5. Drug formulation and design Flashcards
Pharmacodynamics meaning
The study of actions, effects and interactions of drugs in the body -(What does the drug do to the body).
Pharmaceutics meaning
The mode of administration.
Pharmacokinetics meaning
Concerned with absorption, distribution, metabolism, and excretion.
Bioavailability meaning
The rate and extent of drug absorption.
Biotransformation meaning
The rate and extent of drug metabolism or degradation.
2 routes of administrations of drugs to the eye?
Eye drops & Eye ointments
Eye drops vs Eye ointments which one is present in the eye for longer?
Eye ointment- will be present in conjunctival sack for longer.
Pharmacological effects, intensity, duration and rate of onset for different drugs depending on route of admission ?
The pharmacological effects are the
same regardless of the routes of
admission. But the rate of onset,
intensity and duration are very
dependent on the route of
administration.
3 factors considered when determining the route of admission of a drug?
- Required site of action
- Required duration of action
- Stability of drug
Release of drugs in terms of tablets vs injections?
Tablets have a slow and sustained release. Injections have a fast and rapid release.
The physical and chemical stability of a drug relates to?
Relates to the chemical and physical integrity of the drug shelf life.
When drugs enter the body, they are metabolized by?
Metabolism by the liver
When you remove eyedrops from a package, what is checked?
Expiration date, if dose name matches the packet.
Is time noted for drug installation?
Yes, time is noted
Avoid touching lids and lashes when putting eyedrops, why?
To avoid contamination
What happens immediately as eyedrops are put in?
Immediate loss on blinking, drug concentration decreases rapidly. Because drug mixes with tears.
Eyedrops are systemically absorbed by?
- Conjunctiva
- Punctae
Eyedrops are ocullarly absorbed by?
Cornea
How is drug/ eyedrop lost from the eye?
Loss through aqueous humour through normal drainage system.
Major site of eyedrop absorption?
Cornea
Absorption of eyedrops is a passive process, what does this mean?
It needs a concentration gradient where the steeper the gradient, faster the diffusion will be.
To cross the cornea effectively what 2 properties are required by the drug?
The drug needs to have a balance of hydrophilic (water soluble) and lipophilic (lipid soluble) properties.
Lipophilic drugs easily cross the epithelium because?
The phospholipid membrane is uncharged
Which structure is the limiting factor when drugs are crossing the cornea?
Epithelium
What charge is required for the drug to cross the following layers:
Epithelium
Stroma
Endothelium
Epithelium: Uncharged
Stroma: Charged
Endothelium: Uncharged
Molecules in drugs gain or loss a charge depending on?
Depending on which barrier it is crossing
Molecules in drugs gain or loss a charge depending on?
Depending on which barrier it is crossing
Is fluorescein highly charged compared to tear film?
Yes- hence it does not enter the cornea unless corneal epithelium is damaged.
Why is fluorescein not absorbed by healthy stroma?
Because of its charge
The ratio of uncharged to charge in drugs depends on (eyedrop delivery)?
- The pH of tear-eyedrop mixture after instillation.
- The pKa (dissociation constant) of the drug.
pKa meaning?
Dissociation constant.
This is the pH at which the concentrations of the charged and
uncharged forms are equal.
It is an unchanging property of a drug
pKa is a measure of?
Measure of the strength of an acid in a solution
*Stronger the acid, lower the pKa value is
Can pKa of a drug be changed?
pKa Of a drug can’t be changed but the pH of the eye drop formulation can be changed, within limits.
Optometric drugs are bases or acids?
Weak bases with pKa greater than 8
Natural pH of the tear film?
7.4
Endothelium is a single layer of what type of cells?
Squamous cells
Factors affecting eyedrops bioavailability?
- Drug formulation and design- drug ingredients.
- Corneal integrity- greater the corneal damage, more the drug is absorbed.
- Tropical anesthetic administration
- Iris pigment
- Patient specific factors- age, genetic background etc
Eyedrops are absorbed along which 2 surafces?
Cornea and conjunctival surfaces
Onset of Intravenous injections and 2 associated risks?
Rapid onset
Risks: Irreversibility and potential for risk
3 disadvantages of oral admission of drugs?
- Absorption rate is variable.
- Drug can be inactivated by digestive enzymes and acids.
- Requires patient cooperation.
Pressure on the inner canthus is applied after drops installment why?
to reduce escape of drug through lacrimal system
When instilling drops px is asked to blink only when?
Gently only when they feel the drop
Drug absorption in dark iris vs light iris?
Drugs less effective in darker pigmented iris
Tropically applied eyedrops process of absorption?
Trans- corneal diffusion
Describe the absorption of fluorescein in the eyes due to damaged corneal epithelium?
Superficial damage to cornea: staining is seen due to fluorescein pulling. With deep and more serious corneal damages, diffusion of the fluorescein is seen into the layers of the stroma.
pKa is determined by Henderson- Hasselbalch equation, what is it?
pH= pKa+ {log[concentration of uncharged drug] / [concentration of charged drug] }
In Trans- corneal depletion, the ratio of charged: uncharged is maintained by?
This depletion of the uncharged form in the tear film causes more of the charged molecules to lose their charge, so as to maintain the same ratio of charged :
uncharged.
After crossing the epithelium, some of the drug will become charged (again maintaining the charged :uncharged ratio). The charged form will be able to
cross the corneal stroma.
Once a drug passes through endothelium, it next moves to?
Drug passes into aqueous humour before it is taken up by various ocular muscles like the iris.
True or false: drugs are absorbed better in a cornea that is damaged?
True
What is drug formulation?
Balance of components or eye drop ingredients- related to the combination of chemicals when they are mixed. It should be designed to give stability and cause minimal irritation.
4 factors that affect drug formulation?
- pH: determines ratio of charged to uncharged in a drug.
- Tonicity: stings outside range 0.5-2% NaCl.
- Oxidation
- Sterility
What factors in drug formulation affect stability and ratio of charged to uncharged?
pH
4 ways to enhance drug delivery?
- Multiple drops - wait 5 minutes
- Prior use of local anesthetics
- Ointments- however, gives blurry vision
- Slow delivery inserts
What do local anaesthtics due when put prior to eye drops?
Cause a mild punctate keratitis- that speeds up drug absorption
3 ADRs (Adverse drug reactions)
Toxicity - liver and kidney at risk
Hypersensitivity
Allergy
5 individuals with high risk to ADRs
- Pregnant women
- Breastfeeding women
- Elderly people
- Children
- Patients with underlying illness
Immediate instruction given to Px after eyedrops are put in the eyes?
With a tissue Px should occlude the lower punctate by applying gentle pressure.
Relationship between eye drop effectiveness and iris colour?
Drugs bind with pigments in the eye hence less effective in darker coloured iris. Hence, a higher concentration is used in PX’s with darker iris.
Process of eyedrops absorption is known as?
Trans-corneal diffusion
