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C. Year 3: Clinical Pharmacology, Therapeutics and SBOM > Concepts in Pharmacology > Flashcards

Concepts in Pharmacology Flashcards

1
Q

What does pharmacokinetics relate to?

A
  • essentially what the body does to drugs
  • relates to concentrations of drugs in the body
  • looks at metabolism, excretion, absorption and distribution

pharmacokinetics (PK) focuses on determining concentration profiles and the fate of drug molecules in the body, pharmacodynamics (PD) examines the effect of the drug on the body.

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2
Q

What does pharmacodynamics relate to?

A
  • relates to the effect the drug has on the body
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3
Q

What is first pass metabolism?

A
  • a drug must be metabolised prior to reaching circulation, generally in the liver
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4
Q

What does distribution relate to in terms of pharmacokinetics?

1 - how drug is absorbed in GIT
2 - drugs metabolism in liver
3 - drug excreted from kidneys
4 - how drug moves around body

A

4 - how drug moves around body

  • free drug is physiologically active
  • bound drug acts as a reservoir
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5
Q

What does volume of distribution relate to in terms of pharmacokinetics?

A
  • measure of how well a drug is distributed between various body tissues and fluids
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6
Q

There are 2 phases to metabolism. What is the first phase?

1 - modification of drug to more reactive metabolites
2 - conjugation of drug to allow drug to be water soluble
3 - removal of drug from GIT
4 - absorption of drug from the GIT

A

1 - modification of drug to more reactive metabolites

  • oxidation, reduction and hydrolysis are all examples
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7
Q

There are 2 phases to metabolism. What is the second phase?

1 - modification of drug to more reactive metabolites
2 - conjugation of drug to allow drug to be water soluble
3 - removal of drug from GIT
4 - absorption of drug from the GIT

A

2 - conjugation of drug to allow drug to be water soluble

  • this is good, but also means drug can be easily excreted if not used by tissues
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8
Q

Cytochromes P450 (CP450) is a family of enzymes that are able to metabolise drugs, mainly in the liver. What would inhibition of CP450 do to metabolism?

A
  • slow metabolism of a drug
  • drug will remain in the body longer
  • increased risk of becoming toxic
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9
Q

Cytochromes P450 (CP450) is a family of enzymes that are able to metabolise drugs, mainly in the liver. What would induction of CP450 do to metabolism?

A
  • increase metabolism of a drug
  • drug will be cleared from the body quicker
  • may be less therapeutic
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10
Q

Inhibition or induction CP450 can affect the metabolism of drugs. What effect does the antibiotic rifampcin have on warfarin?

A
  • rifampcin induces CP450
  • warfarin is metabolised quicker
  • anti-coagulant effect of warfarin is reduced so patient could clot faster
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11
Q

What is a pro-drug?

A
  • drug is ingested but inactive
  • once metabolised it becomes physiologically active
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12
Q

What is the half life of a drug?

A
  • time required for the concentration of a drug to be reduced by 50% in plasma
  • long half life means drug stays in body for longer
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13
Q

How long does it generally take for a drug to reach steady state?

1 - 1-2 half lives
2 - 2-3 half lives
3 - 3-4 half lives
4 - 3-5 half lives

A

4 - 3-5 half lives

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14
Q

What is an agonist in relation to drugs?

1 - drug acts on receptor like endogenous ligands
2 - competitively competes with endogenous ligand
3 - binds to receptor and irreversibly inhibits ligand
4 - counters effect by binding to receptor causing opposite effect

A

1 - drug acts on receptor like endogenous ligands

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15
Q

What is a competitive antagonist in relation to drugs?

1 - drug acts on receptor like endogenous ligands
2 - competitively competes with endogenous ligand
3 - binds to receptor and irreversibly inhibits ligand
4 - counters effect by binding to receptor causing opposite effect

A

2 - competitively competes with endogenous ligand

  • can be overcome if the concentration of the ligand is higher than the drug or has a higher affinity than the drug
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16
Q

What is a irreversible antagonist in relation to drugs?

1 - drug acts on receptor like endogenous ligands
2 - competitively competes with endogenous ligand
3 - binds to receptor and irreversibly inhibits ligand
4 - counters effect by binding to receptor causing opposite effect

A

3 - binds to receptor and irreversibly inhibits ligand

  • this is what happens in aspirin on platelets
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17
Q

What is a physiological antagonist in relation to drugs?

1 - drug acts on receptor like endogenous ligands
2 - competitively competes with endogenous ligand
3 - binds to receptor and irreversibly inhibits ligand
4 - counters effect by binding to receptor causing opposite effect

A

4 - counters effect by binding to receptor causing opposite effect

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18
Q

What is a chemical antagonist in relation to drugs?

1 - drug acts on receptor like endogenous ligands
2 - competitively competes with endogenous ligand
3 - binds to and inactivates the agonist (endogenous ligand)
4 - counters effect by binding to receptor causing opposite effect

A

3 - binds to and inactivates the agonist (endogenous ligand)

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19
Q

What is a partial agonist in relation to drugs?

