Pharmacology 2 Flashcards
define pharmokinetics
the movement of drugs into and around and out of the body e.g. what the drug does to the body
define pharmdynamics
how drugs work when they reach their site of action
'’what the drug does to the body’’
what are the pharmokinetic actions of drugs
Drugs may act on:
One of the components of the cell
One of the critical chemical pathways of the cell
Transport mechanisms allowing chemicals into and outside of cells
Chemical messaging systems between cells
DNA / RNA replication
what are examples of how cells communicate to each otther
neurotransmitters
e.g. noradrenaline
acetylcholine
gaba
dopamine
serotonin
what is the medicines receptor theory
lock and key’ mechanism of interaction of drug molecules with receptor sites:
Agonist (enhances action) at receptor site
Antagonist (diminishes action) at receptor site
Partial agonist (dampens down action) at receptor site
what is an agonist
Receptor + Drug molecule = enhanced action at receptor
B2 adrenoceptor + B2 agonist, eg.salbutamol
= enhancement of receptor action (maintenance of airway) = further dilates the airways
what is an antagonist
Receptor plus drug molecule = reduced action at receptor:
B1 adrenoceptor + B1blocker, eg. atenolol, propranolol
= vasodilation
= reduced blood pressure
Cholinergic receptor + anticholinergic (cholinergic receptor antagonist) eg. atropine
= dilation of pupil
Serotonin Receptor + SSRI – selective serotonin re-uptake inhibitor
= increases serotonin concentration outside of the receptor
= enhanced mood
what is a partial agoinst
Opiate Receptor + Partial agonist e.g. Buprenorphine
= moderate pain relief
= moderate opiate addiction potential
(synthetic opiate for pain and useful in substance misuse to withdraw from opiated)
what needs to be considered with eye formulations and eye drops
Absorbed through ?
Local or systemic?
How long are they in contact with the eye?
What is compliance like?
What are the risks of preservatives?
How can we avoid / minimise those risks?
how are eye drops absorbed
Principally absorbed through the cornea but absorption through conjunctival mucosa also occurs, giving rise to systemic effects.
High intraocular concentrations in the anterior segment of the eye are achieved if applied regularly.
Drops may be in solution (clear) or in suspension (cloudy).
There is a short drug-eye contact time so they tend to need a frequent application. [note preservative sensitivity]
Generally good compliance.
[Note UD- (unit dose) eye products are preservative free]
what are the advantages of eye ointments formulations
Allow a prolonged contact time; therefore, less frequent applications are required (good for night use). Blur vision.
Help lubrication so that concurrent lubricant use is not always necessary (unless there was previous intensive usage or there is a large abrasion).
Ophthalmic ointments, suspensions and aqueous gels improve bioavailability.
how can eye preparations be prepared differently
can reach the posterior segment of the eye
via intravitreeal injection
periocular injection
systemic adminstration and oral medications
how many drops are there in 1ml of conventional eye drops
Approximately 20 drops in 1mL of conventional eye drops
10mL ~ 200 drops.
(D1 QDS BE 224 drops / D1 QDS RE 112 drops)
(This is an important consideration when ensuring cost-effective issuing of eye preparations).
what needs to be differentiated when sing eye drops as pharmacological treatment vs diagnostically
Aim is to optimise treatment before overfilling the eye.
If more than one type of drop used as a pharmacological treatment, at least 5 minutes should be left between applications, otherwise risk that the second agent will wash out the first drop before it has had time to be fully absorbed.
Compare when preparations are used diagnostically. Pupil dilates immediately. [mydriatics effective if only a small part is absorbed into the eye preparing the eye for further administrations without the 5 min wait]. Only if the immediate dilation does not occur do you have to wait 5 mins before next product is applied.
BEWARE - PATIENTS MAY ASSUME THEY CAN DO THIS AT HOME WITH THEIR REGULAR EYE DROPS!
what types of drugs are orthoptists exempt from using
Local anaesthetics
Fluorescein
Antimicrobials
Lubricants
Mydriatics
Cycloplegics
what drugs have their localised site of action at the cornea
Local anaesthetics
Fluorescein
Antibiotics
Lubricants
what drugs have their localised sites of action in the iris
IRIS:
Mydriatics: (dilate pupil) - Antimuscarinics (cyclopentolate)
what drugs have their localised sites of action in the cillary muscle
CILIARY MUSCLE:
Cycloplegics: (paralyse muscle) - atropine, tropicamide, cyclopentolate
what increases the risk for potential of side effects
Systemic absorption = potential for side effects (drug molecule at the wrong site)
what are antimicrobials
SmPC:
“Fusidic acid eye drops are active against a wide range of gram-positive organisms, particularlyStaphylococcus aureus.
