IC10 Pharm Tech II Flashcards
What class of drug is midazolam (Brand name: nayzilam) ?
Benzodiazepine
What is the MOA of nayzilam/midazolam?
(Think of the MOA of benzodiazepines)
Increase GABA activity
What is midazolam used for?
A nasal spray medicine used for the short-term treatment of seizure clusters
The dosing regimen of midazolam is:
a. 1 dose/spray w onset of symptoms
b. Extra dose if symptoms persist after 10 mins
c. No more than 2 doses per episode
d. Max dose:
- No more than once every 3 days
- No more than 5 times per month
Why do we limit dosing so strictly with the use of midazolam?
There can be a build-up of tolerance. This can result in a greater dose needed to achieve the same level efficacy.
What are the 5 criteria in the Lipinski’s rule?
MW: <500Da
LogP: <5
H bond donors: ≤ 5
H bond acceptors: ≤ 10
Unionised
How do delivery systems help drugs in intranasal delivery?
- Make drugs physically manageable
- Improve solubility
- Improve absorption
- Protect drug from degradation & excretion
- Improve drug retention
- Reduce side effects (through targeting)
- Increasing dosing
- Reduce frequency of administration
Paracellular transport:
a. Are 10 micron particles likely or unlike to undergo paracellular transport?
b. Is paracellular transport a passive or active process?
Paracellular transport:
- Is unlikely for 10 micron particles
- Is a passive process
What are the 5 types of parenteral delivery?
- Intramuscular
- Subcutaneous
- Intravenous
- Intradermal
- Intrathecal
What are the angles to administer for all 5 parenteral delivery methods?
- Intramuscular
- Subcutaneous
- Intravenous
- Intradermal
- Intrathecal
- Intramuscular - 90°
- Subcutaneous - 45°
- Intravenous - 25°
- Intradermal - 10-15°
- Intrathecal - 5-15°
Which parenteral delivery method is used to administer drug to the brain?
The intrathecal method.
Intrathecal delivers the drug into the cerebrospinal fluid, which then directly flows into the brain.
What is the composition of the cerebrospinal fluid?
99% - water
1% - protein, ions, neurotransmitters & glucose
What is the total volume of cerebrospinal fluid & how much is produced per day?
Total volume: 150mL
Vol produced per day: 430-530mL
What are the 2 main benefits of using intrathecal as the your parenteral delivery method?
Intrathecal delivery is able to bypass the blood brain barrier whereas other parenteral delivery method is not able to.
Intrathecal has a smaller volume of distribution - 150mL CSF fluid
Other parenteral delivery method has to distribute across the entire body.
What are the 5 main advantages of parenteral delivery over other methods of delivery (e.g oral)?
- Bypass hepatic 1st pass metabolism
- Ability to control dosage
- Direct access to the brain - intrathecal
- Sustained release - e.g. IM depots
- Ideal for non-compliant, unconscious or dysphagic patients.
What is the percentage of small molecules blocked by the blood brain barrier?
98% of small drug molecules are blocked by the blood brain barrier.
This is due to the BBB’s tight junctions and transcellular transport.
Transcellular transport - contains efflux transporters, carrier mediated transporters, receptor-mediated transporters
The blood brain barrier has 3 types of efflux transporters.
List out the 3 efflux transporters.
- P-glycoprotein (P-gp)
- Breast cancer resistance protein (BCRP)
- Multi-drug resistance proteins (MRP)
These efflux transporters prevent drug from entering the brain.
We learnt the Lipinski’s rule for intranasal delivery.
However, the Lipinski’s rule has been modified for CNS intrathecal delivery.
List out the 5 criteria for the Modified Lipinski’s rule.
Molecular weight: <450 Da
H bond donors: <3
H bond acceptors: <7
LogP: 1-3
Unionised
What are 5 common excipients used in solutions for injections?
- Diluent
- Buffer salts
- Tonicity adjusters
- Preservatives - minimal for intrathecal
- Stabilisers/co-solvents
What is the ideal characteristics of parenteral delivery?
1. Recommended pH of drug formulation
2. Tonicity level
3. Particle size
Ideal pH of parenteral delivery is 7.4, but a wide range is tolerated.
IM - pH 3 to 11
SC - pH 3 to 6
Tonicity - 280 to 290 mOsm/L for large volume parenteral. We want to ensure that the drug delivered is isotonic.
Particle size - no visible particles
What are types of packing & storage for parenteral delivery?
- Glass ampoule - tiny glass bottles with score line for breakage
- Glass vial w rubber stopper
- Pre-filled syringes
If a parenteral formulation is not able to be isotonic, which is preferred, hypotonic or hypertonic?
Hypertonic is preferred.
Hypotonic can cause cells to rupture, permanently losing their function.
Hypertonic can cause cells to become flaccid, but the cells can regain their function when rehydrated.
