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Showing posts with label Anti-inflammatory. Show all posts
Showing posts with label Anti-inflammatory. Show all posts
Other antigout drugs
By Piscean | Saturday, January 21, 2012 | Posted in , , , | With 0 comments

Other antigout drugs
Allopurinol is used to reduce production of uric acid, preventing gouty attacks, and colchicine is used to treat acute gouty attacks.
Pharmacokinetics
Allopurinol and colchicine take somewhat different paths through the body.
All aboard allopurinol
When given orally, allopurinol is absorbed from the GI tract. Allopurinol and its metabolite oxypurinol are distributed throughout the body except in the brain, where drug concentrations are 50%
of those found in the rest of the body. It’s metabolized by the liver and excreted in urine.
Following colchicine’s course
Colchicine is absorbed from the GI tract and is partially metabolized in the liver. The drug and its metabolites then reenter the intestinal tract through biliary secretions. After reabsorption from the intestines, colchicine is distributed to various tissues. It’s excreted primarily in stool and to a lesser degree in urine.
Pharmacodynamics
Allopurinol and its metabolite oxypurinol inhibit xanthine oxidase, the enzyme responsible for the production of uric acid. By reducing uric acid formation, allopurinol eliminates the hazards of hyperuricuria.
Migration control
Colchicine appears to reduce the inflammatory response to mono-sodium urate crystals deposited in joint tissues. Colchicine may produce its effects by inhibiting migration of white blood cells (WBCs) to the inflamed joint. This reduces phagocytosis and lactic acid production by WBCs, decreasing urate crystal deposits and reducing inflammation.
Pharmacotherapeutics
Allopurinol treats primary gout, hopefully preventing acute gouty attacks. It can be prescribed with uricosurics when smaller dosages of each drug are directed. It’s used to treat:
  • gout or hyperuricemia that may occur with blood abnormalities and during treatment of tumors or leukemia
  • primary or secondary uric acid nephropathy (with or without the accompanying symptoms of gout)
  • patients who respond poorly to maximum dosages of uricosurics or who have allergic reactions or intolerance to uricosuric drugs (it’s also used to prevent recurrent uric acid stone formation).

Acute alert
Colchicine is used to relieve the inflammation of acute gouty arthritis attacks. If given promptly, it’s especially effective in relieving pain. In addition, giving colchicine during the first several months of allopurinol, probenecid, or sulfinpyrazone therapy may prevent the acute gouty attacks that sometimes accompany the use of these drugs.
Drug interactions
Colchicine doesn’t interact significantly with other drugs. When allopurinol is used with other drugs, the resulting interactions can be serious:
  • Allopurinol potentiates the effect of oral anticoagulants.
  • Allopurinol increases the serum concentrations of mercapto-purine and azathioprine, increasing the risk of toxicity.
  • Angiotensin-converting enzyme inhibitors increase the risk of hypersensitivity reactions to allopurinol.
  • Allopurinol increases serum theophylline levels.
  •  
    The risk of bone marrow depression increases when cyclophosphamide is taken with allopurinol.
    Adverse reactions to other antigout drugs
    Allopurinol and colchi-cine commonly cause nausea, vomiting, diarrhea, and intermittent abdominal pain.
    Allopurinol
    The most common adverse reaction to allo-purinol is a rash.
    Colchicine
    Prolonged administration of colchicine may cause bone marrow suppression.
Uricosurics and other antigout drugs
By Piscean | | Posted in , , , | With 0 comments
Uricosurics and other antigout drugs
Uricosurics, along with other antigout drugs, exert their effects through their anti-inflammatory actions.
Uricosurics
The two major uricosurics are:
  • probenecid
  • sulfinpyrazone.
Getting the gout out
Uricosurics act by increasing uric acid excretion in urine. The primary goal in using uricosurics is to prevent or control the frequency of gouty arthritis attacks.
Pharmacokinetics
Uricosurics are absorbed from the GI tract.
Distribution
Distribution of the two drugs is similar, with 75% to 95% of probenecid and 98% of sulfinpyrazone being protein-bound.
Metabolism and excretion
Metabolism of the drugs occurs in the liver, and excretion is primarily by the kidneys. Only small amounts of these drugs are excreted in stool.
Pharmacodynamics
Probenecid and sulfinpyrazone reduce the reabsorption of uric acid at the proximal convoluted tubules of the kidneys. This results in excretion of uric acid in urine, reducing serum urate levels.
Pharmacotherapeutics
Probenecid and sulfinpyrazone are indicated for the treatment of:
  • chronic gouty arthritis
  • tophaceous gout (the deposition of tophi or urate crystals under the skin and into joints).
A part-time promoter
Probenecid is also used to promote uric acid excretion in patients experiencing hyperuricemia.
Substitute when acute
Probenecid and sulfinpyrazone shouldn’t be given during an acute gouty attack. If taken at that time, these drugs prolong inflammation. Because these drugs may increase the chance of an acute gouty attack when therapy begins and whenever the serum urate level changes rapidly, colchicine is administered during the first 3 to 6 months of probenecid or sulfinpyrazone therapy.

