chloromycetin®): Effective against gram (+) and gram
(-) organisms. Blood dyscrasias have been reported

2. Topical antiseptics:
a. Povidone-lodine (Betadine): Antibacterial and antifungal scrub
b. Chlorhexidine (Hibiclens: Antibacterial and antifungal, and nonallergenic
c. Hexachlorophene (Phisohex: Antibacterial and antifungal, a neurotoxin
(especially in infants)
d. Benzalkonium Cl (Zephiran Chloride®): A quaternary ammonium
compound. Antifungal and antibacterial depending on the concentration
e. Dakin's Solution (sodium hypochlorite): Active ingredient of commercial
liquid bleaches

3. Astringents: Have drying effects secondary to evaporation. Astringents

precipitate protein, thereby decreasing oozing
a. Burrow's solution: 5% aluminum acetate
b. Domeboro's powder (Pedi-boro®/Bluboro®): Aluminum sulfate and calcium
acetate
c. Dalibour solution: Copper and zinc sulfates with camphor
d. Silver nitrate (0.1-0.5%): Also has antiseptic effects
e. Acetic acid (1-2%): May decrease pseudomonas colonization

4. Drugs to treat Rheumatoid Arthritis;

a. Hydroxychloroquine (Plaquenil®): Can cause muscle weakness that can
affect the DTR's
b. Penicillamine (Cuprimine): Cytotoxic and immunosuppressant (cytotoxic to
lymphocytes and can cause bone marrow depression)
c. Gold salts: Toxicity may affect the CBC with a lowering of the Hb, WBC, and
platelets. Skin reaction in sun-exposed areas
i. Parenteral: Solganal®, Myochrysine®
ii. Oral: Auranofin®
d. Cytotoxics/lmmunosuppressants: Cytotoxic to lymphocytes and can cause
bone marrow suppression, making patients more susceptible to infections
i. Methotrexate (Rheumatrex)
ii. Azathioprine (Imuran®) e. Glucocorticoids

5. Adrenocorticosterolds:
a. Control mechanism: Corticotropin (ACTH) released from the anterior
pituitary stimulates the adrenal cortex to secrete glucocorticoids (cortisol)
and other corticosteroids. The release of ACTH is affected by corticotropin
releasing factor (CRF) from the hypothalamus. ACTH and CRF are subject to
negative feedback inhibition by cortisol/glucocorticoids. ACTH is at its highest
level in the early morning
b. Actions/Side effects of glucorticoids: Any dose of glucocorticoids may exert
a physiologic (replacement) or pharmacologic (anti-inflammatory,
immunosuppressive) effect. Adverse effects can result from too rapid
withdrawal, manifesting as acute renal insufficiency. Glucocorticoids inhibit
the early and the late phases of the inflammatory response. The physiologic
antagonism of histamine, prostaglandin, and kinin-induced vasodilation
occurs. There is an inhibition of prostaglandin and leukotriene synthesis. Also,
leukocyte adherence, chemotaxis, and bacteriocidal/fungicidal activities are
reduced. An inhibition of interleukin1 and T-cell lymphokine release occurs:
i. Hepatic gluconeogenesis/glycogen deposition
ii. Suppression of the HPA axis (after 5-7 days of high dose therapy)
iii. Decrease resistance to infection (signs of infection may be masked)
iv. Possibility of perforation in patients with peptic ulceration or
inflammatory bowel -disease
v. Myopathy: characterized by weakness of proximal muscles of the arms and
legs (tendon rupture)
vi. Osteoporosis (postmenopausal females are at greatest risk), fractures,
aseptic necrosis of the femoral head
vii. Fluid and electrolyte imbalances (sodium and water retention,
hypokalemia)
viii. May increase blood pressure and exacerbate K+ sensitive arrhythmias
ix. Exacerbation of diabetes mellitus
x. Impaired wound healing and skin fragility
xi. Increased frequency of subcapsular cataracts or glaucoma
xii. With high doses, psychologic disturbances (steroid psychosis) may
occur

c. Agents:
i. Short-acting:
 Betamethasone sodium phosphate: Celestone®,
 Dexamethasone sodium phosphate: Decadron®, Hexadrol®
ii. Long-acting:
 Hydrocortisone:
 Dexamethasone acetate: Decadron-LA®
 Triamcinolone acetonide: Kenalog®
 Methylprednisolone acetate: Depo-Medrol®
iii. Mixtures:
 Betamethasone acetate and phosphate: Celestone Soluspan®

6. Drugs to treat gout:

a. Colchicine: This inhibits PMN migration and phagocytosis of urate crystals,
PMN lactic acid production is reduced. Colchicine is used to treat acute gout.
It can be used IV for a more rapid response when there is gastric intolerance
precluding oral therapy (oral dose is .5-1.2 mg followed by .5-1.2 mg every 1-
3 hours until pain is relieved or GI distress develops. No more than 8 mg
should be given) (IV dose is 2 mg administered slowly over 2-5 minutes,
followed by .5-1.0 mg every 6 hours. No more than 4 mg should be given in
24 hours). This medication inhibits spindle
formation during mitosis, therefore decreases DNA activity (DNA activity is a
source of urates)
b. Uricosuric agents:
i. Probenecid (Benemid®): inhibits renal tubular absorption of urate,
approximately doubling the daily excretion of uric acid ( also inhibits the
tubular excretion of most penicillins/cephalosporins, naproxen, indomethacin,
methotrexate, and oral hypoglycemics

