Lecture 2.3

Pharmacology

What are the professional practice learning outcomes for this lecture?

Be able to describe, explain and implement professional practice with specific reference to applying knowledge for the safe and effective use of medicines (MRPBA Domain 1.8a).

What learning outcome relates to understanding medication risks?

Be able to demonstrate understanding of the risks, precautions and contraindications of pharmaceutical use (MRPBA Domain 1.8b).

What pharmacology knowledge should Medical Radiation Practitioners apply?

Be able to apply knowledge of:
Pharmacokinetics
Pharmacodynamics
The potential range of drug and agent reactions
(MRPBA Domain 1.8c).

What learning outcome relates to medication administration?

Be able to safely and effectively deliver medications to patients in accordance with procedures (MRPBA Domain 1.8d).

What learning outcome relates to patient monitoring after medication administration?

Be able to monitor patients after medications for effects and adverse reactions according to established protocols (MRPBA Domains 1.8e and 1.7d).
Sincalide

What is cholecystokinin (CCK)?

Cholecystokinin (CCK) is an endogenous 33-amino acid polypeptide hormone that is secreted from the duodenum in response to a fatty meal.

What is sincalide?

Sincalide is the exogenous active portion (octapeptide) of cholecystokinin (CCK).
It is a synthetic peptide representing the active portion of the endogenous CCK hormone.

Which part of the CCK molecule does sincalide represent?

Sincalide represents the active octapeptide (8-amino acid C-terminal fragment) of the endogenous CCK molecule.

What stimulates endogenous CCK release?

CCK is released from the duodenal mucosa in response to fat entering the duodenum after a meal.
Fat is the physiological stimulus for CCK secretion.

What is the effect of CCK on the gallbladder?

CCK stimulates gallbladder contraction, allowing bile stored within the gallbladder to be expelled into the biliary system.

How does CCK influence the sphincter of Oddi?

CCK stimulates the dorsal vagal complex, which activates vagal efferents to produce relaxation of the sphincter of Oddi.

Besides contracting the gallbladder, what other physiological effect does CCK produce?

In addition to causing gallbladder contraction, CCK:
Relaxes the sphincter of Oddi
• Stimulates bile production
These coordinated actions promote bile flow into the duodenum.

What is Cholecystokinin-8 (CCK-8)?

Cholecystokinin-8 (CCK-8) is the 8-amino acid C-terminal fragment of the full CCK molecule.
This region contains the biologically active portion of the hormone.

What is the primary mechanism responsible for gallbladder contraction after sincalide administration?

The primary mechanism is direct action of circulating CCK/sincalide on the gallbladder after it enters the bloodstream.

When does gallbladder contraction occur following CCK or sincalide administration?

• Gallbladder contraction occurs only after serum CCK/sincalide concentrations reach a threshold level.
Because IV sincalide rapidly achieves this threshold, it is significantly more potent than endogenous hormone release.

Why is intravenous (IV) sincalide more potent than endogenous CCK release?

IV sincalide rapidly produces circulating concentrations above the threshold required for gallbladder contraction, resulting in a stronger and more predictable physiological response than endogenous CCK released after a fatty meal.

What receptors does cholecystokinin act on?

Cholecystokinin acts primarily on CCK receptors located on:
• Gallbladder smooth muscle
• The biliary system
• The gastrointestinal tract
Activation of these receptors produces gallbladder contraction and facilitates bile flow.

What is the primary clinical use of sincalide in Medical Radiation Sciences?

Sincalide is used during hepatobiliary (HIDA) imaging to assess:
• Gallbladder contractility
• Gallbladder emptying
• Gallbladder ejection fraction (GBEF)
It provides a controlled pharmacological stimulus to contract the gallbladder.

What is Gallbladder Ejection Fraction (GBEF)?

• Gallbladder Ejection Fraction (GBEF) is the percentage of bile emptied from the gallbladder following stimulation with sincalide.
It is used to assess gallbladder function during hepatobiliary scintigraphy.

Why is gallbladder ejection fraction measured?

