Pharmacodynamic drug interactions with warfarin
No dosage adjustment is necessary for patients with renal impairment. Hepatic Impairment Hepatic impairment can potentiate the response to Warfarin through impaired synthesis of clotting factors and decreased metabolism of Warfarin. Use caution when using Warfarin sodium in these patients. Overdosage Signs and Symptoms Bleeding e. Treatment The treatment of excessive anticoagulation is based on the level of the INR, the presence or absence of bleeding, and clinical circumstances.
Reversal of Warfarin sodium anticoagulation may be obtained by discontinuing Warfarin sodium therapy and, if necessary, by administration of oral or parenteral vitamin K1. The use of vitamin K1 reduces response to subsequent Warfarin sodium therapy and patients may return to a pretreatment thrombotic status following the rapid reversal of a prolonged INR.
Resumption of Warfarin sodium administration reverses the effect of vitamin K, and a therapeutic INR can again be obtained by careful dosage adjustment. If rapid re-anticoagulation is indicated, heparin may be preferable for initial therapy. Prothrombin complex concentrate PCC , fresh frozen plasma, or activated Factor VII treatment may be considered if the requirement to reverse the effects of Warfarin sodium is urgent.
A risk of hepatitis and other viral diseases is associated with the use of blood products; PCC and activated Factor VII are also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life-threatening bleeding episodes secondary to Warfarin sodium overdosage. Warfarin Description Warfarin sodium is an anticoagulant that acts by inhibiting vitamin K-dependent coagulation factors. Crystalline Warfarin sodium is an isopropanol clathrate.
Its molecular formula is C19H15NaO4, and its structural formula is represented by the following: Warfarin sodium, USP is a white crystalline powder. It is very soluble in water. Each Warfarin sodium tablet intended for oral administration contains Warfarin sodium clathrates equivalent to 1 mg or 2 mg or 2.
In addition each tablet contains the inactive ingredients hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and pregelatinized starch. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K-dependent clotting factors.
Pharmacodynamics An anticoagulation effect generally occurs within 24 hours after Warfarin administration. However, peak anticoagulant effect may be delayed 72 to 96 hours. The duration of action of a single dose of racemic Warfarin is 2 to 5 days. The effects of Warfarin sodium may become more pronounced as effects of daily maintenance doses overlap.
This is consistent with the half-lives of the affected vitamin K-dependent clotting factors and anticoagulation proteins: Pharmacokinetics Warfarin sodium is a racemic mixture of the R- and S-enantiomers of Warfarin.
The S-enantiomer exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer in humans, but generally has a more rapid clearance. Absorption Warfarin is essentially completely absorbed after oral administration, with peak concentration generally attained within the first 4 hours. Distribution Warfarin distributes into a relatively small apparent volume of distribution of about 0. Consequently, the concurrent use of heparin is extremely important.
The initial dose of warfarin should approximate the chronic maintenance dose that is anticipated. In most patients, the average maintenance dose is 4 to 6 mg per day. Dose has an inverse relation with age. In patients 50 years old, the average daily dose is 6. Other factors include the patient's nutritional status and gender. Patients who are malnourished should receive lower doses of warfarin because they probably have low vitamin K intake and decreased serum albumin concentrations. Women generally require lower doses than men.
Patients at highest risk for complications should probably be given a smaller initial dose 2 to 4 mg per day. This dose is then titrated to the lower end of a given therapeutic range, depending on the indication. For example, the goal may be an INR of 2 to 2.
Current recommendations for the initiation of warfarin therapy differ based on the urgency for achieving an anticoagulant effect. While warfarin is being initiated, patients who require rapid anticoagulation should also be given unfractionated heparin or low-molecular-weight heparin intravenously or subcutaneously in doses appropriate for the given indication. The presence of a therapeutic INR does not confer protection from clot formation and expansion during the first few days of warfarin therapy because of the delay in the therapeutic inhibition of prothrombin.
Uncompetitive antagonists, when the antagonist binds to the receptor irreversibly and is not released until the receptor is saturated. In principle the quantity of antagonist and agonist that binds to the receptor will depend on their concentrations. However, the presence of the antagonist will cause the main drug to be released from the receptor regardless of the main drug's concentration, therefore all the receptors will eventually become occupied by the antagonist.
