This document discusses fixed dose ratio combination drug preparations. It notes that combinations can provide advantages like improved compliance, synergistic effects between drugs, and ensuring single drugs are not administered alone. However, it also lists disadvantages like unnecessary side effects from extra drugs, inability to adjust individual drug doses, and issues if one drug is contraindicated. It then discusses factors like age, sex, and pregnancy that can modify a drug's effects. Finally, it defines concepts like tachyphylaxis, drug resistance, and includes multiple choice questions.

1. Fixed dose ratio
combination preparations
& Factors modifying drug
action
Dr. G.VANITHA,MD

2. Fixed dose ratio combination
preparations
Advantages
1.Convenience and better patient compliance
2. Certain drug combinations are synergistic,
e.g.
sulfamethoxazole + trimethoprim
combination oral contraceptives.

3. 3.The therapeutic effect of two components being
same may add up while the side effects being
different may not,
e.g. amlodipine + atenolol as antihypertensive.
4.The side effect of one component may be
counteracted by the other,
e.g. a thiazide + a potassium sparing diuretic.
5. Combined formulation ensures that a single drug
will not be administered.
This is important in the treatment of tuberculosis
and HIV-AIDS
3 S 1.synergistic
2.side effect
3.single drug

4. ANTI TUBERCULOSIS DRUGS[ATT]

5. DISADVANTAGES OF FIXED DOSE
RATIO COMBINATIONS
1. The patient may not actually need all the drugs
present in a combination. He is subjected to
additional side effects
2. The dose of most drugs needs to be adjusted and
individualised. When a combined formulation is
used, this cannot be done without altering the
dose of the other component(s).
E.g Augmentin625[Amoxycillin500mg/clavulinic
acid125mg]

7. 3 . The time course of action of the components
may be different: administering them at the
same intervals may be inappropriate.
4. Altered renal or hepatic function of the
patient may differently affect the
pharmacokinetics of the components.

8. 5. Adverse effect, when it occurs, cannot be
easily ascribed to the particular drug causing it.
6. Contraindication to one component (allergy,
other conditions) contraindicates the whole
preparation.
7. Corticosteroids should never be combined with
any other drug meant for internal use

13. Physiological Factors
AGE
Newborn
– ↓ gastric acid secretion.
– ↓ liver microsomal enzymes (glucuronyl
transferase).
– ↓ Plasma protein binding.
– ↓ GFR & tubular secretion.
– Immaturity of BBB in neonates

14. • GIT absorption of ampicillin and amoxicillin
is greater in neonates due to decreased
gastric acidity.
• Chloramphenicol ----- Grey baby syndrome
Inadequate glucouronidation of chloramphenicol
with drug accumulation.
• Sulfonamides ------ Hyperbilirubinemia &
Kernicterus

15. CHILDREN
• Tetracyclines
Permanent teeth staining
• Corticosteroids
Growth & development retardation
• Antihistaminics
Hyperactivity

16. Old Age
↓ Liver function
diazepam, theophylline.
– ↓ Kidney function
Gentamycin ,Digoxin ,Pencillins are contraindicated in
old people.
– ↓ Plasma protein binding
– ↑ sensitivity to CNS depressants
diazepam, morphine

17. SEX
• Testosterone increases the rate of
biotransformation of drugs.
• Decreased metabolism of some drugs in
female (Diazepam).
• Females are more susceptible to autonomic
drugs ( estrogen inhibits choline estrase).

18. Pregnancy
• ↑ Cardiac output
• ↑ GFR and renal elimination of drugs
• ↑ Vd
• ↑ Metabolic rate of some drugs
• Lipophilic drugs cross placental barrier &
slowly excreted.

25. Tachyphylaxis
• An acute, sudden decrease in response to a
drug after its administration; i.e. a rapid and
short-term onset of drug tolerance.
• It can occur after an initial dose or after a
series of small doses.
• Increasing the dose of the drug may be able
to restore the original response

26. Drug resistance
• Drug resistance is the reduction in
effectiveness of a medication such as
an antimicrobial or an antineoplastic in
treating a disease or condition.
• When an organism is resistant to more than
one drug, it is said to be multidrug-resistant.

27. MCQ’S
1. As per “Drugs and Cosmetic Act” prescription drugs are
included in :
A. Schedule C B. Schedule H C. Schedule P D. Schedule X
2. Alkalinization of urine hastens the excretion of :
A. Weakly basic drugs B. Weakly acidic drugs H
C. Strong electrolytes D. Non polar drugs
3. All these drugs expect one cross the blood brain barrier:
A. Morphine B. Dopamine
C. Propranolol D. Ether
4. Which of the following is a prodrugs:
A. Hydralazine B. Clonidine
C. Captopril D. Enalapril

28. 5. Microsomal enzyme induction can be a cause of:
A. Tolerance B. Physical dependence
C. Psychological dependence D. Idiosyncrasy
6. Glomerular filtration of a drug is affected by its:
A. Lipid Solubility B. Plasma Protein binding
C. Degree of ionization D. Rate of tubular secretion
7. The loading dose of a drug is governed by its:
A. Renal clearance B. Plasma Half- life
C. Volume of distribution D. Elimination rate constant
8. The therapeutic index of a drug is a measure of
its:
A. Safety B. Potency
C. Efficacy D. Dose variability

29. 9. What is true in relation to drug receptors:
A. AII Drugs act through specific receptors
B. AII Drug receptors are located on the surface of the target
cells
C. Agonists induce a conformational change in the receptor
D. Partial agonist have low affinity for the receptors
10. Drug metabolism can be induced by the following
factors expect:
A. Cigarette Smoking B. Acute alcohol Ingestion
C. Exposure to insecticides D. Consumption charcoal
broiled meat

30. ANSWERS
1.B, 2. B, 3. B, 4. D
5. A 6. B, 7. C, 8. A,
9. C, 10. B