Drug interactions
Many drug interactions, some potentially serious, can occur with uricosuric drugs:
  • Probenecid significantly increases or prolongs the effects of cephalosporins, penicillins, and sulfonamides.
  • Serum urate levels may increase when probenecid is taken with antineoplastic drugs.
  • Probenecid increases the serum concentration of dapsone, aminosalicylic acid, and methotrexate, causing toxic reactions.
  • Sulfinpyrazone increases the effectiveness of warfarin, increasing the risk of bleeding.
  • Salicylates reduce the effects of sulfinpyrazone.
  • Sulfinpyrazone may potentiate the effects of oral antidiabetic drugs, increasing the risk of hypoglycemia.
Warning!
Adverse reactions to uricosurics
Adverse reactions to uricosurics include uric acid stone formation and blood abnormalities.
Probenecid
  • Headache
  • Anorexia
  • Nausea and vomiting
  • Hypersensitivity reactions
Sulfinpyrazone
  • Nausea
  • Indigestion
  • GI pain
  • GI blood loss
Other immunosuppressants
By Piscean | | Posted in , , | With 0 comments
Other immunosuppressants
Several drugs used for their immunosuppressant effects in patients undergoing allograft transplantation (transplantation between two people who aren’t identical twins) are also used experimentally to treat autoimmune diseases (diseases resulting from an inappropriate immune response directed against the self). They include:
  • azathioprine
  • basiliximab
  • cyclosporine
  • daclizumab
  • lymphocyte immune globulin (ATG [equine])
  • muromonab-CD3
  • mycophenolate mofetil
  • sirolimus
  • tacrolimus
  • thymoglobulin (antithymocyte globulin [rabbit]).
Also these
Cyclophosphamide, classified as an alkylating drug, is also used as an immunosuppressant; however, it’s primarily used to treat cancer.
Anakinra is an immunosuppressant used to treat adults with moderate to severe active rheumatoid arthritis who haven’t responded to at least one disease-modifying antirheumatic drug.
Pharmacokinetics
Immunosuppressants take different paths through the body.
Absorption
When administered orally, azathioprine and mycophenolate are readily absorbed from the GI tract, whereas absorption of cyclosporine, tacrolimus, and sirolimus is varied and incomplete.
Only I.V.
Anakinra, ATG, basiliximab, daclizumab, muromonab-CD3, and thymoglobulin are administered only by I.V. injection.
Distribution
The distribution of azathioprine, basiliximab, and daclizumab isn’t fully understood. Cyclosporine and muromonab-CD3 are distributed widely throughout the body. Azathioprine and cyclosporine cross the placental barrier. The distribution of ATG isn’t clear, but it may appear in breast milk. Distribution of tacrolimus depends on several factors; 75% to 99% is protein-bound. Sirolimus is 97% protein-bound.
Metabolism and excretion
Azathioprine and cyclosporine are metabolized in the liver. Muromonab-CD3 is consumed by T cells circulating in the blood. The metabolism of ATG is unknown.
Mycophenolate is metabolized in the liver to mycophenolate acid, an active metabolite, and then further metabolized to an inactive metabolite, which is excreted in urine and bile. Concentrations of mycophenolate and acyclovir may increase in the presence of nephrotoxicity.
Azathioprine, anakinra, and ATG are excreted in urine; cyclosporine is excreted principally in bile. It’s unknown how muromonab-CD3 is excreted.
Tacrolimus is extensively metabolized and excreted primarily in bile; less than 1% is excreted unchanged in urine. Sirolimus is metabolized by the mixed function oxidase system, primarily cytochrome P-450 (CYP3A4); 91% is excreted in stool and 2.2% in urine. Metabolism and excretion of basiliximab and daclizumab aren’t understood.
Pharmacodynamics
How certain immunosuppressants achieve their desired effects has yet to be determined.
What’s going on here?
The exact mechanism of action of azathioprine, cyclosporine, and ATG is unknown, but may be explained by these theories:
  • Azathioprine antagonizes metabolism of the amino acid purine and, therefore, may inhibit ribonucleic acid and deoxyribonucleic acid structure and synthesis. It also may inhibit coenzyme formation and function.
  • Cyclosporine is thought to inhibit helper T cells and suppressor T cells.
  • ATG may eliminate antigen-reactive T cells in the blood, alter T-cell function, or both.

