Discuss pharmacodynamics interaction and two example of each
Drug interaction is an event in which the effect of the drugs in the body can be amended when the particular drug is taken along with another drug (drug-drug interaction) or food (drug-food interaction) at the same time or in a rapid succession. The effect can be increase (synergistic) or decrease (antagonistic) in the action of one or both drugs. Drug interaction can be occurs at 2 distinct level which are pharmacokinetic or pharmacodynamics level. In pharmacokinetic interaction, the effects are primary alter the level of absorption, distribution, metabolism and excretion (ADME) of the drugs in the body.
In contrast, pharmacodynamics interaction is an interaction of the drugs which change the effects of another drugs in the body either synergism or antagonism. The synergism effects are further subdivided into addition or potentiation.
Addictive pharmacodynamics interaction
This interaction arises when 2 or more drugs that having identical pharmacodynamics effect are given simultaneously. As a consequence, these addictive effects will in turn lead to enormous response and result in toxicity to occur. Addictive pharmacodynamics interaction is the net effect of two drugs is solely the sum of the effects of each. (1+1=2) For instance: combinations of drugs which extend the QTc interval resulting in ventricular arrhythmias.
I) Examples of addictive drug-drug interaction
1. The combination of ACE inhibitor (for example, Lisinopril, Captopril) with potassium sparing diuretics (Spironolactone or Amiloride) results in augmented hyperkalemia.
2. The combination of Non-Steroidal Anti-inflammatory drugs (NSAIDs) such as ibuprofen or indomethacin with warfarin will increase the risk of bleeding.
3. The combination of thiazide diuretics (for example, hydrochlorothiazide) with beta blocker (for example, propranolol, atenolol) can cause an additive antihypertensive action.
4. The combination of verapamil with beta blocker can cause addictive bradycardia.
5. The combination f glibenclamide with metformin will cause hypoglycemia.
II) Examples of addictive drug-food interaction
1. The combination of alcohol with benzodiazepines (for example, lorazepam or clonazepam) will increase the sedation effects.
2. The combination of alcohol with anti-histamines (for example chlorpheniramine or diphenhydramine) will increase the central nervous system (CNS) depression.
III) Examples of addictive drug-herb interaction
1. The combination of tetracycline with St-John’s wort will increase the photosensitivity effect.
2. The combination of fluoxetine with St-John’s wort will increase the CNS depression.
Potentiation pharmacodynamics interaction
Potentiation pharmacodynamics effect is a situation in which the net effect of 2 drugs that are using concomitantly is greater than the sum of the effects of the individual drugs. For illustration, drug A boosts the effects of drug B, often by increasing the levels of drug B in the blood. For example, 1 + 1 > 2 or 1 + 0 > 2
1+1>2 mean that when one drug enhance the action of another drug. For instance, combination of sulphamethoxazole with trimethoprim to form cotrimoxazole can potentiate the antibacterial effect.
1+0>2 occur when one drug has no effect as own but it will increases the effect another drug. For instance, L-dopa and carbidopa.
Examples of potentiation pharmacodynamics effects
1. The addition of fluoxetine (antidepressant) to Lisinopril (antihypertensive) will potentiate the antihypertensive effect of Lisinopril which in turn decrease the blood pressure.
2. The combination of adrenaline and cocaine will potentiate the inhibition of neuronal uptake.
Antagonism pharmacodynamics effects
Antagonism pharmacodynamics effect is a situation in which the effect of one drug is decreased or diminished by the administration of another. It means that the combined effect of two drugs is less than the sum of the effects of the individual drug.
For example: Effect of Drug A+B < Effect of Drug A + Effect of Drug B
Antagonism effects are subdivided into chemical antagonism, physical antagonism, physiological antagonism and pharmacological antagonism
A) Pharmacological antagonism
It can be subdivided into competitive and non-competitive antagonism. In competitive antagonism, competitive antagonists can bind to the same receptor site as the agonist at a reversible manner. Due to the binding to the same binding site, the inhibitory action of antagonist can be decreased by increase concentration of agonist.
Examples of competitive antagonism pharmacodynamics effects
1) Oral anticoagulants which prolong the blood clotting time by competitively inhibiting the effects of dietary vitamin K
2) Atropine and Acetylcholine. Atropine is a reversible antagonist to Acetylcholine at muscarinic receptor.
In non-competitive antagonism, the non-competitive antagonists will either bind irreversibly to the same site as the agonist, or bind to a different site which reduces the binding of the agonist by an allosteric mechanism.
Example of non-competitive antagonism pharmacodynamics effect
1) Phenoxybenzamine and Adrenaline. Phenoxybenzamine binds irreversibly to ?-adrenergic receptors which reduce the fraction of available receptors and subsequent maximal effect that can be produced by the Adrenaline.
2) Diazepam and Bicuculline are example of non-competitive antagonism in which they bind to different receptor.
B) Physical antagonism
This type of antagonism is based on the physical property of the drugs. For example, charcoal can adsorb alkaloid in alkaloidal poisoning.
C) Chemical antagonism
In this reaction, the drugs do not bind to receptor. They antagonize the effects of one and another by chemical reaction such as neutralization or chelation.
Examples of chemical antagonism
1) Dimercaprol will chelates heavy metal such as lead or arsenic in heavy metal poisoning.
2) Neutralization between Heparin (acidic) and protamine sulphate (alkaline).
3) Calcium sodium edetate form an insoluble complex with arsenic or lead
D) Physiological antagonism
Physiological antagonism is also known as functional antagonism. In this reaction, two drugs will bind to 2 different receptors and antagonize the action of each other.
Examples of physiological antagonism
1) Histamine and Adrenaline. Histamine will bind to histamine receptor and cause bronchoconstriction, decrease of blood pressure and vasodilation. Whereas Adrenaline will bind to adrenergic receptor and cause bronchodilation, increase of blood pressure and vasoconstriction.
2) Insulin and Glucagon on glucose level. Insulin will bind to insulin receptor and cause reduction in blood glucose level whereas glucagon will bind to glucagon receptor and increase the blood glucose level.
In conclusion, all the health care providers should be carefully consider the potential drug interaction before recommending any regimen in order to avoid the occurrence of interaction or adverse effects to patients which can harm their health. Apart from that, health care providers should also counsel the patients on potential drug-food interaction so that patients will know what foods they should avoid when administer particular medications.