Lecture 7 part 2: pharmaceutical aspects of CVD2 Flashcards by Nancy Hu

What are nasogastric tubes? (3 points)

Tubes which run from the outside of the body into the nose, down the oesophagus and to the stomach.
they are 24-36 inches in length
used to administer nutrients, liquids and drugs for a patient unable to swallow (e.g. after a stroke)
made from polyvinyl chloride with plasticizers (e.g. DEHP) to make it more flexible

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What are some examples of medications a post-infarct stroke patient expected to be on? (3 points)

statins
hypoglycaemic agents
anticoagulants

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What questions must be considered regarding medication for stroke patients? (3 points)

can drugs be crushed
can drugs be administered with food
can drugs be administered with liquids

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Why is there a need for off-license use of medications in stroke patients? (1 point)

-there are no commercially available liquid medications formulated for tube administration.

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What are the considerations of giving warfarin via a NG tube? (2 points)

warfarin may bind to food proteins, therefore may require to withold food
Warfrin bindsto plastics and there is an increased binding at lower pH

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Is warfarin better administered with food? (3 points)

Yes it is better to administer warfarin with the food.
Although the onset will be later, after a certain period of time it will be absorbed
If you just give it as an oral suspension it will bind to the surface of the tube and not be absorbed

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What difficulties arise from administering CR tablets via a NG tube? (3 points)

Tablets going through a NG tube will need to be crushed
Crushing a CR tablet bascially destroys the actual property of the formulation thus will release the drug in an extremely high concentration
Some polymers may swell in the water and block the NG tube

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What happens if you cannot find a conventional release formulation of a medicine to administer via a NG tube? (2 points)

re calculate the dose if a CR tablet has to be crushed

- be aware that the patient will experience all the side effects

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What are the two salts metoprolol is available as in NZ?

tartate

- succinate

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How is CR achieved in beataloc? (3 points)

the active ingredient is incorporated in coated beads in a disintegrating tablet
the tablet rapidly disintegrates and hundreds of beads are dispersed in GI fluid
The active compound is released over 20 hours (depends on GI transit times)

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How is CR achieved in metoprolol CR?

-contains polymer coated beads of metoprolol

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can metoprolol succinate beads be crushed?

-no but they can be divided

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What are the brands of metoprolol succinate ?

betaloc CR and metoprolol AFT CR

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What are the brands of metoprolol tartrate?

Lopresor (immediate release)

Slow-Lopresor

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Can you crush lopressor?

yes

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What will you suggest for a patient requiring metoprolol who was stable on betaloc CR 95mg od but now has a NG tube placed due to swallowing difficulties? (2 points)

beataloc is a metoprolol succinate form of the drug

- lopressor (metoprolol tartrate) 50mg can be given bd as these can be crushed.

What is digoxin? (7 points)

Drug with a very narrow therapeutic range (1-2ug/mL)
highly potent drug which needs to be customised to individual
Widely distributed in the body and excreted renally
available as tablets and elixirs
extensively tissue bound
terminal half life ~30-40 hours, extended with renal impairment
Loading dose required, maintenance dose based on elimination rates.

What individual functions is digoxin dosing based on? (3 points)

age
lean body weight
renal function

How does the bioavailability of digoxin elixir compare to the tablet? (2 points)

tablet = 63%

- elixir = 75%

What makes plasticizers in the NG tube interact with substances administered by it? (4 points)

NG tube is made from polycinylchloride combined with 2-di-ethyl-hexyl-pthalate to make it more flexible
the extent of DEHP relase from the PVC is a functional of lipophilicity
foods with high lipid content may cause the DEHP to leak out and interact with drug
Normally it leaks out in trace amounts, but if you are using lipids a lot it might solubilise the plasticizer

What is the relationship between digoxin and food?

-food slows the rate of absorption of digoxin, but does not affect the total amount of digoxin absorbed

What are symptoms of digoxin toxicity? (4 points)

nausea & vomiting
loss of appetite
confusion
blurred vision

How is digoxin monitored?

