Histamine

Table of Contents

Histamine

Introduction

  • Autacoids is a general term that refers to a number of compounds such as: histamine, serotonin, endogenous peptides, prostaglandins, and leukotrienes

    • The formal definition of autacoids is "self-remedy, referring to the action of local hormones

  • Chemistry and Pharmacokinetics

    • The formation of histamine occurs by the removal of a carboxyl group (decarboxylation) from amino acid  L-histidine

    • One of the important issues associated with formation of a biologically active compound is the mechanism that accounts for the compounds inactivation. 

      • Histamine is active biologically, but the first step for its inactivation involves the addition of a methyl group (CH3) followed by a chemical oxidation.

    • Most of the time very little histamine is excreted unchanged because of these metabolic steps.  One exception would be the case of neoplastic disease (cancer).  For instance, significant histamine is excreted unchanged in the presence of these diseases: (a) systemic mastocytosis, (b) gastric carcinoid syndrome or (c) urticaria pigmentosa.

  • Tissue Distribution:

    • The primary site for histamine localization is the mast cell granules (or basophils) 

      • Mast cells are important in that they release histamine in response to potential tissue injury

      • Other sites include the central nervous system where histamine may function as a neurotransmitter and the fundus of the stomach (enterochromaffin-like cells) which are major acid secretagogues [They promotes accretion by activation of acid-producing mucosal parietal cells]

  • Histamine: Storage and Release

    • Immunologic Release:  The most important mechanism for histamine release is in response to an immunological stimulus.  In

      • Mast cells, if sensitized by surface IgE antibodies, degranulate when exposed specific antigen.  Degranulation means liberation of the contents of the mast cell granules, including histamine.  Degranulation is involved in the immediate (type I) allergic reaction.

      • Histamine Modulation   is associated with the inflammatory responses.  Following local injury, histamine first produces a local vasodilation (reddening of the area) followed by an the release of acute inflammation mediators.  Inflammatory cells are involved in this process and include neutrophils, eosinophils, basophils, monocytes & lymphocytes.  In

    •  Mechanical/Chemical Release: A second type of release occurs following chemical or mechanical injury to mast cells.  In these injuries caused degranulation as noted above including again histamine release.  Common drugs such as morphine or tubocurarine can displace histamine from granule storage sites.

Receptor Subtype

Localization

Receptor coupling

Antagonists (partially selective)

H1

Endothelium, brain, smooth muscle

receptor activation causes and increased IP3, DAG (diacylglycerol)  production  

N/A

H2

mass and cells, gastric mucosa, cardiac muscle, brain

receptor activation causes an  increase in cAMP production 

ranitidine (Zantac), cimetidine (Tagamet)

H3

presynaptic: brain, mesenteric plexus (other neurons)

G protein coupled

N/A

  • Receptor subtypes --H1, H2, and H3:

    • intracellular G protein interactions

  • H1:endothelial and smooth muscle cell localization

    • H1 receptor activation causes can increase in phosphoinositol hydrolysis and an increase in intracellular calcium.

  • H2 gastric mucosa, cardiac muscle cells, immune cell localization:

    • Hreceptor activation causes an increase in cyclic AMP.

  • H3: primarily presynaptic

    • activation causes a decrease in  transmitter release {transmitters: histamine,acetylcholine, norepinephrine, serotonin)

       

return to main menu

Organ System Effects: Histamine

  • Cardiovascular:

    • Systolic and diastolic blood pressure:  Vasodilation of arterioles and precapillary sphincters account for histamine's vasodilating effects. Vasodilation may be due in part to nitric oxide liberation.

    • Following from the reduced blood pressure, the heart rate increases by autonomic reflex mechanisms and by direct action.

    • Both H1 and H2 receptors involved in cardiovascular responses.

    • Histamine-associated edema:H1 receptor effects (postcapillary vessels)

      • increase in vessel permeability due to separation of endothelial cells, allowing transudation of fluid and molecules as large as small proteins.

        • responsible for urticaria (hives)

        • endothelial cell separation: secondary to histamine-induced calcium influx causing intracellular actin/myosin-mediated contraction

    • Direct cardiac effects:

      1. increased contractility (positive inotropism)

      2. increased pacemaker rate (positive chronotropism)

  • Gastrointestinal tract: Histamine promotes intestinal smooth muscle contraction which is an H1 receptor mediated effect

  • Bronchiolar smooth muscle activation by histamine causes bronchodilation (H1 receptor mediated )

    • It is not surprising that inhaled histamine is a diagnostic, provocative test for bronchial hyperreactivity (asthma or cystic fibrosis)

  • Nerve Endings: Sensory nerve endings are stimulated by histamine, especially those endings which mediate pain and itching.

