BT_PO 1.80 Describe alterations to drug response due to renal disease

I don’t know about you, but I seem to see a lot of patients with a degree of renal impairment presenting for theatre. Additionally, the peri-operative period is a dangerous time for kidneys. Here is a nice little article on peri-operative AKI (doesn’t strictly address the LO).

Predicted change in normal GFR and SCr with age in a white female. The same creatinine is associated with very different GFR at different ages. Creatinine generation and GFR decline in parallel with age.

Above is an interesting [alarming] slide from the article I have linked to. The same serum creatinine means vastly different things regarding renal function depending on the age. A “normal” creatinine may be anything but….

Anyway, after that cheery bit of news lets get back to the LO at hand.

Miller’s Anaesthesia Ch 72 discusses this topic.

BT_PO 1.80 Describe alterations to drug response due to renal disease

The top four are basic principles or involve drugs we use commonly, so I think you should know these

Increasing the time between doses of a drug may be an effective way to prevent toxicity of renally cleared drugs, in patients with renal impairment T/F

The potassium rise caused by suxamethonium is exaggerated in patients on dialysis T/F

Suggammadex is renally excreted and should be avoided in patients with an eGFR <60ml/min T/F

Plamsa protein levels are decreased in patients with ESRD, which may result in increased free fraction of highly protein bound drugs eg digoxin T/F

This last one is also a drug we use very commonly, but the answer was news to me….

Cephalosporins are 100% excreted unchanged by the kidneys and accumulation may lead to seizures T/F

For those of you wanting to look at things from the opposite direction, here is a post on the effect of anaesthesia on renal function

BT_GS 1.19 Describe the mechanisms of drug interaction

Mechanisms of drug interaction can be classified as: pharmacodynamic, pharmacokinetic, and pharmaceutic.

T/F  the interaction between nitrous oxide and sevoflurane is an example of synergism because the combined effect is greater than would be predicted by simple addition

T/F  the interaction between propofol and remifentanil can be represented by a linear isobologram

T/F  in a patient using buprenorphine patches, morphine can have a reduced effect because buprenorphine is a partial antagonist

T/F  in a patient who has been reversed with neostigmine, but then needs to be urgently reintubated, suxamethonium would have a significantly reduced effect

T/F  cigarette smoking inhibits many of the cytochrome P450 enzymes, thereby slowing the metabolism of many drugs

T/F  competition for plasma protein binding sites between drugs, is a common reason for adverse drug effects in anaesthesia

T/F  if suxamethonium is injected into an IV port immediately after thiopentone, a precipitate will form in the line

Reference

Hemmings & Hopkins, Chapter 9 (Anesthetic drug interactions)

 

BT_GS 1.16 Describe alterations to drug response due to ageing

It is uncommon these days for me to have a day where I don’t anaesthetise at least one older patient. Approximately 15% of the Australian population is aged over 65. There are currently almost half a million Australians aged over 85 yrs of age and this number is expected to double in the next 20 yrs !

Fauja_Singh_in_acti_222195a

This elderly person (Fauja Singh) is a fairly amazing older person, completing a marathon aged 100!

Chronological age does not necessarily correspond to physiological age, but there are certain changes which occur fairly consistently with increasing age.  Acute Pain Management: scientific evidence (10.2.3 in case the link doesn’t work) has summary of the changes that occur with ageing and significance for drug dosing.

BT_GS 1.16 Describe alterations to drug response due to physiological change with particular reference to the elderly

A given bolus dose of propofol in an elderly person, compared with a 40yr old, will have an increased effect due to the decreased size of the central compartment   TRUE/FALSE

Changes in cardiac output in the elderly generally slow the rate of induction with volatile anaesthetic agents    TRUE/FALSE

GFR decreases by about 10% per decade after 50 yrs of age   TRUE/FASLE

Oral bioavailability of some drugs may be increased in the elderly due to a reduction in both liver blood flow and metabolic capacity    TRUE/FALSE

Both albumin and alpha1 acid glycoprotein levels fall equally in the elderly, increasing the free fraction of highly protein bound drugs   TRUE/FALSE

 

 

 

 

SS_PA 1.52 Pharmacokinetic differences in  neonates and children compared with adults and the implications for anaesthesia

A little person I know had an anaesthetic last week having swallowed a curtain hook, probably a couple of months ago. He had not been very keen to eat solid food!!


