Question

Define the pharmacodynamic interactions additive, synergistic, agonist and antagonist

Describe factors which affect drug absorption in relation to organ function

Which electrolyte imbalance is a patient taking furosemide (Lasix), a loop diuretic, most at risk of developing?

Answer 1

1. When two or more drugs given simultaneously or immediately after one, they affect the effect of one another, either they may exhibit synergism or antagonism. The interactions may be at pharmacodyanmic level or pharmacokinetic level. Pharmacodynamic is the study of drug's action, mechanism of action, adverse effect, interaction or contraindications, whereas, pharmacokinetic is the study of drug's absorption, distrubution, metabolism and elimination.

When the action of drug is increased by another drug, it is said to be synergistic effect. If one drugs is inactive, but increases the action of other drug, is said to be the synergism. When both drugs with action on same directio, increases the effect of each other, this type of synergism is said to be additive.

If both the drugs have action on the same direction, and if they are given simultaneously, the enhance in the action is said to be additive effect. For example, if aspirin and paracetamol are given for their analgesic and antipyretic effect, the effect produced by both drug is added.

Antagonism: when one drug is given with other drugs and the action of other drug is decreased or abolished, this effect is said to be antagonism.

Action of drug A + B < Action of A + Action of B

Generally in the antagonistic pair, one drug is inactive and it only decreases the action of other drug.

The antagonism may be:

• Physical antagonism: e.g. charcoal absorbs alkaloids, and hence reduce the alkaloid poisoning.
• Chemical antagonism: e.g. KMnO4 oxidizes alkaloids, and hence used as gastric lavage in alkaloid poisoning.
• Physiological antagonism: e.g. Insulin and glucagon on blood glucose level.
• Receptor antagonism: e.g. Acetylcholine and atropine for cholinergic receptors.

Agonist: These are the agents that activates the receptors and produces action similar to that of the physiological signal molecule. For example, Adrenaline binds to the beta adrenergic receptors and produced the effects similar to that occurs after the stimulation of beta receptors.

2. Absorption is the process of the movement of the drug molecule from the site of its administration into the systemic circulation. There are number of factors that affect the abosoption of any molecule. Those factors are:

Aqueous solubility: Drugs that are in solid state must be disolved in the aqueous phase before they get absorb. Water soluble drugs absorbs faster than solid drugs or oil soluble drugs.

Concentration: The diffusion of drugs also depends on the concentration gradient, higher the concentration higher the absorption.

Surface area of abosoption: If the surface area is more, the rate of absorption is also high.

Vascularity of the absobing surface: Higher the vascularity in the absorbing surface, the amount of absorption also high.

Route of administration: the different route of administrations also have different property and varying rate of absorption.

3. Furosemide (Lasix): It is a high celing (loop) diurectic, and it is an inhibitor or Na⁺-K⁺-2Cl¯ Cotransport. Its main site of action is thick ascending loop of Henle, where it inhibits the absoption of sodium, potassium and clorine by inhibiting Na⁺-K⁺-2Cl¯ Cotransporter. Hence it increases the elimination of sodium and potassium. It also increases the elimination of HCO₃^- ion due to its weak carbonic anhydrase inhibitory action. The elimination of potassium by furosemide makes it at high risk. Because it causes the hypokalemia and produces the symptoms caused due to hypokalemia like fatigue, muscular damage, muscle spasm constipation, arrhythmia, palpitation etc.

Therefore, loss of potassium (hypokalemia) after administration of furosemide develop risks.