-blood levels are taken >6 hours after the last dose

What is a heparin? (3 points)

highly sulfated glycosaminoglycan
has the highest negative charge density of any known biological molecule
cannot cross intestinal epithelium

Why can't heparin cross the intestinal epithelium? (3 points)

- passive diffusion across the intestinal epithelium is restricted to small lipophilic molecules - there is an ionic repulsion between heparin and biological membranes as both are negatively charged - both UH and LMWH must be administered parenterally

What is an example of unfractionated heparin? (6 points)

- multiparin (heparin sodium 5,000 IU/mL) available as solution for injection or solution concentrate for infusion - MW ~15kDa - requires loading dose followed by continuous infusion - anticoagulant response is unpredictable (APTT monitoring required) - metabolised in liver, inactive metabolites are excreted renally - incompatible with many injectables

how is UH given with? (4 points)

- continuous IV infusion in 5% glucose or 0.9%NaCl - intermittent IV injection - SC injection - due to its short half life, infusion or SC injection is preferred over intermittent IV injection

What is the difference between UF and LMWH? (3 points)

- UH means that it contains variable chain length and molecular weight - The anticoagulant effect depends on molecular weight and size, therefore the PK ad effect is not as predictable for heparin - LMWH are fractionated therefore contains known molecular sizes/weights, therefore the PK and effects are more predictable

What is LMWH- enoxaparin? (8 points)

- equally as effective as UH - more convenient to use with od or bd SC dosing - more favourable side effects - predictable response - low interpatient variation - half life = 4 hour (single dose) or 7-12hours (after repeated dosing) - available in prefilled syringes, prefilled graduate syringes and ampoules - renally excreted

What are the advantages of a predictable response with LMWH? (3 points)

- allows for fixed-weight adjustment of SC dose - most patients don't require lab monitoring - out patient treatment is possible

What are the advantages of SC administration of LMWH? (2 points)

- bioavailability more or less 100% | - unlike UH, there is linear absorption with LMWH

Why are the different LMWH products not bioequivalent? (2 points)

- differences in MW | - differences in specific anti-Xa activities

When should the LMWH dose be reduced? (2 points)

- if the patient's CrCl<30mL/min | - could also change to UH

What is SNAC? (4 points)

sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) - small carrier molecule (200-400Da) which enables heparin to be absorbed from the GIT - weak non-covalent interaction between SNAC and heparin - hydrophobic moieties of SNAC drug carrier complex is created with increased lipophilicity which enhances epithelial membrane permeability - drug/carrier interaction is reversible and dissociation occurs in the blood due to dilution effects

What are the pharmacokinetics of amiodarone oral tablets? (4 points)

- oral bioavailability 22-86% incompletely and eratically absorbed with extensive intersubject variation - Half life ~25 days (14-110 days) - aim for lowest effective concentrations due to unpredictability - extensively distributed into tissues including adipose tissue

What are the loading and maintenace doses for amiodarone oral tablets? (2 points)

- loading dose 200mg tds for 1 week followed by 200mg bd for 1 week - maintenance dose: 200mg or less, od

What are the PK of amiodarone IV injections? (7 points)

- 150mg available in each 3mL ampoule - given as 5mg/kg infusion over 20min-2 hour - administered in 250mL of 5% glucose - incompatible with saline - do not mix with other preparations - interacts with PVC infusion bags, administration sets and interacts with plasticizers - may reduce drop size

How does amiodarone interact the PVC infusion bags, administration sets etc? (3 points)

- absorbs onto PVC infusion bags and administration sets - thought to be due to plasticizers - Amiodarone containing solutions may cause plasticizer DEHP to leach out of plastics

What can be done to reduce amiodarone interactions with the administration equipment? (3 points)

- prepare infusion immediately prior to use - use glass or rigid PVC bottles - use non-DEHP containing equipment