Ashifa Maulidya Shibly

04011381419194
PDU GAMMA 2014

DRUG-DRUG INTERACTION
In pharmacodynamic of drug and drug interaction, the drug directly alter the molecular
function or physiological action of other drug
1. Antidepressant and Sympathomimetics
Antidepressants are drugs used for the treatment of major depressive disorder
and other condition. Drugs that used are Tricyclic antidepressants, Monoamine
oxidase inhibitors, and lithium salts.
Tricyclic antidepressant potentiate the action of biogenic amines in the CNS
by blockade of their major means of psychological inactivation.
In Monoamine oxidase inhibitors, the drugs comprise a rather heterogenous
group of drugs that have in common the ability to block oxidative deamination of
naturally monoamines (ex. Dopamine, tyramine, serotonine, cathecolamines) by
inhibiting the enzyme monoamine oxidase. MAO (MAO-A and MAO-B) is important
in regulating the meatabolic degradation of cathecolamines and 5-HT(serotonine) in
neural or target tissues. Hepatic MAO has a crucial defensive role in inactivating
circulating moonoamines or those, such as tyramine, that originate in the gut and are
absorbed into the portal circulation. When MAO is inhibited, biogenic amines are not
deaminated but remain active and produce behavioral and pharmacodynamics effect .
because of their interference with various enzymes the MAO inhibitors prolong and
intensify the effects of other drugs and interfere with the metabolism of various
naturally occuring substances.
Interaction with drugs:
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Sympathomimetic amines
Sympathomimetic amines are potentiated following the use of MAO inhibitors. The
effect is greater with indirectly acting amines (e.g amphetamine). The MAO inhibitor
will cause raised consentration of amines in CNS so it will greater the effect by
releasing the large amount of monoamines from periphery nerve endings

Tyramine
Presumably as a result of hepatic MAO inhibition, tyramine and other monoamines in
food or produced by bacteria in the gut escape oxidative deamination in the liver and
release cathecolamines that are presents in supranormal amounts in nreve endings and
the adrenal medula. The average meal of natural or aged cheeses contains enough
tyramines to provoke a marked rise in blood pressure and other cardiovascular
changes. Other food implicated in this syndrome include beer, wine, pickled herring,
snails,chicken liver, yeast, large quantities of coffeecitrus fruits, etc.

2. NSAIDs and Antihypertensives

During inflammation response, chemical mediators such as histamine, 5hydroxitrptapine, slow-reacting substances of anaphylaxis (SRS-A), various
chemotactic factors, bradykinin, and prostalglandins are liberated locally. In
nanogram amounts, prostalglandin E2 (PGE2) and prostacyclin (PGI2) which are
likely to be generated in inflammation cause erythema and increase local blood flow.
Two important vascular effects of prostalglandins of the E series are not generally
shared by other mediators of inflammation, a longlasting vasoldilator action and the
capacity to counteract the vasoconstrictor effects of substances such as epinephrine
and angiotensin.
NSAIDs analgesic and antiinflammatory effects are mostly derived from
cyclooxygenase (COX) inhibition and consequent decrease in prostaglandin synthesis.
There are at least two, genetically, functionally and structurally different moieties of
this enzyme: constitutive (COX-1) and inducible (COX-2). COX-1 is permanently
active in many bodily structures, regulating normal tissue activities, while COX-2 is
activated by inflammation, trauma or infection. Its inhibition leads to decreased PGI2
production in the vascular endothelium, with no change in TxA2 synthesis in the
platelets, predisposing to vasoconstriction, thrombosis and endothelial lesion.
Moreover, all NSAIDs impede physiological prostaglandin synthesis in the kidneys
resulting in fluid retention and local vasoconstriction.
The mechanism of the hypertensive effects of NSAIDs seems primarily related to
their ability to block the cyclo-oxygenase pathway of arachidonic acid metabolism,

with a resultant decrease in prostaglandin formation . The prostaglandins are

important in normal modulation of renal and systemic vascular dilatation, glomerular
filtration, tubular secretion of salt and water, adrenergic neurotransmission, and the
renin-angiotensin-aldosterone system.
Hypertentive patients use NSAIDs for a variety of indications. NSAIDs inhibit
prostalglandin-mediated vasodilatation and promote water0salt retntion. Both this
mechanisms may contribute to reversing the effect of hypotintisive drugs ,particularly
those agents whose mechanisms depends on modulating prostalglandins, renin,or
sodium water balance. Blockade of salutary effects of prostaglandins by NSAIDs
results in a complex series of events culminating in attenuation of the effects of many
antihypertensive agents like diuretics, ACE inhibitor, beta-blockers, and ARBs.
Calcium channel blockers and centrally acting antihypertensive seems to be the least
affected.

Sumber:
Gilman, Alfred Goodman. (1978). Goodman and Gilmans The Pharmacological Basis of
Therapeutics ,sixth edition. New York: Macmillan Pulishing.