this is a lecture of " drug interactions " , shows:
-definitions
-types
-mechanisms
-high risk people
-how to handle a drug interaction
-resources
-online app.
...........
hope u enjoy the lecture :)
3. Definition
An interaction is said to occur when the
effects of one drug are changed by the
presence of other drug, herb, food, drink.
An interaction occurs when
pharmacokinetics or pharmacodynamics of
drug are changed.
4. Types
Drug - drug interactions.
Herbal - drug interactions.
Food - drug interactions.
Drink - drug interactions.
Pharmacogenetic interactions.
6. Absorption interactions
Two important items we should consider:
( rate of absorption and absorbed amount )
- Rate of adsorption is not clinically important
in multiple doses e.g. anticoagulants.
- But in single doses we should reach
therapeutic level rapidly e.g. hypnotics and
analgesics.
8. 1- altered PH
Some drugs are absorbed from
stomach (acidic media), so when this
media become neutral or alkaline, this
will affect the absorption of drug.
Ex :
- antacid and ciprofloxacin
9. 2- Altered bacterial flora
Bacterial flora has a marked role in
metabolization of some drugs.
Long term antibiotics may kill normal
flora and affect drug absorption.
Ex :
erythromycin and digoxin
13. Distribution interactions
There is an important factor :
Vd
Protein binding interactions :
- unbound molecules remain free and
pharmacological active.
- bound molecules are pharmacological
inactive.
Some drugs may compete others for
binding to protein depending on affinity
and concentration.
15. Metabolism (biotransformation)
Most drugs are chemically altered
within Liver to less toxic and less lipid-
soluble metabolites.
Hepatic metabolism has two pathways
:
◦ Phase 1 (modification)
◦ Phase 11 (conjugation)
21. Enzyme Induction
Notes:
◦ Onset of enzyme induction is slow (days
– 2weeks).
◦ Also slow to solve.
◦ We can overcome this problem by
increase the dose
22. Enzyme Inhibition
Most common than enzyme
induction.
This interaction decrease drug
metabolism and so increase its
concentration in serum.
It takes 2-3 days
EX :
Ritonavir inhibit metabolism of
sildenafil by inhibiting CYP 3A4
23.
24. Notes :
◦ If serum levels within therapeutic
ranges so it is not clinically important.
◦ Some drugs can be metabolized by more
than one of CYP450 isoenzymes, so the
reaction may be not clinically important.
25. Excretion
Most drug are excreted in Urine or
Bile.
Some drugs are reabsorbed from
renal tubules or enterohepatic
recirculation.
Some drugs are excreted in acidic
urine, so changing urine PH will affect
there serum level.
These interaction is rare.
26. Excretion
Mechanisms :
◦ Altered urine PH
◦ Change in active tubular secretion.
Some drugs may compete for excretion.
E.g. probenecid and penicillin.
◦ Enterohepatic recirculation.
E.g. penicillins and oral contraceptives.
28. Pharmacodynamics interactions
they occur when the effects of a drug
are changed due to presence of
another drug at its site of action either
directly (on the same receptor) or
indirectly (on different receptor).
Two types :
◦ Synergistic interactions.
◦ Antagonist interactions.
29. Synergistic interactions
When two drugs have the same effect
are given together, so the total effect
will increase.
It may be desired :
◦ e.g. sulfonamides and trimethoprim.
May be not desired :
◦ e.g. K-sparing drugs (ACEIs , K-sparing
diuretics) and K-supplement >> cause
hyperkalemia.
34. Liquorice
Liquorice contain glycyrrhizin
(glycyrrhizinic or glycyrrhizic acid)
Glycyrrhizinic acid is hydrolyzed in the intestine to
pharmacologically active compound glycyrrhetic
acid which inhibit 11 betahydroxysteroid
dehydrogenase.
This increase cortisol in kidney and act as
aldosterone (fluid retention, hypokalemia,
hypertension)
Ex:
◦ Liqourice and antihypertensive
35. Patients in high risk of drug
interactions
Polypharmacy people (elder)
Hepatic disorders
Renal disorders
Genetic factors
36. How to handle an
interaction?!
If the previous solutions don’t work ?!!!
Adjust drug dosage with monitoring of drug
level and physiological functions
Is the the
interaction
clinically
important?!
No
Yes
Using the
dose space
will solve the
interaction?!
Yes
No
Using
alternative will
solve the
interaction?!
Yes
No
42. References
Stockley’s Drug Interactions 9th E
Book.
Color Atlas of Pharmacology 3rd E
book.
Material of Dr. Mohamed Emam.
Notebook of drug interaction of
pharmacology department-Benisuef
pharmacy faculty.
