Factors Modifying Drug Effects

Question 1

Dose Must be Adjusted to Patient

Answer 1

Body Size

• Weight
• Surface Area

Age

• Neonate
• Child
• Elderly

Gender

Pathological State

Tolerance

Genetic Factors

Question 2

Neonates

Answer 2

Differences in Distribution:

• -Higher Body water
• -Lower Protein Binding
• -Underdeveloped Blood Brain Barrier

Metabolic Deficiency (Not fully developed yet):

• -Glucuronide (phase II conjugation)
• -P450 Systems (phase I oxidation)

Decreased Renal Function

Question 3

Kernicterus

Answer 3

Irreversible Brain Damage in Neonates due to Bilirubin entering the CNS.

Most Neonates have normally elevated Bilirubin and Low plasma proteins to carry the bilirubin.

Sulfonamide drug competes with bilirubin for protein binding, increasing the level of free bilirubin in blood.

The high levels of unbound bilirubin cross the not yet fully developed BBB, causing Kernicterus.

Question 4

Children

Answer 4

Increased Drug Biotransformation (typically more rapid than adults)

Compliance problems (adherence)

Form of preparation

Question 5

Elderly

Answer 5

Both Pharmacokinetic (body act on drug) and Pharmacodynamic (drug act on body) changes occur.

Pharmacokinetic Changes:
--Decreased Body Water
--Decreased Lean Body Mass
--Increased Body Fat
--Decreased Serum Albumin
---Decreased Hepatic Blood Flow
==> Decreased Hepatic Metabolism

–Decreased Biotransformation: especially Oxidative (P450); decrease more marked in men than women.

–Decreased Renal Excretion:
May get Accumulation of Drugs that are mainly excreted in the Urine.

Pharmacodynamic Changes:

• -Some Homeostatic Responses are Diminished.
  e. g. Less effect of Exercise on Heart Rate (Less Tachycardia) and Greater Increase in Systolic BP (due to Decreased Tissue Response)

Compliance Problems (often Unintentional):
–Confusion
–Cost
–Physical Disabilities:
Tremor can make it difficult to take a “spoonful”
Childproof may = Patient-proof
Poor Vision make it difficult to read instructions/labels.

Polypharmacy:
–Increased Risk of Drug Interactions

Increased Effects of CNS Depressants (make drowsy):

• Benzodiazepines
• “Hidden” ingredients in OTC drug, e.g. antihistamines

Question 6

Gender

Answer 6

Differences in Body Composition and Clearance

Question 7

Pregnancy and Lactating/Nursing Patient

Answer 7

Possible risk to fetus during pregnancy.

Nursing: Most drugs are excreted into Breast Milk.
–Usually concentration is too low to affect infant.

Exceptions:

• Tetracyclines: may affect Teeth
• Isoniazid
• Most Sedatives and Hypnotics

(Ionization of drugs, weak bases, causing “ion trapping” in Milk.)

Question 8

Pathological State

Answer 8

Changes in Biotransformation and Excretion:

• -Hepatic Disease
• -Renal Disease

Changes in Response to “Normal” Drug Levels:
1)Thyroid Disease (when not yet treated):
Altered Sensitivity:
–Increased sensitivity to CNS Depressants and Opioids in Hypothyroidism.
–Increased sensitivity to Epinephrine, Cardiovascular Stimulants in Hyperthyroidism.

2) Increased sensitivity to respiratory depressants in respiratory disease.
3) Increased sensitivity to cardiovascular stimulants in cardiovascular disease and in adrenocortical imbalance.

Question 9

Tolerance

Answer 9

Tolerance = Reduced effect of drug with Repeated Administration

Pharmacodynamic:
–Cellular Adaptation

Pharmacokinetic:
–Altered Handling, e.g. enzyme induction

Behavioral:
–May adapt behavior to appear unaffected, deliberately

Tachyphylaxis (Rapid Tolerance):

• -Often due to Fatigue of System
• -or Depletion of Essential Substance (transmitter, messenger)

Question 10

Genetic Factors (Idiosyncracy)

Answer 10

Patient has a response to a drug that is different than anticipated; may be due to genetics.

Question 11

Route of Administration

Answer 11

Absorption affected by

• -Surface Area
• -Perfusion at Site

Oral Administration may be affected by

• -Food
• -GI tract Motility (increased in diarrhea, decreases absorption; if motility is decreased, increases absorption)
• -First Pass Metabolism

Question 12

Form of Preparation

Answer 12

Solution is more rapidly absorbed than particles

Question 13

Time of Administration

Answer 13

Oral relative to Meal times

Drugs affecting excitability relative to sleep-wake cycle

Question 14

Additive Effect

Answer 14

Two drugs with same effect.

When given in combination, they give a summation of effects.

Question 15

Synergism

Answer 15

Two drugs with same effect.

When given in combination, effect is greater than the sum of the two effects.