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PHARM > PHARM REVISION QUIZ PART 1 > Flashcards

PHARM REVISION QUIZ PART 1 Flashcards

1
Q

What is the method of drug absorption in the body used by most medication?

A

passive diffusion

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2
Q

what is the difference between transcellular and paracellular?

A
  • Most absorption occurs through cells (transcellular)

- Some occurs between cells (paracellular)

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3
Q

what is fick’s law

A
  • Rate of diffusion = SA x concentration difference x permeability
  • Things that affect permeability
    Molecular size, lipid solubility, presence of charged or ionised molecules
  • If a molecule is not charged/ ionised it is better absorbed
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4
Q

explain how drugs work in different pH environments

A

uncharged/unionised drugs are absorbed better. Acidic drugs (weak acid) are more unionised in acidic pH’s and basic drugs (weak base) are more unionised in alkali environments.

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5
Q

What are the Lipinski rules?

  • A rule-based approach to ADME optimization
  • An orally- active drug likely has no more than one violation of the following:
  • MW: molecular weight
  • HBD: No more than ? H-bond donors
  • HBA: No more than ? H-bond acceptors
  • Log P < ? (partition coefficient)
A
  • MW: molecular weight <500 da
  • HBD: No more than 5 H-bond donors
  • HBA: No more than 10 H-bond acceptors
  • Log P < 5 (partition coefficient)
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6
Q
  1. Aspirin is a weak acid with a pKa of 3.5. If taken orally, what determines the rate of absorption for aspirin in the stomach?
  • pH in the stomach
  • Active transporters in the intestine
  • Glomerulus filtration rate
  • First pass metabolism
  • Dosage
A

a

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7
Q

. What property reduces drug movement across a membrane?

  • Extensive ionisation
  • Low polarity
  • High lipid solubility
  • Molecular weight > 2000 Da
  • Small surface area
A

a

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8
Q

What route of administration enables a drug to be administered quickly and with the highest bioavailability?
iv, im, sc

A

iv first. Intramuscular injections are absorbed faster than subcutaneous injections. This is because muscle tissue has a greater blood supply than the tissue just under the skin

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9
Q
  1. What is the main route of absorption for licensed medicines?
  • Passive diffusion
  • Facilitated diffusion
  • Filtration
  • Active transport
  • Ion trapping
A

a

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10
Q

. According to the Lipinski’s rules, what feature increases the drug-likeness?

  • No more than 10 H bond donors
  • Molecular weight of 500 dalton
  • Partition coefficient of more than 5
  • Reliance on active transporters
A

No more than 10 H bond acceptors. not b because should be less than

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11
Q

Why are LA’s sometimes administered with adrenaline?

A
  • Adrenaline produces vasoconstriction which keeps the LA localised in to the area of injection.
  • Vasoconstriction inhibits absorption of the LA from the extracellular spaces into the blood- this reduces the possibility of systemic toxicity.
  • Also prevents bleeding and prolongs LA action
  • Beware: local hypoxia particularly in extremities: fingers, toes nose.
  • Also, absorption of adrenaline can lead to arrythmias.
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12
Q

Describe ow LAs are ‘ion trapped’ inside cells when administered with an alkaline solution

A

LA’s are WEAK BASES (more unionised in alkaline environment)

  • LA’s work best in its ionised form so why is it administered in an alkaline solution where as a weak base it will be more unionised in an alkaline solution,
  • This is because we know that ionised substances do not pass through the membrane well so they need to be unionised to pass through the membrane.
  • However, when it gets through the membrane the conditions are more acidic meaning that the LA become a proton acceptor and hence becomes ionised.
  • Because the LA is now in its ionised form it is now trapped and cannot move back through the membrane easily and hence moves into the inactivate Na+ channels and blocks them. (LA’s act on the part
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13
Q

How does local anaesthetics work exactly?

