3 - Pharmacokinetics and Pharmacodynamics Flashcards

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1
Q

What is pharmacokinetics and pharmacodynamics?

A

- Pharmacokinetics: what the body does to the drug

- Pharmacodynamics: what the drug does to the body

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2
Q

What are some of the pharmacokinetic facts we need to know about a drug before it can be approved for use?

A
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3
Q

What are some factors that can affect the pharmacokinetics/Vd of a drug?

A
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4
Q

What is bioavailabilty and what is it affected by?

A

Amount of drug that gets to the systemic circulation unchanged!

Affected by: formulation, age, food (chelation), vomiting, malabsorption (Crohn’s), first pass metabolism in liver and gut

100% in IV

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5
Q

Why is metformin available in different preparations?

A
  • Modified slow release only needs to be taken once a day, less likely to have GI side effects
  • More expensive to have extended release but patients more likely to adhere if less side effects
  • Most of the time different preparations are just branding, e.g nurofen period pain
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6
Q

What are some factors that affect the distribution of a drug?

A
  • Blood flow
  • Lipophilicity
  • Hydrophilicty
  • Protein binding (difficult to distribute when bound)
  • Vd
  • Pregnancy
  • Hypoalbuminaemia
  • Renal failure
  • Other drugs displacing the original drug from protein binding
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7
Q

What is the multicompartment model of drug distribution?

A
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8
Q

When prescribing a patient a second drug, when should you be really careful with the first drug interactions?

A
  • Second drug may displace first so more first drug that can elicit a response
  • Be careful if first drug is highly protein bound, has a narrow therapeutic index, low Vd
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9
Q

How do you work out the volume of distribution?

A
  • Larger Vd than body water means it is absorbed by the adipose tissue
  • Larger weight, more adipose so larger Vd so need higher dose
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10
Q

What are the two phases of drug metabolism?

A
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11
Q

What CYP’s are affected by smoking and alcohol, and what else can they be affected by?

A
  • Age
  • Hepatic disease
  • Blood flow to liver
  • Alcohol and Cigarette smoking (CYP450 inhibited in acute, induced in chronic)
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12
Q

What changes can CYP450 enzymes make to a drug?

A
  • Can inactivate active drugs
  • Can activate inactive drugs, e.g Levodopa
  • Can covert active drug into another one e.g codeine to morphine
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13
Q

What is the most common CYP that metabolises drugs and what CYP is an example of genetic variations?

A
  • CYP3A4
  • CYP2D6 absent in some caucasians and over expressed in 30% of Africans. Has substrates like beta blockers and SSRIs
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14
Q

When dosing two different patients for a drug, what should you think about in terms of the metabolism of the drug?

A
  • Race
  • Sex (women slower ethanol metaboliser)
  • Self induced metabolism with drugs e.g Carbamazepine
  • If they are taking St John’s Wort (inducer of CYP3A4)
  • Weight
  • Smoking and drinking status
  • Age
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15
Q

What routes can drugs be eliminated from the body?

A
  • Mainly through the kidney
  • Faeces
  • Hair
  • Sweat
  • Tears
  • Saliva
  • Breast milk
  • Genital secretions
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16
Q

What type of drug molecules are excreted renally?

A
  • Low weight polar molecules
  • Clearance mainly affected by GFR
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17
Q

What type of drug molecules are excreted hepatically and therefore into the faeces?

A

Usually high molecular weight molecules, conjugated with glucaronic acid

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18
Q

How can cardiac disease affect the elimination of a drug?

A
  • Reduces perfusion to the organs, like liver and kidney so less clearance
19
Q

What is the definition of zero and first order kinetics?

A

First: rate of elimination proportional to drug level, can determine half life

Zero: rate of elimination constant, most drugs in high concentrations, can’t calculate half life and more likely to have toxicitiy

20
Q

What is renal clearance and the units for this equation?

A
  • Volume of blood cleared per unit time (ml/min)
  • Rate of elimination/Drug conc in plasma
21
Q

How do you work out the half life of a drug?