“The sustained release formulation of Fusidic acid eye drops ensures a prolonged contact with the conjunctival sac. Twice daily application provides sufficient fusidic acid concentrations in all relevant tissues of the eye. Fusidic acid penetrates well into the aqueous humour.”
NB Contains Benzalkonium chloride, [Preservatives can cause eye irritation or may discolour contact lenses. Soft contact lenses must not be worn during treatment]
name 2 examples of antimicrobials
chloramphenicol and fusidic acid
describe the pharmokinetics of fusidic acid
The sustained release formulation of Fusidic acid eye drops ensures a prolonged contact with the conjunctival sac. Twice daily application provides sufficient fusidic acid concentrations in all relevant tissues of the eye. Fusidic acid penetrates well into the aqueous humour.”
Absorption – local with good penetration into aqueous and vitreous humour
Distribution – N/A but trace amounts highly protein bound
Metabolism – N/A but trace amounts in liver
Elimination – N/A but trace amounts non-real (biliary)
describe the pharmacodynamics of fusidic acid
Active against a wide range of gram+ve organisms, particularlyStaphylococcus aureus.
Action as a ‘bacteriostat’ damaging the bacterial cell,
Bacterial protein synthesis inhibitor = bacteriostatic in action because it does not kill the invading bacteria (bacteriocidal), it inhibits bacterial protein synthesis by blocking peptide chain elongation.
bacterial cells stop dividing almost within 2 minutes after contact with the antibiotic in vitro, DNA and RNA synthesis continue for 45 mins / 1 to 2 hours respectively
what is a common visual effect of fusidic acid
vision becoming blurred (transient)
describe the pharmacokinetics of atropine
Absorption – Atropine is readily absorbed from the gastro-intestinal tract and mucous membranes; it is also absorbed from the eye.
Distribution – no data
Metabolism – It is incompletely metabolised in the liver
Elimination – is excreted in the urine as unchanged drug and metabolites
describe the pharmacodynamics of atropine
Anticholinergic agent
Atropine is a competitive antagonist of acetylcholine which binds to the muscarinic receptor in order to inhibit the parasympathetic nervous system.
EyeAlterations are produced by muscarinic antagonism in two muscles: inhibition of iris sphincter muscle causes mydriasis, while relaxation of ciliary muscle produces cyclopegia.
Dilation of the pupil normally occurs within half an hour following local application and lasts for seven days or longer. Paralysis of accommodation in one to three hours with full recovery in three to seven days.
name some examples of antimuscaranics
atropine , cyclopentalate and tropic amide
what antimuscarnic drug produces the quickest maximum effect ion mydriasesis
tropic amide (0.5%/1%)
what is time taken to produce the maximum effects of mydriasis by cyclopentalate 0.5%/1%
60 miniutes
what is the time taken to produce thee maximum effects of mydriasis by tropic amide 0.5/1%
40 skins
how long does it take to produce the maximum effects of cycloplegia by atropine 1%
6hrs
how long does it take to produce the maximum effects of cycloplegia by cycloplentalate 0.5/1%
1hr
how long does it take to produce the maximum effects of cyloplegica by tropic amine 0.5/1%
0.5hrs
name some examples of local anaesthetics
lidocaine
fluroscein
oxybuporcaine
proxymetacaine
tetracaine
what is fluroscien used for
Fluorescein does not stain a normal cornea, but conjunctival abrasions are stained yellow or orange, corneal abrasions or ulcers are stained a bright green and foreign bodies are surrounded by a green ring. It can be used in diagnostic examinations including tonometry and in the fitting of hard contact lenses.
what is lidocaine used for
Lidocaine is an established topical anaesthetic which blocks the sensory nerve endings of the cornea. (Diffusion)
describe the pharmokinetics of lidocaine
Absorption – local with good penetration into aqueous and vitreous humour
Distribution – N/A but trace amounts highly protein bound
Metabolism – N/A but trace amounts in liver
Elimination – N/A but trace amounts non-real (biliary)
what is the prevalence of dry eye
Dry eyes affect about 7 in 100 people in their 50’s and about 15 in 100 people in their 70’s.
