| Drug:
Epinephrine or Adrenalin
(generic) |
| Drug Class: Sympathomimetic |
| Mechanism of Action: in asthma it
induces beta-2 mediated bronchodilation.
It also has alpha-mediated effects
that can constrict bronchial vessels, thus reducing
fluid congestion. |
| Indications: 1) treatment of acute
hypersensitivity (anaphylactoid reactions
to drugs, animal serums and other allergens), 2) treatment of acute
asthmatic attacks to relieve bronchospasm not controlled
by inhalation or subcutaneous administration of other solutions of the drug,
and 3) treatment and prophylaxis of cardiac arrest and attacks of transitory
atrioventricular (A-V) heart block with syncopal seizures (Stokes-Adams
Syndrome). |
| Side Effects: unwanted cardiovascular
side effects due to beta-1 and alpha-1 & 2 stimulation (increased heart
rate, blood pressure). |
| References: www.rxlist.com
& Katzung's text |
| Drug: Albuterol
(generic, Proventil, Ventolin ®) |
| Drug Class: Beta-2 Selective Sympathomimetic |
| Mechanism of Action: Stimulates beta-2
adrenergic receptors, causing an increase in cAMP levels & bronchodilation |
| Indications: the prevention and relief
of bronchospasm in patients with reversible obstructive airway disease and
for the prevention of exercise-induced bronchospasm. |
| Pharmacokinetics: oral or inhalant
administration. Some degree of tolerance may develop with chronic use (loss
of bronchoprotective action). |
| Side Effects: reflex tachycardia |
| References: www.rxlist.com
& Katzung's text |
| Drug: Ipratroprium
bromide (Atrovent ®) |
| Drug Class: antimuscarinic bronchodilator |
| Mechanism of Action: a quaternary
derivative of atropine. The degree of muscarinic
involvement in bronchomotor responses varies amongst patients.
In some patients only a modest relief of bronchoconstriction can be produced,
while in others it can be quite effective. |
| Indications: administered either alone
or with other bronchodilators, especially beta adrenergics, is indicated
as a bronchodilator for maintenance treatment
of bronchospasm associated with chronic obstructive pulmonary
disease, including chronic bronchitis and emphysema. |
| Contraindications: should be used
with caution in patients with narrow-angle glaucoma, prostatic hypertrophy
or bladder-neck obstruction. |
| Pharmacokinetics: can be delivered
in high doses to muscarinic receptors in the airways because it is poorly
absorbed and does not readily enter into the CNS. |
| Side Effects: few |
| References: www.rxlist.com
& Katzung's text |
| Drug: Beclamethasone
(QVAR, Vanceril ®), Budesonide
(Pulmicort ®), Fluticasone (Flovent
®) |
| Drug Class: Coritcosteriods |
| Mechanism of Action: Inhibit phospholipase
A2 and thereby inhibit the production of inflammatory
cytokines. They do not relax airway smooth muscle directly,
but reduce bronchial reactivity. Their effect may be due in part to potentiating
the effects of beta agonists, but their most important action is to inhibit
the lymphocytic and eosinophilic mediated airway inflammation in asthmatics.
Corticosteroids are not curative. |
| Indications: routinely prescribed
for patients who require more than occasional
inhalations of a beta-2 agonist for relief of symptoms.
|
| Pharmacokinetics: aerosol treatment
is the most effective way to decrease systemic adverse effects of corticosteroid
therapy when treating asthmatic patients. |
| References: Katzung's text |
| Drug: Theophylline
(generic, Elixophyllin, Slo-Phyllin, Theo-Dur, Theo-24 ®) |
| Drug Class: Methylxanthine |
| Mechanism of Action: produces direct
bronchodilation and has some anti-inflammatory actions in the airway. At
therapeutic doses theophylline inhibits cell
surface receptors for adenosine. These receptors modulate
adenyl cyclase activity, and adenosine can cause contraction of airways
and provoke histamine release from mast cells. At high concentrations methylxanthines
can also inhibit phosphodiesterase, thereby elevating cAMP. |
| Indications: treatment of the symptoms
and reversible airflow obstruction associated with chronic asthma and other
chronic lung diseases, e.g., emphysema and chronic bronchitis. |
| Pharmacokinetics: Theophylline should
only be used where methods to measure blood levels are available due to
its narrow therapeutic index.
Therapeutic levels range from 5-20 mg/L, and levels above 40 mg/L may cause
seizures or arrhythmias. Theophylline is metabolized by the liver with plasma
clearance that can be effected by liver disease, cigarette smoking, or by
changes in diet. Children clear theophylline faster than adults. |
| Side Effects: Low doses - mild cortical
arousal & deferral of fatigue. High doses - convulsions, cardiac arrhythmias,
death. Because of the high morbidity and mortality associated with theophylline-induced
seizures, treatment should be rapid and aggressive. The initial treatment
for seizures is i.v. diazepam. Repetitive seizures are treated with phenobarbital.
The doses of these drugs required to treat theophylline induced seizures
may be close to those causing respiratory arrest. |
| Major drug interactions: the
list is long (see reference) |
Notes: Aminophylline is a theophylline-ethylenediamine
complex. Theophylline can be taken orally, and it's low cost makes it
attractive for economically disadvantaged patients with societies where
health care resources are limited. |
| References: www.rxlist.com
& Katzung's text |
| Drug: Cromolyn
sodium (generic, Intal ®) and Nedocromil
sodium (Tilade ®) |
| Drug Class: Asthma medication |
| Mechanism of Action: believed to act
by altering the function of delayed chloride channels in the cell membrane
to produce an inhibitory effect on mast cells
and eosinophils that prevents the release of cell mediators.
The inhibitory effect on mast cells appears to be specific for those in
the lung, and explains its ability to blunt the early response to antigen
challenge. Its effect on eosinophils is responsible for inhibiting the inflammatory
response to inhaled allergens. |
| Indications: a prophylactic
agent indicated in the management of patients with bronchial
asthma |
| Pharmacokinetics: inhaled in metered
doses. Poorly absorbed. |
| Side Effects: minor and few, localized
throat irritation |
| References: www.rxlist.com (
Cromolyn
& Nedoromil)
& Katzung's text |
| Drug: Phenylephrine
(generic, Neo-Synephrine ®) |
| Drug Class: Nasal decongestant |
| Mechanism of Action: alpha1 selective
adrenergic agonist |
| Indications: reduce
the discomfort of hay fever and, to a lesser extent, the
common cold by decreasing the volume of the nasal mucosa. |
| Pharmacokinetics: commonly applied
as the active ingredient in a nasal spray.