A
  • Can only do if 1st order
  • Large Vd means small elimination rate which means long half life
22
Q

What are some examples of drugs that are zero order?

A
  • High doses of normal drugs
  • Phenytoin
  • Salicyclic acid (aspirin)
  • Alcohol
23
Q

What are some characteristics of a drug that would mean you need to closely monitor the patient whilst they were on the drug?

A
  • Zero order kinetics
  • Long half life
  • Narrow therapeutic window
  • Drug/drug interactions
  • Reported toxic effects
24
Q

How do you get to a steady state of a drug and how can this be used in an equation?

A
  • Reached in 5 half lives, if large half life give loading dose
  • Same with termination, takes 5 half lives to be removed from body so important when prescribing new drugs to ask about old drugs, e.g amiodarone
  • Need to get to steady state for optimal therapeutic benefit
25
Q

How can you work out Css?

A

Therefore to change drug plasma concentration need to change dose of drug or dose interval

26
Q

When would you give a loading dose, and how would you calculate this?

A
  • If you need a drug to have a rapid onset or if it has a long half life
  • e.g digoxin for AF with heart failure has half life of a week so give a loading dose. if too high can get digitoxic
27
Q

When designing a dosing schedule of a drug for a patient what are some factors we need to think about?

A
28
Q

How can you measure a patient’s response to a drug to see if it is achieving what we want it to?

A
  • Physiological measurements, e.g BP after antihypertensives
  • Feeling
  • Appearance
  • Primary and secondary prevention
29
Q

How do we work out therapeutic index?

A
30
Q

What is an inverse agonist and a neutral antagonist?

A
  • Inverse Agonist –> Binds to the same receptor as drug but induces a pharmacological response opposite to that of the agonist so antagonises and opposes
  • Neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either
31
Q

Why is the volume of distribution apparent and how is it worked out?

A

As it is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma

32
Q

What is the difference between clearance and elimination rate?

A
  • Clearance is volume of blood completely cleared per unit of time, it is a proportionality factor and stays constant
  • Elimination rate is amount cleared and as the concentration of drug in the plasma decreases, the elimination rate decreases
33
Q

How can you work out clearance if the drug is at steady state concentration?

A
34
Q

If a patient needs a loading dose of a drug via IV of 1521mg and the iv can adminster 10mg/ml at a maximum of 50mg/min, what is the smallest rate of infusion?

A
  • 1521/10 = 152.1 ml needs to be administered
  • Maximum of 5ml/min
35
Q
A
36
Q

What is a functional antagonist?

A
37
Q

Why do we titrate drugs when introducing and terminating them?

A
  • For maximum benefit without adverse effects
  • Helps identify safe and optimal level on individual patient level
  • Start low and work up to full dose or until side effects are seen
38
Q

Is the plasma steady state reached quicker if the rate of infusion of an IV drug drug is doubled?

A

No - the steady state concentration will be higher but still takes 5 half lives

39
Q

A 46 year old femal patient (70kg) is prescribed ramipril. She takes 5mg OD. The peak plasma concentration is 0.06mg/L. What is the apparent volume of distribution?

A

1.2L/kg

(remember to divide the litres by kg)

40
Q

Why does the combination preparation of buprenorphine and naloxone help manage patients who are susceptible to narcotic abuse?

A
  • Stops withdrawal symptoms as the buprenorphine can still activate some receptors but naloxone antagonist has a higher affinity
  • If patient decides to inject the drug to get the buprenorphine fix it will not be very good due to the bioavailability
41
Q

Why is adrenaline administered with lidocaine for local anaesthesia?

A

Has a vasoconstrictive effect to lower the elimination of lidocain so it stays around in the area for longer

42
Q

If two patients are prescribed the same drug but one is 10kg heavier than the other, what will this mean for the doses needed?

A

Patient who is 10kg heavier will need a higher dose as drug will have a higher volume of distribution as goes into more of the adipose

43
Q

Why are beta-blockers contraindicated in asthmatics?

A

Bronchoconstriction at B2 receptors

44
Q

Why do you get a dry cough with ACEi?

A

Build up of bradykinin (bronchial vasodilator)