Women are affected more often than men.
what are the causes of dry eye
Ageing
Medication - : diuretics some antidepressants; antihistamines; some treatments for anxiety;incontinence drugs; beta-blockers such as atenolol, etc;
Illness - may occur with rheumatoid arthritis, systemic lupus erythematosus (SLE), and Sjögren’s syndrome.
Increased evaporation of tears e.g. from central heating or air conditioning.
Low blink rate e.g. spending a long time looking at a computer, TV etc Windy conditions when you are outside. Inability to cover the eyes completely when closing the eyelids. Damage to the outer part of the eyes, eyelids, etc, from disease, injury or surgery.
Blepharitis (inflammation of the eyelids)
when should prervative free preperations of ocular lubricants be considereed
Preservative-free preparations should be considered where;
the patient has a documented allergy or evidence of epithelial toxicity to the preservatives contained in a preparation
the patient needs to use more than 4-6 applications of eye drops containing preservative a day
immediately following eye surgery until healing is confirmed.
when should a more viscous lubricating eye drop be used
If a patient needs to use dry eye drops more frequently than 4 times daily, a more viscous lubricating eye drop should be used.
Eye ointments are used for local treatment of lids, for prolonged treatment at night and to reduce the number of drops given.
If drops and ointment are used at the same time, drops should be given first.
what do preservative free formulations contain
Some preservative-free formulations are available in 10ml bottles. These are usually patented designs containing either a filter or valve to prevent the entry of microorganisms
what are preservative free formulations registered as and when should they be used
As these preparations are registered as medical devices, they are not subject to medicinal product licensing requirements. Thus the requirement for eye drops to have a four week shelf-life after opening does not apply and these multi-dose products can be used for 2-6 months after opening.
[Price ++ / cost effective due to shelf life / less risk of damage over time - no preservative
what formulations contain vanishing preservatives
formulations contain ‘vanishing’ preservatives:
Eg. sodium chlorite or sodium perborate (PURITE® used in Optive drops).
Sodium chlorite degrades to sodium and chloride free radicals and water upon exposure to UV light after instillation.
Sodium perborate is converted to sodium borate, hydrogen peroxide, water and oxygen on contact with the tear film.
BUT In higher concentrations, sodium perborate has been reported to be an eye irritant. For patients with severe dry eye, even vanishing preservatives may not totally degrade, due to a decrease in tear volume, and may be irritating (use PF preparations)
what is sodium cromglycate used for
it inhibits the degranulation of sensitised mast cells which occurs after exposure to specific antigens by inhibiting the release of histamine and various membrane derived mediators from the mast cell. It has no vasoconstrictor or antihistamine activity.
how is sodium cromoglycate absorbed systemically
it is poorly absorbed into the systemic circulation. Trace amounts (less than 0.01%) of the sodium cromoglicate penetrates into the aqueous humour and clearance from this chamber is virtually complete within 24 hours after treatment is stopped.
how does sodium cromoglycate act
Acts locally for the relief and treatment of seasonal and perennial allergic conjunctivitis. [OTC ‘self-care’ agenda]
describe the pahrmacokinetics of sodium cromoglycate
Absorption – local – poorly absorbed in to systemic circulation. Trace amounts (less than 0.01%) penetrates into the aqueous humour and clearance from this chamber is virtually complete within 24 hours after treatment is stopped.
Distribution – N/A
Metabolism – N/A
Elimination – N/A
q
describe the mechanisms of a local anaesthetic
you Get a diffusion of sodium ions from inside a cell to outside a cell local aesthetic acts as a blocker to the sodium ion channel i.e. you can get pocked by a needle but there won’t be a influx of sodium ions - therefore the brain fails to detect the signals - so an anaesthetic is an atognist that blocks the influx of odium ions from high conc outside the cell to a low conc side the cell
what is a calcium channel blocker an example of
lowers bp
calcium channel blocker stops the contraction of muscle
calcium channel blockers correct and overreacting normal process
calcium normally infuses from high concentration to low concentration within the cell na Dif thats too overactive the Smoot=h muscle can become too rigid therefore a ca2+ blocker can be given
what to proton pump inhibitors
dampens down the natural process of producing too much gastric acid but we maintain enough for it to help with digestion e.g.