Phenylephrine is unpredictably absorbed from the GI tract if taken orally. |
| Side Effects: rebound hyperemia. Repeated
topical use may cause ischemic changes in the mucous membranes. |
| Notes: Other formulations of phenylephrine
can also be given systemically to raise blood pressure in hypotensive states
(e.g. during spinal anesthesia or shock like states). |
| References: Katzung's text |
| Drug: Pseudoephedrine
(generic, Sudafed ®) |
| Drug Class: Nasal decongestant |
| Mechanism of Action: similar to ephedrine
- has both an alpha and beta agonist properties,
and to act as an indirectly acting agaonist (tyramine like
effect). Alpha receptor effects in the respiratory mucosa produces vasoconstriction,
which shrinks swollen nasal mucous membranes; reduces tissue hyperemia,
edema, and nasal congestion; and increases nasal airway patency. Also, drainage
of sinus secretions is increased, and obstructed eustachian ostia may be
opened. |
| Indications: relief of nasal congestion
or eustachian tube congestion. |
| Contraindications: patients taking
MAO inhibitors. Use with
caution in patients with hypertension or men with prostatic enlargement.
|
| Pharmacokinetics: oral decongestants
have a prolonged duration of action,
but do not achieve as high local concentrations compared to topical agents
administered in nasal sprays |
| Side Effects: oral decongestants cause
more systemic effects, including nervousness & insomnia compared to
topical agents. It has peripheral effects similar to epinephrine and central
effects similar to, but less intense than, amphetamines. At the recommended
oral dosage, it has little or no pressor effect in normotensive adults.
|
Notes: pseudoephedrine is an isomer
of ephedrine that is less potent in terms of producing tachycardia, increased
blood pressure & CNS stimulation. |
| References: www.rxlist.com
, & Katzung's text |
| Drug: Oxymetazoline
(generic, Afrin, Neo-Synephrine 12 Hour ®) |
| Drug Class: Long- Acting Topical
Nasal Decongestant |
| Mechanism of Action: direct acting
alpha agonist (1 & 2) |
| Indications: for the temporary relief
of nasal (of the nose) congestion or stuffiness caused by hay fever or other
allergies, colds, or sinus trouble. |
| Contraindications:concomitant
use of MAO Inhibitors |
| Pharmacokinetics: Long
acting topical decongestant |
| Side Effects: in large doses it may
produce hypotension due to a CNS clonidine like effect |
Notes: oxymetazoline is also found
in some formulations of Visine ® |
| References: Katzung's text |
| Drug: Codeine
(generic) |
| Drug Class: Antitussive, narcotic
analgesic |
| Mechanism of Action: unclear. The
physiological mechanism of cough is complex, and little is known about the
specific mechanism of action of the opioid antitussive drugs. The receptors
involved appear to be different than those involved with the other actions
of opioids. It is likely that both central & peripheral effects may
play a role. |
| Indications: opioid analgesics are
amongst the most effective drugs for suppression of cough. |
| Contraindications: use with caution
in patients on MAO inhibitors |
| Pharmacokinetics: Taken orally. Low
doses (tablets or syrup) are sufficient to relieve cough |
| Side Effects: Cough suppression by
opioids may allow accumulation of secretions and lead to airway obstruction.
Other possible side effects: constipation, drowsiness, nausea/vomiting,
addictive potential. |
| References: Katzung's text |
| Drug: N-acetylcysteine
(Mucomyst ®) |
| Drug Class: Mucolytic |
| Mechanism of Action: used as a mucolytic
("mucus dissolving") agent to help break up the thick mucus often
present in people suffering from chronic respiratory ailments. It opens
disulfide bonds, reducing the viscosity of mucous. Dilution of thick mucus
makes it easier to cough up, or drain, from the nasal passages and other
congested areas. |
Indications: to reduce congestion
related to sinusitis, bronchitis, asthma, and other respiratory diseases.
It's often used to ease congestion in people with pneumonia and other
chronic respiratory diseases. |
Notes: also used in the treatment
of acetaminophen overdose |
| Drug: Dornase
alpha (Pulmozyme ®) |
| Drug Class: Treatment of Cystic
Fibrosis |
| Mechanism of Action: Dornase alpha
is a genetically engineered form of the human enzyme, deoxyribonuclease
or DNAse. Dornase alpha breaks
down the DNA and thereby reduces the thickness of the fluids in the lungs
of patients with cystic fibrosis (see Notes). |
| Indications: treatment of cystic
fibrosis, the most common fatal genetic disease in developed
countries. |
Notes: The lungs continually secrete
fluid into the airways to keep them moist. In cystic fibrosis, the fluid
becomes thick because the amount of water it contains is reduced. The
thickened fluid is difficult to cough up or spit out. It blocks the airways,
making breathing difficult and promoting the growth of bacteria and infection.
Infection destroys the tissues of the lungs, and it is the slowly progressive
destruction of the lungs that is the major cause of disability and death
in children with cystic fibrosis. The thick fluid contains high concentrations
of deoxyribonucleic acid (DNA). |
| References: www.medicine.net |
| Drug: Isoniazid
or INH (generic) |
| Drug Class: Antimycobacterial (anti-tuberculosis) |
| Mechanism of Action: Inhibits biosynthesis
of mycolic acids which are important for mycobacterial cell wall synthesis;
bactericidal in dividing cells. Bacteriostatic in resting cells. |
| Indications: subsceptible strains
of tuberculosis |
| Contraindications: isoniazid drug
hypersensitivity including drug -induced hepatitis; previous isoniazid-associated
hepatic injury. |
| Side Effects: Isoniazid induced hepatic
toxicity is the most frequent major toxic effect. 10-20% of patients develop
a peripheral neuropathy (that can be minimized with simultaneous administration
of pyridoxine). Isoniazid can induce hemolytic anemia in G-6-P dehydrogenase
deficiency. |
| Pharmacokinetics: Well absorbed orally.
Widely distributed in various tissues. Metabolized in liver-acetylation,
renal excretion. Plasma half-life in fast acetylators is 70 min and in slow
acetylators is 2-5 hr. |
| Major drug Interactions: |
| Notes: Severe and sometimes fatal
hepatitis associated with isoniazid therapy has been reported and may occur
or may develop even after many months of treatment. The risk of developing
hepatitis is age related. |
| Reference: www.rxlist.com |
| Drug: Rifampin
(generic, Rifadin, Rimactane ® ) |
| Drug Class: Antimycobacterial |
| Mechanism of Action: Inhibits RNA
synthesis by inhibiting DNA dependent RNA polymerase; bactericidal |
| Indications: administered along with
isoniazid, ethambutol or another antituberculosis drug to prevent the emergence
of drug-resistant myocbacteria. Also used to treat infections by Gram+ and
Gram-cocci, Methicillin resistant Staph; Gram- organisms- Legionella, H.
influenzae. |
| Contraindications: history of rifampin
hypersensitivity |
| Side Effects: Orange-red colored urine
and feces, rash. |
| Pharmacokinetics: Well absorbed orally.
Widely distributed, enterohepatic circulation, deacetylation, biliary excretion.
|
| Major drug Interactions: Rifampin
is a strong inducer of P-450 enzymes, which increases the elimination of
other drugs including anticoagulants, some anticonvulsants, protease inhibitors
and contraceptives. |
| Reference: Katzung's text |
| Drug: Ethambutol
(Myambutol ®) |
| Drug Class: Antimycobacterial |
| Mechanism of Action: Inhibits synthesis
of arabinogalactan, an essential component of mycobacterial cell wall. Bacteriostatic.
Enhances the activity of lipophilic drugs such as rifampin. |
| Indications: administered along with
isoniazid or rifampin to inhibit the growth of M. tuberculosis and other
susceptable mycobacteria. |
| Contraindications: |
| Side Effects: Optic neuritis resulting
in decrease of visual acuity and loss of ability to differentiate red from
green. |
| Pharmacokinetics: Well absorbed orally.
