Clinical Pharmacology and Renal Disease Flashcards

1
Q

What is the therapeutic index?

A

Quantitative measure - relative safety of the drug
Ratio comparison of the does that produces desired effect and which causes toxicity

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2
Q

What does it mean if the drug has a narrow therapeutic index?

A

Prescribe with care
Ratio is very close (largest non-toxic: minimum effective)

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3
Q

What is the measurement of clearance?

A

PK measurement
Volume of plasma from which the drug would be totally removed per unit time

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4
Q

What is low clearance equal to?

A

High systemic exposure

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5
Q

What is renal clearance mainly a function of?

A

Glomerular filtration
Tubular secretion
Reabsorption

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6
Q

What is filtration dependant on?

A

Drug must be free in plasma - Vd and protein binding
Kidney perfusion
Health of kidneys - specifically glomerulus

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7
Q

What is total renal clearance?

A

No secretion/ reabsorption

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8
Q

What is used to measure GFR?

A

Creatine and insulin

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9
Q

Explain active renal secretion

A

Mainly occurs in proximal tubule
Can clear drugs too large to filter
Weak acid/base, nucleoside P-glycoprotein transporters
Saturable

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10
Q

What drugs are actively secreted?

A

B-lactam antibiotics, frusemide, ranitidine, ribavirin and verapamil

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11
Q

What is secretion equal to?

A

When renal clearance more than GFR

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12
Q

Describe passive tubular reabsorption

A

Lipid solubility and conc. gradient
Depends on urine flow rate and pH

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13
Q

What can be used to increase clearance of weak acids (aspirin)?

A

Urinary alkalisation
More alkaline the tubular fluid pH the more likely the drug is ionised so more likely reabsorbed

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14
Q

Explain how volume of drug influences plasma conc.

A

Drugs with high Vd have longer elimination half life
Drug cleared from plasma redistributes from other tissues. Shift from compartments to plasma - plasma conc. maintained

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15
Q

What is half life equal to?

A

0.693 x (Vd/clearance)

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16
Q

Describe steady state

A

Attained approx. after 4-5 half lives
Peaks and throughs
Can take a while to get to steady state
Vd used to calculate loading does

17
Q

When is nephrotoxicity worse in patients?

A

Polypharmacy
Renally impaired
Age
Renal disease
Other illnesses - volume depleted, dehydrated and hypotensive

18
Q

What do we do about avoiding nephrotoxicity?

A

Measuring GFR
Recognise other risk factors and drugs with narrow TI
Know which drugs can be used safely with low GFR
Importance of reducing loading/ maintenance doses
Importance of TDM

19
Q

What needs to be considered when prescribing in renal impairment?

A

Risk/ benefit ratio
Severity of toxicity and possible adverse effects
Availability of TDM

20
Q

What should be done when prescribing in renal impairment?

A

Use drugs with wide therapeutic index
Consider changing to drug which isn’t renally excreted
Reduce dose and dose frequency

21
Q

Describe acute kidney injury

A

Clinical syndrome with multiple contributory factors - pre-renal (impacted perfusion), intra-renal or post-renal (structural obstruction)

22
Q

What are common causes of AKI?

A

Acute tubular necrosis - death of tubular epithelial cells
Glomerulonephritis - collection of conditions causing glomerular damage
Interstitial nephritis - inflammatory

23
Q

How do drugs exert nephrotoxic effects?

A

Immune drug effects
Combination of nephrotoxic drugs
Insoluble drug in urine
Increase in drug conc. within cells
Intracellular drug accumulation
Drug-uromodulin interaction
Direct drug nephrotoxicity

24
Q

What drugs can cause acute tubular necrosis - AKI?

A

Aminoglycoside antibiotics, amphotericin B, cisplatin, statins, Colistimethate, foscarnet and radiocontrast agents (rare)

25
Q

What drugs can cause acute interstitial nephritis (latency)?

A

Penicillin, cephalosporins, cocaine, omeprazole and herbal medicines

26
Q

What biotherapeutics can cause glomerulonephritis?

A

Thrombotic microangiopathy - cyclosporine, chemotherapeutic drugs and 19-oestrogen containing oral contraceptives

27
Q

What drugs can cause drug-associated obstruction of urine outflow?

A

Acyclovir, sulphonamides, triamterene, methotrexate and Vitamin C in large doses

28
Q

Describe nephrotic syndrome

A

Due to glomerular dysfunction and marked by heavy proteinuria
Hypoalbuminemia

29
Q

What are some drugs impacted by nephrotic syndrome?

A

DMARDs like gold and penicillinamine
NSAIDs, interferon and captopril

30
Q

What can NSAIDs cause?

A

AKI in 35% of drug induced AKI
Tow forms - haemodynamically mediated and immune mediated

31
Q

When should nephrotoxic drugs be avoided?

A

Volume depleted with renal disease
And if on other nephrotoxic drugs