A
  • So, when a nerve cell reaches threshold it depolarises and Na+ flows in. LA’s block the inward flow of Na+ ions. This therefore blocks the generation and conduction of action potentials (AP).
  • No AP’s no information sent to CNS no perception of pain.
  • Most LA’s block AP’s in their inactive state with the LA in its ionised form. (Although, some block of Na+ channels in its closed state with LA in its un-ionised state and some block of Na+ channels in its open state with LA in its ionised form- LAH+)

lignocaine normally used as has longer half life and lasts longer in the body

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14
Q

Outline the mechanism of use-dependent block. Why is it clinically important?

A
  • LA’s give a use dependence block- clinically important
  • Use dependent drugs only work when there is high activity therefore there is fewer side effects as low activity neurons are not affected.
  • Low activity- few Na+ channels go into inactivated state, High activity many Na+ channels enter inactivated state,
  • This is the same principle with other drugs examples: anti-epileptic, class 1 cardiac anti-arrhythmic.
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15
Q

All nerve fibres use Na+ channels to generate and conduct APs. So why are pain fibres blocked before other sensory or motor nerves?

A
  • LA’s block small diameter axons before larger ones. LA’s also block un-myelinated fibres before myelinated ones.
  • Nociceptive (pain) fibres are conducted in A-delta fibres (Which are small and myelinated) and C fibres (unmyelinated axons)
  • Therefore, pain sensation is lost first however with increasing concentrations/ time LA’s block all axonal conduction causing local paralysis e.g. remember at the dentist when the LA didn’t wear of yet lol.
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16
Q

Do most drugs obey first-order or zero-order kinetics?

A

first

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17
Q

What is first order kinetics in drug clearance?

A
  • When a constant fraction of drug is removed + has a constant half life
  • Therefore, the time to remove the drug is independent of the dose so if you increase the [dose] the same fraction is removed (but if the dose is bigger then the amount of the fraction will be bigger meaning the time needed remains the same regardless of the dose)
  • First order kinetics id more predictable and is therefore preferable as it is safer.
  • Constant fraction of drug is removed –> constant clearance
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18
Q

A few drugs obey zero-order kinetics how does this work?

A

A constant amount of the drug is removed

  • Therefore, the bigger the dose the longer the time to remove it.
  • Clearance is not constant
  • This is sometimes called saturation kinetics as it is associated with when all proteins are saturated and so only a certain amount can be removed at a time.
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19
Q

How can zero-order kinetic drugs be problematic?

A
  • If you combine zero-order kinetics with too high a dose then you can potentially lead to excessive accumulation of the drug in the system and if the drug is particularly toxic or can be toxic over a certain concentration then this could cause severe side effects.
  • E.g. alcohol, phenytoin (cardiac drug)
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20
Q

What happens when a person overdoses on a substance? in terms of first and zero order kinetics

A

when a person overdoses on substances e.g. alcohol this could saturate all of the 1st order kinetic receptors and so the drug will have to be removed in zero order kinetics until the concentration comes down and then it can work in 1st order kinetics. This happens because the first order kinetics met its saturation point.

In theory any drug can show zero or first order kinetics. However, most drugs when used sensibly within the recommended dosage will show first order kinetics.

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21
Q

What are the 4 pharmacokinetic parameters?

A
  • Volume distribution (Vd)
  • Half-life ( t1/2)
  • Clearance (CL)
  • Bioavailability (F)
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22
Q

Explain volume distribution

A
  • Vd= isn’t actually a real thing in the body but helps with calculations
  • Apparent Volume of distribution = total amount a drug / [Plasma]

The volume of distribution (Vd) is a pharmacokinetic parameter representing an individual drug’s propensity to either remain in the plasma or redistribute to other tissue compartments.