Metabolized partially to a dicarboxylic acid derivative. 75% excreted unchanged
in urine. |
| Reference: Katzung's text |
| Drug: Pyrazinamide
(generic) |
| Drug Class: Antimyocobacterial |
| Mechanism of Action: Inhibits electron
transport in mycobacteria. Exact mode of action not known. Mycobacterial
fatty acid synthase I gene invovlved in mycolic acid biosynthesis may be
a target. Bactericidal. |
| Indications: used along with isoniazid
and rifampin for short course (e.g. 6 month) regimens as a"sterilizing"
agent against residual intracellular organisms that may cause a relapse
of infection by tubercle bacilli. |
| Side Effects: hepatotoxicity (1-5%),
nausea, vomiting, hyperuricemia |
| Pharmacokinetics: Well absorbed orally.
Distributed widely. Hydrolyzed to pyrazinoic acid. Renal excretion. |
| Reference: Katzung's text |
| Drug: Clofazimine
(Lamprene ®) |
| Drug Class: Antimycobacterial (Leprosy drug) |
| Mechanism of Action: binds to DNA
and inhibits template function; weak bactericidal. |
| Indications: an alternative to dapsone
(sulfone) for treating resistant leprosy or patients intolerant to dapsone. |
| Side Effects: Red colored urine. Nausea
vomitting, diarrhea and abdominal pain, red brown pigmentation of skin. |
| Pharmacokinetics: Absorbed orally
45-62%. Deposits in fatty tissues. Biliary excretion. Red colored urine.
|
| Reference: Katzung's text |
| Drug:Clarithromycin
(Biaxin ®) |
| Drug Class: Macrolide antibiotic |
| Mechanism of Action: binds to the
50S ribosomal subunit of susceptible microorganisms and inhibits the translocation
step, resulting in inhibition of protein synthesis. Clarithromycin is active
in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative
microorganisms as well as most Mycobacterium avium complex (MAC) microorganisms. |
| Indications: disseminated mycobacterial
infections due to Mycobacterium avium, or Mycobacterium intracellulare.
Treatment of mild to moderate infections caused by susceptible strains of
the designated microorganisms in the conditions: Pharyngitis/Tonsillitis
due to Streptococcus pyogenes (but the usual drug of choice is a penicillin);
Acute maxillary sinusitis due to Haemophilus influenzae or Streptococcus
pneumoniae; Acute bacterial exacerbation of chronic bronchitis due to Haemophilus
influenzae, or Streptococcus pneumoniae; Pneumonia due to Mycoplasma pneumoniae,
Streptococcus pneumoniae, or Chlamydia pneumoniae (TWAR). |
| Contraindications: hypersensitivity
to any of the macrolide antibiotics. Concomitant administration of clarithromycin
with pimozide, or other drugs that prolong the QT interval is contraindicated
due to likelihood of producing a long QT syndrome & arrhythmias |
| Side Effects: diarrhea, nausea |
| Pharmacokinetics: Clarithromycin is
rapidly absorbed from the gastrointestinal tract after oral administration.
The absolute bioavailability of 250-mg clarithromycin tablets was approximately
50%. |
| Major drug Interactions: |
| Reference: www.rxlist.com |
| Drug: Thalidomide
|
| Drug Class: Antimycobacterial (Leprosy drug) |
| Mechanism of Action: Thalidomide is
an immunomodulatory agent with a spectrum of activity that is not fully
characterized, but may involve downregulation of both TNF-alpha and adhesion
moleucules involved in leukocyte migration. |
| Indications: for the acute treatment
ofthe cutaneous manifestations of moderate to severe erythema nodosum leprosum
(ENL) |
| Contraindications: IF THALIDOMIDE
IS TAKEN DURING PREGNANCY, IT CAN CAUSE SEVERE BIRTH
DEFECTS OR DEATH TO AN UNBORN BABY. THALIDOMIDE SHOULD NEVER
BE USED BY WOMEN WHO ARE PREGNANT OR WHO COULD BECOME PREGNANT WHILE TAKING
THE DRUG. |
| Side Effects: The most serious toxicity
associated with thalidomide is its documented human teratogenicity |
| Major drug Interactions: Medications
known to be associatedwith peripheral neuropathy should be used with caution
in patients receiving thalidomide. Thalidomide has been reported to enhance
the sedative activity of barbiturates, alcohol, chlorpromazine, and reserpine. |
| Reference: www.rxlist.com |
| Drug: Lidocaine
(Xylocaine ®) |
| Drug Class: Antiarrhythmic (Class
Ib), Local anesthetic |
Pharmacokinetics:
- Initially distributes rapidly into a smaller "central
compartment" that includes the heart, lung, liver, kidney &
brain when given i.v.
- Lidocaine then distributes into peripheral tissues
(e.g. skeletal muscle & fat) with a timecourse having a half life
of 8 mins.
- Lidocaine's total Vd is 1.1 L/kg (77 liters in
a 70 kg patient)
- Loading doses cannot be given as a single bolus
because toxicity will occur due to high drug levels achieved in the
central compartment.
- Elimination half life from the body is 90-110 mins
- The time to achieve
90% of the steady-state drug level with continuous dosing
is 3.3 elimination half-lives
(e.g. ~5 hrs for lidocaine).
- CHF - results in
a reduction in Vd (due to poor perfusion of tissues)
requiring smaller (1/3 to 1/2) loading doses.
- CHF - reduces lidocaine
clearance due to poor liver perfusion, typically requiring
a 1/2 reduction of infusion rates to maintain the same steady state
plasma level.
- Note: elimination t1/2 = 0.69 Vd/Cl
- CHF- may not change
elimination t1/2 due to equal changes in both Vd &
Cl.
- Liver disease can also reduce lidocaine clearance.
|
| Side Effects: (related to overdose)
lightheadedness, tinnitus, metalic taste, blured vision, numbness, twitching,
convulsions, hypotension |
| References: Lertora's handout |
| Drug: Cimetidine
(generic, Tagamet, Tagamet HB ®) |
| Drug Class: First Generation H2
Antihistamine |
| Mechanism of Action: Selective blocker
of parietal cell H2 histamine receptors, thereby suppressing
both basal & meal-stimulated acid secretion. The volume of gastric secretion
and concentration of pepsin are also reduced. H2 blockers reduce acid secretion
stimulated by both histamine, gastrin & cholinomimetic agents through
two mechanisms: 1) histamine released from ECL cells by gastrin or vagal
stimulation is blocked from binding to the parietal H2 receptor; and 2)
direct stimulation of the parietal cell by gastrin or ACh results in diminished
acid secretion in the presence of an H2 blocker. This may be due to the
ability of H2 blockers to reduce parietal cell cAMP levels, which in turn
reduces the intracellular activation of protein kinases by gastrin or ACh.
|
| Indications: ulcers
(peptic, acute
stress related), Gastroesophageal
Reflux Disease (GERD). Therapeutic doses of H2 blockers
reduce 60-70% of the total 24-hr acid secretion. They are especially effective
(90%) at inhibiting nocturnal acid secretion (which is largely dependent
on histamine), but have a modest impact (60-80%) on meal-stimulated acid
secretion (which is stimulated by gastrin & ACh as well as histamine).
