2.2 Pharmacodynamics, DDIs and Toxicology Flashcards
What are the 4 principal classes of receptor site?
Receptors
Ion channels
Carriers/transporters
Enzymes
What is the active state?
Receptor which carries out a specific task
What is the inactive state?
Not active- no receptor activation
What is an agonist?
Ligand which binds to a receptor to move it into the active state
What is an antagonist?
Ligand which binds to a receptor but keeps it in the inactive state
What is a partial agonist?
Ligand bound to a receptor but the receptor action is not at 100%
What is a partial antagonist?
Ligand bound to a receptor and the receptor action is low but not at 0%
What is the affinity of a drug?
The tendency of a drug to bind to a specific receptor type
What is the efficacy of a drug?
The maximal effect of a drug when bound to a receptor
What is the agonist potency?
The drug concentration at which 50% of the maximal response is obtained
What is the antagonist potency?
Concentration of the drug which reduces maximal response by 50%
What is the therapeutic window?
The concentration range at which drugs produce a clinically useful effect without exerting toxic effects.
How can DDIs affect the absorption of a drug?
Oral drugs can be affected by drugs which alter gut motility and passive absorption
How can DDIs affect the distribution of a drug?
Can be affected by competition of drugs at protein/lipid binding sites.
How can DDIs affect the metabolism of a drug?
Affected by induction or inhibition of enzymes in the liver
How can DDIs affect the elimination of a drug?
Affected by changes in protein binding, inhibition of tubular secretion and changes in urine/pH
What does inhibition of CYP450 enzymes do to a drug’s half life?
Increases
What does induction of CYP450 enzymes do to a drug’s half life?
Decreases
What does inhibition of CYP450 enzymes do to a drug’s clearance?
Decrease
What does induction of CYP450 enzymes do to a drug’s clearance?
Increase
How can DDIs be useful?
Some DDIs can enhance the clinical effects of a specific drug
Give 5 classes of drugs that have common DDIs
Anticonvulsants Anticoagulants Antidepressants Antibiotics Antiarrhythmics
How does renal disease affect drug pharmacology?
Reduction in clearance of renally excreted drugs
Some drugs are nephrotoxic or can create electrolyte imbalances
How does hepatic disease affect drug pharmacology?
Reduced metabolism of drugs in the liver causing the half lives of the drugs to increase
How does cardiac disease affect drug pharmacology?
Falling cardiac output leads to lower organ perfusion so metabolism in the liver and clearance in the kidneys is reduced.
How does hypoalbuminaemia affect drug pharmacology?
Less albumin means there are less drug binding sites so the free drug concentration is in a higher concentration
What is an ‘on-target’ ADR?
An exaggerated therapeutic effect, usually caused by a drug working on the same receptor in a different area of the body
What is an ‘off-target’ ADR?
Drugs reacting with other receptor types to the one intended
When a build up of metabolites become toxic
Give 6 examples of CYP450 inducers
Phenytoin Carbamazepine Rifampicin Alcohol (Chronic) Barbiturates Sulphonylureas
Give 8 examples of CYP450 inhibitors
Omperazole Disulfiram Erythromycin Valproate Isoniazid Ciprofloxacin Ethanol Sulphonamides
