Transcript FACTORS THAT CHANGE DRUG ACTION

FACTORS THAT CHANGE
DRUG ACTION
FACTORS AFFECTING DRUG
ACTIONS
RELATED TO THE DRUG
*PHYSICOCEHEMICAL
PROPERTIES OF DRUG
*PHARMACEUTICAL DOSAGE
FORMS
*PHARMACODYNAMİC
PROPERTIES
*DRUG INTERACTIONS
RELATED TO THE PATIENT
*AGE
(Pregnancy, lactation, pediatric and
geriatric populations)
*SEX
*GENETIC FACTORS
*HEPATIC AND RENAL
DISEASES
*OTHER PATHOLOGICAL
CONDITIONS
*COMPLIANCE
EFFECT OF AGE
Newborn and babies have increased gastric emptying time
Intestinal peristaltism is slow and irregular
Gastric acid secretion is slow and irregular, gastric juice is
neutral(acid sensitive oral penicillins have high systemic
bioavailability)
Since the skin is thin, absorption of drugs from skin in newborn
and babies is increased
EFFECT OF AGE
Distribution
In newborn and babies plasma protein binding is lower
BBB is not developed well in the newborn
Metabolism
In the newborn metabolising enzymes are not sufficiently
Developed (Gray baby syndrome)
Elimination
In newborn and babies, glomerular filtration rate and tubular
Secretion are also insufficient. Doses of drugs such as penicillins
and aminoglycosides need to be regulated.
CALCULATION OF DOSE
There are several formulas:
Pediatric dose = [(4x Age + 20)/72] x adult dose
Ausberger Formula
Pediatric dose = (Weight/72) x adult dose
Clark formula
Pediatric dose = (Body area (m2)/1.8) x adult dose
OLD PEOPLE
 In older people PK of drugs change.
 After age 25, every year functions of
organisms related to drug action decline.
 Stomach acid secretion decreases, gastic
emptying time increases, absorption surface
declines (Abs rate↓)
Distribution
The ratio of lipid tissue to muscle tissue increases
in older people. Volume of distribution of lipid
soluble drugs ↑.
Blood flow to tissues decreases and distribution
takes longer.
Plasma albumin level ↓. Highly albumin bound
drugs free fraction increase and their effects ↑.
Metabolism
Efficiency of oxidation of CYP enzymes ↓(more in
men)
First pass effect decreases (Propranolol’s
elimination ↓)
Glucurunidation is not very much effected
Elimination
Glomerular filtration and tubular secretion ↓.
Receptor number and sensitivity ↓. ReceptorGprotein-enzyme coupling efficiency ↓, cAMPdependent kinase efficiency ↓.
Effects of several drugs increase in older people
 Hypnotic drugs (1/2 dose)
 Anxiolytic drugs (1/2 dose)
 Morphine, meperidine
 Phenothiazines and neuroleptic drugs
extrapyramidal effects, hypotension
 Anticholinergic drugs
 Thiazides hypokalemia
 Sufonylureas hypoglycemia
DISEASE PRESENT
Shock, chf blood flow to tissues ↓ and absorption
after parenteral and GI administration
decreases. However blood flow from elimination
organs also ↓ and they balance each other.
Kidney diseases, decrease in renal clearance
effects ionized and polar drugs.Gentamycin’s hl
increases to 30-60 h compared to 2h.
Drug choice in diseases: renal vs hepatic!
FEMALE VS MALE
Females metabolize antiepileptic drugs faster.
Males are less susceptible to tricyclic
antidepressants.
CYP enzymes sensitivity decrease in old age.........
Side effects of neuroleptics tardive dyskinesia and
succinylcholines myalgia are observed more
frequently in women.
Administration route effects drug bioavailability
Oral
Paranteral
Local
Circadian rythm
Slow acetylation of isoniazid is an example of
autosomal recessive inheritance.
G-6-phosphate-deficient hemolysis is an example
of X-linked inheritance.
In slow
acetylators
isoniazid causes
neuropathies.
Plasma
cholinesterase
activity
distribution in
the population
Sleep apnea
after
succinylcholine
occurs for
prolonged
periods of time
in people who
have a
defective
plasma
cholinesterase
In G6PD deficient people
due to reduced amount of
GSH, primaquine
nitrofurantoin and fava
beans cause hemolysis.