These agents usually promote healing of ulcers among 90% of patients within
3-7 weeks. |
| Contraindications: pregnancy (can
cross into the placenta & into breast milk). |
| Pharmacokinetics: Commonly given orally
twice a day. The duration of acid inhibition is less than 6 hrs. H2 blockers
are cleared by a combination of hepatic metabolism, glomerular filtration
& renal tubular secretion. Dose reduction is required in patients with
moderate to severe renal (& possibly hepatic) insufficiency. In the
elderly there is a decline of up to 50% in drug clearance & a significant
reduction in Vd. |
| Side Effects: headaches, diarrhea,
muscular pain, hallucinations & confusion in elderly patients. Cimetidine
inhibits binding of dihydrotestosterone to androgen receptors, inhibits
the metabolism of estradiol & increases serum prolactin levels. Chronic
use may cause gynecomastia
or impotence in men & galactorrhea
in women. |
| Major drug interactions: cimetidine
has multiple interactions due to inhibition
of cyt P450 & P-glycoprotein.
The other H2 blockers have fewer drug interactions. |
Notes:
|
| References: www.rxlist.com
& Katzung's text |
| Drug: Misoprostol
(Cytotec ®) |
| Drug Class: Prostaglandin analog
(synthetic) |
| Mechanism of Action: a methyl analog
of PGE1. It is believed to stimulate mucus
& bicarbonate secretion & enhance mucosal blood
flow, thereby helping protect the stomach by forming a protective barrier
against acid. It also binds to prostaglandin receptors on parietal cells,
reducing histamine-stimulated cAMP production & causing
modest inhibition of acid secretion. |
| Indications: prevention
of NSAID (including aspirin)-induced gastric ulcers in patients
at high risk of complications from gastric ulcer, e.g., the elderly and
patients with concomitant debilitating disease, as well as patients at high
risk of developing gastric ulceration, such as patients with history of
ulcer. |
| Contraindications: contraindicated,
because of its abortifacient property, in women
who are pregnant. Women of childbearing potential
should be told that they must not be pregnant when misoprostol therapy is
initiated, and that they must use an effective contraception method while
taking misoprostol. |
| Side Effects: diarrhea, increased
uterine contractions |
References: www.rxlist
& Katzung's text
|
| Drug: Omeprazole
(Prilosec ®), Esomeprazole
(Nexium ®) & others |
| Drug Class: Proton pump inhibitors
(prodrug) |
| Mechanism of Action: Proton pump inhibitors
are administered as inactive pro-drugs & are given as acid-resistant
enteric-coated formulations. They form covalent disulfide bonds with the
H/K ATPase, which causes irreversible
inactivation. |
| Indications: Gastroesophageal Reflux
Disease (GERD), peptic
ulcer disease, nonulcer dyspepsia
(a pain in the upper middle part of your stomach), stress
induced gastritis, gastrin-secreting tumors (Zollinger-Ellison
syndrome). |
| Pharmacokinetics: administer on an
empty stomach 1 hr before a meal to achieve maximal effective concentrations
when proton pump secretion will be maximal. Not all pumps are inactivated
with the first dose & up to 3-4 days of treatment are needed to reach
the maximal acid-inhibiting potential. |
| Side Effects: minor |
| Major drug interactions: they inhibit
the metabolism of warfarin, diazepam & phenytoin (via competitive P-450
metabolism) |
Notes: Esomeprazole
(the purple pill) is the S-isomer of omeprazole
|
| Reference: Katzung's text |
| Drug: Sucralfate
(generic, Carafate ®) |
| Drug Class: Mucosal Protective
Agent |
| Mechanism of Action: Sucralfate is
a salt of sucrose complexed to sulfated aluminum hydroxide. In acidic solutions
it forms a viscous, tenacious paste that binds selectively to ulcers or
erosions for up to 6 hrs. It is believed that the negatively charged sucrose
sulfate binds to positively charged proteins
in the base of ulcers or erosions, forming a physical barrier
that restricts further caustic damage. |
| Indications: treatment of duodenal
ulcer. |
| Pharmacokinetics: Less than 3% of
intact drug gets absorbed into the body. The remainder
gets excreted in the feces. |
| Side Effects: constipation, black
stool |
| Major drug interactions: don't
take with H2 blockers or antacids,
which reduce the acidic environment required for activation of sucralfate. |
References: www.rxlist.com
& Katzung's text
|
| Drug: Bismuth
subsalicylate (Pepto-Bismol,
others ®) |
| Drug Class: Colloidal Bismuth Compound |
| Mechanism of Action: like sucralfate,
bismuth coats ulcers and erosions, creating a protective layer against acid
and pepsin. It may also stimulate prostaglandin, mucus & bicarbonate
secretion. It also has direct antimicrobial effects (e.g. against H.
pylori) and binds enterotoxins (useful in treating traveler's diarrhea).
It also reduces stool frequency and liquidity in acute infectious diarrhea,
due to salicylate inhibition of intestinal prostaglandin & chloride
secretion. |
| Indications: treatment of dyspepsia
& acute diarrhea, prevention of traveler's diarrhea |
| References: Katzung's text |
| Drug: Calcium
carbonate (Tums ®)
, magnesium hydroxide, sodium bicarbonate (Alka
Seltzer ®), aluminum
hydroxide (Amphojel ®) |
| Drug Class: Antacids |
| Mechanism of Action: weak bases that
react with gastric HCl to form water & a salt, thereby lowering the
acidity in the stomach. |
| Indications: dyspepsia & acid-peptic
disroders |
| Pharmacokinetics: effective for a
few hours after administration. |
| Side Effects: Al & Mg are often
combined because when used alone Al containing formulations can cause constipation,
and Mg containing formulation can cause an osmotic diarrhea. |
| Major drug interactions: may affect
the absorption of other medications by binding the drug, or by altering
a drug's pH-dependent solubility. Examples: tetracyclines, flouroquinolone,
itraconazole, iron. |
Reference: Katzung's text
|
| Drug: Metoclopramide
(generic, Reglan ®) |
| Drug Class: Prokinetic drug |
| Mechanism of Action: The primary prokinetic
mechanism is by acting as a cholinergic agonist.
In addition, it is a D2 dopamine receptor
antagonist, which may potentiate cholinergic smooth muscle
stimulation in the GI tract. D2 receptor blockade in the chemoreceptor trigger
zone of the medulla (area postrema) produces a potent antinausea
& antiemetic
action. The GI effects incease esophageal peristaltic amplitude, increase
lower esophageal sphincter pressure & enhance gastric emptying. |
| Indications: Gastroesophageal reflux
disease, impaired gastric emptying without obstruction (gastroparesis),
reflux esophagitis, prevention of vomiting |
| Side Effects: CNS side effects include
restlessness, drowsiness, dystonias, parkinsonian features. |
Notes: used in combination with
antihistamines to reduce extrapyramidal side effects, or with corticosteroids,
to counter metoclopramide-induced diarrhea. Cisapride
is a similar drug that was removed from the market due to its potential
to cause serious cardiac arrhythmias (torsade de pointes). It will not
be covered on exams.
|
| Drug:
Diphenoxylate (generic, Lomotil ®) |
| Drug Class: Opioid Agonist |
| Mechanism of Action: activate
presynaptic opioid receptors in the enteric nervous system to block ACh
release & decrease peristalsis. Results in prolongation
of gastrointestinal transit time. |
| Indications: mild to moderate diarrhea |
| Side Effects: no analgesic effects
in standard doses. Higher doses have CNS effects & prolonged use can
lead to opioid dependence. |
Notes: commercial preparations
commonly contain small amounts of atropine to discourage overdosage. The
anticholinergic effects of atropine may contribute to the antidiarrheal
action. Less expensive than loperamide.