    • These effects are H1 receptor mediated effect and represent part of the local reaction to insect stings (urticarial responses)

  • Secretory tissue:

    • Histamine cause the stimulation of release by secretory tissues.  For example, a significant increase in gastric acid secretion is caused by histamine.  Other examples of increased release include gastric pepsin.

    • Mechanism of Action: Considering the gastric parietal cells, histamine interacts with H2 receptors and initiates a second messenger response which proceeds by (1.)  Increasing adenylyl cyclase activity which (2.)  Results in an increase in the second messenger, cyclic AMP which (3.)  Causes an increase in intracellular calcium levels.  The increase in calcium triggers release.  This releasing characteristic of calcium applies broadly in physiology.

return to main menu

  • Histamine:Clinical Pharmacology-- uses

    •  Pulmonary Function: histamine aerosol may be used to test for bronchial hyperreactivity.

  •   Toxicities include:

    •  Flushing, hypotension, tachycardia, headache, bronchoconstriction, gastrointestinal disturbances

      •  Should not be given to asthmatics (except with extreme caution in pulmonary function testing)

      •  Should not be given to patients with active ulcer disease or gastrointestinal hemorrhage.

  • Histamine Antagonists Introduction:

    • physiologic antagonists: example -- epinephrine, agents that produce opposing effects, acting and different receptors

    • release inhibitors: reduced mast cell degranulation: example: cromolyn and nedocromil

    • receptor antagonists: selective blockade of histamine receptors (H1, H2, H3 types)

Nursing Implications: Antihistamines

Antihistamine Antiemetics (Dramamine, Hydroxyzine (Atarax,Vistaril), Diphenhydramine (Benadryl), Promethazine (Pherergan))

  •  Therapy is most effective when given prophylactically for motion sickness.
  •  The most common side effects are drowsiness, dry mouth, HA and jitters.
  •  Antihistamines cause additive depression with concurrent use of CNS depressants and alcohol.

Antihistamines for Allergies (Terfenadine (Seldane), Loratidine (Claritin), Temaril)

  •  Monitor BP, HR, I & O. Auscultate breath sounds; inspect for rash, Monitor CBC, WBC with differential, platelent count.

  •  Warn patient to avoid driving or operating hazardous equipment if drowsiness blurred vision or dizziness occurs. Notify MD if blurred vision occurs.

  •  Do not crush or chew sustained –release forms, as this releases the drug all at one time.

  •   A potentially fatal drug interaction exists between astemizole (Hismanal), loratidine (Claritin), or terfenadine (Seldane) and itraconazole (Sporanox) or ketoconazole (Nizoral)..

Histamine H2 –Receptor Antagonists (Cimetidine (Tagamet), Ranitidine (Zantac)

  •  Cimetidine (Tagamet): is incompatible with many other drugs for infusion. Read medication labels carefully as pre-filled syringes vary as to route, and may need to be diluted IV. Give once daily doses at HS.

  • Ranitidine (Zantac): too rapid IV administration has been associated with bradycardia, tachycardia and PVC’s.

  • Monitor HR, BP, and LOC, assess for constipation or diarrhea as SE.

 

  • H1 receptor antagonists:

    • General properties:

      • H1 antagonists include both first-generation and second-generation compounds

        • Both categories of agents are orally active and are metabolized by the liver using the cytochrome P450 drug-metabolizing system

        • The average duration of pharmacological action is about 4-6 hours

          • Meclizine (Antivert) and several second-generation drugs far longer acting, with effects lasting 12-24 hours. 

      • First-generation agents tend to be relatively more sedating and more likely than second-generation drugs to block autonomic receptors -- for example antimuscarinic effects [blockade of cholinergic, muscarinic-type receptors]

      • Second-generation agents   are relatively less sedating compared to the earlier first-generation agents and exhibit less CNS penetration, which accounts for reduced sedation.  Some of the second-generation agents are metabolized by a cytochrome P450 type that  is inhibited by other drugs, such as the antifungal agent ketoconazole (Nizoral). Therefore, plasma concentrations of certain second generation H1 antagonists may increase, even the toxic levels, if the patients also taking drugs such as ketoconazole (Nizoral) or  erythromycin estolate (Ilosone).

