Factors that affect drug action

Body size, Age, Sex, Species, Race, Diet and plane of nutrition, Genetics, Route of administration, Environment, Psychological, Disease states, Enzyme inhibitors and inducers are factors that affect drug action in animals.

Body size

influence the conc. achieved at the site of action. Doses are normally given for adults of medium build. In extreme cases – dose to be actually calculated based on per kg dose. Body surface area is also an important parameter- used in calculation of dose for anticancer drugs.

(BSA in sq.m. = K x BW in Grams^2/3 x 10 ^–4 (K= 10 for dogs, 10.1 cats)

Age

drug behavior differs in infants and children. – low GFR, Blood Brain Barrier more permeable, absorption is altered poor metabolizing capacity up to 4 weeks of age

In the old, poor metabolizing capacity, low PP binding, slower Absorption – dose alteration needed in both cases

Sex

Females smaller in size and may need lower dose.

Pregnancy induced changes – delayed absorption, plasma albumin falls, acid glycoprotein increases, renal blood flow increases, induction of CYP 450 enzymes – all these affect the kinetics of drug. Besides – possibility of drug affecting fetus or the young ones thro’ milk

Species

changes in sp. in the pattern of metabolism – rabbits resist. Atropine, dogs are poor acetylators, cats deficient in glucuronidation.

Race

Blacks need higher atropine to dilate pupil Mongols need lower dose. Fewer reports of aplastic anemia after chloramphenicol use in Asians compared to the West.

Diet and plane of nutrition

Drug action is more predictable in good plane of nutrition.

Genetics

G-6-PD deficiency hemolysis with antimalarial agents Malignant hyperthermia after halothane in some human individuals and pigs.

Route of administration

Besides kinetics, in some cases route may alter action- eg. MgSO₄ – orally purgation, skin – decrease swelling, i/v – CNS and cardiac depression  Iodine – antiseptic and antigoitre

Environment

Insecticides, tobacco smoke, charcoal broiled meat – induce metabolism. Hypnotics taken at night at bed work well.

Psychological

beliefs, attitudes, expectations – more in humans. Placebo (Latin – I shall please) used in trials and to treat otherwise normal patients (hypochondriacs). Placebos induce endorphins in brain analgesia.

Disease states

1. Diseases of GI tract –orally given drugs – altered absorption
2. Liver diseases – Bioavailability of drugs with First pass metabolism
3. Increased – Renal disease affects excretion of drugs
4. In all the above – change of dose needed.
5. Immunocompetence – Normally in very young and very old patients immunity is compromised. So, bacteriostatic to be replaced by bactericidals.
6. Drug interactions – physical or chemical inactivation or incompatibility
7. Food drug interactions – availability of food delays absorption.
8. Ingredients of food may cause specific interactions
9. Pharmacological Interactions – may be beneficial – epinephrine + local anesthetics pre-anaesthetics, antibacterial combinations
10. penicillin + probenecid, ampicillin + sulbactam harmful interactions – aminoglycosides with Neuromuscular blocking agents

Enzyme inhibitors and inducers

1. Tolerance and Tachyphylaxis – Tolerance is the requirement of higher dose to produce given response –
2. Natural – individual less sensitive to drug (rabbits)
3. Acquired – by repeated use of the drug in an individual who was initially responding – may be due to faster elimination of the drug on long use or changes in receptor sensitivity (downregulation)
4. Cross tolerance – tolerance among closely related drugs ( morphine and pethidine)
5. Tachyphylaxis – rapid development of tolerance – after only a few doses
6. Seen in ephedrine, tyramine – which deplete stores of catecholamines