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Drug interactions

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Characteristics of those drugs prone to adverse drug ... Perhaps increasing clinical effects of the ... Examples: Sulphonamide antimicrobials. Pre-term neonates ... – PowerPoint PPT presentation

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Title: Drug interactions


1
Drug interactions
  • BDS lecture

2
Learning objectives.
  • Characteristics of those drugs prone to adverse
    drug interaction.
  • Pharmacokinetic and pharmacodynamic mechanisms.
  • Characteristics of those patients most at risk.

3
A couple of definitions
  • The INDEX drug
  • The drug which is effected by drug interaction
  • The INTERACTING drug
  • The drug that interacts with the index drug.
  • Perhaps increasing clinical effects of the index
    drug (causing harm).
  • Perhaps decreasing clinical effects of the index
    drug (causing harm).

4
Characteristics of index drugs
  • Effects on vital body systems
  • E.g. clotting, blood pressure, cardiac
    conduction, (contraception).
  • Small therapeutic index.
  • Steep dose-response relationship.

5
Characteristics of index drugs
  • Effects on vital body systems
  • E.g. clotting, blood pressure, cardiac
    conduction, (contraception).
  • Small therapeutic index.
  • Steep dose-response relationship.

6
Therapeutic effect
Toxic effect
requiring dose to achieve effect
DRUG DOSE
7
Characteristics of index drugs
  • Effects on vital body systems
  • E.g. clotting, blood pressure, cardiac
    conduction, (contraception).
  • Small therapeutic index.
  • Steep dose-response relationship.

8
Shape of dose-response curves.
Effect
Log drug concentration
9
Pharmacodynamic mechanisms
  • Two drugs acting upon the same (or similar)
    mechanism in the same direction (i.e. two
    agonists).
  • E.g. Two beta-blockers additive
  • E.g. Morphine plus diazepam additive
  • E.g. Pen-G plus gentamicin synergistic
  • Two drugs acting upon the same (or similar)
    mechanism in opposite directions (i.e. agonist
    plus antagonist).
  • E.g. Beta-blocker plus salbutamol antagonistic
  • E.g. Frusemide plus NSAID indirectly antagonistic

10
PHARMACOKINETIC MECHANISMS
  • Probably no overlap in the therapeutic effects
    of the two drugs.
  • Impossible to predict from first principles.
  • Look up BNF Appendix 1.
  • Absorption
  • Distribution
  • Metabolism
  • Excretion

11
Absorption
  • From the gut, in the case of two drugs
    administered together.
  • Chelating agents (e.g. calcium resonium).
  • Resins (e.g. cholestyramine).

12
Distribution plasma protein binding
R
Drug in free solution in plasma water
Albumin
13
Distribution plasma protein binding
R
Drug in free solution in plasma water
Albumin
14
Distribution.
  • Examples
  • Sulphonamide antimicrobials.
  • Pre-term neonates.
  • Bilirubin (kernicterus).

15
METABOLISM.
  • Characteristics of index drug
  • Effects on vital body systems
  • E.g. clotting, blood pressure, cardiac
    conduction, (contraception).
  • Small therapeutic index.
  • Steep dose-response relationship.
  • Terminated by metabolism.

16
METABOLISM
  • Examples of INDEX drugs.
  • Coumarin anticoagulants.
  • ENHANCED EFFECTS bleeding
  • REDUCED EFFECTS thrombosis-related issues
  • Oestrogen component of the combined OCP
  • REDUCED EFFECTS unplanned pregnancy
  • The interactions usually involve the CYP450
    family of mixed-function oxidases.

17
METABOLISM
  • Examples of INTERACTING DRUGS
  • CYP450 Inducers
  • Increase cellular content of the protein.
  • Thus interactions take time (several days) to
    envolve.
  • Effects of the INDEX drug are reduced.
  • Carbamazepine
  • Rifampicin
  • Phenobarbitone

18
METABOLISM
  • Examples of INTERACTING DRUGS
  • CYP450 Inhibitors
  • Compete with INDEX drug at enzymes active site.
  • Thus interactions become apparent very fast
    (often within a day).
  • Effects of the INDEX drug are enhanced.
  • Erythromycin
  • Metronidazole

19
EXCRETION
  • Characteristics of index drug
  • Effects on vital body systems
  • E.g. clotting, blood pressure, cardiac
    conduction, (contraception).
  • Small therapeutic index.
  • Steep dose-response relationship.
  • Terminated by irreversible excretion.

20
EXCRETION
  • Some strong acids/bases are actively
    secreted/reabsorbed by renal tubules.
  • Digoxin excretion may be reduced by verapamil and
    quinidine
  • Some drugs sensitive to changes in urinary pH or
    sodium balance.
  • Lithium excretion may be reduced by diuretics and
    NSAIDs
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