NOTE* In diabetics using probenecid, a false positive test may result for
urinary glucose using Clinitest® reagents may be observed ii.
Sulfinpyrazone (Anturane): similar to probenecid in action
c. Xanthine oxidase inhibitors:
i. Allopurinol (Zyloprim): Inhibits xanthine oxidase which converts xanthine
into uric acid. This drug is contraindicated in an acute attack (acts as a
competitive inhibitor of the enzyme)
d. NSAIDs: Used for symptomatic relief of acute gouty arthritis

7. NSAIDs:
a. Actions:
i. Analgesia
ii. Anti-inflammatory
iii. Antipyresis
iv. Gastric symptoms
v. Inhibition of platelet aggregation (reversible)
vi. Exacerbation of symptoms of aspirin-intolerant patients
vii. Other: CNS symptoms, hepatic injury with elevation of serum
transaminase, cutaneous reactions
b. Indications:
i. Arthritis
ii. Tendonitis
iii. Soft-tissue inflammation
iv. Mild to moderate pain

NOTE* The action of NSAIDs are compared to aspirin in reducing symptoms

c. Groups:
i. Salicylates:
 Diflunisal (Dolobid®)
ii. Propionic acids:
 Ibuprofen (Motrin®)
iii. Acetates:
 Naproxen (Naprosyn®/Anaprox®)
 Fenoprofen (Nalfon®)
 Ketoprofen (Orudis®)
 Etodolac (Lodine®)
 Flurbiprofen (Ansaid®)
iv. Pyrole acetic acids:
 Indomethacin Indocin®)
 Sulindac (Clinoril®)
 Tolmetin (Tolectin®)
 Nabumetone (Relafen®)
v. Oxicams:
 Piroxicam (Feldene®)
vi. Phenylacetic acids
 iclofenac (Voltaren®)
vii. Pyrazoles:
 Phenylbutazone (Butazolidin®)
viii. Fenamates:
 Meclofenamic acid (Meclomen®)

d. Drug interactions with NSAIDs:

i. Anticoagulants: May prolong prothrombin time
ii. ACE inhibitors: Reduce the antihypertensive effect
iii. Beta Blockers: Reduce the antihypertensive effect
iv. Lithium: Lithium levels increased
v. Loop diuretics: Effect of diuretics decreased
vi. Methotrexate: Increased risk of methotrexate toxicity
v. Thiazides: Decreased antihypertensive/diuretic actions
vi. Probenecid: Increased concentrations of NSAIDs

8. Laxatives/Antidiarrheals:
a. Laxatives: Are used for the treatment of constipation secondary to the use
of opiate analgesics for postoperative pain relief. Are classified by differences
in mechanism (active or passive), intensity of effect, and time to the onset of
action
i. Passive (24-72 hours): Metamucil®, Colace®, Chronulac®
ii. Active (6-8 hours): Ex-lax®, Senokot®, Dulcolax®
iii. Saline cathartics (30 minutes-3 hours): Magnesium citrate, Milk of
Magnesia®)
iv. Suppositories (15 minutes-1 hour): Glycerin, Dulcolax
b. Antidiarrheals should not be used for the treatment of acute diarrhea
associated with broad-spectrum antibiotics because of possible exacerbation
of pseudomembranous colitis
i. Passive (non-opiate): Kaopectate®, Pepto-Bismol®
ii. Opiates and others (decrease GI motility): Lomotil®, Imodium®

9. Muscle relaxants: Decrease skeletal muscle tone for use in acute muscle
spasms. Can be used after muscle or tendon transfer. All agents cause a
degree of sedation or CNS dysfunction. Most agents are combined with
acetominophen or aspirin
a. Centrally acting agents:
i. Metaxalone (Skelaxin®): contraindicated in patients prone to hemolytic
anemia
ii. Carisoprodol (Soma®): Contraindicated in acute intermittent porphyria
iii. Cyclobenzaprine (Flexeril®): Contraindicated in patients who have cardiac
pathologies or those receiving MAO inhibitors
iv. Orphenadrine (Norflex®): Contraindicated in glaucoma or prostatic
hypertrophy
v. Chlorzoxazone (Paraflex®)

10. Antiemetics: May be required postoperatively to control nausea and

vomiting. Drug-induced vomiting is believed to be mediated by dopamine
impulses within the chemoreceptor trigger zone of the CNS, therefore
dopamine receptor antagonists are generally effective
a. Phenothiazines: These drugs exert dopamine-receptor antagonism, plus
provide variable blockade of alpha-adrenergic (hypotension), chlolinergic
(atropine-like), and histamine receptors. Therefore these drugs should be
used with caution in patients with cardiovascular disease
i. Prochlorperazine (Compazine®)
ii. Chlorpromazine (Thorazine®)
iii. Promethazine (Phenergan)
b. Nonphenothiazines:
i. Trimethobenzamide (Tigan®): Contraindicated in patients who have
hypersensitivity to local anesthetics
ii. Benzquinamide (Emete-Con): May increase blood pressure, especially
in

patients receiving epinephrine or other pressure agents

iii. Hydroxyzine (Atarax®/Vistaril®):

