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Pharmacology > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Define pharmacodynamics

A

Study of the drug effect and mechanisms of action

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2
Q

Define pharmacogenetics

A

The effect of genetic variability in the pharmacokinetics and pharmacodynamics of a drug on an individual

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3
Q

What are the main processes in drug therapy?

A

Pharmaceutical process - is the drug getting into the patient
Pharmacokinetic - is the drug reaching its site of action
Pharmacodynamic - is the drug producing the required pharmacological effect
Therapeutic process - is the pharmacological effect being translated into a therapeutic effect

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4
Q

What are the components of the pharmacokinetic process?

A

Absorption
Distribution
Metabolism
Elimination

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5
Q

What is bioavailability (F)?

A

The fraction of a dose that finds it way into a body compartment - usually the circulation

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6
Q

What is the bioavailability for an IV bonus?

A

100%

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7
Q

How is bioavailability calculated?

A

The area under the curve in a graph of plasma concentration against time

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8
Q

What factors can affect bioavailability?

A

Absorption

  • drug formulation
  • age
  • food - lipid soluble > water soluble
  • vomiting, malabsorption etc

First pass metabolism

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9
Q

Where can first pass metabolism occur?

A

Gut lumen - gastric acid, proteolytic enzymes, grapefruit juice
Gut wall - p-glycoprotein efflux pumps drugs out of the intestinal enterocytes back into the lumen
Liver

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10
Q

What is first pass metabolism?

A

Any metabolism occurring before the drug enters the systemic circulation

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11
Q

What are the two key factors affecting distribution?

A

Protein binding

Volume of distribution

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12
Q

Which proteins can drugs bind to?

A

Albumin (acidic drugs)
Globulins (hormones)
Lipoproteins (basic drugs)
Acid glycoproteins (basic drugs)

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13
Q

What factors can affect protein binding?

A

Hypoalbuminaemia
Pregnancy
Renal failure
Displacement by other drugs

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14
Q

How can volume of distribution be calculated?

A

Dose divided by [drug] at t0

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15
Q

What is the relationship between half life and volume of distribution?

A

Half life is proportional to Vd

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16
Q

What can tissue distribution be affected by?

A 
Specific receptor sites in tissues
Regional blood flow
Lipid solubility 
Active transport 
Disease states
Drug interaction
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17
Q

What is the aim of drug metabolism?

A

Normally so that drugs can be water-soluble and so eliminated rapidly from the body

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18
Q

What happens in phase 1 metabolism?

A

Oxidation and reduction

Uses CYP450 enzymes

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19
Q

What can affect CYP450 enzyme activity?

A 
Enzyme-inducing and inhibiting drugs
Age
Liver disease
Hepatic blood flow
Cigarettes
Alcohol
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20
Q

Where can CYP450 enzymes be found?

A

Liver
Gut
Lung

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21
Q

What are the main enzyme inducer drugs?

A

Phenytoin
Carbamazepine

Barbiturates
Rifampicin
Alcohol
Sulphonylureas

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22
Q

What are the main enzyme inhibiting drugs?

A

Omeprazole

Disulfiram
Erythromycin 
Vaporic acid
Isoniazid
Cimetidine
Ethanol (acute)
Sulphonamides
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23
Q

What are the different routes of elimination of drugs?

A 
Kidney
Lungs
Breast milk
Sweat
Tears
Genital secretions 
Bile
Saliva
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24
Q

What three processes determine renal excretion of drugs?

A

Glomerular filtration
Passive tubular reabsorption
Active tubular secretion

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25
Q

Define clearance

A

Ability of the body to excrete a drug

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26
Q

Relationship between clearance and GFR?

A

Normally equal

If GFR decreases, so does clearance

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27
Q

What is the relationship between half life and clearance?

A

Half life is inversely proportional to clearance

As clearance increases, half life decreases

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28
Q

What are first order kinetics?

A

Rate of elimination is proportional to drug level.
A constant fraction of drug is eliminated per unit of time.
Half-life can be defined.
Linear

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29
Q

What are zero order kinetics?

