prescribing in special circumstances

Question 1

3 categories or risks when prescibing

Answer 1

• Risks particular to the drug, which we discuss in the adverse drug reactions session
• Risks associated with the prescriber and the context in which they are working, which we will discuss in the risk and error in prescribing session
• Risks generated by the individual characteristics of the person, including their comorbidity (co-existing illnesses), co-existing treatment (discussed in the Drug interactions session) and special circumstances (a broader term that extends to non-pathological states that may influence prescribing)

Question 2

what is an allergy

Answer 2

In the context of drug therapy, allergy is a term that is generally taken to refer to immunologically-mediated adverse reactions

Question 3

2 main risks associated with allergy to a drug

Answer 3

• The risk of immunological toxicity if a drug is prescribed which the person is allergic to
• The risk of inadequate treatment if a person is unable to receive the best available treatment, because they are allergic to it, or because they are inappropriately labelled as allergic

Question 4

what is drug intolerance

Answer 4

Drug intolerance is a broader term that includes immunologically-mediated adverse reactions (‘allergies’) and non-immunological reactions

Question 5

drugs that will have increased toxicity in renal impairment

Answer 5

o Kidneys are the main route of clearance for water soluble drug- minority of drugs used
o e.g. acyclovir, gentamicin, digoxin, gabapentin- kidneys important for clearance. Half-life will increase and so will concentrations in body tissues= increased risk of toxicity esp in drugs with a narrow therapeutic index.
o Not water-soluble drugs: hepatic metabolism, but may rely on kidneys for clearance of water-soluble metabolites e.g. morphine- metabolised in liver to various substances, including morphine 6 glucuronide- more potent opioid agonist than morphine hence greater effect in renal impairment

Question 6

how do NSAIDs cause nephrotoxicty

Answer 6

renal impairment has less tolerance to further insult. Typical examples include NSAIDs via effects on regulation on glomerular perfusion. PGs maintain the size of the afferent arteriole, NSAIDs block PG synthesis which reduces the signal to the afferent arteriole to dilate, so afferent arteriole becomes more constricted, less flow and pressure in glomerulus= less glomerular filtration.

Question 7

how does gentamicin cause kidney damage

Answer 7

o Gentamicin (aminoglycoside) in nephrotoxicity- some is taken into cells lining renal tubule. Tubular cells exposed to higher conc than in blood= damage- acute tubular necrosis.

Question 8

how does allopurinol cause renal damage

Answer 8

o Allopurinol- incite inflammatory process in interstitium- acute interstitial nephritis.

Question 9

how do acyclovir and methotrexate cause renal damage

Answer 9

in high doses e.g. viral encephalitis, can precipitate in renal filtrate- crystalluria, crystals block tubules and block renal function

Question 10

what drugs might become less effective in renal impairment

Answer 10

o Nitrofurantoin- remains largely unchanged in the urine, if kidneys aren’t working, not exceted in urine so not in high enough conc in urine to fight infection. Also get higher levels in the blood cinreasing the risk of adverse effects
o Thiazide diuretics: need to be secreted into the tubular fluid to access the target (Nal/Cl transporter in luminal surface of DCT), if less is secreted into the tubule then the effect is lower

Question 11

markers for renal function

Answer 11

creatinine conc
eGFR
Cr clearance

Question 12

3 ways liver disease can affect prescribing

Answer 12

• Altered pharmacokinetics: reduced protein binding, reduced hepatic metabolism and excretion (particularly for drugs subject to significant first-pass metabolism)
• Altered pharmacodynamics: increased sensitivity to the effects of drugs, particularly those that can cause bleeding, renal impairment, sedation, constipation and hypokalaemia)
• Risk of hepatotoxicity: although the drugs may not be ‘more hepatoxic’ in a person with hepatic impairment, they may have ‘more to lose’ from any hepatotoxic effects that occur

Question 13

describe 1st pass metabolism and how it can be affected in liver disease

Answer 13

o First pass metabolism: venous blood flow from GI tract passes through the liver before joining the systemic circulation- filtering before it goes round the circulation around the body- applies to many orally given drugs- may be metabolised at first pass through the liver- IV dose will be lower than oral dose to get the same clinical effect and in severe liver disease giving the same dose may result in a greater amount of the drug entering the systemic circulation so need to reduce the oral dose more than the equivalent IV dose.
o High first pass metabolism: most beta blockers, benzo, morphine, pethidine

Question 14

what drugs should be avoided in liver failure

Answer 14

anticoagulants, NSAIDs, nephrotoxic drugs, drugs that cause sedation, constipation and hypokalaemia

Question 15

drugs inappropriate in hepatotoxicity

Answer 15

include atorvastatin, azithromycin and methotrexate.

Question 16

how does cardiac failure affect prescribing

Answer 16

Cardiac failure reduces hepatic and renal perfusion, giving rise to many of the same pharmacokinetic considerations as described for hepatic and renal impairment (reduced metabolism/excretion). In addition, people with cardiac failure are likely to have increased sensitivity to vasodilatory drugs and drugs with negative inotropic effects

Question 17

how does mental health affect prescribing

Answer 17

There may be pharmacodynamic implications, for example a potential for increased sensitivity to neuropsychiatric affects. There may also be non-pharmacological considerations, including:
• How information is presented about treatment options
• The implication of mental health conditions on the shared decision-making framework
• The legal considerations around prescribing without the consent of the person, under the authority of the Mental Health Act
• Stigma associated with certain mental health conditions and their treatment (and the adverse effects of treatment, such as tardive dyskinesia)
Treatment of mental health conditions may also involve the use of high-risk medicines, such as valproic acid (valproate), lithium and clozapine

Question 18

2 considerations in pregnancy pharmacology

Answer 18

• The effect of pregnancy on the pharmacokinetics of the drugs
• The effect of exposure of the fetus to drugs

Question 19

how does pregnancy affect prescribing

Answer 19

Increase in plasma volume and CO in pregnancy- reduce albumin conc, decreased protein binding of drug. Hepatic and renal blood flow increased- increased drug elimination. Might matter for a drug with a narrow therapeutic index.
Consider: Foetal toxicity, miscarriage risk, neonatal withdrawal

Question 20

give 5 examples of teratogenic drugs and their effects

Answer 20

Thalidomide: phocomelia
Many anticonvulsants: various effects esp learning/behaviour effects
Warfarin: foetal anticoagulation, foetal warfarin syndrome prefer heparin as it doesn’t cross the placenta
Retinoids- acne treatment: various structural and developmental defects
ACEi: renal defects, patent ductus (2nd and 3rd trimester)
Opioids, benzos: neonatal withdrawal syndrome

Question 21

drugs that should be avoided in breastfeeding

Answer 21

• Cytotoxic drugs that may interfere with cellular metabolism of the infant (e.g. methotrexate (Links to an external site.))
• Drugs of abuse, for which adverse effects on the infant during breastfeeding have been reported (e.g. amfetamine, cannabis, cocaine, heroin)
• Radioactive compounds (e.g. radioiodine)

Question 22

drugs that have been associated with adverse effects in some infants, and should generally only be given with careful risk assessment and monitoring

Answer 22

• Atenolol (Links to an external site.): because, unusually among beta blockers, it is water soluble, so more readily excreted in breast milk
• Aspirin (Links to an external site.): because of the risk of Reye’s syndrome in the infant
• Bromocriptine (Links to an external site.): which can inhibit lactation
• Lithium (Links to an external site.): which is present in breast milk in concentrations that may cause toxicity