  • Histamine Pharmacodynamics:

    • Histamine H1 Receptor Blockade:

      • H1 receptor blockers exhibit competitive antagonism for H1 receptor sites whereas little effects at H2 receptor sites and negligible effects of H3 sites are observed.  

      • H1 receptor blockers  prevent bronchiolar or gastrointestinal smooth muscle constriction

      • H1 receptor blockers do not completely prevent cardiovascular effects (some of these effects are mediated by H2 receptors)

      • H1 receptor blockers  cannot affect increases in gastric acid secretion or mast cell histamine release because these effects are H2 receptor site-mediated.

Receptor Type: Sites of Action

H1

endothelium, brain, smooth muscle

H2

mast cells, gastric mucosa, cardiac muscle, brain
  • Histamine Pharmacodynamics continued: Some important histamine promoted effects occur not true histamine's interaction with histamine receptors but by histamine interaction with other receptors.  Many of these interactions are responsible for "side effects" associated with antihistamines medications.  One prominent example is the side effect of sedation.  The side effect is the basis for antihistamine use as a sleep aid.

    • Non-Histamine Receptor-Mediated Effects

      • First-generation H1 receptor blockers cause effects mediated by many other receptor systems. These other effects in the mediated by  muscarinic cholinergic receptors, alpha adrenergic receptors, serotonergic receptors and local anesthetic receptor sites.

      • Sedation: Sedation is a common side effect of first-generation H1 antagonists and provided the rationale for these agents to be used has sleep-aids, i.e. hypnotics.  These agents may produce a paradoxical excitement and children and toxic reactions can include stimulation, agitation, or even coma. The newer H1 antagonists, by contrast, cause minimal or no sedation.

      • Anti-emetic/Antinausea: Some first-generation H1 antagonists prevent motion sickness.  In this application these agent should be used as prophylaxis.  Therefore they should be taken well in advance of the activity which might be expected to induce motion-sickness.  

      • Anti-Parkinsonism:  Certain first-generation H1 antagonists, because of their antimuscarinic properties, turn out to be effective in suppressing Parkinsonian symptoms which are side-effects of some antipsychotic medications.  The antipsychotic drugs involved here tend to be "first-generation" agents which have numerous neurological side effects.  The side effects are much less prevalent with newer antipsychotic drugs, such as olanzapine (Zyprexa) or risperidone (Risperdal).

      • Anticholinergic effects: Some first-generation H1 antagonists have strong antimuscarinic actions (atropine-like effects).  Prominent anticholinergic effects include blurred vision (loss of accommodation) and urinary retention.  Therefore patients who may have benign prostatic hypertrophy may exhibit significant worsening of their clinical state due to antimuscarinic effects.  Probably benign prostatic hypertrophy would be one example of the syndrome for which there would be a relative contraindications for these drugs.

      • Alpha adrenergic blocking effects: Some first-generation H1 antagonists block alpha adrenergic receptors. Alpha-adrenergic receptor blockade can cause orthostatic (postural) hypotension.  

      • Serotonergic blockade: Some first-generation H1 antagonists block serotonin receptors

      • Local Anesthetic effects:

        • Many first-generation H1 antagonists are local anesthetics, exhibiting sodium channel blockade [similar in general to that caused by procaine (Novocain) and lidocaine (Xylocaine)].

        • For example, diphenhydramine (Benadryl) and promethazine (Pherergan) are more potent than procaine (Novocain) as a local anesthetic

return to main menu

Clinical Uses: H1 Histamine Receptor Blockers

  • Allergic Reactions:

    • The pharmacological objective in the use of these medications is to treat or prevent symptoms of allergic reaction.

    • H1 histamine receptor blockers are drugs of choice to treat  allergic rhinitis and urticaria.  In both cases, histamine is the primary mediator of the symptoms

    • By contrast, in asthma their multiple mediators and   H1 histamine receptor blockers are ineffective.

    • Angioedema (hives) may be initiated by histamine but are maintained by bradykinins.  In this clinical setting H1 histamine receptor blockers are also ineffective.

    • For atopic dermatitis, diphenhydramine which is a H1 histamine receptor blocker proves effective in control of itching and for sedation.

    • For allergic conditions, an example being hay fever, the H1 histamine receptor blockers are effective for symptomatic relief.  The goal is to minimize sedating effects while retaining beneficial symptomatic relief.