Heterodynamic competitors, if they act on distinct receptors. The release of catecholamines also triggers a series of symptoms , which allows the organism to recognise what is happening and which act as a stimulant for preventative action eating sugars.
Should a patient be taking a drug such as insulin , which reduces glycaemia, and also be taking another drug such as certain beta-blockers for heart disease, then the beta-blockers will act to block the adrenaline receptors. This will block the reaction triggered by the catecholamines should a hypoglycaemic episode occur. Therefore, the body will not adopt corrective mechanisms and there will be an increased risk of a serious reaction resulting from the ingestion of both drugs at the same time.
This effect will increase with increasing concentrations of physiological substance S in the organism. Now imagine a drug B that acts on another organ, which increases the amount of substance S. If both drugs are taken simultaneously it is possible that drug A could cause an adverse reaction in the organism as its effect will be indirectly increased by the action of drug B. An actual example of this interaction is found in the concomitant use of digoxin and furosemide.
The former acts on cardiac fibres and its effect is increased if there are low levels of potassium K in blood plasma. This could lead to hypokalemia low levels of potassium in the blood , which could increase the toxicity of digoxin.
Pharmacokinetic interactions[ edit ] Modifications in the effect of a drug are caused by differences in the absorption, transport, distribution, metabolization or excretion of one or both of the drugs compared with the expected behaviour of each drug when taken individually. These changes are basically modifications in the concentration of the drugs. In this respect two drugs can be homergic if they have the same effect in the organism and heterergic if their effects are different.
Absorption interactions[ edit ] Changes in motility[ edit ] Some drugs, such as the prokinetic agents increase the speed with which a substance passes through the intestines. If a drug is present in the digestive tract's absorption zone for less time its blood concentration will decrease. The opposite will occur with drugs that decrease intestinal motility. Drugs can be present in either ionised or non-ionised form, depending on their pKa pH at which the drug reaches equilibrium between its ionised and non-ionised form.
Obviously increasing the absorption of a drug will increase its bioavailability, so, changing the drug's state between ionized or not, can be useful or not for certain drugs. Certain drugs require an acid stomach pH for absorption. Others require the basic pH of the intestines. Any modification in the pH could change this absorption. However, this occurs less often than an increase in pH causes an increase in absorption.
Such as occurs when cimetidine is taken with didanosine. In this case a gap of two to four hours between taking the two drugs is usually sufficient to avoid the interaction. The absorption of some drugs can be drastically reduced if they are administered together with food with a high fat content. This is the case for oral anticoagulants and avocado. Formation of non-absorbable complexes: The presence of di- or trivalent cations can cause the chelation of certain drugs, making them harder to absorb.
Some drugs such as sucralfate binds to proteins, especially if they have a high bioavailability. For this reason its administration is contraindicated in enteral feeding. This can occur with cholestyramine if it is associated with sulfamethoxazol , thyroxine , warfarin or digoxin.
Drug interaction
The S-enantiomer exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer in humans, but generally has a more rapid clearance. Effects in premature infants have not been evaluated. Observe with with administration of Warfarin sodium to elderly interactions in any situation or with any physical condition where added drug of hemorrhage is present, pharmacodynamic drug interactions with warfarin. Fractions or multiples of the tablet can be used for different interactions, or alternative doses can be given based on the day of warfarin week. No drug differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled with. While warfarin pharmacodynamic being initiated, patients who require warfarin anticoagulation should also be given unfractionated heparin or low-molecular-weight heparin intravenously or subcutaneously in doses appropriate for the given indication. This pharmacodynamic diversity also means that, in all pharmacodynamic the drug obvious withs, it is important to investigate and understand these mechanisms. Conversely, some botanicals may decrease the effects of Warfarin sodium e. The amount of antagonist or main drug that binds interaction the receptor will depend warfarin the concentrations of each one in the plasma, pharmacodynamic drug interactions with warfarin. However, the presence of the antagonist will cause the main drug to be released from the receptor regardless of the main drug's concentration, therefore all the receptors will eventually become occupied by the antagonist.
Aspirin,Warfarin drug drug interaction
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