|
| References: Katzung's text |
| Drug: Agar,
Methylcellulose, Psyllium seeds, Bran |
| Drug Class: Bulk
laxatives - hydrophillic colloids & fibers |
| Mechanism of Action: they are indigestible
food biproducts that absorb water, foming a bulky substance that distends
the intestine & stimulates peristaltic movement. |
| Indications: constipation. (Constipation
can typically be better treated or prevented with a high fiber diet, adequate
fluid intake & exercise.) |
| Side Effects: bacterial digestion
of plant products can cause bloating & flatus. |
| References: Katzung's text |
| Drug: Castor
Oil, Cascara, Senna, Aloe, Bisacodyl |
| Drug Class: GI Irritants &
Stimulants (Cathartics) |
| Mechanism of Action: castor oil is
broken down to ricinoleic acid in the small intestine, which causes GI irritation
& increased GI motility. Cascara, senna & aloe contain emodin, which
stimulates colonic activity. Bisacodyl is also a GI stimulant |
| Indications: constipation |
| References: Katzung's text |
| Drug:
Atovaquone (Mepron ®) |
| Drug Class: Antiprotozoal |
| Mechanism of Action: a benzimidazoles
that disrupts mitochondrial electron transport in plasmodia/nematodes |
| Clinical Indications: an alternate
drug (to trimethoprim- sulfamethoxazole) for treatment of
mild to moderate P jiroveci pneumonia. When combined with proguanil
(Malarone ®),
it is highly effective against falciparum malaria. |
| Side Effects: fever, rash, nausea,
vomiting, diarrhea, headache, insomnia |
| Pharmacokinetics: Administering atovaquone
with fatty food enhances its absorption by approximately two- fold. The
half- life of atovaquone is long (2-3 days) due to enterohepatic cycling
and eventual fecal elimination. |
| Major drug Interactions: Rifampin
reduces plasma levels of atovaquone |
| Reference: www.rxlist.com
& Katzung's text |
| Drug: Mebendazole
(generic, Vermox ®) |
| Drug Class: Antihelminitic |
| Mechanism of Action:a synthetic benzimidazoles
that inhibits microtubule synthesis |
| Clinical Indications: ascariasis,
trichuriasis, hookworm & pinworm infection. It kills
hookworm, ascaris & trichuris eggs. |
| Side Effects: mild nausea, vomiting
(infrequently) |
| Pharmacokinetics: tablets should be
chewed before swallowing. |
| Major drug Interactions: cimetidine
inhibits the metabolism of mebendazole |
| Reference: www.rxlist.com
& Katzung's text |
| Drug: Thiabendazole
(Mintezol ®) |
| Drug Class: Antihelmintic |
| Mechanism of Action: a benzimidazole
that inhibits microtubule synthesis in nematodes. It is a chelating agent
that forms stable complexes with a number of metals (but not calcium). |
| Clinical Indications: an alternative
drug to ivermectin for treatment of strongyloidiasis (threadworm)
and cutaneous larva migrans (CLM, sandworm disease). |
| Contraindications: pregnancy,
presence of hepatic or renal disease |
| Side Effects: Thiabendazole is
much more toxic than other benzimidazoles or ivermectin. Common
side effects include dizziness, anorexia, nausea & vomiting. |
| Pharmacokinetics: rapidly absorbed
after ingestion, plasma half life is 1.2 hrs. Undergoes hepatic metabolism,
with renal clearance of its metabolites. Can be absorbed through the skin. |
| Major drug Interactions: competes
for metabolism with xanthene derivatives (e.g. theophylline) & can result
in toxic levels of these drugs if given cocomitantly without dosage adjustment. |
| Reference: www.rxlist.com
& Katzung's text |
| Drug: Albendazole
(Albenza, Zentel ®) |
| Drug Class: Antihelmintic (broad spectrum) |
| Mechanism of Action: a benzimidazole
carbamate (prodrug). The active form inhibits microtubule synthesis in nematodes.
|
| Clinical Indications: A
drug of choice for ascariasis (roundworm), enterobiasis (pinworm), hookworm,
cutaneous larva migrans, intestinal capillariasis & gnathostomiasis.
Also a treatment of choice for surgical removal
or asperation of Hydatid cysts. |
| Contraindications: cirrhosis |
| Side Effects: Relatively free of side
effects. Mild & transient epigastric distress. |
| Pharmacokinetics: Administered on
an empty stomach when used against intraluminal parasites, but with a fatty
meal when used against tissue parasites. Eratic oral absorption (increased
with fatty meal) with first-pass metabolism to produce the active metabolite
albendazole sulfoxide. |
| Reference: www.rxlist.com
& Katzung's text |
| Drug:
Pyrantel pamoate (Antiminth, Combantrin,
Pin-rid, Pin-X ®) |
| Drug Class: Anthelmintic (broad spectrum) |
| Mechanism of Action: a neuromuscular
blocking agent in mature and immature forms of susceptible helminths within
the GI tract. that causes release of ACh & inhibition of cholinesterase,
resulting in paralysis. This is followed by expulsion of worms. |
| Clinical Indications: highly effective
for treatment of pinworm, ascaris (roundworm)
& Trichostrongylus orientalis infections. Moderately
effective against both species of hookworm.
Not effective against trichuriasis or strongyloidiasis. Effective only within
the GI lumen (it is poorly absorbed) & it is therefore not effective
against migratory stages in tissues or against ova. |
| Contraindications: use with caution
in patients with liver dysfunction (aminotransferase elevations have been
noted in a small number of patients). |
| Side Effects: adverse effects are
infrequent, mild & transient. GI upset, headache. |
| Pharmacokinetics: Poorly absorbed
from the GI tract. Over half of the drug is recovered unchanged in the feces. |
| Reference: www.healthdigest.org/drugs |
| Drug: Ivermectin
(Mectizan, Stromectol ®) |
| Drug Class: Antihelmintic |
| Mechanism of Action: paralyzes nematodes
& arthropods by intensifying GABA-mediated signals in peripheral nerves.
In onchocerciasis, ivermectin is microfilaricidal. It does not kill adult
worms, but blocks the release of microfilariae for months after therapy. |
| Clinical Indications: Drug of choice
against strongyloidiasis (a
roundworm) & onchocerciasis (a
worm causing river blindness) |
| Contraindications: Pregnancy. Other
drugs that enhance GABA activity (e.g. barbiturates, benzodiazepines &
valproate). |
| Side Effects:Typically infrequent.
In onchocerciasis, adverse effects can result from the killing of microfilariae
& includes fever, headache, dizziness (the Mazotti reaction). |
| Pharmacokinetics: Plasma half life
is ~16 hrs. |
| Major drug Interactions: Other drugs
that enhance GABA activity (e.g. barbiturates, benzodiazepines & valproate). |
| Reference: www.rxlist.com |
| Drug:Diethylcarbamazine
(Hetrazan ®)
* |
| Drug Class: Antihelmintic |
| Mechanism of Action: immobilizes microfilariae
& alters their surface structure, displacing them from tissues &
making them more susceptible to destruction by host defense mechanisms.
Mode of action is unknown. |
| Clinical Indications: A drug of choice
against filiariasis, loiasis & tropical
eosinophilia. It is efficacious & lacks serious toxicity.
