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PH3704- Pharmaceutical technology > Radiopharmaceutics (4) > Flashcards

Radiopharmaceutics (4) Flashcards

1
Q

Why isn’t it as straightforward as paracetamol

A
  • Most radiopharmaceuticals do not have a pharmacological effect
  • chemically small quantities- difficult to study, little in-vitro testing
  • Relies on reporting- numbers small
    • Lots of evidence anecdotal
    • Difficult to establish cause and effect
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2
Q

Some interactions are useful

A
  • Diuretics
  • Vasodilators
  • Expected interactions are not a problem
  • BUT- What about the unexpected
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3
Q

Types of interaction

A
  • Classified by C.Sampson
    • Patient medication as a possible cause of unexpected biodistribution of radiopharmaceutcial; a regional survey
    • Drugs and chemicals which affect the purity, biodistribution and PK of radiopharmaceuticals
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4
Q

Categories

A
  1. Unusual handling of the radiopharmaceutical as a result pharmacological effect
  2. In-vivo physicochemical interaction between radiopharmaceutical and patients medication
  3. Drug-induced disease affecting the transport of radiopharmaceuticals
  4. Drugs which interfere with the radiolabelling of white cells
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5
Q

1) Unusual handling of the radiopharmaceutical as a result of pharmacological effect

Definition

A
  • A pharmacological interaction occurs when the intended effect of a drug at it’s usual dose alters the biodistribution of the radiopharmaceutical
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6
Q

Direct pharmaceutical effect

A
  • The pharmacological effect of a drug causes the organ to function differently
  • Largest group-most reports
  • Effect predicted and expected from the mode of action of the drug i.e. class effect
    • These have usually been previously reported
  • Effect unexpected- not class related ‘Drug effect’
  • It is important to determine if drug effects are drug specific or class specific
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7
Q

Example 1: Hepatobiliary studies

A
  • Hepatobiliary function is investigated using 99mTc labelled compounds of imnodiacetic acid (IDA) e.g. mebrofenin
  • This is cleared from the circulation by the hepatic cells and secreted like bilirubin into the bile carrier mechanism
  • Various conditions may delay movement of the radiopharmaceutical through the hepatobiliary system resulting in delayed gallbladder visualisation- prolonged tasting, TPN, Viscous bile
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8
Q

Drugs which interact with hepatobiliary imaging agents

A
  • Opioid analgesic- cause constriction of the sphincter of Oddi increasing pressure in the common bile duct; could increase transit time of RP (radiopharmaceutical)
    • Class specific
  • Enzyme inducer- Phenobarbitone enhance and accelerate biliary excretion of RP increasing accurate differentiation between extrahepatic biliary atresia and neonatal hepatitis
    • Class specific
  • Anaesthetic -Halothane showed to cause a marked decrease in hepatic blood flow, reduced uptake of RP in liver
    • Drug-specific
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9
Q

Example 2: Effect of cytotoxic drugs

A
  • Cytotoxic drugs + 99m-Tc PYP (Blood pool imaging)
  • Intense renal uptake was reported (Lutrin et al 1978)
  • Suggested that it was due to altered renal tubular function or reduced GFR
    • Class specific
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10
Q

Example 3: Thyroid imaging

A
  • Any drug which interferes with the uptake of iodine, or blocks it’s release from the thyroid can interfere with the uptake of tracer and lead to misdiagnosis
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11
Q

Drugs which can affect thyroid imaging with 123-I

A
  • Thyroxine
  • Amiodarone
  • Iodine containing contrast media
  • Vitamin preparations
  • Anti-histamines
  • Steroids
  • Seafood containging high levels of iodine
  • Iodine based cough medicine
  • Hair dye
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12
Q

Drugs which can affect thyroid therapy with 131-I or imaging with 123-I

A
  • Hyperthyroidism: Carbimazole and Propylthiouracil interfere with the organification of iodine so would prevent the therapeutic effect of radioiodine
  • Withdraw 1 week before therapy
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13
Q

Drugs which can affect thyroid imaging with 123-I

A
  • Hypothyroidism
    • Biological t1/2 of thyroxine (T4)-7 days- ideally 1 month due to residual
    • Biological t1/2 of liothyronine (T3) 2 days
  • Therefore stop T4 28 days before test, use T3 for 14 days then stop 14 days
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14
Q

Example 4: Heart investigations with 99m-Tc- Tetrofosmin/Adenosine

A
  • The following drugs could lead to false negative results
    • Beta-blockers may blunt the response to exercise-induced stress- should be stopped for 5 half-lives 24-48hrs
    • Calcium channel blockers- Diltiazem and verapamil
    • Dipyridamole- blocks uptake of Adenosine- we use adenosine due to its small half-life- any side effects will not last very long
    • Patients also instructed to abstain from caffeine for 12 hours tea, coffee and soft drinks such as cola, energy drinks (blocks Adenosine receptor)
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15
Q

Example 5: drugs which affect the monoamine transporter uptake mechanism

There are several different Monoamine transporters

A
  1. The Norepinephrine transport NET
  2. The Dopamine transporter DAT
  3. The serotonin transporter SERT
  • A mixture of drug and class-specific interaction
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16
Q

nerve synapse

A

*

17
Q

Example: MIBG (metoiodo-benzyl-guanidine)

Norepinephrine transporter NET

A
  • mIBG is meta-iodobenzylguanidine
  • Catecolamine analogue- attaches to receptors in body
  • May interact with anything which affects receptor- e.g. Beta-blockers and agonists, reserpine, some antidepressents
  • Used for tumours of adrenal medulla
18
Q

