Drug interactions Flashcards
Classify the ways that drugs interact with each other
PHYSICOCHEMICAL IINTERACTIONS
- Pharmaceutical incompatibility
- Chelating agents
PHARMAKOKINETIC INTERACTIONS
- Absorption
- Distribution
- Metabolism
- Excretion
PHARMACODYNAMIC INTERACTIONS
- Additive
- Summative
- Synergistic
- Potentiation - Antagonism
- Competitive
- Non-competitive
- Physiological - Indirect
Give examples of drugs that have physicochemical drug interactions
- Pharmaceutical incompatibility
- Acidic heparin has its action terminated by strongly basic protamine - Chelating agents
- Desferroxamine chelates iron
- Penacillamine chelates heavy metals e.g. in Wilson’s disease
- Tetracyclines chelate Ca2+ and Fe3+ in the GIT - Mix Thiopentone and Sux in same syringe –> formation of a complex
- Paraldehyde reacts with plastic syringes (glass syringes needed)
Give examples of pharmacokinetic drug interactions with respect to drug absorption
ABSORPTION
- Activated charcoal absorbs drugs in the GIT
- Metoclopramide, antimuscarinics and opioids affect gastric emptying
- VC delay LA distribution
Give examples of pharmacokinetic drug interactions with respect to drug distribution
- Beta Blockers - Reduces CO and so can slow delivery of sux to the NMJ slowing onset.
- Aspirin can displace bilirubin from albumin in neonates –> kernicterus
Aspirin and sulphonamides can alter protein binding of phenytoin which decreases therapeutic window
Give examples of pharmacokinetic drug interactions with respect to drug metabolism
ENZYME INDUCTION can cause ineffectiveness of:
- Oral contraceptives
- Corticosteroids
- Anticoagulants
ENZYME INHIBITION
1. Allopurinol inhibits xanthine oxidase which leads to increased toxicity of mercaptopurine
Give examples of pharmacokinetic drug interactions with respect to drug excretion
Aspirin, indomethacin and sulphonamides compete for active transport systems that secrete them. So they can all increase the plasma concentration of each other
Prostaglandins –> renal capillary VD –> NSAIDS decrease renal blood flow
Alter urinary pH –> affect elimination of weak acids and weak bases
What are the three types of additive reactions? give an example of each and name and draw the diagram used to illustrate these
Summative
- net effect = sum of individual actions
- e.g. reduced VA with opioids
- e.g. reduced propofol with midazolam
Synergistic
- net effect > sum of individual actions
- E.g. sulphonamide + trimethoprim antibiotics are bacteriostatic alone but bacteriocidal when combined.
- e.g. Clonidine and opiates
Potentiation
- One drug increases the effect of another
- Aminoglycosides / Magnesium increase competitive neuromuscular blockade of NDMR
the isobologram: inhibition, summation, synergism
Classify the types of pharmacodynamic antagonistic drug interactions and give examples of each
Direct (competitive)
- Same receptors
- Flumazenil reversing benzo
- Naloxine reversing opioids
Indirect
- Neostigmine reversal NDMR (Achase inhibition)
Competitive
- Occurs when competing ligands bind reversibly with their receptors
- E.g. Rocuronium and increased Ach (with neostigmine)
Non-competitive
- Occurs when ligand binds irreversible with its receptor
- E.g. Ketamine antagonism of glutamate at the NMDA receptor
Physiological
- Histamine and adrenalin on airways
Give two examples of indirect pharmacodynamic drug interactions
- MAOs and Pethidine related hypertensive crisis / serotonin syndrome
- Diuretics induce hypokalaemia which increases digoxin toxicity
Why does the therapeutic window for phenytoin narrow when aspirin / indomethacin / sulphonamides are administered
aspirin / indomethacin / sulphonamides displace phenytoin from plasma proteins increasing the free drug fraction. As only the free drug fraction is the active and the fact that phenytoin’s metabolic enzyme system is readily saturated, its meatbolism cannot increase and so the levels of active drug rise
Summarise the P40 enzyme inducers and inhibitors
INHIBITORS HIV (PIs) Anti-TB (INH) Antibiotic (Macrolide) Antifungal (-azoles) Antidepressant (Norfluoxetine) Antiarrhythmic (Amio/Verap/Dilt) Antihistamine (cimetidine) Etomidate Omeprazole
Acute alcohol
Broccoli
INDUCERS HIV (EFV / NVP) Anti-TB (Rifampicin/Rifabutin) Antibiotic (Chloramphenicol) Antifungal (Griseofulvin) Anticonvulsant (Barb / CMZ / Phenytoin) Stimulant (Modafinil) Glucocorticosteroids
Chronic alcohol
Cigarette Smoking (and polycyclic hydrocarbons - grilled meat)
Grapefruit Juice
Give examples of drugs most notably affected by metabolic enzyme inducers and inhibitors
Inducers
- Reduced effect of oral contraceptives –> pregnancy
- Reduced effect of anti-coagulants –> VTE/CVE
Inhibitors
- Warfarin toxicity
How is the excretion of aspiring influenced by the administration of NaHCO3 and why
Aspirin is a weak acid (pKa 2.97)
Acids ionize at pH above their pKa.
So at pH of 2.97 aspirin is 50% ionized and unionized
If the pH increased –> more aspirin ionizes. Since it is only the unionized portion that can be reabsorbed by the tubule, the increased fraction of ionized aspirin is trapped in the filtrate and excreted in urine.
What is the cytochrome P450 system.
It is a family of proteins within the smooth endoplasmic reticulum of hepatocytes. These enzymes mediate oxidation and reduction of many drugs.
Which isoforms of the P450 system are most important in human drug metabolism
CYP 3A4. There are a total of 7 isoforms which are most active in human drug metabolism