Important points about Vd:

  • Indicate the extent of distribution for a drug
  • Clinically important for adjusting dosage
  • Influenced by lipid/water solubility, binding to plasma proteins.

basically helps to determine dosage (not dosing regimines or intervals just dosage)

23
Q

Explain Plasma clearance

A
  • The volume of plasma cleared of a drug per time (ml/min)
  • CL = rate of elimination/ [drug plasma]
  • A constant for 1st order reactions
24
Q

what is bioavailability (F)

A
  • F: Fraction of drug in circulation compared to dose
  • Measures the extent of absorption
  • Calculated by equal oral/ iv doses, measure AUC oral/ AUC iv (area under curve)
  • E.g. oral dose, F= 0.1 (10%. Bioavailabilty)
25
Q

What is steady state?

A
  • This is state of equilibrium where drugs going in = drugs going out
  • Dosing rate x f= clearance X Css (concentration at steady state)
  • So steady state allows you to estimate the dosage rate
  • Multiple dosing leads to ‘steady state’, building up the drug concentration in a controlled manor to the therapeutic level.
  • Additional doses administered before [drug] falls to zero.
  • [Drug] variation depends on half-life and dose interval.
26
Q

A.) A 70kg patient with asthma is to be treated with theophylline (non-selective phosphodiesterase inhibitor, causes broncho-relaxation) It has as Narrow therapeutic range and potentially fatal effects in overdose.
• Treatment aims at a ‘steady state’ level of 15 mg/ml in plasma
• The clearance of the drug is 48ml/min/70kg and its half-life is 8h
• Treatment by intravenous bolus injection
Calculate the dosing rate.

B.) How would you use the steady state principle in this instance to make sure there is no toxic effects of the drug?

A

Dosing rate x F = clearance x Css (Bioavailability is 1 because nothing loss in IV)
Dosing rate x 1 = 48ml/min/70kg x 15mg/ml
–>dosing rate = 720mg/min/70kg
–> daily dose = ~1.02g for this patient (720µg x 1440 min = 1.02 g) (shows how much you give per min so this is per day).

  • Instead of giving the full 1.02 grams in one go per a day. The same dose can be given in more frequent and smaller amounts.
  • This causes much smaller fluctuations and steady state will eventually be reached where the drug going in will be equal to the drug going out.
  • In this case it is after about 4/5 half-lives.
27
Q

What should you do in emergency situations when the half- life of drug is too long and the drug is potentially toxic at really high levels?

A
  • For drugs with a long half life achievement of steady state can be accelerated by a loading dose.
  • Here a combination of a loading dose and maintenance dose is used. This is when a larger (loading dose) is used to go straight to the desired drug concentration level and then smaller doses are used to maintain this level in the long run.
  • So, this is ideal in an emergency situation, the principle is still the same it is just a different way to reach steady state.
28
Q
  1. A drug with a half-life of 4 h reaches an initial blood concentration of 16 mg/ml. Assuming first-order kinetics, what is the drug concentration after 16 h?
    - 1 mg/ml
    - 2 mg/ml
    - 4 mg/ml
    - 0.1 mg/ml
    - 0.2 mg/ml
A
  • 1 mg/ml
  • 2 mg/ml
  • 4 mg/ml
  • 0.1 mg/ml
  • 0.2 mg/ml

Answer: 1 mg/ml

29
Q
  1. For a drug that obeys first-order kinetics, what parameter remains a constant?
    - Rate of drug absorption
    - Amount of drug eliminated per hour
    - Rate of drug elimination
    - Speed of onset of clinical benefits
    - Time for drug concentration to reduce by half
A

Answer: Time for drug concentration to reduce by half

30
Q

What does the volume of distribution determine?

  • Dosage interval
  • Dosage
  • Route of administration
  • Time to reach steady state
  • Bioavailability
A

DOSAGE

31
Q

In regular dosing, what will happen if you increase the dosage given at the same intervals?

  • No change to the time required to reach steady state
  • Decrease the time required to reach steady state
  • Increase the time required to reach steady state
  • Increase the clearance
  • Decrease the drug fluctuation
A

A

32
Q

What is the definition of renal clearance of a drug?

  • Volume of blood cleared of drug per unit time
  • Rate of elimination
  • Volume of urine cleared of drug per unit time
  • Rate constant proportionate to half-life
  • Amount of drug removed per unit time
A

Answer: Volume of urine cleared of drug per unit time

33
Q

What are the 2 phases of drug metabolism?