They do know this much…
In patients receiving kidney allografts, azathioprine suppresses cell-mediated hypersensitivity reactions and produces various alterations in antibody production. Muromonab-CD3, a monoclonal antibody, is understood to block the function of T cells.
Anakinra, basiliximab, and daclizumab block the activity of interleukin. Mycophenolate inhibits responses of T and B lymphocytes, suppresses antibody formation by B lymphocytes, and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.
Yea or nay?
Cyclosporine: Miracle drug or death sentence?
Organ transplantation can save a life. However, cyclosporine, an immunosuppressant used to reduce the risk of organ rejection, may also cause cancer.
Does cyclosporine encourage cells to become cancerous?
It has long been believed that when the immune system is weakened by immunosuppressants, it loses its ability to fight and kill cancerous cells. Recent research suggests that cyclosporine may also encourage abnormal cells to become cancerous and perhaps even grow aggressively. This research has raised concern about the use of cyclosporine in organ transplantation.
A double-edged sword
However, this concern needs to be balanced against the life-threatening risk of organ rejection. Scientists are now looking for ways to block this tumor-promoting effect of cyclo-sporine.
Sirolimus is an immunosuppressant that inhibits T-lymphocyte activation and proliferation that occur in response to antigenic and cytokine stimulation; it also inhibits antibody formation.
Pharmacotherapeutics
Immunosuppressants are used mainly to prevent rejection in patients who undergo organ transplantation. 
Drug interactions
Most drug interactions with this class of drugs involve other immunosuppressant and anti-inflammatory drugs and various antibiotic and antimicrobial drugs.
  • Allopurinol increases the blood levels of azathioprine.
  • Verapamil increases blood levels of sirolimus.
  • Voriconazole shouldn’t be given with sirolimus because the combination inhibits CYP3A4 enzymes, resulting in increased sirolimus levels.
  • When mycophenolate is taken with antacids or cholestyramine, mycophenolate levels decrease.
  • Coadministration of mycophenolate with acyclovir, especially in patients with renal impairment, may increase concentrations of both drugs.
  • Cyclosporine levels may increase if cyclosporine is taken with ketoconazole, calcium channel blockers, cimetidine, anabolic steroids, hormonal contraceptives, erythromycin, or metoclopramide.
  • The risk of toxicity to the kidneys increases when cyclosporine or sirolimus is taken with acyclovir, aminoglycosides, or amphotericin B.
  • Taking anakinra, ATG, basiliximab, cyclosporine, daclizumab, muromonab-CD3, sirolimus, or thymoglobulin with other immunosuppressants (except corticosteroids) increases the risk of infection and lymphoma (neoplasm of the lymph tissue; typically malignant).
  • Barbiturates, rifampin, phenytoin, sulfonamides, and trimethoprim decrease plasma cyclosporine and sirolimus levels.
  • Serum digoxin levels may increase when cyclosporine is taken with digoxin.
  • Anakinra shouldn’t be given to patients with active infections or neutropenia.
Warning!
Adverse reactions to noncorticosteroid immunosuppressants
All noncorticosteroid immunosuppressants can cause hypersensitivity reactions. Here are adverse reactions to individual drugs.
Azathioprine
  • Bone marrow suppression
  • Nausea and vomiting
  • Liver toxicity
Cyclosporine
  • Kidney toxicity
  • Hyperkalemia
  • Infection
  • Liver toxicity
  • Nausea and vomiting
Daclizumab
  • GI disorders
  • Hypertension
  • Hypotension
  • Chest pain
  • Tachycardia
  • Edema
  • Dyspnea
  • Pulmonary edema
  • Thrombosis
  • Bleeding
  • Renal tubular necrosis
Lymphocyte immune globulin
  • Fever and chills
  • Reduced white blood cell (WBC) or platelet count
  • Infection
  • Nausea and vomiting
Muromonab-CD3
  • Fever and chills
  • Nausea and vomiting
  • Tremor
  • Pulmonary edema
  • Infection
Mycophenolate mofetil
  • Nausea
  • Diarrhea
  • Leukopenia
  • Headache
  • Weakness
  • Urinary frequency
  • Leg cramps or pain
  • Liver function test result abnormalities
  • Rash
Sirolimus
  • Anemia
  • Thrombocytopenia
  • Hyperlipidemia
  • Hypertension
Tacrolimus
  • Nausea and vomiting
  • Diarrhea
  • Constipation
  • Tremor
  • Leukopenia
  • Hypertension
  • Nephrotoxicity
  • Hepatotoxicity
Thymoglobulin
  • Abdominal pain
  • Diarrhea
  • Dyspnea
  • Fever and chills
  • Headache
  • Infection
  • Nausea and vomiting
  • Reduced WBC or platelet count
  • Systemic infections
  • Dizziness
Mineralocorticoids
By Piscean | | Posted in , , , | With 0 comments
Mineralocorticoids
Mineralocorticoids affect electrolyte and water balance. These drugs include:
  • fludrocortisone acetate, a synthetic analogue of hormones secreted by the adrenal cortex
  • aldosterone, a natural mineralocorticoid (the use of which has been curtailed by high cost and limited availability).
Pharmacokinetics
Fludrocortisone acetate is absorbed well and distributed to all parts of the body.
Metabolism and excretion
Fludrocortisone acetate is metabolized in the liver to inactive metabolites. The drug is excreted by the kidneys, primarily as inactive metabolites.
Pharmacodynamics
Fludrocortisone acetate affects fluid and electrolyte balance by acting on the distal renal tubule to increase sodium reabsorption and potassium and hydrogen secretion.
Pharmacotherapeutics
Fludrocortisone acetate is used as replacement therapy for patients with adrenocortical insufficiency (reduced secretion of glucocorticoids, mineralocorticoids, and androgens).
Seasoning reasoning
Fludrocortisone acetate may also be used to treat salt-losing congenital adrenogenital syndrome (characterized by a lack of cortisol and deficient aldosterone production) after the patient’s electrolyte balance has been restored.