    • The Second-generation H1 histamine receptor blockers, for example terfenadine (Seldane) or astemizole (Hismanal) are beneficial because they exhibit minimal sedation while being effective in management of allergic rhinitis and chronic urticaria.  At present, these medications tend to be more expensive than first-generation histamine receptor H1 antagonists.  

return to main menu

Allergic Rhinitis
  • H1 antihistamines are effective for treating nasopharyngeal itching, sneezing,  watery rhinorrhea, and ocular itching, tearing, erythema.

    •  Side effects associated with older H1 antihistamines include sedation, visual disturbance, urinary retention, and arrhythmias

  • Newer H1 antihistamines:( terfenadine (Seldane) astemizole (Hismanal))

    • These agents exhibit less sedation associated with their reduced ability to cross the blood brain barrier.

    • However, there are very important drug-drug interactions associated with this category.

      • For example, macrolide antibiotics such as erythromycin, clarithromycin (Biaxin), ketoconazole-class broad-spectrum antifungal drugs, inhibit  terfenadine (Seldane) or astemizole (Hismanal) metabolism.

      • Toxic levels of terfenadine (Seldane) or astemizole (Hismanal) may induce potentially fatal cardiac arrhythmias.

      • These new H1 antihistamines are contraindicated for concurrent use with macrolide antibiotics and ketoconazole-class and fungal drugs or in the presence of impaired hepatic function or inpatients predisposed to arrhythmias.

  • Topical alpha-adrenergic agonists:

    • Phenylephrine (Neo-Synephrine) or oxymetazoline (Afrin) reduce nasal congestion/obstruction.

      • Efficacy duration: limited due to rebound rhinitis and systemic effects which may include insomnia, irritability, and hypertension -- the latter which is seen more commonly with oral alpha adrenergic agonists.

  •  Oral alpha-adrenergic agonists may be useful in diminishing antihistamine-mediated sedation while improving antihistamine efficacy in relieving congestion.  However, there is a concern that these agents due to their potentially hypertensive effects, may precipitate adverse cardiovascular effects, such as stroke.  Recently, there has been an effort to remove such "pressor" agents from common over-the-counter cold medications.

  •  Cromolyn sodium: This agent is a liquid provided as a nasal metered-does spray. Cromolyn sodium (Intal) is not associated with side effects and typically is used prophylactically to reduce episodic allergen nasal mast cell activation.  This agent may be used as part of a anti-asthma drug regimen.

  • Intranasal glucocorticoids:

    • Intranasal glucocorticoids are the most potent drugs available for management of established rhinitis (seasonal or perennial) and including vasomotor rhinitis

      • Topical-to-systemic activity greater for: flunisolide (AeroBid) or budesonide (Rhinocort), compared to beclomethasone (Banceril) or triamcinolone (Aristocort).

    • Despite the different route of administration,  intranasal-administered glucocorticoids exhibit the same efficacy but with reduced systemic side effects compared to same agent administered orally.

    • Side effects include local irritation, which is the most frequent side effect to Candida over-growth which is an unusual side effect

    • Topical high potency glucocorticoids exhibit superior efficacy compared antihistamines during pollen season.

  • Immunotherapy (hyposensitization): This approach is based on repeated, subcutaneous injections of gradually increasing allergen (specific for the symptom complex) over a period of 3-5 years.

    • Contraindications include significant cardiovascular disease and unstable angina

    • Cautious use applies to patients receiving beta adrenergic blockers (due to difficulty in managing possible anaphylactoid responses to treatment)

    • Clinical Management Sequence:

      1. Identification of allergens confirmed by allergens-specific IgE skin testing and/or serum assay.

      2. Avoidance of offending allergen

      3. Mild symptoms: prophylaxis with topical cromolyn sodium or single (bedtime) dose of  chlorpheniramine (Chlor-Trimeton) or astemizole (Hismanal) or terfenadine (Seldane) (decision based on side effects and presence of other concurrent medications or disease.

      4. Prominent symptoms: Topical beclomethasone (Banceril) or if needed budesonide (Rhinocort) or flunisolide (AeroBid)

      5. Management failure: immunotherapy

Clinical Uses: H1 Histamine Receptor Blockers continued

  • Motion Sickness:
    • Scopolamine and certain first-generation H1 blockers are among the most effective drugs for motion sickness prevention
    • Diphenhydramine and promethazine  are the H1 blockers with the greatest effectiveness
    • Cyclizine (Marezine) and  meclizine are also effective agents and are less sedating than those above. 
     
