Pharmacodynamic interaction:

Pharmacodynamic drug Interactions
PHARMACODYNAMIC INTERACTIONS

In pharmacodynamic DI there is a change in a person response on administration of a drug is an significant factor in PDI. These changes are particularly tough to categorize given the through a number of different mechanisms. 


This wide variety also means that, in all but the most understandable cases it is important to examine and know these mechanisms. The well-founded feeling exists that there are more unidentified interactions than known ones. At some point the medications straightforwardly vie for specific receptors e.g. beta-2 agonist for example, salbutamol and beta-blockers, for example, propranolol yet regularly the response is more roundabout  and includes the impedance with physiological systems. These communications are a great deal less simple to group about than those which are pharmacokinetic .


Epidemology:

The purpose of this to focus on hospital admissions which is caused by a specific type of ADR that can be expected to be preventable in almost all cases. The use of multi drug can increase the risk of DDIs. Ageing of the population and the increasing number of available drugs show the importance and awareness of DI in both clinical and forensic works.


The incidence of combinations of drug having serious ADI was generally low i.e 0.71%  but it was noted for the two individually drugs studies a common anticoagulant warfarin 33% and a new-generation antidepressant venlafaxine 46%. Toxicity of serotonine and adverse cardiovascular effects were the most prominent possible adverse outcomes.


Polypharmacy is common in children hospital in the United States and has been known as a major risk factor for exposure to potential drug-drug interactions. In hospital admission the reported incidence of drug-drug interaction is range from 0% to 2.8% in a review which is include nine studies all of which had some design faults. In harvard medical practice AE is 8% where as in US OPD have 10% DI out of 50 patient .



Risk factor:

The risk factor in patient include i.e poly pharmacy, multiple prescriber, multiple pharmacy, genetic, specific population such as females, malnutrition, critically ill patient, and narrow therapuetic index drugs. One-third of the population was visible to polypharmacy, and 6% were showing to potential DI during 1 year. Patient factors related with improved possibility of potential DI were high age, or a high number of concurrently drugs used and a high number of prescribers [16].


Out come of drug interaction:


  • loss of therapeutic effect.
  • Toxicity.
  • unexpected increse in pharmacology activity.
  • Beneficial effect.
  • Chemical or physical interaction.



 Factor contribution to the occurrance of drug-drug interaction:



pharmacokinetic interaction.
multiple pharmacological effect.
Multiple prescriber.
Use of otc medication.
Patient non-complaince.
Drug abuse .

Pharmacokinetic interaction:

Significantly change the PK profile and result in the DI in the situation that interferes with the distribution, absorption, metabolism, or excretion of drugs. Such interaction has the potential to decrease the suitability or rise the danger of toxicities of influenced specialists .


Multiple pharmacological effect:

 Most of the drug utilized as a part of current treatment has the ability to impact numerous physiological frameworks. There are two medications are direct together will frequently influence a portion of the same system. The potential medication association between the medications, there regularly the propensity just to be worried with the essential impact of the medication is included and to ignore the auxiliary exercises they have.

Consolidate treatment with a phenothiazine antipsychotic e.g. chlorpromazine, a tricyclic energizer e.g. amitriptyline, and an antiparkinson operator e.g. trihexyphenidyl  is a started in some patient. It has considered different primary effect of each agent. However anticholinergic activity of all three possesses. Any of the medications might be slight in the anticholinergic impact; the added substance impacts of the three specialists might be critical .


Multiple prescriber:

It is exceptionally fundamental for some individual to check more than one doctor and to be seeing at least one authority notwithstanding a family doctor is very common for a patient e.g. dental specialists, podiatrists who might be recommend the medicine. It is extremely troublesome for one prescriber to know about all the solution that have been recommend by other for a specific patient and such circumstance consummation could emerge.


For instance one doctor may endorse a pharmaceutical competent for bringing about sluggishness or tiredness e.g. certain antihistamine, opioid analgesic for a patient for whom another physician has prescribe an antianxiety agent of an excessive depressant effect with a possible consequences. The patients have seeing the different physician he or she frequently will have the remedy apportioned by a similar drug store. In this manner, the drug specialist can assume an imperative part in the identification and counteractive action of medication related problem .



Use of otc drug:

 Many person hide the use of OTC drugs while possible for a numerous drug used in little
era may have the same API but work inversely then incite side
effects. Usually when using prescribe drug along with OTC e.g. aspirin, antacids and
decongestant  etc measured having incompliance to patients. Interaction also may result from the simultaneous utilization of at least two items accessible without a remedy.


