Review the pharmacokinetics and pharmacodynamics of drug-drug interactions

1. Review the pharmacokinetics and
pharmacodynamics of drug-drug
interactions
DRUG-DRUG INTERACTIONS

2. DRUG-DRUG INTERACTIONS

3. How do different drugs effect different
parts of the body?
DRUG-DRUG INTERACTIONS

4. DRUG-DRUG INTERACTIONS

5. DRUG-DRUG INTERACTIONS
Pure opioid agonists (ex. morphine) stimulate
mu and kappa receptors among others,
causing both analgesia and adverse effects
(respiratory depression, euphoria,
constipation, etc). Pure opioid antagonists
(ex. naloxone), will occupy mu receptors and
block opioid agonists from binding to these
receptors. Given alone, an opioid antagonist
will not cause any specific effects. Mixed
agonist/antagonist medications (ex.
pentazocine), cause analgesia by acting as
agonists at kappa receptors but antagonists at
mu receptors. Addition of one of these
medications to a patient already receiving a
pure mu agonist may cause withdrawal
symptoms.

6. DRUG-DRUG INTERACTIONS

7. DRUG-DRUG INTERACTIONS

8. DRUG-DRUG INTERACTIONS

9. DRUG-DRUG INTERACTIONS

10. DRUG-DRUG INTERACTIONS
Bradycardia, palpitations, or
hypotension, may occur from use of
opioids. Concurrent use of other
medications that can cause one or
more of these reactions will cause
additive effects. Therapeutic doses of
opioids can produce peripheral
vasodilation, decreased blood pressure
(orthostatic hypotension may occur)
and heart rate. Some opioids (ex.
morphine) cause histamine release
which can contribute to a descrease in
blood pressure. Use of phenothiazines
can increase the risk of morphine-
induce hypotension.

11. DRUG-DRUG INTERACTIONS

12. DRUG-DRUG INTERACTIONS

13. DRUG-DRUG INTERACTIONS

14. DRUG-DRUG INTERACTIONS
Some patients, particularly the elderly,
may have reduced renal elimination. This
is an important consideration for many
medications, especially those used in pain
management. Use of a medication that
relies on renal clearance for elimination in
a patient with reduced renal elimination,
will likely result in drug accumulation,
with potential for increased adverse drug
effects or toxicity. In some cases, a
reduction of the dosage may be
appropriate (ex. Morphine), whereas
other medications should be avoided
altogether in such patients (ex.
Meperidine).

15. DRUG-DRUG INTERACTIONS

16. DRUG-DRUG INTERACTIONS
Opioids cause decreases in respiratory
rate due to their direct effects on
brainstem respiratory centers. There is a
decrease in respiratory volume due to a
slower rate of breathing, as well as
decreased responsiveness of respiratory
centers to carbon dioxide. These
responses may be exaggerated when a
patient is sleeping. Use of higher doses of
opioids (too rapidly titrating doses),
concurrent use of multiple opioids, or use
of an opioid with another class of
medications causing decreased
respirations may increase risk of
respiratory depression.

17. DRUG-DRUG INTERACTIONS

18. DRUG-DRUG INTERACTIONS
Various mechanisms for causing nausea or
vomiting exist. The vomiting center, found
in the medulla, receives signals from many
sources, one of which is the chemoreceptor
trigger zone (CTZ) therefore, this is a CNS-
medicated effect. Opioids represent one
class of medications that stimulate the CTZ
to trigger nausea and/or vomiting. These
adverse effects tend to be more common
in ambulatory patients, suggesting that
there is also a vestibular component to
opioid-induced nausea or vomiting. Several
medications or classes of medications can
cause nausea or vomiting, and if given
together, may create a significant
problem.

19. DRUG-DRUG INTERACTIONS

20. DRUG-DRUG INTERACTIONS

21. DRUG-DRUG INTERACTIONS

22. DRUG-DRUG INTERACTIONS

23. DRUG-DRUG INTERACTIONS

24. DRUG-DRUG INTERACTIONS