  • Nausea and Vomiting (Pregnancy)
    •  H1 blockers are not recommended for use in management of nausea and vomiting associate with pregnancy because:
      • Difficulty in assessment of possible birth defects associated with certain H1 (benedictin) antagonists and known teratogenic effects of others (e.g., doxylamine) in animal models.
  •  H1 blockers: Toxicity 

    •  Uncommon toxic effects following systemic demonstration:
      • excessive excitation and convulsions in children
      • orthostatic (postural) hypotension
      • Allergic responses
    • Drug allergy -- relatively common, following topical use of H1 antagonists
    • First-generation overdosage: similar to atropine overdosage
    •  Second-generation overdosage: may induce cardiac arrhythmias

return to main menu

Drug-Drug Interactions

  • Second-generation H1 blockers:
    •   Myocardial toxicity:

      •  Toxicity follows combination of terfenadine or astemizole combined with ketoconazole (Nizoral), itraconazole (Sporanox), or macrolide antibiotics (e.g.,erythromycin) because-

      • Q-T (ECG) prolongation

      •  Ventricular arrhythmias which may be potentially fatal.

      • Terfenadine (Seldane)/astemizole (Hismanal) are contraindicated in patients taking ketoconazole (Nizoral), itraconazole (Sporanox), macrolide antibiotics, and patients with diminished liver function.

        • patients taking ketoconazole (Nizoral), itraconazole (Sporanox), macrolide antibiotics, and patients with diminished 

      •  Fexofenadine (Allegra), a metabolite of terfenadine (Seldane), is safer

H2 Receptor Antagonists

  • Introduction-- overview

    • H2 receptor antagonists inhibit histamine-induced stomach acid secretion

    • Interest in these drugs: based on the high incidence of peptic ulcer disease (and related gastrointestinal disease)

    • H2 receptor antagonists: frequently prescribed, available as over-the-counter preparations in some dosage forms.

  • Pharmacology of H2 receptor blockers:

H2 receptor blocker

Mechanism of Elimination

 Cimetidine (Tagamet)

Mainly renal

 Ranitidine (Zantac)

Mainly renal

 Famotidine (Pepcid)

Mainly renal

 Nizatidine (Axid)

Mainly renal

Pharmacodynamics:H2 Receptor Antagonists

  • Mechanism of action: H2 Receptor Antagonists involves selective competitive antagonism at H2 receptor sites.

  • Effects on organ systems

    • Acid secretion and gastric motility

      • The most important action is a reduction in gastric acid secretion due to H2 receptor blockade.

      • Blockade of gastric acid secretion in the presence of H2 receptor blockade following histamine, gastrin, cholinomimetics (acetylcholine-like drugs such as bethanechol (Urecholine)) and  vagal stimulation.

      • Reduced gastric acid volume

      • Decreased pepsin concentration

    • Other effects: unrelated to H2 receptor blockade

      •  Cimetadine (to lesser degree ranitidine; not famotidine or nizatidine): inhibits cytochrome P450 microsomal drug metabolizing system

      •  Cimetadine and ranitidine inhibit renal clearance of basic drugs that use renal secretory transport systems

      •  Cimetadine, by binding to androgen receptors, produce antiandrogen effects

Clinical Uses: H2 Receptor Antagonists

  •  Peptic Ulcer Duodenal Disease:

    • H2 receptor antagonists (low toxicity) by reducing gastric acidity has significantly advanced treatment of peptic ulcer disease

      •  Other agents that reduce gastric acid include:

        1. antimuscarinic drugs (at high dosages required, side effects are significant)

        2. antacids which require frequent dosing and may be associated therefore with  poor patient compliance

        3. Omeprazole (Prilosec) and lansoprazole (Prevacid) (proton pump blockers and) are very effective in reducing gastric acid by directly inhibiting an enzyme-pump which produce hydrogen ions (protons) in the stomach thus decreasing pH

      •  Sucralfate (Carafate) (a coating agent)  promotes healing

      •  Antibiotics are prominent in current therapy because of the importance of H. pylori in gastric ulcer disease.  

Nursing Implications: Antiulcer-antacids

  • Remind the patient to chew antacid tablets, not to swallow them whole.

  • Encourage the patient to alternate aluminum or calcium salts with magnesium salts to prevent diarrhea or constipation unless a specific antacid is ordered.