A

Phase 1 introduces chemically reactive groups (simpler than p2)

  • Main process is oxidation within the liver
  • Addition of O2 molecules to carbon, nitrogen, sulphur molecules in the drug structure.
  • Carried out by cytochrome P450 enzymes

Phase 2 increases water solubility for drug excretion

  • Conjugates the phase 1 product with an endogenous substance through production of stable covalent bonds.
  • E.g., glucuronidation (reaction with glucose)
34
Q

Explain how paracetamol is an exception to the 2 phases of drug metabolism`

A
  • Instead of going through phase 1 and phase 2 paracetamol jumps straight to phase 2 using either glucuronidation or sulphate conjunction.
  • Phase 1 is used only when glucuronidation and sulphate conjunction is saturated or when there are abnormally high levels of Cytochrome P450 e.g., due to alcohol abuse.
  • However, using the phase 1 pathway produces a toxic intermediate so extensive use of paracetamol over long periods of time can cause liver damage.
35
Q

Give an overview of excretion via the kidney

A

Glomerulus filtration
- Filters more than 20kDa molecules
- Amount excreted depends on levels of drug bound to plasma proteins
Reabsorption
- As molecules pass through tubules they are concentrated, creating a large concentration gradient for reabsorption- hence need to make drugs water soluble
Tubular secretion
- Acid/base molecule carriers transporting molecules into tubular fluid.
- Lower levels of unbound drug in plasma proteins to release more free drug for secretion by carriers.
So Excretion= filtration – reabsorption + secretion

Renal clearance

  • The volume of plasma cleared of drug per unti time in one pass through the kidney.
  • The drug cleared from blood and appears in urine.
  • E.g. the plasma [drug] is 10 µg/ml; drug is appearing in urine at 500 µg/min, then its renal clearance is 50 ml of plasma per min
  • ↓ renal elimination  ↑ plasma half-life
  • plasma CL = hepatic CL + renal CL
36
Q

What is renal clearance

A
  • The volume of plasma cleared of drug per unti time in one pass through the kidney.
  • The drug cleared from blood and appears in urine.
  • E.g. the plasma [drug] is 10 µg/ml; drug is appearing in urine at 500 µg/min, then its renal clearance is 50 ml of plasma per min
  • ↓ renal elimination  ↑ plasma half-life
  • plasma CL = hepatic CL + renal CL
37
Q

What factors affect drug metabolism and excretion?

A

Age
- Cyto P450 activity reduced in neonates/elderly
- GFR reduced greatly in neonates/elderly
- Increased % fat content in elderly
Genetics
- 45% in Europe & USA; 80-90% Asians fast acetylators
- 1/3000 slow metabolism by pseudocholinesterase
Disease
- Liver disease impairs drug metabolism - drug toxicity
- Renal disease may alter pharmacokinetics
Drug metabolising enzymes
- Can be induced by other drugs or lifestyle factors
- Can be inhibited by other drugs or lifestyle factors

38
Q

What is the difference between pharmacokinetics and pharmacodynamics?

A

Pharmacokinetics is how a body processes a drug. (the effects of the body on the drug)

Pharmacodynamics is the effects of drug on the body

39
Q 
One litre contains 100 mg of a drug. If 10 mg of the drug was removed after 1 h, what is the clearance?
•	100 ml/h 
•	10 ml/h 
•	1 ml/h 
•	1000 ml/h 
•	10000 ml/h
A

Answer: 100 ml/h

40
Q 
What enzyme is most likely responsible for altered drug metabolism in patients with liver diseases?
•	Cytochrome P450 
•	Aldehyde dehydrogenase 
•	Aromatase 
•	Alkaline phosphatase 
•	HMG-CoA synthase
A

Cytochrome P450

41
Q 
What scenario promotes paracetamol toxicity?
•	Decreased body fat 
•	First-order kinetics 
•	Chronic alcoholism 
•	Increased levels of glutathione 
•	Increased rate of glucuronidation
A

