Pharmacodynamics

Question 1

How do drugs work?

Answer 1

Depression
Stimulation
Destruction
Replacement

Mostly by interacting with endogenous proteins (either activating, antagonising, blocking, inhibiting)

Question 2

Where do drugs work?

Answer 2

Cell surface receptors
Nuclear receptors
Enzyme inhibitors 
Ion channels 
Transport inhibitors
Inhibitors of signal transduction proteins

Question 3

What are some unconventional mechanisms of action?

Answer 3

Disrupting of structural proteins 
Being enzymes
Covalently linking to macromolecules 
Reacting chemically with small molecules
Binding free molecules or atoms

Question 4

Describe some basic concepts in receptor theory

Answer 4

Agonists and antagonists
Complete and partial agonist / antagonist
Competitive and non-competitive
Specificity and selectivity

Question 5

What is an ideal drug?

Answer 5

One that interacts with one site but not other sites causing unwanted effects.

Real drugs act at more than one binding site - collateral damage.

Question 6

What is drug selectivity?

Answer 6

The more selective the drug for its target, the less chance that it will interact with different targets and have less undesirable side effects.
E.g. penicillin

Question 7

What is drug specificity?

Answer 7

Targeting drugs against specific receptor subtypes often allows drugs to be targeted against specific organ

Question 8

What is affinity?

Answer 8

Defines the tendency of a drug to bind to a specific receptor type

Question 9

What is efficacy?

Answer 9

Ability of a drug to produce a response as a result of the receptor or receptors being occupied.

Describes the maximum effect of a drug.

Question 10

What is potency?

Answer 10

Dose required to produce the desired biological 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 = toxic dose / effective dose

Question 12

What is a 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

Why are protein bringing interactions important?

Answer 13

IV drugs
Drugs with short half life
Narrow therapeutic index

e.g. phenytoin

Question 14

What usually causes drug interactions?

Answer 14

A’s

Anticonvulsants
Antibiotics
Anticoagulants
Antidepressants / antipsychotics 
Antiarrhythmics

Question 15

What is the effect of renal disease on drugs?

Answer 15

Toxicity as unable to clear drugs properly.

Falling GFR (acute or chronic)

Reduced clearance of renally excreted drugs: digoxin, aminoglycosides antibiotics

Distrubances of electrolytes may predispose to toxicity: especially potassium

Nephrotoxins will further damage kidney function.

Question 16

What is the effect of hepatic disease on drug metabolism?

Answer 16

Reduced clearance of hepatic metabolised drugs

Reduced CYP450 activity

Much longer half lives

Toxicity

Classic = opiates in cirrhosis, small doses accumulating leading to coma.

Question 17

What effect does cardiac disease have on drug metabolism?

Answer 17

Falling CO will lead to:

• Excessive response to hypotension agents
• Reduced organ perfusion: reduced hepatic blood flow and clearance, reduced renal blood flow and clearance.

Question 18

What is an adverse drug reaction?

Answer 18

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.

Question 19

How do you classify ADRs?

Answer 19

Major (permanent / life threatening)

Moderate (requiring additional treatment)

Mild (trivial / unnoticable)

OR

A -augmented pharmacological effects 
B - bizarre effects
C - chronic effects
D - delayed effects
E - end-of-treatment effects

Question 20

What makes a patient at high risk for ADRs?

Answer 20

Poly pharmacy

Patients at the extremes of age

Multiple medical problems

Use of drugs with narrow therapeutic indexes

Drugs are being used near their minimum effective concentration (failure if metabolism increases)

Use of drugs with narrow therapeutic indexes (increase risk of toxicity)

Question 21

List causes of variability in drug responses

Answer 21

1. Body weight and size
2. Age and sex
3. Genetics - pharmacogenetics
4. Condition of health
5. Placebo effect
6. Dose, formulation, route of administration
7. resistance, tolerance, allergy
8. Interactions