11. Opioid analgesics and antagonists: Opioid analgesics exert their

actions by combining with one or more subtypes of opioid receptors within
the CNS, peripheral nervous system, or smooth muscles. The receptors
designated mu, kappa, or sigma are the most significant. Opioid analgesics
are classified into 3 groups based on the action at these receptors
12. Morphine/Morphine-like agents/Antagonists: Morphine exerts its
actions largely through agonistic behavior at the mu and kappa receptors
a. Actions:
i. Analgesic response characterized by a reduction in the sensory intensity
and the emotional response to pain
ii. Sedation and euphoria (behavioral)
iii. Depression of autonomic reflexes yields respiratory depression,
pupillary constriction, suppression of cough reflex, orthostatic hypotension
iv. Peripheral effects: constipation, increased urethral tone, weak
bronchoconstriction
b. Precautions:
i. Contraindicated in diarrhea characterized by pseudomembrane formation
ii. Use cautiously in patients with bronchial asthma, chronic obstructive
pulmonary disease or cor pulmonary
c. Drug interactions:
i. May potentially affect other CNS depressants
ii. May cause toxic reactions in patients receiving MAO inhibitors
d. Agonists-Antagonists:
i. Agonists: Dependence/abuse are less with these, and withdrawal symptoms
are less than with morphine-like drugs
ii. Antagonists (Naloxone/Narcan®): this antagonizes the mu, kappa, and
sigma receptors, thereby preventing or reversing opiate-induced respiratory
depression, sedation, hypotension and psychomimetic effects of sigma
agonists such as pentazocine. Should be used to achieve complete or partial
reversal of opiate induced CNS depression and can be used to diagnose
suspected opioid overdose

13. Analgesic combinations: The analgesic effect of the opioids can be

enhanced by the concurrent administration of a non-narcotic analgesic. Also
these may contain caffeine, antacids, or barbiturates
a. Codeine combinations: Tylenol® with codeine, empirin with codeine, APC
with codeine, Fiorinal®
b. Oxycodone combinations: Percodan®, Tylox®, Percocet®
c. Hydrocodone combinations: Vicodin®, Lortab®, Dolo-Pap®
d. Pentazocine combinations: Talwin Compound®, Talacen®
e. Propoxyphene combinations: Darvon® with ASA, Darvon-N® with ASA,
Darvocet-N 50/ N-100®, Darvon Compound®

14. Antidepressants for chronic pain syndromes: Any antidepressant

may be used to treat pain but the heterocyclic compounds are more popular.
The dosages are generally 1 /2 of those used for the treatment of depression
a. Amitryptyline (Elavil®): 25-100 mg
b. Doxepin (Apadin): 25-100 mg
c. Imipramine (Tofranil®): 50-100 mg

15. Antihistamines: Nearly all mammalian tissue contain histamine, with

the highest concentration found in the lungs, skin, and stomach. Histamine is
also stored in the mast cells and in circulating basophils where it is released
by antigenic stimuli or indirectly by organic bases. Responses to stimuli are
mediated by 2 distinct populations called H1 and H2. Antihistamines are H1-
receptor antagonists
a. Actions:
i. Reduce prominent vasodilation, vasodilation, increased microvascular
permeability, and bronchoconstriction caused by histamine
ii. Variable anticholinergic, antipruritic, sedative, and antiemetic effects
iii. Since related to local anesthetics, demonstrate local anesthetic
activity

b. Indications:
I. Adjunct in the treatment of pruritus and allergic reactions ii. Nocturnal leg
cramps
iii. As local anesthesia in patients allergic to amides and ester-linked
compounds
iv. Perioperative medication
16. Anxineytics (Sedative-Hypnotics): Benzodiazepines
a. Major effects:
i. Anxiolytic action (that is distinguished from the effects of reduced
conscious excitability)
ii. Sedation/sleep induction
iii. Skeletal muscle relaxation
iv. Anticonvulsant action
v. Antiemetic effect
b. Indications:
i. Perioperatively, for the relief of anxiety
 Valium®- 10 mg PO or IM
 Ativan®-0.05 mg/kg IM up to 4 mg
 Librium®- 50-100 mg PO or IM 1 hour before surgery
ii. Conscious sedation
iii. Sleep induction:
 Dalmane®- 15-30 mg
 Restoril®- 15-30 mg
 Halcion®- .25-.5 mg
 Ativan®- 2-4 mg
iv. Skeletal muscle relaxation:
  Valium®- 5-10 mg 3-4 times daily
v. Termination of acute seizures
 Valium®- 5-10 mg IV, repeated every 10-15 minutes prn, or 2-3 mg IV
repeated every 5 minutes
c. Precautions:
i. Contraindicated in acute narrow angle glaucoma
ii. IV administration may result in apnea or hypotension