• Gallbladder ejection fraction helps determine whether the gallbladder contracts normally.
Reduced emptying may indicate gallbladder dysfunction, even when gallstones are absent.

Which condition is commonly investigated using a sincalide-stimulated HIDA scan?

A sincalide-stimulated HIDA scan is commonly used to investigate chronic acalculous cholecystitis (biliary dyskinesia)by assessing gallbladder function.

What does a reduced gallbladder ejection fraction suggest?

A reduced gallbladder ejection fraction suggests impaired gallbladder contractility, which may indicate chronic gallbladder dysfunction or biliary dyskinesia.

How is sincalide administered during hepatobiliary imaging?

Sincalide is administered by intravenous infusion to produce a controlled and reproducible contraction of the gallbladder during imaging.

Why is sincalide administered as a slow infusion rather than a rapid IV bolus?

A slow IV infusion produces a more physiological gallbladder contraction and reduces adverse effects such as abdominal cramping and nausea compared with rapid administration.

What are the common adverse effects of sincalide?

Common adverse effects include:
• Abdominal cramping
• Nausea
• Vomiting
• Abdominal discomfort
These effects result from stimulation of gallbladder and gastrointestinal smooth muscle.

Why can sincalide cause abdominal cramping?

Sincalide stimulates forceful contraction of the gallbladder and gastrointestinal smooth muscle, which may produce temporary abdominal pain or cramping.

What contraindication is particularly important before administering sincalide?

Sincalide should not be administered when acute cholecystitis or complete biliary obstruction is suspected, as stimulating gallbladder contraction may worsen pain or complications.

Why should caution be exercised when administering sincalide during pregnancy?

Sincalide should be used cautiously in pregnancy because stimulation of smooth muscle may have unwanted physiological effects. The risks and benefits should be carefully assessed before administration.

What should be monitored after administering sincalide?

Patients should be monitored for:
• Abdominal pain
• Nausea
• Vomiting
• Other adverse reactions
Monitoring ensures that any significant reactions are recognised and managed promptly.

Why is understanding the normal physiology of CCK important in hepatobiliary imaging?

Understanding the physiological actions of CCK helps explain:
Why sincalide contracts the gallbladder.
Why it relaxes the sphincter of Oddi.
How it promotes bile flow.
Why it is an effective pharmacological agent for assessing gallbladder function during HIDA imaging.

What is morphine?

Morphine is a naturally occurring opioid analgesic derived from the opium poppy. It is a μ (mu) opioid receptor agonist used for analgesia and has important applications in hepatobiliary nuclear medicine.

What is the mechanism of action of morphine?

Morphine acts as a μ-opioid receptor agonist, producing:
• Analgesia
• Sedation
• Reduced pain transmission within the central nervous system

Why is morphine used during hepatobiliary (HIDA) imaging?

Morphine is administered to:
• Increase pressure within the biliary system.
• Promote filling of the gallbladder with radiotracer.
• Improve the diagnostic accuracy of hepatobiliary scintigraphy.

How does morphine affect the sphincter of Oddi?

Morphine causes contraction of the sphincter of Oddi.
This temporarily obstructs bile flow into the duodenum, redirecting bile into the gallbladder if the cystic duct is patent.

Why does sphincter of Oddi contraction improve HIDA imaging?

Constriction of the sphincter of Oddi increases pressure within the biliary tree, encouraging radiotracer-containing bile to enter and fill the gallbladder.
This improves visualisation of the gallbladder during imaging.

When is morphine administered during hepatobiliary imaging?

Morphine is administered when the gallbladder has not visualised after an appropriate period of imaging, despite tracer being present within the biliary tree.
It assists in differentiating acute cholecystitis from delayed gallbladder filling.

What does gallbladder visualisation after morphine administration indicate?

If the gallbladder becomes visible after morphine administration, it suggests that:
The cystic duct is patent.
Acute cystic duct obstruction is unlikely.

What does failure of gallbladder visualisation after morphine administration suggest?

Failure of the gallbladder to fill following morphine administration suggests:
Cystic duct obstruction
Acute cholecystitis
This finding supports the diagnosis when interpreted alongside the clinical presentation.

