42 Section 1/ General Principles of Pharmacologydrugs like morphine, barbiturates, phenothi-
azines, benzodiazepine can produce more
CNS depression.
In gastrointestinal disease:
- The absorption of orally administered
drug is altered e.g. achlorhydria
reduces aspirin absorption. - Absorption of amoxycillin is
reduced in coeliac disease.
Other important diseases in which the
drug action is altered are: - The hyperthyroid patients are
relatively resistant to inotropic
action but more prone to arrhythmic
action of digoxin. - In congestive heart failure the drug
elimination is retarded due to
decreased perfusion and congestion
of liver, also reduced glomerular
filtration and increased tubular
reabsorption. - In head injury, morphine (in normal
dose) can cause respiratory failure.
In severe pain, hypnotics may cause
mental confusion.
- Tolerance: Tolerance is a condition
when there is a requirement of higher
dose of a drug to produce a given
response. - Drug resistance: It is tolerance of
micro-organisms to inhibitory action of
antimicrobials e.g. staphylococci to
penicillin. - Other drugs: Drugs may modify the
response to each other by pharmacokinetic
or pharmaco-dynamic interaction between
them.
Tachyphylaxis is the rapid development
of tolerance in which there is a marked
reduction in response even after repeated
doses of a drug. It is not necessary that
tolerance develop equally to all the action
of the drug, e.g. tolerance of morphine
occurs to its analgesic and euphoric action
and not to its constipating and miotic
actions. Likewise in phenobarbitone,
tolerance occurs to its sedative action and
not to its anti-epileptic action.
Cross tolerance is development of
tolerance to pharmacologically related
drugs e.g. morphine and barbiturates.CHEMICAL CHARACTER OF DRUGSSTRUCTURE ACTIVITY
RELATIONSHIP (SAR)
The effect of certain structural
compounds in relation to its activity,
duration of action and mechanism can be
altered by changing the structure of drugs
of known activity. A new product can show
different reactions, different relation
between the drugs and cell constituents and
perhaps even new mechanism of action.
The structure activity relationship is
useful in synthesis of new active compounds
with more specific actions with lesser
unwanted effect, and to know about their
mechanism of action.DRUG RECEPTORSThe drug receptors are macromolecular sites
which are situated on the surface or inside
the effector cells with which specific agonist
combines to produce its response. Antago-