Drug interactions
As is the case with adverse reactions, the drug interactions associated with mineralocorticoids are similar to those associated with glucocorticoids.
Corticosteroids
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Corticosteroids
Corticosteroids suppress immune responses and reduce inflammation. They’re available as natural or synthetic steroids.
There’s no improving on nature
Natural corticosteroids are hormones produced by the adrenal cortex; most corticosteroids are synthetic forms of these hormones. Natural and synthetic corticosteroids are classified according to their biological activities:
  • Glucocorticoids, such as cortisone acetate and dexamethasone, affect carbohydrate and protein metabolism.

  • Mineralocorticoids, such as aldosterone and fludrocortisone acetate, regulate electrolyte and water balance.
Glucocorticoids
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Glucocorticoids
Most glucocorticoids are synthetic analogues of hormones secreted by the adrenal cortex. They exert anti-inflammatory, metabolic, and immunosuppressant effects. Drugs in this class include:
  • beclomethasone
  • betamethasone
  • cortisone
  • dexamethasone
  • hydrocortisone
  • methylprednisolone
  • prednisolone
  • prednisone
  • triamcinolone.
Pharmacokinetics
Glucocorticoids are well absorbed when administered orally. After I.M. administration, they’re absorbed completely.
Distribution
Glucocorticoids are bound to plasma proteins and distributed through the blood.
Metabolism and excretion
Glucocorticoids are metabolized in the liver and excreted by the kidneys.
Pharmacodynamics
Glucocorticoids suppress hypersensitivity and immune responses through a process that isn’t entirely understood. Researchers believe that glucocorticoids inhibit immune responses by:
  • suppressing or preventing cell-mediated immune reactions
  • reducing levels of leukocytes, monocytes, and eosinophils
  • decreasing the binding of immunoglobulins to cell surface receptors
  • inhibiting interleukin synthesis.

Taking the red (and more) out
Glucocorticoids suppress the redness, edema, heat, and tenderness associated with the inflammatory response. They start on the cellular level by stabilizing the lysosomal membrane (a structure
within the cell that contains digestive enzymes) so that it doesn’t release its store of hydrolytic enzymes into the cells.
Now I get it!
How methylprednisolone works
Tissue trauma normally leads to tissue irritation, edema, inflammation, and production of scar tissue. Methylprednisolone counteracts the initial effects of tissue trauma, promoting healing.

No leaks, no drips
As corticosteroids, glucocorticoids prevent the leakage of plasma from capillaries, suppress the migration of polymorphonuclear leukocytes (cells that kill and digest microorganisms), and inhibit phagocytosis (ingestion and destruction).
To ensure a job well done, glucocorticoids decrease antibody formation in injured or infected tissues and disrupt histamine synthesis, fibroblast development, collagen deposition, capillary dilation, and capillary permeability.

Warning!
Adverse reactions to cortico-steroids
Corticosteroids affect almost all body systems. Their widespread adverse effects include:
  • insomnia
  • increased sodium and water retention
  • increased potassium excretion
  • suppressed immune and inflammatory responses
  • osteoporosis
  • intestinal perforation
  • peptic ulcers
  • impaired wound healing.
Diabetes and more
Endocrine system reactions may include:
  • diabetes mellitus