How is morphine administered during hepatobiliary scintigraphy?

Morphine is administered by slow intravenous injection according to established departmental protocols to minimise adverse effects while achieving the desired biliary response.

What is the onset of action of intravenous morphine?

Following IV administration, morphine has a rapid onset of action, making it suitable for pharmacological intervention during hepatobiliary imaging.

How is morphine metabolised?

Morphine is metabolised primarily in the liver by glucuronidation, producing metabolites including:
Morphine-3-glucuronide (M3G)
Morphine-6-glucuronide (M6G)

How is morphine eliminated from the body?

Morphine and its metabolites are eliminated predominantly by the kidneys.
Renal impairment may prolong its effects because metabolite clearance is reduced.

What are the common adverse effects of morphine?

Common adverse effects include:
• Sedation
• Respiratory depression
• Nausea
• Vomiting
Constipation
Hypotension
Bradycardia

What is the most serious adverse effect of morphine?

The most significant adverse effect is respiratory depression.
Patients should be monitored closely after administration, particularly those receiving IV morphine or those with underlying respiratory disease.

Why should patients be monitored after morphine administration?

Patients should be monitored for:
• Respiratory rate
• Level of consciousness
• Blood pressure
• Heart rate
• Oxygen saturation
• Adverse opioid effects
Prompt recognition of respiratory depression or excessive sedation is essential for patient safety.

What are the contraindications to morphine administration?

Morphine should be avoided or used with extreme caution in patients with:
• Respiratory depression
Acute severe asthma
Hypersensitivity to opioids
Significant respiratory compromise
These conditions increase the risk of serious adverse effects.

Why should morphine be used cautiously in patients with renal impairment?

Morphine metabolites are primarily excreted by the kidneys.
In renal impairment:
Metabolites accumulate.
Opioid effects may be prolonged.
The risk of sedation and respiratory depression increases.

Why should morphine be used cautiously in elderly patients?

Older patients are generally more sensitive to opioids and have an increased risk of:
• Respiratory depression
Excessive sedation
Hypotension
Falls
Dose adjustment and careful monitoring may be required.

What observations should be performed after morphine administration?

Patients should be assessed for:
• Respiratory rate
• Oxygen saturation
• Blood pressure
• Heart rate
Conscious state
Pain relief
Adverse reactions
Monitoring should continue until the patient is clinically stable.

What opioid antagonist reverses the effects of morphine?

Naloxone is a competitive opioid antagonist that rapidly reverses:
• Respiratory depression
• Sedation
Other opioid effects
It is used in opioid overdose or significant opioid-induced respiratory depression.
Phenobarbital

What is phenobarbital?

Phenobarbital is a long-acting barbiturate with:
• Anticonvulsant
Sedative
• Enzyme-inducing properties
It also has important applications in hepatobiliary nuclear medicine.

What is the mechanism of action of phenobarbital?

Phenobarbital enhances the activity of gamma-aminobutyric acid (GABA) at the GABA_A receptor, producing central nervous system depression.

Why is phenobarbital used before hepatobiliary scintigraphy?

Phenobarbital is administered before hepatobiliary imaging to:
• Stimulate bile flow.
• Improve biliary excretion.
• Increase diagnostic accuracy in neonatal jaundice investigations.

Which condition is phenobarbital commonly used to investigate in nuclear medicine?

Phenobarbital is commonly used when investigating neonatal jaundice, particularly to help differentiate:
• Biliary atresia
• Neonatal hepatitis

How does phenobarbital improve hepatobiliary imaging?

Phenobarbital induces hepatic enzymes and increases bile production and secretion.
This enhances radiotracer excretion into the biliary system, improving interpretation of hepatobiliary scans.

How long is phenobarbital usually administered before a hepatobiliary scan?

Phenobarbital is generally administered for several days before imaging to allow adequate hepatic enzyme induction before the hepatobiliary examination.

What result is expected after phenobarbital pretreatment in neonatal hepatitis?

In neonatal hepatitis, phenobarbital pretreatment often improves bile flow, allowing radiotracer to enter the bowel during hepatobiliary imaging.