Increase the risk of an excessive response to these agents with two nonprescription products promoted for different purposes contain the same active ingredient in the same situation. Acetaminophen is included in many products for its action is antipyretic and analgesic and is included nonprescription sleep-aid formulation. They purchase for different condition may contain the same active ingredients that the patient are unaware to the products and therefore  with the use of products increased risk of the problem they might assume to be safe because they do not require a prescription.


Patient non complaince:

For a variety of reasons, many patients do not take medication in the manner intended by the prescription. Some patient are not receive proper instruction from the prescriber and pharmacist as to how and when take their medication. In some cases patient are particularly involving that have taking to the other medication, confusion about the instruction may develop even though the patient may have understood them initially.

It is understandable that the older patient who may have may be taking five or six medication at several time at day at different time can become confused or forget to take their medication, although these occurrences  are by no means unique to the geriatric population, In the situation involving in the noncompliance usually a result in a patient are not taking the enough medication, some circumstances could lead to use excessive of the medication that why increasing the drug interaction.
 For example some patient is forgotten a dose of the medication, then in the next time double medication can be taken. Some other patient may act on assumption that if one tablet dose that have been prescribed provides partial but not complete relief of symptoms, a two tablet dose will be even more effective .

Drug abuse or misuse:

Some drugs are individual to man handle or intentionally abuse medications may likewise prompt to an expanded frequency of medication connection. The antianxiety specialists, opioid pain relieving, and amphetamines are among the operator frequently manhandled, and the wrong utilization of these medications can bring about various issues, including an expanded potential for medication communication .

Mechanism of drug drug interaction:

Altered bioavailibility:

This alteration may occur when the amount of object drug reach the systemic circulation which is interfered by a perpetrator drugs. This only occur when orally drug administered and absorbtion or first pass metabolism is changed. Drug which have low oral bioavailibilty are mostly effected but those who have high bioavailibility are less effected e.g. Alendronate have low oral bioavailibility. Alendronate co administration with calcium decrease bioavailibility and result is no absorbtion of Alendronate. On other hand co-administration of dabigatran with verapamil increase bioavailibility and can result in an increased risk of bleeding .

Altered metabolism:
Changes in the metabolism of a drug is very important causes of unexpected drug interaction. These occur when as a result of changing in drug clearance or oral bioavailibilty. There are some enzyme famly which is involed in drug metabolism i.e CYP450 which is the most important for drug metabolism. In this one drug induce these enzyme for other drug so metabolism is effected.
Inhibition of CYP450 increase the conc of some drugs by decreasing its metabolism


e.g. clarithromycin is a strong antagonist of CYP3A catalist simvastatin metabolism. Thus increasing the risk of myopathy as observed. Drug inhibition of CYP450 is also used as a therapeutic monitoring tool e.g. ritonavir an antiviral agent which is a strong inhibitor of CYP3A which reduce metabolism of other protease inhibitors and thus increasing their effectiveness in treating HIV.
Induction of a CYP450 decreasing the conc of some drugs by increasing their metabolism e.g. carbamzipine is a strong inducer of CYP3A that increase the metabolism of the combine oral contraceptive, thus increasing the risk of unwanted pregnancy.

Prodrug:

Most of drugs are depen upon CYP450 for conversion to their active state. As this is usually depending upon a single enzyme pathway. Prodrugs are particularly prone to change in metabolism. Inhibition of such enzyme may lead to prevent the convertion of prodrugs to active drugs which may lead to inappropriate conc of the active drug and therapeutic failure e.g tamoxifen is metabolized by CYP2D6 to its active form endoxifen and concomitant thearapy with strong CYP2D6 inhibitor paroxetine has been associated with increased death rate in breast cancer .

Altered distribution:

This occur when the conc of drug at the side of action is altered without necessarily changing its circulation conc. This is a particular problem with those drugs which target intracellular or central nervous system. Most drugs cause more alteration in the cell membrane transport of other drugs e.g. verapamil inhibit efflex transporters i.e P-glycoprotien increasing the conc of substrates such as digoxin and cyclosporine. Probencid block anion transport result in increasing the conc of substrates such as methotrexate and pencillines. DI involved in transport are less understood as compared to the DI involvingin metabolism .

Altered clearance:

This can also occur when excretion or metabolism of the OD is effected by a perpetrator drug. OD with a narrow therapuetic index drug are mainly effected, as amodest changes in conc may be clinically imported. Perpetrator drugs known to strongly effect drug metabolism are more likely to cause large conc in alterations and hence clinical consequence as observed.

Altered excreation:

Some of drugs are eliminated from the body in unchanged form usually in the urine or with bilary tract in the stool. Changes in the drug clearance may result due to effets on renal tubular funtion or urine PH e.g. probencid decrease the renal clearance of anionic drugs such as methotrexate and penicillin .

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