SS_PA 1.52 Describe how the pharmacokinetics of drugs commonly used in anaesthesia in neonates and children differ from adults and the implications for anaesthesia

Water soluble drugs have a larger volume of distribution in neonates TRUE/FALSE

Drugs that depend on redistribution into fat compartments for their termination of action have longer durations of action in neonates    TRUE/FALSE

The absorption of oral drugs is more rapid in neonates compared with adults   TRUE/FALSE

The relationship between weight and drug elimination is linear in children  TRUE/FALSE

Remifentanil’s half life is unchanged in neonates    TRUE/FALSE

BT_GS 1.21 Isomers

I think isomerism is a very cool little trick of nature! How amazing to think that one chemical structure can have such different properties due to the orientation of the same atoms on a single carbon, and also that our bodies are able to recognise these differentially.

We sometimes talk about enantiomers as being non superimposable mirror images of each other, which made me think of mirror twins ( apologies for the high class nature of the “journal” I took this from! However, if you are interested in twins, these episodes of Insight from SBS may interest you)

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No photos of mirrors today, just this (not perfect) reflection of Cradle Mountain in Dove Lake, Tasmania. One of my favourite parts of the world. I have seen the lake surface truly glass like, but do not have an image of it to share with you.

BT_GS 1.21 Describe and give examples of the clinical importance of isomerism

Ketamine, propofol and bupivacaine are all presented as racemic mixtures for use in Australia TRUE/FALSE

The D isomer of amphetamine is more potent as a CNS stimulant than the L isomer TRUE/FALSE

The (+) enantiomer of tramadol is more potent inhibitor of serotonin reuptake than the   (-) enantiomer TRUE/FALSE

D isomers of naturally occurring catecholamimes are 10x more potent than the L isomers TRUE/FALSE

Thiopentone is a drug which has stereoisomers TRUE/FALSE

SS_PA 1.80 Describe the maximum safe doses of local anaesthetic agents in different age groups

TRUE/FALSE  Neonates are more prone to develop methaemogolbinaemia with prilocaine administration due to the presence of foetal haemoglobin

TRUE/FALSE  Transfer of local anaesthetics across the placenta is inversely proportional to drug lipophilicity

TRUE/FALSE  Methaemoglobin reductase requres NADH as an electron donor

TRUE/FALSE  Methaemoglobin reductase is functionally deficient in the neonate

TRUE/FALSE  Children are more prone to cocaine toxicity due to reduced cholinesterase activity

SS_PA 1.51 : paediatric pharmacokinetics

As promised…

SS_PA 1.51  : Describe how the pharmacokinetics of drugs commonly used in anaesthesia in neonates and children differ from adults and the implications for anaesthesia

Neonates require larger doses of neuromuscular blockers per kg than adults   TRUE/FALSE

Neonates require larger doses of remifentanil per kg than adults   TRUE/FALSE

Neonates require a larger induction dose of thiopentone per kg than adults   TRUE/FALSE

Higher doses of EMLA can be more safely used in neonates than older children   TRUE/FALSE

Surgical stress decreases the concentration of alpha 1 acid glycoprotein   TRUE/FALSE

SS_PA 1.51 : paediatric pharmacokinetics

Staying on the theme of routes of administration today..

SS_PA 1.51  : Describe how the pharmacokinetics of drugs commonly used in anaesthesia in neonates and children differ from adults and the implications for anaesthesia

Oral medications are absorbed slowly in infants due to decreased gastric emptying and intestinal motility  TRUE/FALSE

Nasal midazolam tastes good  TRUE/FALSE

Gastric pH is lower in infants than in adults  TRUE/FALSE

The solubility coefficients of an inhaled anaesthetic will determine its volume of distribution  TRUE/FALSE

In Evers & Maze the author states  ‘Other factors causing a more rapid “wash-in” of inhalational anesthetics include the greater fraction of cardiac output distributed to the vessel-rich tissue group (e.g., the lungs)’ What do you think of this comment?

(hint – keep reading this chapter on paediatric pharmacology – you might even be able to spend the rest of the week testing your retention of the material)