  • hyperlipidemia
  • adrenal atrophy
  • hypothalamic-pituitary axis suppression
  • cushingoid signs and symptoms (such as buffalo hump, moon face, and elevated blood glucose levels).
Pharmacotherapeutics
Besides their use as replacement therapy for patients with adrenocortical insufficiency, glucocorticoids are prescribed for immunosuppression and reduction of inflammation and for their effects on the blood and lymphatic systems.
Drug interactions
Many drugs interact with corticosteroids:
  • Aminoglutethimide, barbiturates, phenytoin, and rifampin may reduce the effects of corticosteroids.
  • Their potassium-wasting effects may be enhanced by amphotericin B, chlorthalidone, ethacrynic acid, furosemide, and thiazide diuretics.
  • Erythromycin and troleandomycin may increase their effects by reducing their metabolism.
  • They reduce the serum concentration and effects of salicylates.
  • The risk of peptic ulcers associated with nonsteroidal anti-inflammatory drugs and salicylates increases when these agents are taken with corticosteroids.
  • The response to vaccines and toxoids may be reduced in a patient taking corticosteroids.
  • Estrogen and hormonal contraceptives that contain estrogen increase the effects of corticosteroids.
  • The effects of antidiabetic drugs may be reduced, resulting in increased blood glucose levels
Histamine-1 receptor antagonists
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Histamine-1 receptor antagonists
The term antihistamine refers to drugs that act as histamine-1 (H1) receptor antagonists; that is, they compete with histamine for binding to H1-receptor sites throughout the body. However, they don’t displace histamine already bound to the receptor.
It’s all about chemistry
Based on chemical structure, antihistamines are categorized into five major classes:
  • Ethanolamines include clemastine fumarate, dimenhydrinate, and diphenhydramine hydrochloride.
  • Alkylamines include brompheniramine maleate, chlorphenir-amine maleate, and dexchlorpheniramine maleate.
  • Phenothiazines include promethazine hydrochloride.
  • Piperidines include azatadine maleate, cetirizine hydrochloride, cyproheptadine hydrochloride, desloratadine, fexofenadine hydrochloride, loratadine, and meclizine hydrochloride.
  • Miscellaneous drugs, such as hydroxyzine hydrochloride and hydroxyzine pamoate, also act as antihistamines.
Pharmacokinetics (how drugs circulate)
H1-receptor antagonists are well absorbed after oral or parenteral administration. Some can also be given rectally.
Distribution
With the exception of loratadine and desloratadine, antihistamines are distributed widely throughout the body and central nervous system (CNS).
Less penetration, fewer effects
Fexofenadine, desloratadine, and loratadine, which are nonsedating antihistamines, minimally penetrate the blood-brain barrier so that little of the drug is distributed in the CNS, producing fewer effects there than other antihistamines.
Memory jogger
Anti- is a familiar prefix meaning “opposing.” That’s exactly what antihistamines do: They oppose histamine effects (or allergic reactions).
Metabolism and excretion
Antihistamines are metabolized by liver enzymes and excreted in urine; small amounts appear in breast milk. Fexofenadine, mainly excreted in stool, is an exception. Cetirizine undergoes limited hepatic metabolism.
Pharmacodynamics (how drugs act)
H1-receptor antagonists compete with histamine for H1 receptors on effector cells (the cells that cause allergic symptoms), blocking histamine from producing its effects.

