2.2 Pharmacodynamics Flashcards
How do most drugs work?
By interacting with endogenous proteins
Name some places where drugs work
Cell surface receptors, nuclear receptors, enzyme inhibitors, ion channel blockers, Transport inhibitors
What shapes are michaelis menten curve?
Rectangular hyperbola
Drug response proportional to drug concentration
Describe drug 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
Describe drug specificity
Targeting drugs against specific receptor
subtypes often allows drugs to be targeted
against specific organ
What does affinity define?
The tendency of a drug to bind to a specific receptor type
Define efficacy
Ability of a drug to produce a response as a result of the receptors being occupied
What does efficacy describe?
The maximum effect of a drug
Describe potency
Dose required to produce the desired biological response
Describes the difference doses of two drugs required to exact the same effect
What is the equation for therapeutic index?
Therapeutic index = EC50 adverse effect / EC50 desired effect
Therapeutic index = toxic dose / effective dose
What is the therapeutic window?
The range of doses that can effectively treat a condition while still remaining safe
What is the therapeutic window between?
The lowest dose that has a positive effect and the highest dose before the negative effects outweighs the positive effects
Give some examples of drugs with a narrow therapeutic window
Warfarin, aminophylline, gigoxin and aminoglycoside antibiotics
What do fatty meals do to gastric transit time?
Slow it down
What is the principle behind drinking alcohol following a fatty meal?
Gpfatty meals slow down gastric transmpit time
Alcohol takes longer to get through stomach
Most alcohol absorbed in duodenum so prolong time to get there giving a constant drip effect
What is the problem with taking iron and tetracycline?
Bind together to form a chelate
Drug isn’t absorbed
How can absorption be altered?
Altered p-glycoprotein activity
Why may women and men have different alcohol concentrations when drinking the same amount?
Women have more water
Men have more water so concentration of alcohol lower in men
In which situations is it important to thinkabout protein binding interactions?
Drugs given IV
short half life (rapidly cleared)
Narrow therapeutic index
Eg phenytoin
What can effect metabolism in gut wall/portal system?
Changes in blood flow
What is the timescale for inhibition if CYP450?
Quick onset
Several hours to days
What is CYP450 inhibition related to?
Half life and clearance of affected drug
Plasma concentration at time of interaction
In which phase does enzyme induction occur?
Phase 1
How long does enzyme induction take to happen?
Days to weeks
Name two drugs that can act together to cause enzyme induction
Carbamazepine and warfarin
Name some drugs that are CYP450 inducers
Phenytoin
Carbamazepine
Barbiturates
Rifampicin
Name some drugs that are CYP450 inhibitors
Omperazole Disulfiram Erythromycin Valproate Isoniazid
What may drugs prolonging QT interval cause?
Torsade des pointes
When is drug disease interaction more common?
Extremes of age
Chronic medical conditions
Name some renally excreted Drugs
Digoxin, aminoglycoside antibiotics
What effect will hepatic Disease have on drug half life?
Will be longer
What impact can falling cardiac output have on drugs?
Excessive response to hypotension agents
Reduced organ perfusion
So reduced hepatic and renal blood flow and clearance
What effect can grapefruit juice have on CYP450?
Inhibits many isoenzymes
Decreasing clearance of drugs like simvastatin, amiodarone, terfenadine
What effect can cranberry juice have on drug food interaction?
Inhibits some CYP
Decreased clearance of warfarin, enhanced anticoagulant effect and increased risk of haemorrhage
What is an adverse drug reaction?
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
What is a major ADR?
Permanent or life threatening
What is a moderate ADR?
Requiring additional treatment
What can increase the risk of ADR?
Inappropriate prescribing
Polypharmacy
Extremes of age- altered PK and co morbidity
Narrow therapeutic index
Drugs used near minimum effective concentration
What biological causes can cause variable drug response?
Body weight and size Age and sex Genetics Condition of health Placebo effect
What are some causes of variability in drug response related to conditions of administration?
Dose, formulation ROA
Repeated administration may lead to resistance, tolerance, allergy
Drug interaction