A

Where rate of elimination is constant and independent of drug concentration. Gives a straight line when linear

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30
Q

What does clearance/volume of distribution equal?

A

k - the elimination constant

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31
Q

How can half life be calculated?

A

(0.693 x Vd) / clearance

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32
Q

How do HRH factors affect clearance?

A

Heart - CVS system factors affect blood flow to the main organs of elimination

Renal - factors affecting renal elimination

Hepatic - factors affecting hepatic elimination

33
Q

Why are zero order kinetics unpredictable?

A

Fixed rate of elimination per unit time
Therefore, small dose changes can produce large increments of dose or lead to toxicity
Cannot calculate a half life

34
Q

When is drug monitoring required?

A

Zero order kinetics
Long half life
Narrow therapeutic window
Risk of DDIs
Known toxic effects eg bone marrow suppression
Monitoring therapeutic effect eg BP, glucose

35
Q

After how many half-lives is a steady state achieved?

A

4 to 5

Irrespective of dose or frequency of administration

36
Q

Define pharmacokinetics

A

Study of the movement of a drug through the body

What the body does to the drug

37
Q

Give pharmacokinetic features of digoxin

A

Large Vd
Excreted by kidneys
Long half life

38
Q

What does a loading dose allow?

A

Achieve a rapid therapeutic dose level - can skip forward a few days if there is a long half life

39
Q

Antidote for digoxin?

A

Digifab

40
Q

Symptoms of a digitoxic patient?

A

Bradycardia
Xanthopsia (see yellow)
Vomiting

41
Q

Which pathway is most paracetamol metabolised by normally?

A

Glucaronide and sulphate pathways

42
Q

Which is the bad pathway for paracetamol and why?

A

P450 oxidation

Produces NAPQI which is conjugated with glutathione to produce inactive metabolites

43
Q

How is a paracetamol overdose treated?

A

Glutathione replacement - N-acetylcysteine

44
Q

Equation to work out loading dose?

A

Loading dose = Vd x target drug concentration

45
Q

Way does the slope of an elimination curve represent?

A

The elimination rate constant (k)

k = ratio of clearance to Vd

46
Q

At what types of sites can drugs work?

A 
Cell surface receptors
Nuclear receptors
Enzyme inhibitors
Ion channel blockers
Transport inhibitors
Inhibitors of signal transduction proteins
47
Q

Define affinity

A

The tendency of a drug to bind to a specific receptor type

48
Q

Define efficacy

A

The 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

49
Q

Define potency

A

Dose required to produce the desired biological response.

Describes the different doses of two drugs requires to exact the same effect

50
Q

How is the therapeutic index calculated?

A

EC50 of adverse effect / EC50 of desired effect
i.e.
Toxic dose (TD50) / effective dose (ED50)

51
Q

What is the therapeutic index (in words)

A

The range of doses that can effectively treat a condition while still remaining safe

52
Q

What is the difference between time of onset of drugs that inhibit and drugs that induce CYP enzymes (like how long does it take for the effects of the DDIs to be seen?)

A

Inhibition of enzymes happens quickly (hours to days)

Induction of enzymes happens over days to weeks

53
Q

How to calculate the loading dose?

A

Vd x CpSS (steady state plasma concentration)

54
Q

Give some examples of DDIs

A

Agonism/antagonism at the same receptor

Agonism/antagonism at different receptors

Non-selective drugs

Enhanced effect by other means eg digoxin toxicity enhanced by hypokalaemia caused by a loop diuretic

55
Q

Example of agonism/antagonism at the same receptor? (DDI)

A

Opiate analgesics and naloxone

Beta blockers and beta 2 agonists

56
Q

Example of agonism/antagonism at different receptors?

A

Amlodipine and bendroflumethiazide

Warfarin and aspirin

57
Q

Give an example of a drug which is not selective which can lead to ADRs

A

Antidepressants - interact with many receptor subtypes

  • adrenergic
  • noradrenergic
  • serotoninergic
  • cholinergic
58
Q

Which drugs commonly have DDIs?

