DRUG INTERACTIONS

1
DRUG INTERACTIONS
2
Definition

• pharmacological or clinical response to the
  administration of a drug combination is different
  from that anticipated from the known effects of
  the two agents given alone
• whwn the effects of one drug are changed by the
  presence of another drug, food, drink or by some
  chemical environmental agent

3
Therapeutic DI - potentiation

• Post-transplantation immunosupression
• corticosteroids, cyclosporine, azathioprine
• Malignancy
• alkylating agents (cyclophosphamide),
  antimetabolites (methotrexate, fluorouracil)
• Hypertension
• Asthma

4
Incidence

• Incidence of potential prescription 4-5
• Hospital admissions..1
• ! Most in ambulatory (outpatients) settings
• ! UNDERESTIMATION
• ! Geriatric patients - polypharmacy, polymorbidity

5
Documentation and reliability

• Interactions in animals
• Case-reports - one or a few patients reposted
  spontaneously
• Trials of drug combiantions in healthy volunteers
• Terapeutic RCT (randomised placebo-controlled
  trials)

6
Individual variation

• Drug metabolism - susuceptibility to microsomal
  enzyme induction
• genetic activity of P-450
• poor x extensive slow x fast metabolisers
• digoxin x antibiotics - in only about 10
  patients

7
Drug interactions

• Pharmaceutical
• incompability prior to administration (syringes,
  infusions)
• Pharmacodynamic
• competition at receptor sites, physiological
  system
• Pharmacokinetic
• absorption, distribution, metabolism, elimination
  phase

8
Combination of mechanisms

• Aspirin - interferation with absorption and renal
  tubular secretion of drugs increasing toxicity
  of oral anticoagulants gastroinestinal erosions
• Amiodarone - increasing the serum digoxin by
• inhibition of renal excretion
• inhibition of hepatobiliary excretion
• displacement from tissue binding sites

9
Induction of metabolism

• Enzyme-inducing agents
• barbiturates, phenytoin, carbamazepine,
  aminoglutethimide, alcohol, rifampicin, cigarette
  smoking
• Stimulation of metabolism of
• warfarin, paracetamol, oral contraceptives

10
Inhibition of metabolism

• Enzyme inhibitors
• cimetidine
• CCB (diltiazem, verapamil)
• amiodarone
• macrolide antibiotics (ery, clar, trol)
• azole antifungals (keto, itra, mico)
• SSRI (fluoxetine, fluvoxamine)
• grapefruit juice