5 mechanisms of interaction

A
  1. Inhibition of sodium-dependent uptake system- The NET transporter e.g. TCA’s, cocaine, labetalol
  2. Inhibition of uptake by active transport into vesicles- i.e. inhibition of granular uptake within the terminal e.g. reserpine
  3. Competition for transport into vesicles e.g. serotonin
  4. Depletion of content from storage vesicles
    • e.g. labetalol, reserpine
  5. Calcium channel-mediated inhibition
    • Calcium channel blockers
19
Q

Other possible unknown mechanism

A
  • Effect of dose: phenoxybenzamine at high dose may reduce or prevent MIBG uptake
  • This does not happen at normal doses
20
Q

Post-synaptic neurone

A
21
Q

Prior to MIBG

A
  • Radiopharmacist prepares a list of interacting drugs, updated regularly
    • Resperpine (no longer used in UK)
    • TCA
    • Sympathomimetics
    • Neuroleptics
    • Labetalol
    • IV-Phenoxybenzamine
    • Calcium channel blockers
    • Amiodarone- difficulty of long t1/2
22
Q

123-I Ioflupane (DaTSCAN)

The Dopamine Transporter DAT

A
  • Ioflupane is a cocaine analogue
  • Drug which bind to the dopamine transporter with high affinity can affect studies
  • Dopamine agonist/antagonists acting on post synatpic recpeotrs do not interfere
23
Q

Drugs which should be stopped prior to DaTSCAN

A
  • Radiopharmacist prepares a list of interacting drugs
  • CNS stimulants- dexamfetamine, methylphenidate and modafinil
    • Anti-depressant- Amoxapine
    • Anxiolytic- Buspirone
    • Amfebutamone (Bupropion)
    • Sibutramine
    • Pimozide
    • Benzatropine
    • SSRI- very weak DAT inhibitor
    • Cocaine
24
Q

Stopping medication prior to mIBG and DaTSCAN: process

A
  • Medication history took when arranging mIBG or DaTSCAN
  • Stop interacting drugs for 5 biological half-lives
  • Clinicians must be consulted- particularly important for antihypertensive and neuroleptics
25
Q

2) In-vivo physicochemical interaction between radiopharmaceutical and patients medication

A
  • These are as a result of a genuine reaction between a drug and radiopharmaceutical
  • Little is known about the mechanism of action of these interactions at the molecular level- possibly the formation of local complexes alters biodistribution
26
Q

IM Iron Dextran and MDP

A
  • MDP is chelated, producing an insoluble complex
  • Instead of localising throughout the skeleton activity is observed in the gluteal region at site of iron injection
  • Thought that local complexation reaction between reduced Tc and ferric hydroxide occurs
27
Q

Bisphosphonates and MDP

A
  • Bisphosphonates used for Paget’s cause reduced skeletal uptake of TC diphosphonates
  • Tc can form preferential complexes with circulating Bisphosphonates, and so the amount taken up into the skeleton is reduced
28
Q

Aluminium and colloids

A
  • Aluminium- containing drugs (e.g. antacids) colloidal radiopharmaceuticals preparations
  • Aluminium causes colloid particles to flocculate together
  • Distribution of the colloid can effect radiopharmaceuticals
29
Q

3) Drug-induced disease affecting the transport of radiopharmaceuticals

A
  • This occurs when an extension of the expected pharmacological effect or an adverse reaction to a drug alters the biodistribution of the RP
  • Many drugs can cause or aggravate disease iatrogenic disease
  • Example- 1
    • Drug-induced liver damage could cause altered liver uptake of radiopharmaceuticals
30
Q

Hepatotoxic drugs

A
  • Paracetamol, aspirin, tetracycline- reduce liver uptake
  • TPN theapy- cause fatty liver disease
  • Erythromycin- false +ve scan with T-BIDA
  • MTX- diffuse accumulation of MDP in liver
31
Q

Example-2

A
  • Drug-induced renal toxicity will affect behaviour of renal imaging agnets or of agents which are renally excreted
  • Nephrotoxic drugs
    • Many drugs can cause nephrotoxicity and decrease in GFR
      • Aminoglycosides, penicillins, cytotoxics, amphotericin, cyclosporin
    • Conversely diuretics e.g. furosemide can improve renal function
32
Q

Example 3: Pulmonary toxicity

A
  • The most common drug is bleomycin which can cause pulmonary interstitial fibrosis- this can cause high lung uptake of 67-Gallium citrate
  • Other drugs which may cause abnormal lung uptake- amiodarone, busulphan and nitrofurantoin
33
Q

Other factors which may cause unusual handling of RP

A
  • Radiation therapy
  • Diet
  • Degree of hydration- renal studies
  • Caffeine intake
  • Fasting status- affects absorption and motility in the gut
  • Alcohol
34
Q

4) Drugs which interfere with the radiolabelling of white cells

A
  • Many factors can influence the radiolabelling of blood cells- e.g. white cell count, volume, temperature
  • Increasingly there is evidence to suggest that drug treatment may also interfere
35
Q

Example

A
  • Chemotaxis of leucocytes may be affected by
    • Anti-biotics
    • Corticosteroids
  • In study 7 out of 15 patients reported to have unusually low labelling efficiencies were on corticosteroids
36
Q

Drugs which interfere with leucocyte labelling

A
37
Q

Conclusion

A
  • Patient drug therapy can interfere with radiopharmaceutical uptake and distribution
  • Much of the evidence is anecdotal and the mechanisms unclear
  • Knowing the important and likely interactions can help prevent repeat radiation doses, and in some events, incorrect diagnosis

PH3704- Pharmaceutical technology (22 decks)

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