Antagonizing tactics
H1-receptor antagonists produce their effects by:
  • blocking the action of histamine on the small blood vessels
  • decreasing dilation of arterioles and engorgement of tissues
  • reducing the leakage of plasma proteins and fluids out of the capillaries (capillary permeability), thereby lessening edema
  • inhibiting most smooth-muscle responses to histamine (in particular, blocking the constriction of bronchial, GI, and vascular smooth muscle)
  • relieving symptoms by acting on the terminal nerve endings in the skin that flare and itch when stimulated by histamine
  • suppressing adrenal medulla stimulation, autonomic ganglia stimulation, and exocrine gland secretion, such as lacrimal and salivary secretion.

Straight to the head
Several antihistamines have a high affinity for H1 receptors in the brain and are used for their CNS effects. These drugs include diphenhydramine, dimenhydrinate, promethazine, and various piperidine derivatives.
No stomach for this
H1-receptor antagonists don’t affect parietal cell secretion in the stomach because their receptors are H2 receptors, not H1
 .
Pharmacotherapeutics (how drugs are used)
Antihistamines are used to treat the symptoms of type I hypersensitivity reactions, such as:
  • allergic rhinitis (runny nose and itchy eyes caused by a local sensitivity reaction)
  • vasomotor rhinitis (rhinitis not caused by allergy or infection)
  • allergic conjunctivitis (inflammation of the membranes of the eye)
  • urticaria (hives)
  • angioedema (submucosal swelling in the hands, face, and feet).
Now I get it!
How chlorpheniramine stops an allergic response
Although chlorpheniramine can’t reverse symptoms of an allergic response, it can stop the progression of the response. Here’s what happens.
Release the mediators
When sensitized to an antigen, a mast cell reacts to repeated antigen exposure by releasing chemical mediators. One of these mediators, histamine, binds to histamine-1 (H1) receptors found on effector cells (the cells responsible for allergic symptoms). This initiates the allergic response that affects the respiratory, cardiovascular, GI, endocrine, and integumentary systems.
The first one there wins
Chlorpheniramine competes with histamine for H1-receptor sites on the effector cells. By attaching to these sites first, the drug prevents more histamine from binding to the effector cells.

