Pharmacodyamics Flashcards
Where do drugs work
- Cell Surface Receptors
- Nuclear Receptors
- Enzyme Inhibitors
- Ion Channel Blockers
- Transport Inhibitors
- Inhibitors of Signal Transduction Proteins
What are unconventional mechanisms o action
•Disrupting of Structural Proteins e.g. vinca alkaloids for cancer, colchicine for gout
• Being Enzymes
e.g. streptokinase for thrombolysis
• Covalently Linking to Macromolecules e.g. cyclophosphamide for cancer
• Reacting Chemically with Small Molecules e.g. antacids for increased acidity
• Binding Free Molecules or Atoms
e.g. drugs for heavy metal poisoning, infliximab (anti-TNF)
What are agonists and partial ageists
Ss
What are competitive and non competitive antagonists
Ss
What is collateral damage
Acts at more than one binding site - not ideal (ideal interact at one site but not others so no side effects
What is selectivity
• The more the selective a drug is for its target, the less chance that it will interact with different targets and have less undesirable side effects.
• eg. Penicillin target
– enzyme involved in bacterial cell wall biosynthesis. Mammalian cells does not have a cell wall, so penicillin has few side effects.
What is specificity
• Targeting drugs against specific receptor subtypes often allows drugs to be targeted against specific organ
• eg adrenergic receptors – heart β1 receptors
– lungs β2 receptors
– More specific a drug acts less action on other organ.
Wat is affinity
S
What is efficacy
- Efficacy - Ability of a drug to produce a response as a result of the receptor or receptors being occupied.
- Efficacy describes the maximum effect of a drug
What is potency
- Potency - Dose required to produce the desired biologic response.
- Potency describes the different doses of two drugs required to exact the same effect
What is the therapeutic index
The therapeutic index is the relationship between concentrations causing adverse effects and concentrations causing desirable effects
Therapeutic index = EC50 (adverse effect) /EC50 (desired effect)
TI = ec50 (diverse)/ ec50 (desired)
What is I teh therapeutic window
The therapeutic window is the range of dosages that can effectively treat a condition while still remaining safe. It is the range between the lowest dose that has a positive effect, and the highest dose before the negative effects outweigh the positive effects.
What are drugs with narrow therapeutic window
Examples of drugs with narrow therapeutic windows include Warfarin, Aminophylline, Digoxin and aminoglycoside antibiotics Note: peak and trough blood levels
Define Mtc ad mec
MTC = Minimum toxic concentration MEC = Minimum effective concentration
Describe pharmacodynamic drug-drug interactions
Interactions either enhance or reduce therapeutic outcome through actions on the receptors
Drug interactions can occur via different receptors or different tissues
Compare agonist/antagonism at same and difference receptors
Agonism/antagonism at same receptor Egs. Opiate analgesics and Naloxone Beta blockers and Beta2 agonists
Agonism/antagonism at different receptors Eg. Amlodipine and Bendrofluazide Warfarin and Aspirin
Anticonvulsants
Antibiotics
Anticoagulants
Antidepressants/Antipsychotics Antiarrhythmics
What are the protein binding interactions important for
Important for:
– intravenously given drugs
– a short half-life (rapidly cleared) – narrow therapeutic index
• eg Phenytoin
Describe establish
Ss
What is enzyme induction
• Increase the amount of enzyme present for a specific action
• Usually phase 1 processes
• Rate depends on drug and enzyme – Usually takes days to weeks to happen
• Carbamazepine and warfarin (CYP 3A4)
– CBZ induces CYP3A4 faster metabolism (↓ effect) – Slow onset-care when one drug stopped
Describe cyp450 pharmacogenetics
Ss
Describe renal disease effect on metabolism
Falling GFR (acute or chronic):
• Reduced clearance of renally excreted drugs:
Digoxin, aminoglycoside antibiotics
• Disturbances of electrolytes may predispose to toxicity: esp potassium
• Nephrotoxins will further damage kidney function
Describe hepatic disease effect on clearance
Reduced clearance of hepatic metabolised drugs Reduced CYP 450 Activity
Much longer half lives
Toxicity
Classic = opiates in cirrhosis, small doses accumulating leading to coma
How will cardiac disease affect clearance
Falling cardiac output will lead to: Excessive response to hypotensive agents Reduced organ perfusion: • Reduced hepatic blood flow and clearance • Reduced renal blood flow and clearance
Describe the efffects of grapefruit juice/cranberry juice
Grapefruit Juice
Inhibits several CYP450 isoenzymes Clearance of many drugs
• Simvastatin
• Amiodarone (long QT) • Terfenadine (long QT)
May lead to exposures to drug of up to 16 fold!
Cranberry Juice
Used therapeutically in UTI treatment
• Inhibits bacterial adherence to urothelium
Inhibits CYP2C9 isoform
• Clearance of warfarin
• Enhanced anticoagulant effect
• Risk of haemorrhage
• Pts should be advised not to drink cranberry juice if on warfarin
What is an adverse drug reaction
An adverse drug reaction (ADR) is an unwanted or harmful reaction which occurs after administration of a drug or drugs and is suspected or known to be due to the drug(s)
How are adverse drug effects classified
Ss
Whar are risks for adrs
Polypharmacy
•Patients at the extremes of age
altered PK profile (renal and hepatic) co-morbidities
•Multiple medical problems
•Use of drugs with narrow therapeutic indexes
risk of toxicity
•Drugs are being used near their minimum effective concentration
risk of treatment failure if metabolism increased
What are causes of vaiability in drug response
Those related to the biological system
1. Body weight and size
2. Age and Sex
3. Genetics - pharmacogenetics 4. Condition of health
5. Placebo effect
Those related to the conditions of administration
1. Dose, formulation, route of administration.
2. Resulting from repeated administration of drug:
drug resistance; drug tolerance-tachyphylaxis; drug allergy
3. Drug interactions:
chemical or physical;
GI absorption;
protein binding/distribution; metabolism (stimulation/inhibition); excretion (pH/transport processes); receptor (potentiation/antagonism); changes in pH or electrolytes.
