Pharmacokinetics 1 & 2 Flashcards

1
Q

Intention of a regimen (dosage wise)

A

To provide a dosage that can keep concentrations of the drug in a certain therapeutic window to keep it effective

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2
Q

Volume Distrivution (Vd)

A

Apparent volume in which a drug is dissolved in the body

Indicates how much is absorbed by cells vs how much is still lingering in blood

(Conc at T=0 is plasma conc)

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3
Q

Clearance (CL) (and units)

A

The volume of plasma cleared of a drug in unit time

ml/min or L/h

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4
Q

What is clearance of a drug composed of

A

Clearance = Renal Clearance + Hepatic Clearance (some combination of the two, different per drug)

**note that renal clearance is where the relevance of eGFR comes from

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5
Q

Exponential Decay and First Order Elimination

A

Drugs are cleared from the body in an exponential correlation with time;

Thus when drug concentration is logged and plotted against time, there is a negative linear relationship (first order)

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6
Q

First Order Kinetics and Formula

A

Rate of elimination is proportional to concentration of drug

Formula allows you to predict plasma concentrations of drug at some point in future

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7
Q

Rate constant (k) of first order kinetic formula

A

k is fraction eliminated per unit time

e.g. k=0.1/day, 10% eliminated per day

Thus, k= CL/Vd or CL = k x Vd

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8
Q

How to keep drugs in steady state

A

Administration dose = Elimination dose

Keeps drugs at equilibrium desired level

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9
Q

Why do some drugs (like digoxin) have very low plasma concentrations

A

Those drugs become concentrated in fat and other tissue, reducing the concentration in plasma - High Volume of Distribution

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10
Q

Discuss IV Infusion

A

Most reliable and straight forward type of drug infusion

What would be used in an emergency

IV infusion is a zero-order process. Plasma concentration just goes up alone with dosage

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11
Q

What two simultaneous things are occurring to blood plasma during IV administration

A

Zero-order infusion of a drug; (mostly) first-order elimination

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12
Q

How to calculate the infusion rate of a maintenance dose

A

Infusion Rate = Clearance x Css

Css = concentration steady state

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13
Q

Units for infusion rate (vague)

A

Unit / Time

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14
Q

Use Aminophylline to calculate maintenance infusion rate

Only 80% of the drug is the active ingredient (theophylline)

Clearance = 0.039 L/h/kg
and thus 70kg man ->2.73 L/h

Css = 10-20 mg/L (15)

A

(Used sometimes in severe asthmatic attacks as a bronchodilator; Given by IV infusion)

Infusion = CL x Css = 2.73*15
= 40.95 mg/h

But the drug is infused as active; so

40.95/0.8 = 51 mg/h (FINAL ANSWER)

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15
Q

What factors affect overall plasma concentration in oral dosing

A

Rate of Dissolution
Rate of Absorption

For graph, think liquid vs fine pills vs big pills (of the same drug)

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16
Q

When are sustained release oral drugs generally used

A

Used in longer term control; half life is reduced due to the bottle neck as rate of absorption is slower than administration

17
Q

Compare the rise to peak and after peak portions of a rapid release vs sustained release oral dosing

A

Rapid Release:
Rise to peak - Absorption + elimination
After peak - Elimination only

Sustained Release
Prolonged absorption super-imposed on half life
(half-life is a contextual one, not a true one in this case as absorption occurs simultaneously)

18
Q

Bioavailability

A

Fraction of drug absorbed (F)

F = AUC oral /AUC iv
(AUC is area under curve)

**Because IV would be 100% absorption

19
Q

Why are pschoactive drugs given at night

A

If taken at night, the adverse effects (like sleepiness) are avoided

20
Q

Calculate dose given based on bioavailability

A

Dose given = Amount needed/F

21
Q

Approximately how many half lives does it take for repeated oral drugs to reach steady state (and why)

A

Approximately 5 half lives

50% –> 25% + 50% –> 12.5% + 75% –> 6.25% + 87.5% –> 3.125% + 93.75 = approx 97%

22
Q

Why some penicillins are taken before food

A

If taken with food, they would get taken up in the stomach and be dissolved by the stomach acid

23
Q

Formula for dosage of repeated oral regiment

A

Css is concentration at steady state
(CL x Css is infusion rate)

Tau is dosage interval (twice a day would be 12 [hrs])

F is bioavailability

24
Q

Calculate Loading Dose and maintenance dose for ugent medication

A

Loading Dose = (Target Css x Vd)/F

Maintenance dose = (Target Css x CL x tau)/F

25
Q

Purpose of Loading Dose

A

To achieve a rapid rise of plasma conentration to reach Css (used for emergencies)

26
Q

How to avoid toxicity with a loading dose

A

Giving the drugs in divided doses

27
Q

Compare the doses given for drugs of large vs smalls Therapeutic windows

A

Large TW (e.g. Penicillins) have a maximal dose strategy, so less doses are given, but each dose is towards the upper end of the TW

Small TW have a target level strategy, often given intravenously

28
Q

Managing drugs with a short half life

A

Short half life (approx 1h) with wide therapeutic window: 3-4 times daily

Short half life with narrow TW: IV

29
Q

Managing drug dosages with a medium half life

A

Its kind of just about being logical at this point. Look at the half life and calculate tau around that

30
Q

Managing drug dosages with a long half life

A

> 24 hours
e.g. digoxin

Maintenance dose = amount eliminated in 24 hours (to improve adherence)

tau = 1 (day)

Dose = (Css x Clearance x tau) / F

31
Q

Gentamicin

A

Antibacterial used IV

An exception to standard drug dosages

Its trough must be sub therapuetic to avoid toxicity in the ears and kidney

Half life is significantly impaired with patients with abnormal kidneys

32
Q

Creatinine clearance

A

This rate is related to the kidney; abnormal levels indicate kidney damage

The value is needed when determining suitability and dosage of gentamicin

33
Q

Single Daily Dose Gentamicin

A

Single dose of gentamicin is given over 30-60 mins

6-14 hours afterwards, plasma sample is taken and it is plotted onto a hartford nomogram to figure out the ideal dosage

34
Q

Short vs Long Acting Drugs

A

Short (e.g. salbutamol) are more of a current treatment while long (e.g. salmeterol) are more preventative

Short has quick onset and offset; long has the opposite