What result is expected after phenobarbital pretreatment in biliary atresia?

In biliary atresia, radiotracer still fails to enter the bowel despite phenobarbital pretreatment because the extrahepatic biliary ducts are absent or obstructed.

What are the common adverse effects of phenobarbital?

Common adverse effects include:
• Drowsiness
• Sedation
• Dizziness
• Ataxia
• Behavioural changes (particularly in children)

Why should patients receiving phenobarbital be monitored?

Patients should be monitored for:
Excessive sedation
• Respiratory depression (particularly at higher doses)
Neurological changes
Adverse drug reactions
Careful monitoring helps ensure safe medication administration and early recognition of complications.

Besides being a sedative, what other major pharmacological action does phenobarbital have?

Phenobarbital also acts as an anticonvulsant by enhancing inhibitory neurotransmission through the GABA_A receptor.

How does phenobarbital interact with the GABA_A receptor?

Phenobarbital acts as a positive modulator (agonist) of the GABA_A receptor, increasing inhibitory neurotransmission within the central nervous system.

Why is phenobarbital described as a long-acting barbiturate?

Phenobarbital has a long duration of action, allowing prolonged anticonvulsant and sedative effects compared with many other barbiturates. This prolonged action is also useful for enzyme induction before hepatobiliary imaging.

Why isn't phenobarbital administered immediately before a hepatobiliary scan?

Phenobarbital requires time to induce hepatic enzymes, so it must be administered days before imaging rather than immediately beforehand.

How does enzyme induction by phenobarbital improve hepatobiliary imaging?

Enzyme induction enhances:
• Hepatic uptake of the radiopharmaceutical.
• Bile production.
• Biliary excretion.
This improves interpretation of hepatobiliary scintigraphy in neonates with jaundice.

Why is hepatobiliary scintigraphy performed after phenobarbital pretreatment in infants with prolonged jaundice?

The scan assesses whether bile can pass from the liver into the bowel after maximal stimulation of hepatic function, helping distinguish biliary atresia from neonatal hepatitis.

What imaging finding suggests neonatal hepatitis after phenobarbital pretreatment?

Visualization of radiotracer within the bowel following phenobarbital pretreatment suggests that bile flow is present, making neonatal hepatitis more likely than biliary atresia.

What imaging finding suggests biliary atresia after phenobarbital pretreatment?

Persistent absence of bowel activity despite adequate phenobarbital pretreatment suggests biliary atresia, indicating failure of bile to reach the intestine.

Why is early diagnosis of biliary atresia important?

Early diagnosis allows timely surgical management, improving the likelihood of preserving liver function and reducing long-term complications. This is why accurate hepatobiliary imaging is clinically important.

What central nervous system effects commonly occur with phenobarbital?

Common CNS effects include:
• Sedation
• Drowsiness
• Dizziness
Reduced alertness
These effects result from depression of central nervous system activity.

Why should excessive sedation be monitored after phenobarbital administration?

Excessive sedation may impair:
• Consciousness
• Airway protection
• Respiratory function
Patients should therefore be monitored following administration.

Which biliary medications are covered in this lecture?

The lecture focuses on three principal medications used in hepatobiliary imaging:
Sincalide
Morphine
Phenobarbital
Each has a different pharmacological role in improving the diagnostic accuracy of hepatobiliary scintigraphy.

What is the primary role of sincalide in hepatobiliary imaging?

Sincalide is used to stimulate gallbladder contraction and measure gallbladder ejection fraction, allowing assessment of gallbladder function.

What is the primary role of morphine in hepatobiliary imaging?

Morphine is used to contract the sphincter of Oddi, increasing biliary pressure and promoting gallbladder filling to help diagnose acute cholecystitis.

What is the primary role of phenobarbital in hepatobiliary imaging?

Phenobarbital is administered before imaging to enhance hepatic function and bile excretion, helping differentiate biliary atresia from neonatal hepatitis during hepatobiliary scintigraphy.

How does phenobarbital increase bile excretion?