Microfilariae of all species are rapidly killed; adult parasites are killed
more slowly, often requiring several treatments. |
| Contraindications: use with caution
in patients with hypertension or renal disease. |
| Side Effects: generally mild &
transient |
| Pharmacokinetics: Should be taken
after meals. rapidly absorbed from GI tract; plasma half-life is 2-3 hrs
if urine is acidic, 10 hrs if uring is alkaline. |
| Note:
*Available in the USA only from the Parasitic Disease Drug Service, CDC,
Atlanta. |
| Reference: Katzung's text |
| Drug: Nifurtimox
* |
| Drug Class: Antihelmintic |
| Mechanism of Action: unclear |
| Clinical Indications:The most commonly
used drug for American trypanosomiasis (Chaga's
disease). Not effective in the treatment
of chronic Chaga's disease. |
| Side Effects: nausea, vomiting, fever,
rash. |
| Pharmacokinetics: Well absorbed orally
with a plasma half life of ~3 hrs. |
| Major drug Interactions: |
| *Available in the USA only from
the Parasitic Disease Drug Service, CDC, Atlanta. |
| Reference:
http://www.nlm.nih.gov/medlineplus/druginfo/ & Katzung's text |
| Drug: Suramin
* |
| Drug Class: Antihelmintic |
| Mechanism of Action: unknown |
| Clinical Indications: First line therapy
for early hemolymphatic African trypanosomiasis
(African sleeping sickness). |
| Side Effects: Adverse effects are
common & can include fatigue, nausea, vomiting. Later reactions include
proteinuria, hemolytic anemia, agranulocytosis. |
| Pharmacokinetics:Given i.v. &
has complicated pharmacokinetics w/ short initial half-life and a terminal
half-life of ~50 days. It is slowly cleared by renal excretion. It does
not enter the CNS & is therefore ineffective agains advanced disease. |
| *Available in the USA only from
the Parasitic Disease Drug Service, CDC, Atlanta. |
| Reference: http://www.nlm.nih.gov/medlineplus/druginfo/
& Katzung's text |
| Drug: Pentamidine
(Pentam 300, Pentacarinat ®)
|
| Drug Class: Antiprotozoal |
| Mechanism of Action: |
| Clinical Indications: Alternative
drug for Pneumocystosis caused by P jiroveci. It
has somewhat lower efficacy & greater toxicity than trimethoprim-sulfamethoxazole.
Alternative drug to suramin for African sleeping sickness. |
| Side Effects: significant
toxicity, seen in 50% of patients. The drug should be given
slowly over 2 hours with patient monitoring. (Rapid i.v. administration
can cause severe hypotension, tachycardia, dizziness & dyspnea.) I.m.
use can cause pain at the injection site & sterile abscesses. Pancreatic
toxicity is common. Hypoglycemia due to inappropriate insulin release may
occur 5-7 days after onset of drug therapy. Reversible renal insufficiency
is common. Rash, metalic taste, etc.... |
| Pharmacokinetics: Administered parentally.
|
| Reference: www.rxlist.com |
| Drug: Praziquantel
(Biltricide ®) |
| Drug Class: Antihelmintic |
| Mechanism of Action: increases the
permeability of trematode & cestode cell membranes to calcium, resulting
in paralysis, dislodgement & death. |
| Clinical Indications: Drug of choice
for treatment of schistosome infections
of all species & cestode infections,
including cysticercosis. |
| Pharmacokinetics: tablets are taken
with liquid after a meal, swallowed without chewing (because the bitter
taste can cause retching & vomiting). Most of the drug is metabolized
to inactive forms after a first pass in the liver. Half life is 0.8-1.5
hrs. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). |
| Major drug Interactions: Cimetidine
increases plasma levels of parziquantel. Phenytoin, carbamazepine &
corticosteroids reduce it's bioavailability. |
| Reference: www.rxlist.com |
| Drug: Chloroquine
(generic, Aralen ®) |
| Drug Class: Antimalarial, antiprotozoal |
| Mechanism of Action: the mechanism
of plasmodicidal action of chloroquine is not completely certain. It probably
acts by concentrating in parasite food vacuoles, preventing the polymerization
of the hemeoglobin product, heme, into hemozoin and thus eliciting parasite
toxicity due to the build up of heme. It is not active against liver stage
parasites (and primaquine must be added for the radical cure of these species). |
| Clinical Indications: for malaria
and extraintestinal amebiasis. Effective against
nonfalciparum and sensitive falciparum malaria.
Resistance to chloroquine is now very
common against strains of P. falciparum, and uncommon
but increasing for P vivax. |
| Contraindications: patients with psoriasis
or porphyria, in whom chloroquine may precipitate attacks of these diseases.Avoid
use in patients with retinal or visual field abnormalities or myopathy.
|
| Side Effects: Usually well tolerated.
Side effects such as nausea, vomiting, etc. may be reduced by dosing after
meals. Pruritis is common, primarily in Africans. |
| Pharmacokinetics: Typically given
orally. Chloroquine is rapidly and almost completely absorbed fromthe gastrointestinal
tract. Excretion of chloroquine is quite slow, but is increased by acidification
of the urine. Slightly more than half of the urinary drug products can be
accounted for as unchanged chloroquine. Large i.m. injections or rapid i.v.
infusions of chloroquine can result in severe hypotension & respiratory
& cardiac arrest. Parenteral administration
is best avoided. |
| Major drug Interactions: antidiarrheal
agents (kaolin) & calcium- and magnesium-containing antacids interefere
with chloroquin absorption. |
| Notes: Chloroquine does not prevent
relapses in patients with vivax or malariae malaria because it
is not effective against exoerythrocytic forms
of the parasite, nor will it prevent vivax or malariae infection
when administered as a prophylactic. |
| Reference: www.rxlist.com
& Katzung's text |
| Drug: Quinine
( generic ®) |
| Drug Class: Antimalarial (P. falciparum) |
| Mechanism of Action: Unknown. Quinine
is effective as a malarial suppressant and in control of overt clinical
attacks. Its primary action is schizontocidal, no lethal effect is exerted
on sporozoites or preerythrocitic tissue forms. |
| Clinical Indications: a
first line therapy (along with its stereoisomer quinidine)
for falciparum malaria -
especially severe disease. Resistance to quinine is uncommon but increasing.
It is not effective against liver stage parasites.
Quinidine is the standard therapy for parenteral treatment of severe falciparum
malaria (parenteral quinine is not available in the USA). |
| Contraindications: if signs of severe
cinchonism, hemolysis or hypersensitivity occur. |
| Side Effects: cinchonism:
tinnitus, headache, headache, nausea, dizziness, visual disturbances. |
| Pharmacokinetics: Rapidly absorbed
after oral administration. Primarily metabolized by the liver & excreted
in the urine. Parenteral quinine is not available in the USA, although quinidine
is available. Because of it's potential for causing cardiotoxicity &
unpredictable pharmacokinetics, i.v. quinidine should be administered
with cardiac monitoring. Therapy should be changed to oral quinine
as soon as the patient has improved & can tolerate oral medications.
Dosage should be reduced in renal insuficiency. |
| Major drug Interactions: do not give
to a patient taking mefloquine,
and used with caution in patients who have previously received mefloquin
therapy. Quinine can raise plasma levels of warfarin &
digoxin. Aluminum containing antacids interfere with absorption. |
| Note: Quinine is gametocidal against
P. vivax and P. ovale but not P. falciparum. Chloroquine
is more effective and less toxic than quinine against non-falciparum malarias.
