Pharmacodyamics

Question 1

Where do drugs work

Answer 1

• Cell Surface Receptors
• Nuclear Receptors
• Enzyme Inhibitors
• Ion Channel Blockers
• Transport Inhibitors
• Inhibitors of Signal Transduction Proteins

Question 2

What are unconventional mechanisms o action

Answer 2

•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)

Question 3

What are agonists and partial ageists

Answer 3

Ss

Question 4

What are competitive and non competitive antagonists

Answer 4

Ss

Question 5

What is collateral damage

Answer 5

Acts at more than one binding site - not ideal (ideal interact at one site but not others so no side effects

Question 6

What is selectivity

Answer 6

• 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.

Question 7

What is specificity

Answer 7

• 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.

Question 8

Wat is affinity

Answer 8

S

Question 9

What is efficacy

Answer 9

• 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

Question 10

What is potency

Answer 10

• Potency - Dose required to produce the desired biologic response.
• Potency describes the different doses of two drugs required to exact the same effect

Question 11

What is the therapeutic index

Answer 11

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)

Question 12

What is I teh therapeutic window

Answer 12

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.

Question 13

What are drugs with narrow therapeutic window

Answer 13

Examples of drugs with narrow therapeutic windows include Warfarin, Aminophylline, Digoxin and aminoglycoside antibiotics Note: peak and trough blood levels

Question 14

Define Mtc ad mec

Answer 14

MTC = Minimum toxic concentration
MEC = Minimum effective concentration

Question 15

Describe pharmacodynamic drug-drug interactions

Answer 15

Interactions either enhance or reduce therapeutic outcome through actions on the receptors
Drug interactions can occur via different receptors or different tissues

Question 16

Compare agonist/antagonism at same and difference receptors

Answer 16

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

Question 17

What are the protein binding interactions important for

Answer 17

Important for:
– intravenously given drugs
– a short half-life (rapidly cleared) – narrow therapeutic index
• eg Phenytoin

Question 18

Describe establish

Answer 18

Ss

Question 19

What is enzyme induction

Answer 19

• 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

Question 20

Describe cyp450 pharmacogenetics

Answer 20

Ss

Question 21

Describe renal disease effect on metabolism

Answer 21

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

Question 22

Describe hepatic disease effect on clearance

Answer 22

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

Question 23

How will cardiac disease affect clearance

Answer 23

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

Question 24

Describe the efffects of grapefruit juice/cranberry juice

Answer 24

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

Question 25

What is an adverse drug reaction

Answer 25

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)

Question 26

How are adverse drug effects classified

Answer 26

Ss

Question 27

Whar are risks for adrs

Answer 27

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

Question 28

What are causes of vaiability in drug response

Answer 28

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.