Phenobarbital induces hepatic microsomal enzymes, increasing hepatocyte activity and enhancing the excretion of substances into bile.
This results in increased bile elimination, which improves hepatobiliary imaging.

What are hepatic microsomal enzymes?

Hepatic microsomal enzymes are drug-metabolising enzymes within hepatocytes.
Phenobarbital stimulates these enzymes, increasing hepatic metabolism and biliary excretion of substances. (This was emphasised by the lecturer in the transcript.)

Why are hepatic microsomal enzymes important in newborns with jaundice?

In some newborns, hepatic microsomal enzymes are not yet fully active.
As a result:
Bilirubin is cleared less efficiently.
Jaundice may occur despite a structurally normal biliary system.
Phenobarbital can stimulate enzyme activity before hepatobiliary imaging. (Transcript explanation.)

Why is phenobarbital given before imaging a jaundiced neonate?

Phenobarbital is administered to determine whether poor biliary excretion is due to:
Immature hepatic enzyme activity, or
• Biliary atresia.
Improved tracer excretion after pretreatment suggests functioning hepatocytes rather than biliary atresia.

What is biliary atresia?

• Biliary atresia is a congenital condition in which the extrahepatic biliary system is absent or severely obstructed, preventing bile from reaching the bowel.
It differs from delayed maturation of hepatic function. (Expanded explanation from the transcript.)

How does hepatobiliary scintigraphy differentiate biliary atresia from immature hepatic function?

After phenobarbital pretreatment:
Tracer enters the bowel → functioning biliary system (immature hepatic function/neonatal hepatitis more likely).
No bowel activity → biliary atresia is more likely.
This is the key diagnostic purpose of phenobarbital pretreatment.

Besides hepatobiliary imaging, what is the most common modern clinical use of phenobarbital?

Although previously used widely as a sedative, phenobarbital is now most commonly used as an anticonvulsant to manage seizures. (This point was emphasised in the transcript.)

Why has phenobarbital become less common as a sedative?

Phenobarbital has largely been replaced by safer sedative medications, but it remains clinically useful because of its:
• Anticonvulsant properties.
Hepatic enzyme induction.
Role in hepatobiliary imaging.
(Expanded explanation from the transcript.)

How can phenobarbital affect the metabolism of other medications?

Because phenobarbital induces hepatic microsomal enzymes, it can increase the metabolism of many drugs.
This may:
Reduce their plasma concentration.
Shorten their duration of action.
Alter therapeutic effectiveness.
(Emphasised in the transcript.)

Why are drug interactions common with phenobarbital?

Phenobarbital induces hepatic drug-metabolising enzymes.
As a result, many medications are metabolised more rapidly, making drug interactions an important clinical consideration. (Transcript explanation.)

Why is understanding biliary elimination important in Medical Radiation Sciences?

Many substances administered in MRS—including:
• Radiopharmaceuticals
• Contrast media
• Some medications
are eliminated through the hepatobiliary system.
Understanding biliary pharmacology helps predict imaging findings and drug behaviour. (Expanded from the transcript.)

What is the overall role of sincalide in hepatobiliary scintigraphy?

Sincalide is used to evaluate gallbladder function by stimulating physiological gallbladder contraction and allowing measurement of the gallbladder ejection fraction (GBEF).

What is the overall role of morphine in hepatobiliary scintigraphy?

Morphine is used to increase biliary pressure by contracting the sphincter of Oddi, improving gallbladder filling and assisting in the diagnosis of acute cholecystitis.

What is the overall role of phenobarbital in hepatobiliary scintigraphy?

Phenobarbital is administered before imaging to:
• Stimulate hepatic microsomal enzymes.
Increase bile production and excretion.
Improve interpretation of neonatal hepatobiliary scans.
Help differentiate biliary atresia from delayed hepatic maturation.

What are the three major biliary medications and their primary imaging roles?

Medication	Primary role
Sincalide	Stimulates gallbladder contraction and measures GBEF
Morphine	Contracts the sphincter of Oddi to improve gallbladder filling
Phenobarbital	Induces hepatic enzymes to improve biliary excretion and neonatal hepatobiliary imaging