Not just for allergies
Antihistamines can have other therapeutic uses:
  • Many are used primarily as antiemetics (to control nausea and vomiting).
  • They can also be used as adjunctive therapy to treat an anaphylactic reaction after the serious symptoms are controlled.
  • Diphenhydramine can help treat Parkinson’s disease and drug-induced extrapyramidal reactions (abnormal involuntary movements).
  • Because of its antiserotonin qualities, cyproheptadine may be used to treat Cushing’s disease, serotonin-associated diarrhea, vascular cluster headaches, and anorexia nervosa.
Drug interactions
Antihistamines may interact with many drugs, sometimes with life-threatening consequences:
  • They may block or reverse the vasopressor effects of epinephrine, producing vasodilation, increased heart rate, and very low blood pressure.
  • They may mask the toxic signs and symptoms of ototoxicity (a detrimental effect on hearing) associated with aminoglycosides or large dosages of salicylates.
  • They may increase the sedative and respiratory depressant effects of CNS depressants, such as tranquilizers or alcohol.
  • Loratadine may cause serious cardiac effects when taken with macrolide antibiotics (such as erythromycin), fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ciprofloxacin, and clarithromycin.
Warning!
Adverse reactions to antihistamines
The most common adverse reaction to antihistamines (with the exceptions of fexofenadine and loratadine) is central nervous system (CNS) depression. Other CNS reactions include:
  • dizziness
  • lassitude and fatigue
  • disturbed coordination
  • muscle weakness.
Gut reactions
GI reactions may include:
  • epigastric distress
  • loss of appetite
  • nausea and vomiting
  • constipation
  • diarrhea
  • dryness of the mouth, nose, and throat.
They can get the heart racing
Cardiovascular reactions may include:
  • hypotension
  • hypertension
  • rapid heart rate
  • arrhythmias.
A sensitive issue
Sensitivity reactions can also occur.
Antihistamine
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Antihistamines
Antihistamines primarily act to block histamine effects that occur in an immediate (type I) hypersensitivity reaction, commonly called an allergic reaction. They’re available alone or in combination products by prescription or over-the-counter.

Histamine-1 receptor antagonists
The term antihistamine refers to drugs that act as histamine-1 (H1) receptor antagonists; that is, they compete with histamine for binding to H1-receptor sites throughout the body. However, they don’t displace histamine already bound to the receptor.
It’s all about chemistry
Based on chemical structure, antihistamines are categorized into five major classes:
  • Ethanolamines include clemastine fumarate, dimenhydrinate, and diphenhydramine hydrochloride.
  • Alkylamines include brompheniramine maleate, chlorphenir-amine maleate, and dexchlorpheniramine maleate.
  • Phenothiazines include promethazine hydrochloride.
  • Piperidines include azatadine maleate, cetirizine hydrochloride, cyproheptadine hydrochloride, desloratadine, fexofenadine hydrochloride, loratadine, and meclizine hydrochloride.
  • Miscellaneous drugs, such as hydroxyzine hydrochloride and hydroxyzine pamoate, also act as antihistamines.
Pharmacokinetics (how drugs circulate)
H1-receptor antagonists are well absorbed after oral or parenteral administration. Some can also be given rectally.
Distribution
With the exception of loratadine and desloratadine, antihistamines are distributed widely throughout the body and central nervous system (CNS).
Less penetration, fewer effects
Fexofenadine, desloratadine, and loratadine, which are nonsedating antihistamines, minimally penetrate the blood-brain barrier so that little of the drug is distributed in the CNS, producing fewer effects there than other antihistamines.
Memory jogger
Anti- is a familiar prefix meaning “opposing.” That’s exactly what antihistamines do: They oppose histamine effects (or allergic reactions).
Metabolism and excretion
Antihistamines are metabolized by liver enzymes and excreted in urine; small amounts appear in breast milk. Fexofenadine, mainly excreted in stool, is an exception. Cetirizine undergoes limited hepatic metabolism.
Pharmacodynamics (how drugs act)
H1-receptor antagonists compete with histamine for H1 receptors on effector cells (the cells that cause allergic symptoms), blocking histamine from producing its effects.

Antagonizing tactics
H1-receptor antagonists produce their effects by:
  • blocking the action of histamine on the small blood vessels
  • decreasing dilation of arterioles and engorgement of tissues
  • reducing the leakage of plasma proteins and fluids out of the capillaries (capillary permeability), thereby lessening edema
  • inhibiting most smooth-muscle responses to histamine (in particular, blocking the constriction of bronchial, GI, and vascular smooth muscle)
  • relieving symptoms by acting on the terminal nerve endings in the skin that flare and itch when stimulated by histamine
  • suppressing adrenal medulla stimulation, autonomic ganglia stimulation, and exocrine gland secretion, such as lacrimal and salivary secretion.