Hence quinine is not a drug of choice for non-falciparum malaria. |
| Reference: www.rxlist.com
& Katzung's text |
| Drug: Primaquine
(generic) |
| Drug Class: Antimalarial (P. vivax
& P. ovale) |
| Mechanism of Action: Mechanism of
action not known, but the drug binds to and may alter the properties of
DNA leading to decreased protein synthesis. Active
against the hepatic stages of all human malarial parasites.
Some gametocytes are destroyed while others cannot undergo maturation division
in the gut of the mosquito. |
| Clinical Indications: For therapy
of acute vivax and ovale malaria, it is given as a 14 day drug regimen to
eradicate liver hypnozoites
following acute therapy with chloroquine (which eradicates
erythrocytic forms). Also used as a single dose to render
falciparum gametocytes noninfective to mosquitoes (to disrupt
transmission of malaria). |
| Contraindications: Concomitant use
with quinacrine. In clients with rheumatoid arthritis or lupus erythematosus
who are acutely ill or who have a tendency to develop granulocytopenia or
methemoglobenemia. Concomitant use with other bone marrow depressants (e.g.
quinidine) or hemolytic drugs. Patients should
be evaluated for normal G6PD levels before giving primaquine. Avoid in pregnancy
(because the fetus is relatively G6PD defecient
and therefore at risk of hemolysis.) |
| Side Effects: Usually well tolerated.
Side effects such as nausea, vomiting, etc. may be reduced by dosing after
meals. May cause hemolysis or methemoglobinemia (cyanosis), especially in
patients with G6PD deficiency or other hereditary metabolic defects. |
| Pharmacokinetics: Well absorbed from
GI tract. t1/2 elimination: 4 hr. Rapidly metabolized. Never given parentally
because of marked hypotension. |
| Major drug Interactions: myelosuppresant
drugs, quinidine |
| Reference: www.healthdigest.org/drugs/
& Katzung's text |
| Drug: Mefloquine
(generic, Lariam ®) |
| Drug Class: Antimalarial |
| Mechanism of Action: Unknown, chemically
related to quinidine. Has strong bllod schizonticidal activity against P.
falciparum and P. vivax, but not against hepatic stages or
gametocytes. |
| Clinical Indications: the drug
of choice for chemoprophylaxis against chloroquine-resistant strains of
malaria. Recommended by the CDC for chemoprophylaxis
in all malarious areas except those with no chloroquine resistance (where
chloroquine is prefered) and some rural areas of SE Asia with a high prevalence
of mefloquine resistance. As with chloroquine, eradication of P. vivax
and P. ovale requires a course of primaquine. |
| Contraindications: history of epilepsy,
psychiatric disorders, arrhythmia or drug sensitivity. Should not be given
with quinidine, quinine, or halofantrine and caution is required when using
these drugs after mefloquine chemoprophylaxis. |
| Side Effects: nausea, vomiting, dizziness,
and infrequently seizures & psychosis. |
| Pharmacokinetics: Orally administration
only (parenteral use causes severe local irritation). Well absorbed &
eliminated slowly (half-life of 20 days). Can be given once a week for chemoprophylaxis.
The parent drug and metabolites are slowly excreted, mainly in the feces.
|
| Major drug Interactions: quinidine,
quinine or halofantrine |
| Notes: Mefloquine is not appropriate
for treating severe or complicated malaria since quinine and quinidine are
more rapidly active and drug resistance is less likely with those agents. |
| Reference: www.rxlist.com
& Katzung's text |
| Drug: Pyrimethamine
+ Sulfadoxine
(Fansidar
®) |
| Drug Class: Antimalarial |
| Mechanism of Action: Folic acid antagonists.
The rationale for there combination is a synergistic effect to inhibit folic
acid synthesis, and a differential requirement between host and parasite
for nucleic acid precursors involved in growth. This activity is highly
selective against plasmodia and Toxoplasma gondii. Pyrimethamine is chemically
related to trimethoprim. It acts slowly against erythrocytic forms of susceptible
strains of all four human malaria species. It is not adequately gametocidal
or effective against liver stages. |
| Clinical Indications: Fansidar is
commonly used to treat uncomplicated falciparum
malaria. Also considered appropriate
therapy after chloroquine treatment failure. Used as a presumptive
therapy for travelers who develop fever while traveling
in malaria-endemic regions & are unable to obtain medical evaluation.
|
| Contraindications: Use with caution
in patients with renal or hepatic dysfunction. Must give folate supplements
in patients that are pregnant. |
| Side Effects: GI symptoms, skin rashes,
erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Fatalaties have occured, and fansidar should be discontinued
at the first signs of skin rash. |
| Pharmacokinetics: Slowly but adequately
absorbed from the GI tract. |
| Notes: In many areas resistance to
folate antagonists and sulfonamides is common of P. falciparum and
less common for P. vivax. |
| Reference: www.rxlist.com
& Katzung's text |
| Drug: Trimetrexate
(Neutrexin ®) |
| Drug Class: Treatment of Pneumonia in AIDS |
| Mechanism of Action: a competitive
inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and
mammalian sources. |
| Clinical Indications: trimetrexate
glucuronate for injection with concurrent
leucovorin administration (leucovorin protection) is indicated
as an alternative therapy for the treatment
of moderate-to-severe Pneumocystis carinii pneumonia
in immunocompromised patients, including patients
with the acquired immunodeficiency syndrome (AIDS), who are intolerant of,
or are refractory to, trimethoprim-sulfamethoxazole therapy or for whom
trimethoprim-sulfamethoxazole is contraindicated |
| Contraindications: patients with clinically
significant sensitivity to trimetrexate, leucovorin, or methotrexate. It
can cause fetal harm when administered to a pregnant
women |
| Side Effects: severe hematologic,
hepatic, renal, and gastrointestinal toxicities. |
| Drug Interactions: trimetrexate is
metabolized by a P450 enzyme system, drugs that induce or inhibit this drug
metabolizing enzyme system may elicit important drug-drug interactions that
may alter trimetrexate plasma concentrations. Agents that might be coadministered
with trimetrexate in AIDS patients for other indications that could elicit
this activity include erythromycin, rifampin, rifabutin, ketoconazole, and
fluconazole. Cimetidine reduces trimetrexate metabolism. |
| WARNING: NEUTREXIN (TRIMETREXATE GLUCURONATE
FOR INJECTION) MUST BE USED WITH CONCURRENT
LEUCOVORIN (LEUCOVORIN PROTECTION) TO AVOID POTENTIALLY
SERIOUS OR LIFE-THREATENING TOXICITIES |
| Reference: www.rxlist.com
|
| Herb: Melatonin |
| Intended Use: Prevent jet lag & to induce sleep (reduce insomnia) |
| Mechanism of Action: A serotonin derivative that is released by the pineal gland & is believed to be inolved in regulating sleep-wake cycles. Melatonin release coincides with darkness & is suppressed by daylight. |
| Clinical Trials: Results for reducing jet lag are unclear due to flaws in trial design. It may or may not help one return to a normal sleep pattern. Maximizing exposure to daylight on arrival at a new destination may also aid in resetting one's circadian clock.Trials results for melatonin's ability to reduce insomnia are also unclear due to study limitations. However it seems to increase REM sleep & improve sleep onset & duration in healthy volunteers. |
| Contraindications: pregnancy or desire to conceive (see below) |