A
  • drug that elicits only a small effect compared to the endogenous ligand
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20
Q

What does EC50 relate to?

1 - maximum biological effect of a drug
2 - half the maximum concentration of a drug
3 - half life of a drug

A

2 - half the maximum concentration of a drug

21
Q

What does ED50 relate to?

1 - maximum biological effect of a drug
2 - half the maximum concentration of a drug
3 - half life of a drug
4 - effective dose for 50% of the population to obtain a therapeutic effect

A

4 - effective dose for 50% of the population to obtain a therapeutic effect

22
Q

What does TD50 relate to?

1 - maximum biological effect of a drug
2 - the median toxic dose of a drug or toxin is the dose at which toxicity occurs in 50% of cases
3 - half life of a drug
4 - effective dose for 50% of the population to obtain a therapeutic effect

A

2 - the median toxic dose of a drug or toxin is the dose at which toxicity occurs in 50% of cases

23
Q

What does efficacy relate to in terms of drugs?

A
  • largest effect of a drug, regardless of the dose
24
Q

What does potency relate to in terms of drugs?

A
  • concentration of drug required to elicit a specific effect, normally EC50 or ED50
25
Q

Hoe can we calculate the therapeutic index (TI), which is a measure of the therapeutic window?

A
  • TI = TD50 / ED50

TD50 = dose required to elicit a toxic effect in 50% of the population

ED50 = dose required to achieve a therapeutic effect in 50% of the population

26
Q

A 55-year-old woman with hypertension is prescribed a thiazide diuretic.Thiazide A in a dose of 5 mg produces the same decrease in blood pressure as 500 mg of thiazide B. Which of the following statements best describes these results?

(A) Thiazide A is more efficacious than thiazide B
(B) Thiazide A is about 100 times more potent than thiazide B
(C) Thiazide A has a wider therapeutic window than thiazide B
(D) Thiazide A has a longer half-life than thiazide B
(E) Toxicity of thiazide A is lower than that of thiazide B

A

(B) Thiazide A is about 100 times more potent than thiazide B

5:500 is a 100 times more potent

27
Q

Prior to clinical trials in patients with heart failure, an animal study was carried out to compare two new positive inotropic drugs (A and B) to a current standard agent (C). The results of cardiac output measurements are shown in the graph below.

Which of the following statements is correct?
(A) Drug A is the most effective
(B) Drug B is the least potent
(C) Drug C is the most potent
(D) Drug B is more potent than drug C and more effective than drug A
(E) Drug A is more potent than drug B and more effective than drug C

A

(D) Drug B is more potent than drug C and more effective than drug A

28
Q

Sugammadex is a new drug that reverses the action of rocuronium and certain other skeletal muscle-relaxing agents. It appears to interact directly with the rocuronium molecule and not at all with the receptor on which rocuronium acts.Which of the following terms best describes sugammadex?

(A) Partial agonist
(B) Physiologic antagonist
(C) Chemical antagonist

A

(C) Chemical antagonist

Sugammadex interacts directly with rocuronium and not with the receptor on which rocuronium acts; therefore, it is a chemical antagonist. The answer is C

29
Q

A68 year old man came to hospital complaining of chest pain that had developed whilst he was running for a bus. Thepain was crushing in nature and was located in the centre of his chest, radiating to his left arm and jaw. Hereported using his spray (GTN) and the pain subsequently resolved.

His past medical history included angina, hypertension and hypercholesterolaemia. His regular medications were amlodipine, ramipril and atorvastatin. Hewas an ex-smoker with a 20-pack year history and drank 25units of alcohol per week. Examination Systems examination was unremarkable.Question: Why is the sublingual formulation of GTN favoured in acute angina?

A
  • absorbed sublingually so very fast acting as not metabolised
30
Q

A researcher is studying the bioavailability of commonly used antimuscarinics to treat irritable bowel syndrome. Medication A is administered in a 100 mg daily dose orally and 60 mg of the drug is absorbed from the gastrointestinal tract unchanged.

Thus, the bioavailability of Medication A is
1 - 50%
2 - 60%
3 - 70%
4 - 80%
5 - 90%

A

2 - 60%

The answer is B: 60%.
Medication A has a bioavailability of 60%. Bioavailability is the fraction of administered drug that reaches the systemic circulation. In this example, if 100 mg of Medication A is administered orally, and 60 mg of this drug is absorbed unchanged, the bioavailability is 0.6, or 60%. Determining bioavailability is important for calculating drug dosages for various routes of administration other than the intravenous route.

31
Q

A researcher is studying the pharmacokinetics and pharmacodynamics of a potential chemotherapeutic agent on mice. He calculates the ED50 to be approximately 2 mg/kg, and the TD50 is approximately 300 mg/kg. Calculate the therapeutic index for the new agent?