Straight to the head
Several antihistamines have a high affinity for H1 receptors in the brain and are used for their CNS effects. These drugs include diphenhydramine, dimenhydrinate, promethazine, and various piperidine derivatives.
No stomach for this
H1-receptor antagonists don’t affect parietal cell secretion in the stomach because their receptors are H2 receptors, not H1
 .
Pharmacotherapeutics (how drugs are used)
Antihistamines are used to treat the symptoms of type I hypersensitivity reactions, such as:
  • allergic rhinitis (runny nose and itchy eyes caused by a local sensitivity reaction)
  • vasomotor rhinitis (rhinitis not caused by allergy or infection)
  • allergic conjunctivitis (inflammation of the membranes of the eye)
  • urticaria (hives)
  • angioedema (submucosal swelling in the hands, face, and feet).
Now I get it!
How chlorpheniramine stops an allergic response
Although chlorpheniramine can’t reverse symptoms of an allergic response, it can stop the progression of the response. Here’s what happens.
Release the mediators
When sensitized to an antigen, a mast cell reacts to repeated antigen exposure by releasing chemical mediators. One of these mediators, histamine, binds to histamine-1 (H1) receptors found on effector cells (the cells responsible for allergic symptoms). This initiates the allergic response that affects the respiratory, cardiovascular, GI, endocrine, and integumentary systems.
The first one there wins
Chlorpheniramine competes with histamine for H1-receptor sites on the effector cells. By attaching to these sites first, the drug prevents more histamine from binding to the effector cells.

Not just for allergies
Antihistamines can have other therapeutic uses:
  • Many are used primarily as antiemetics (to control nausea and vomiting).
  • They can also be used as adjunctive therapy to treat an anaphylactic reaction after the serious symptoms are controlled.
  • Diphenhydramine can help treat Parkinson’s disease and drug-induced extrapyramidal reactions (abnormal involuntary movements).
  • Because of its antiserotonin qualities, cyproheptadine may be used to treat Cushing’s disease, serotonin-associated diarrhea, vascular cluster headaches, and anorexia nervosa.
Drug interactions
Antihistamines may interact with many drugs, sometimes with life-threatening consequences:
  • They may block or reverse the vasopressor effects of epinephrine, producing vasodilation, increased heart rate, and very low blood pressure.
  • They may mask the toxic signs and symptoms of ototoxicity (a detrimental effect on hearing) associated with aminoglycosides or large dosages of salicylates.
  • They may increase the sedative and respiratory depressant effects of CNS depressants, such as tranquilizers or alcohol.
  • Loratadine may cause serious cardiac effects when taken with macrolide antibiotics (such as erythromycin), fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ciprofloxacin, and clarithromycin.
Warning!
Adverse reactions to antihistamines
The most common adverse reaction to antihistamines (with the exceptions of fexofenadine and loratadine) is central nervous system (CNS) depression. Other CNS reactions include:
  • dizziness
  • lassitude and fatigue
  • disturbed coordination
  • muscle weakness.
Gut reactions
GI reactions may include:
  • epigastric distress
  • loss of appetite
  • nausea and vomiting
  • constipation
  • diarrhea
  • dryness of the mouth, nose, and throat.
They can get the heart racing
Cardiovascular reactions may include:
  • hypotension
  • hypertension
  • rapid heart rate
  • arrhythmias.
A sensitive issue
Sensitivity reactions can also occur.
Anti-inflammatory, anti-allergy, and immunosuppressant drugs
By Piscean | | Posted in , , , | With 0 comments
Drugs and the immune system
Immune and inflammatory responses protect the body from invading foreign substances. These responses can be modified by certain classes of drugs:
  • Antihistamines block the effects of histamine on target tissues.
  • Corticosteroids suppress immune responses and reduce inflammation.
  • Noncorticosteroid immunosuppressants prevent rejection of transplanted organs and can be used to treat auto immune disease.
  • Uricosurics prevent or control the frequency of gouty arthritis attacks.