| Side Effects: Partial inhibition of ovulation in women (by supressing LH secretion), decreased sperm quality (by aromatase inhibition in the testes). Next-day drowsiness, tachycardia, depression. |
| Reference: Katzung's text |
| Herb: Ma-huang (ephedra) |
| Intended Use: diet suppressant, bronchodialator, stimulant |
| Mechanism of Action: contains ephedrine & ephedrine-like alkaloids. Ephedrine has both direct (alpha and beta) agonist effects and indirect (amphetamine or tyramine - like) sympathomimetic effects. |
| Clinical Trials: In Dec 2003, the FDA issued a consumer alert to alert consumers to immediately stop buying and using ephedra products. The alert was based mainly upon a review of recent adverse event reports that indicated an increased risk of stroke, myocardial infarction and sudden death in those using ephedra containing dietary supplements. The FDA also announced a plan to ban the sale of all food supplements containing ephedrine in the near future. |
| Contraindications: cardiovascular disease |
| Side Effects: higher than normal incidence of myocardial infarction, stroke and sudden death. Hypertension, insomnia. |
| Pharmacokinetics: tachyphylaxis develops with repeated dosing. |
| Notes: There is considerable variability in the amount of ephedrine & it's isomers from "batch to batch". |
| Reference: Katzung's text |
| Herb: St. John's wort (Hypericum perforatum) |
| Intended Use: Antidepressant |
| Mechanism of Action: A variety of compounds (e.g. hyperforin & hypericin) are believed to be involved in producing its antidepressant effect. Research suggests that they may inhibit the reuptake of serotonin, norepinephrine & dopamine, down-regulate the experssion of cortical beta receptors and up-regulate the experssion of serotonin receptors. Other mechanisms have also been proposed. |
| Clinical Trials: Clinical trials suggest that St. John's wort may have a similar efficacy as some prescribed antidepressants for mild to moderate depression. However, clinical trials indicate that it is not effective against major or severe depression. |
| Contraindications: Drugs metabolized by cyt-P450 or transported by P-glycoprotein |
| Side Effects: photosensitization |
| Pharmacokinetics: Onset of effect takes 2-4 weeks. |
| Major drug Interactions: use cautiously with other antidepressants, stimulants & MAO inhibitors due to the risk of producing a serotonin syndrome. St. John's wort can induce hepatic cyt- P450 enzymes and the P-glycoprotein drug transporter. This has led to case reports of subtherapeutic levels of digoxin, birth control drugs (& subsequent pregnancy), cyclosporin, HIV protease inhibitors (e.g. indinavir), warfarin, anticonvulsants, etc. |
| Notes: St. John's wort is a plant/bush that grows 1-3 feet tall. Found in Europe, US, Australia & other countries. The name Wort is thought to be derived from the Old English word for plant. The origins of the designator "St. John" might be attributable to it’s medicinal usage by the Knights of St. John in Jerusalem to heal the wounds of Crusaders or that it blooms around the Christian Feast of St. John. |
| Reference: www.rxlist.com & Katzung's text. |
| Herb: Ginkgo (Ginkgo Biloba) |
| Intended Use: treatment of cerebrial insufficiency & Alzheimer dementia |
| Mechanism of Action: has antioxidant and free-radical scavenging properties that may reduce ischemic injury and oxidative stress. Ginkgo has been shown to increase blood flow and reduce blood viscosity (antiplatelet effect). Enhancment of nitric oxide may be involved. |
| Clinical Trials: Trials have suggested that ginkgo is more effective than placebo, and possibly comparible to pentoxifylline in relieving the symptoms of intermittent claudication (a leg pain that develops after walking & is associated with peripheral artery disease). Analysis of ginkgo's effectiveness on cerebral insufficiency & dementia so far suggest either questionable or small improvements (e.g. a 3% increase in cognition) at best. Ginkgo is currently under investigation as a prophylactic agent for dementia of the Alzheimer type. |
| Side Effects: antiplatelet properties |
| Major drug Interactions: Ginkgo has antiplatelet properties & should not be used in combination with other anticoagulant medications. |
| Notes: an extract from the leaves of the ginkgo tree |
| Reference: Katzung's text & http://www.herbs.org/ |
| Herb:Ginseng |
| Intended Use: to improve physical and mental performance, enhancement of immune function |
| Mechanism of Action: active principles appear to be a dozen or more triterpenoid saponin glycosides called ginsenosides or panaxosides. |
| Clinical Trials: Previous clinical trials have had small sample size & report either an improvement in mental function & physical performance, or no effect.Some randomized trials evaluating "quality of life" and enhancement of immune function have claimed significant effects. Others have indicated a decrease in postpradial glucose indices & a lower epidemiological incidence of cancer. To quote Katzung's text: "Until better clinical trials are published, no recommendation can be made regarding the use of ginseng." |
| Side Effects: weak estrogenic effects (vaginal bleeding & mastalgia), insomnia, nervousness, hypertension |
| Major drug Interactions: use cautiously when taking any other psychiatric, estrogenic or hypoglycemic medication. Should not be used in combination with warfarin (ginseng has antiplatelet properties). |
| Notes: derived from several plants belonging to the species Panax |
| Reference: Katzung's text |
| Herb: Saw Palmetto |
| Intended Use: Treatment of benign prostatic hyperplasia |
| Mechanism of Action: inhibits the 5-alpha reductase enzyme responsible for breakdown of testosterone to dihydrotestosterone. Active ingredients are unclear. The effect is similar to that produced by finasteride, which is also used for the same disorder. In vitro palmetto also inhibits the binding of dihydrotestosterone to androgen receptors, inhibits prostatic growth factors, blocks alpha-1 adrenergic receptors & inhibits inflammatory mediators produced by the 5-lipoxygenase pathway. |
| Clinical Trials: Clinical trials suggest it may be more effective than placebo in reducing nocturnal urinary frequency, daytime urinary frequency and increasing peak urinary flow. Another clinical trial found it to be less effective than finasteride at reducing prostate volume (6% vs 18%, respectively). Small comparitive trials of saw palmetto vs. alpha-blockers showed greater improvement with alpha-blockers. |
| Side Effects: 1-3% hypertension, decreased libido. |
| Notes: derived from saw palmetto berries. |
| Reference: Katzung's text |
| Herb: Dehydroepiandrosterone (DHEA) |
| Intended Use: Relief of age-related disorders, weight loss, reduced risk of heart disease, prevention of cancer, boosting the immune system |
| Mechanism of Action: a precursor hormone (to as many as 50 different hormones) that is secreted by the adrenal cortex & CNS. It is converted to androstenedione, testosterone & androsterone. In peripheral tissues aromatase converts DHEA to estradiol. In the plasma, DHEA is converted to DHEA sulfate (DHEAS). |
| Clinical Trials: Studies (often with small sample size) have shown unclear beneficial effects on weight loss, cholesterol levels, Alzheimer's dx. etc. |
| Side Effects: Adrongenic side effects are common. Women complain of masculinizing effects, men may experience gynecomastia & breast tenderness. May worsen prostrate cancer & other hormone-dependent cancers due to elevation of hormone levels. Euphoria, mania & cardiac arrhythmias may occur. |
| Reference: Katzung's text |