1 - 0.02
2 - 2
3 - 5
4 - 50
5 - 150

A

5 - 150

  • TI = TD50 / ED50
  • TI = 300 / 2 = 150
32
Q

The table given below showed the various opioids EC50 concentration and maximum response. Provide a rank order of potency for the opioids in the table below (most potent first):

A
  • divide the max response by the EC50. The lower the number the less of the drug needed to be given, meaning it is more potent

1st = Fentanyl
2nd = Buprenorphine
3rd = Methadone
4th = Tramadol
5th = Codeine

33
Q

Three novel drugs to treat Alzheimer’s disease have undergone phase I trials. A graph of the biologic effect versus log drug concentration is plotted in the following graph. Which of the following statements is true?

(A) Drug A is less potent than Drug B
(B) Drug A has lower efficacy than Drug B
(C) Drug C shows lower potency than Drugs A and B
(D) Drug C is best administered orally
(E) Drug C is most likely to be approved for use

A

(C) Drug C shows lower potency than Drugs A and B

A) Drug A is more potent than Drug B, but both show the same efficacy.

(B) Drug A and B have the same efficacy

(D) One cannot determine how this drug should be administered from the information provided

(E) One cannot determine potential for approval for clinical trials based on the information provided.

34
Q

Why is the site of infection important to consider when prescribing antibiotics?

A
  • sufficient levels of antibiotics must reach the source of infection
35
Q

What is ‘Antimicrobial stewardship’?

1 - where a pharmacist checks antibiotics prescription before you can prescribe
2 - only prescribing antibiotics when they are needed
3 - only prescribing antibiotics when a consultant signs them off

A

2 - only prescribing antibiotics when they are needed

  • aim is to reduce antibiotic resistance
36
Q

Although empirical treatment is often needed, should narrow or broad spectrum antibiotics generally be prescribed?

A
  • narrow spectrum
37
Q

If there is clear evidence of a bacteria infection, which of the following should be performed?

1 - prescribe antibiotics based on experience
2 - prescribe empirically
3 - prescribe only when blood/sputum cultures are returned
4 - prescribe according to local guidelines

A

4 - prescribe according to local guidelines

38
Q

Which of the following is DOES NOT play a role in preventing adverse drug reactions?

1 - Indications for drug use
2 - Mechanisms
3 - Drug within the Body
4 - Cautions
5 - Contraindications
6 - Adverse Effects
7 - Interactions
8 - Colleagues recommendations

A

8 - Colleagues recommendations

39
Q

Which 2 of the following is are NOT human factors that play a role in preventing adverse drug reactions?

1 - Cognitive overload
2 - Stressed/Angry
3 - Age
4 - Hungry
5 - Gender
6 - Late
7 - Tired
8 - Toilet
9 - Rushed

A

3 - Age
5 - Gender

40
Q

When we thing about safe prescribing, there are special groups that we need to think about including young children, older adults, pregnant women, breastfeeding, hepatic failure, renal failure and autism. Why is pharmacokinetics important here?

M = metabolism
A = absorption
D = distribution
E = excretion

A
  • impacts upon how body can process the drug
  • renal failure means drugs can become nephrotoxic
  • breastfeed means drug could be transferred to baby
  • drug may be teratogenic
41
Q

If a patient has an increased heart rate, how can this affect drug excretion?

A
  • increased HR = increased cardiac output
  • cardiac output = increased eGFR
  • increased eGFR = drug is excreted quicker
42
Q

Creatinine is the waste product of creatine phosphate from protein metabolism and muscle. What is creatinine clearance?

A
  • level of creatinine being filtered into urine by the kidneys
  • if low it suggests renal problems
43
Q

Which of these will reduce the anticoagulant effect of warfarin?

1 - Aspirin
2 - Citalopram
3 - Levetiracetam
4 - Prednisolone
5 - Rifampicin

A

5 - Rifampicin

  • acts as a CP450 inducer
  • warfarin’s anti-coagulant ability is diminished
  • Reduced international normalised ratio (INR) is a measure of how long it takes blood to clot
44
Q

Which of these can increase the anticoagulant effect of warfarin?

1 - Alcohol (chronic)
2 - Amoxicillin
3 - Grapefruit juice
4 - Metronidazole
5 - Morphine sulfate

A

4 - Metronidazole

  • acts as an inhibitor of CP450
  • means INR could be reduced
45
Q

What is pharmacogenetics?

A
  • use of genetics to personalise medicine better
46
Q

A 70 year old woman with Community Acquired Pneumonia and is confused on admission. Here results are as follows:

U and E’s: Ur=6.9 and Cr = 91mmol/L
eGFR= 51mls/min
CURB-65 = 2

Which of the following is the highest priority to check before prescribing antibiotics?

1 - Allergy status
2 - Blood culture results
3 - Medication history
4 - Recent antibiotic course(s)
5 - Renal function

A

1 - Allergy status

  • allergies are very important
47
Q

If a patient has been prescribed a medicine, does that automatically mean they are taking the medicine?

A
  • no
48
Q

In addition to prescribed drugs what are the other most common groups methods of getting drugs that we must ask about?

A
  • over the counter
  • general sales list
  • herbal medicines
  • recreational drugs
  • diet (cranberry and grapefruit)

C. Year 3: Clinical Pharmacology, Therapeutics and SBOM (25 decks)

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