A 
Anticonvulsants
Antibiotics
Anticoagulants
Antidepressants/antipsychotics
Antiarrhythmics
59
Q

Which foods can cause interactions and how?

A

Grapefruit juice - inhibit several CYP450 enzymes which reduces clearance of drugs

Cranberry juice - inhibits CYP2C9

60
Q

Which drugs should you not have grapefruit juice with?

A

Simvastatin

Amiodarone

61
Q

Which drugs should you not have cranberry juice with?

A

Warfarin - enhances its anticoagulant effect

62
Q

How can renal disease lead to adverse effects?

A

Reduced clearance

Disturbances of electrolytes may predispose to toxicity, especially potassium

63
Q

How can hepatic disease affect drug activity?

A

Reduced clearance of hepatically metabolised drugs
Reduced CYP450 enzymes
Longer half-lives

64
Q

What is the classic drug to be careful of in hepatic disease?

A

Opiates in cirrhosis - small doses can accumulate leading to coma

65
Q

How can cardiac disease affect drug activity?

A

Excessive response to hypotensive agents
Reduce organ perfusion
-hepatic
-renal

66
Q

What factors increase the risk of ADRs?

A

Careless prescribing
Polypharmacy
Patients at extremes of age due altered PK profile and co-morbidities
Multiple medical problems
Drugs with narrow therapeutic index
Drugs used near their minimum effective concentration - increased risk of treatment failure

67
Q

What are the different severities of ADRs?

A

Major - permanent/life threatening
Moderate - requires additional treatment
Mild - trivial/unnoticeable

68
Q

What are some patient causes of variability in drug response?

A 
Body weight
Age
Gender
Genetics
Condition of health 
Placebo effect
69
Q

What are some causes related to administration that can affect drug response?

A 
Dose
Formulation
Route of administration
Repeated administration of drugs
-allergies
-resistance
-tolerance
70
Q

What are some causes of variability in drug response due to drug interactions/kinetics

A 
Chemical/physical
GI absorption
Protein binding/distribution
Metabolism (stimulation/inhibition)
Excretion 
Receptor (potentiation/antagonism)
Changes in pH/electrolytes
71
Q

Define specificity

A

Drug is limited to one receptor - the complementary drug and receptors
Will not activate other receptors even at high concentrations

72
Q

Define selectivity

A

The clinical effect the drug has and can be measured with specific therapeutic indices
Increase the conc can cause it to bind to other receptors
But has a greater affinity for one receptor

73
Q

What are some pharmacokinetic-related DDIs which affect absorption?

A
  • changes in gut motility eg opiates and atropine increase Cmax and Tmax
  • calcium salts bind to tetracyclines to reduce their absorption
  • cholestyramine binds to warfarin and digoxin to reduce their absorption
74
Q

What are some pharmacokinetic-related DDIs which affect distribution?

A

Object drugs administered at a dose where there are more binding sites than molecules. Precipitant drugs administered so there are more molecules than binding sites so they displace object drugs

Administering a precipitation drug can cause object drug levels to rise to toxic levels

75
Q

What are some pharmacokinetic-related DDIs which affect metabolism?

A

Can affect the metabolism of themselves or other drugs by induction or inhibition of enzymes

76
Q

What are some pharmacokinetic-related DDIs which affect excretion?

A

Can decrease the protein binding of another drug which accelerates its excretion.

Can inhibit tubular secretion resulting in increased plasma levels eg NSAIDs can reduce tubular secretion

77
Q

What are on target ADRs?

A

ADRs which are due to the exaggerated therapeutic effect of the drug eg due to increased dosing
-drugs for hypertension can cause dizziness

Often include effects on the same receptor type but found in different tissues

78
Q

What are off target ADRs?

A

Involves interaction of other receptor subtypes secondarily to the one intended for the therapeutic effect
Can occur with metabolites that can act as a toxin
Also includes inappropriate immune responses

Pharmacology (23 decks)

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