Chronic alcoholism

42
Q

What change modifies the pharmacokinetic properties of an orally active drug?
• Decreased cholesterol level
• Decreased lung volume
• Increased production of endogenous ligands
• Increased expression of sodium channels
• Decreased glomerulus filtration rate

A

Decreased glomerulus filtration rate

43
Q 
What feature relates to the pharmacokinetics of a drug?
•	Rank order of potency 
•	Rate of diffusion across membranes 
•	Ion chancel activation 
•	Receptor selectivity 
•	Antibody response
A

Answer: Rate of diffusion across membranes

44
Q 
What feature relates to the pharmacodynamics of a drug?
•	EC50 values 
•	Rate of elimination by the liver 
•	Rate of diffusion across membranes 
•	Binding to plasma protein 
•	Dosage regime
A

EC50 values

The EC50 is the concentration of a drug that gives half-maximal response.

45
Q

is aspirin a weak acid or weak base and hence in what conditions will it be more unionised. How does this affect how it will cross a biological membrane

A

weak acid
more unionised in acidic conditions (gives away H+)

ionisation reduces the ability of drugs to cross biological membrane

46
Q

what is the bioavailability of aspirin like?

A

Overall, due to the small size of the drug and very large surface area, thin and highly vascularised nature of the small intestine for absorption, all the aspirin does enter the bloodstream

47
Q

how would you deal with someone who has overdosed on a basic drug?

A

Examples of basic drugs: amphetamines, morphine

Therapeutic strategy in case of overdose of basic drugs is to acidify the urine so you would …. Give large dose of ammonium chloride or ascorbic acid

be aware ammonium chloride causes gastric irritation/nausea so ascorbic acid preferred. be careful for metabolic acidosis.

48
Q

Which of the following is the best at increasing the urinary excretion of aspirin after overdose?

  Sodium bicarbonate 
  Ascorbic acid 
  N-acetyl cysteine 
  Charcoal 
  Ammonium chloride
A

sodium bicarbonate

49
Q

What happens to acid drugs at basic conditions?

  • Become ionised and lipophobic
    • Become ionised and membrane permeant
  • Become unionised and membrane permeant
  • Become unionised and slowly excreted by the kidneys
  • Become ionised and lipophilic
A

Become ionised and lipophobic

50
Q

Under what conditions can ammonium chloride or ascorbic acid be used to manage drug overdose?

Avoid metabolic acidosis after overdose with basic drugs

When overdose with drugs occur

Avoid hypokalaemia after overdose with acid drugs

In toxin overdose

When overdose with basic drugs occur

A

When overdose with basic drugs occur

51
Q

!Which of the following best describes the effects of urinary alkalinisation as an antidote to overdose with an acid drug?

Urinary alkalinisation causes the acidic drug to act as a proton acceptor which increases the renal excretion of the acid drug

Urinary alkalinisation increases the ionised form of the toxin and hence less is reabsorbed from the renal tubules

Urinary alkalinisation reduces the ionised form of the acidic drug and hence less is reabsorbed from the renal tubules

Alkalinisation of the urine ionises the acidic drug and increases its absorption in the cell membranes of the small intestine

Urinary alkalinisation affects the lipophilicity of the acidic drug and hence more is reabsorbed from the renal tubules

A

Urinary alkalinisation increases the ionised form of the toxin and hence less is reabsorbed from the renal tubules

52
Q

Which of the following is the most abundant metabolite of aspirin?

Gentisic acid 
  Salicyluric acid 
  Salicylic acid o-sulfate 
  Acetyl salicylic acid 
  Salicylate
A

Salicyluric acid

53
Q

Which of the following is the minor and only active metabolite of aspirin?

Acetyl salicylic acid 
  Salicyluric acid 
  Salicylic acid o-sulfate 
  Gentisic acid 
  Salicylic acid acyl glucuronide
A

Gentisic acid

PHARM (3 decks)

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