  • Instruct the patient to increase fluid intake to 2500-3000 ml/day and to increase dietary intake of fruits and fiber to prevent constipation. The increased fluids also help to prevent kidney stones.

  • Antacids may interfere with the absorption of other medications. Review all medications, and dose at appropriate times.

  • Remind the patient to take a small amount of water after dose of antacid liquid to ensure that the antacid dose is carried to the stomach.

Nursing Implications: Antiulcer – other

  • Watch for similar effects and side effects as for other antiulcer drugs.
  • Instruct the patient to avoid administering antacids with tetracycline’s, digoxin, or quinidine. It is important to review the complete list of medications as antacids may interfere with the absorption of any other drugs.
  • Teach patient on sodium restriction to avoid antacids high in sodium.

 

  • Gastric Ulcer:

    • H2 receptor antagonists reduce symptoms and promote healing for benign gastric ulcers

  •  Gastroesophageal Reflux Disorder (erosive esophagitis)

    • H2 receptor antagonists, at higher dosages than for management of peptic or gastric ulcer disease,are used as one component of treatment. Proton pump blockers (e.g. omeprazole) are usually also administered.

  • Hypersecretory Disease:

    •  Zollinger-Ellison syndrome is associated with acid hypersecretion which is caused by gastrin-secreting tumor.  This disorder is often fatal; however, H2 receptor antagonists often control symptoms.

    •  Systemic mastocytosis and multiple endocrine adenomas are hypersecretory conditions in which H2 receptor antagonists often control symptoms.

  •   Toxicity:H2 receptor antagonists:

    • Overview: these agents are generally well tolerated.  The most common side effects include diarrhea, dizziness, somnolence, headache and rash.

      • Cimetidine (Tagamet) has the most adverse effects whereas, nizatidine (Axid) has the fewest adverse effects.

    • CNS effects are uncommon.  However, in the elderly confusional of states, delirium, and slurred speech may occur.  These effects are often associate with cimetidine (Tagamet) and are unusual with ranitidine (Zantac).

    • Endocrine effects are also relatively uncommon.  However cimetidine (Tagamet) does exhibit antiantherogenic effects because the drug blinds to androgen receptors and therefore can cause gynecomastia (men) and galactorrhea (women).

      •  Endocrine effects not associated with famotidine, ranitidine, nizatidine

    • Other uncommon side effects include blood dyscrasias [cimetidine (Tagamet): granulocytopenia, thrombocytopenia, neutropenia, aplastic anemia which is extremely rare], hepatotoxicity  with reversible cholestatic effects, reversible hepatitis, liver enzyme test abnormalities.

    • Use in pregnancy:

      • Harmful effects on the fetus have not been observed when H2 blockers are prescribed to pregnant women even though  H2 blockers are secreted into breast milk and may affect nursing infants.

        • The general rule, however is that since these drugs across the placenta, they should only be prescribed when absolutely required.

        • Since these drugs to cross the placenta, the drugs should only be prescribed when absolutely required. 

  • Drug-drug Interactions: 

    • Cimetidine (Tagamet) is the prominent agent in this category for drug-drug interactions.  This observation occurs because cimetidine (Tagamet) is particularly effective in inhibiting the cytochrome P450 drug metabolizing system therefore influencing the metabolism of other drugs.  Additionally, cimetidine (Tagamet) reduces liver blood flow and the combination of effects on blood flow and metabolism tend to decrease the clearance (removal from the body) of certain drugs.

Cimetadine inhibits clearance of these agents (partial listing):

 warfarin

 phenytoin (Dilantin)

 propranolol (Inderal)

 metoprolol (Lopressor)

 labetalol (Trandate, Normodyne)

 Quinidine gluconate (Quinaglute, Quinalan)

caffeine

 lidocaine (Xylocaine)

theophylline

 alprazolam (Xanax)

 triazolam (Halcion)

chlordiazepoxide (Librium)

carbamazepine (Tegretol)

ethanol

tricyclic antidepressants

 metronidazole (Flagyl)

calcium channel blockers

 sulfonylureas

 diazepam (Valium)

 flurazepam (Dalmane)

return to main menu

 

  • Burkhalter, A, Julius, D.J. and Katzung, B. Histamine, Serotonin and the Ergot Alkaloids (Section IV. Drugs with Important Actions on Smooth Muscle), in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 261-286.

  • Friedman, L. S. and Peterson, W.L. Peptic Ulcer and Related Disorders In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 1597-1616.