Introduction to Pharmacology Flashcards
What is pharmacodynamics?
- How a drug works – mechanism drug exploits to achieve its intended therapeutic effects
- Fundamental mechanisms of drug action:
o Autonomic nervous system – controls breathing & digestion
o Antibacterial activity
o Antiviral activity
o Anti-inflammatory drugs
Describe the autonomic nervous system and drugs?
- Controls basic yet essential functions e.g. heart rate, breathing, digestion
- Overall activity of this system controlled by balance of sympathetic & parasympathetic branch
- Sympathetic:
o Fight & flight response - increases heart rate and dilates airways to make breathing easier - Parasympathetic:
o Chill & relax – reduces BP & kicks in digestion - Both theses systems work similarly – controlled by group of chemicals (neurotransmitter – chemical messenger that sends signals within body)
o Key difference between the 2 systems is the type of neurotransmitter involved
Sympathetic – noradrenaline is neurotransmitter (then bio-transformed into adrenaline) - Adrenergic drug works on sympathetic branch
Parasympathetic – acetylcholine is neurotransmitter - Cholinergic drug works on parasympathetic branch
Describe neurotransmitter, their location and what happens when neurotransmitter acts on receptor?
Neurotransmitter housed in pre-synaptic membrane (junction/terminal through which neurotransmitter can leave)
Gap called synapse
Then post-synaptic membrane where receptors are embedded
It is the action of the neurotransmitter on these receptors that gives rise to physiological changes like increase in heart rate or dilation of pupils seen as a result of autonomic nervous system function
Once neurotransmitter has crossed synapse, reached receptor & activated it – we see expected response
What aer receptors in sympathetic system called? What are receptors in parasympathetic system called?
Receptors associated with sympathetic system are referred to as alpha & beta receptors and receptors associated with parasympathetic are referred to as muscarinic receptors
Describe aqueous humour production?
- Controlled by sympathetic branch of autonomic nervous system
- Controlled by activation of alpha and beta receptors by noradrenaline
o When alpha receptor activated – reduction/inhibition of aqueous humour production
o When beta receptor activated – increase in production of aqueous humour production - All glaucoma drugs have same primary course of action: reduce IOP – either by:
o Increasing aqueous humour drainage via trab meshwork & uveal scleral outflow (‘widening plug hole’)
o ‘Turn off tap’ – reduce rate of aqueous humour production
Describe agonists? Adrenergic agonist? Cholinergic agonist?
- Activate post-synaptic membrane receptors
- Mimic action of body’s own (endogenous) neurotransmitters (Mimetics is another name for agonists)
- Stimulate post-synaptic receptors (Stimulants is another name for agonists)
- Agonists can be full agonist or partial agonist
o Full agonist:
Produces maximal activation
Fits in to receptor
o Partial agonist:
Most of drugs in optometry/ophthalmology
Fits in to receptor but does not produce maximal activation - Adrenergic agonist:
o AKA Sympathomimetic – mimetic (agonist), sympatho (works on sympathetic branch of ANS)
o Agonist – drug copies activity of body’s neurotransmitter at the receptors
o Adrenergic – working on sympathetic branch of ANS
o Examples:
Brimonidine (alphagan)
Apraclonidine (Iopidine) - Alpha-2-agonists – both Glaucoma medications
- Cholinergic agonist:
o AKA Parasympathomimetic – mimetic (agonist), parasympatho (parasympathetic branch of ANS)
o Agonist – activates receptors
o Cholinergic – works on parasympathetic branch of ANS – works on muscarinic receptors
o Examples:
Pilocarpine – pupillary mioses by mimicking action of acetylcholine on iris sphincter muscle
Describe antagonists? Adrenergic agonist? Cholinergic agonist?
- Blocks or occupy post-synaptic membrane receptors
- Reduce activity of endogenous neurotransmitters (lytic)
- Antagonist slots into receptor but does not activate it (it blocks it) – when neurotransmitter arrives and tries to bind to receptor, it is blocked so don’t see expected physiological response
- Adrenergic antagonist:
o AKA sympatholytic – sympatho (works on sympathetic branch), lytic (interrupting, stopping or breaking down process)
o Example:
Timolol – glaucoma medication – beta blocker – block beta receptors - Cholinergic antagonist:
o AKA parasympatholytic
o Example:
Tropicamide – dilates pupil – blocks activity of acetylcholine on iris sphincter muscle receptors – iris dilater muscle is relatively unopposed and so dilates pupil
Describe receptor selectivity?
- Drugs which operate by interacting with receptors on post-synaptic membrane need to be selective for different types of receptors
- Example of timolol:
o Glaucoma med
o Beta-blocker – lowers IOP by inhibiting synthesis of aqueous humour
By acting as antagonist at beta receptors – offsets expected increase in production of aqueous humour when that receptor would normally be activated by noradrenaline - Drug which shows selectivity for certain receptor types is able to identify which receptor it should be interacting with
- 2 sub-types of alpha & beta receptor:
o Alpha-2-agonist (glaucoma meds):
Brimonidine, Apraclonidine
These drugs show receptor selectivity for alpha-2 receptor
o Beta blocker:
Timolol – generic beta-blocker – will act on either beta-1 or beta-2 receptor
Describe pharmacokinetics, the timeline and modes of administration?
- Time-based description of drug activity through body
- Timeline:
o 1. Administration – e.g. tablet or eye drop
o 2. Absorption into body
o 3. Distribution
o 4. Metabolism (processed)
o 5. Excretion (get rid of drug once used) - Modes of Administration:
o 1. Oral – tablet/lozenge/syrup (important to optoms)
o 2. Ocular – eyedrops (important to optoms)
o 3. Nasal – spray
o 4. Sublingual/Buccal – gel on inside of mouth, drug absorbed along gum line or under tongue
o 5. Epidermal
o 6. Rectal
o 7. Vaginal
o 8. Parenteral (injection directly into px, infusion, implant) (important to optoms)
Enteral = to/through epithelium of GI tract
Par = not so drug not being administered through GI tract - These injection swill be given either by ophthalmologist, registered nurse practitioner or an optometrist who have undergone appropriate training
o E.g. anti-VEGF drugs through intra-vitreal injections for wet AMD
o All 1-7 modes rely on GI tract at some point, 8 does not
Describe oral administration?
- Example: painful eye so advise paracetamol or ibuprofen or allergic conjunctivitis and advise oral anti-histamine
- Px swallows tablet, drug acted upon by acids in stomach once tablet been broken down, drug absorbed by blood vessels of digestive tract
- Drug carried via circulation to liver (acts like giant filter)
o Liver decides amount of drug that ends up in pxs systemic circulation (blood stream) - Drug must pass through liver before accessing general circulation
o Takes it to heart, lungs, eye - First pass metabolism reduces proportion of active drug available at target site
o Liver acts as safety device
Describe blepharitis and tx?
- Eyelid telangiectasia – BVs are dilated & a little irregular - shows eyelid margin inflammation has been present for long time (Chronic)
- Non-pharmacological: lid hygiene measures, twice daily. Hot compresses
- Artificial tears for associated dry eye (evaporative DE) – use 4x a day
- Review px in 6-8 weeks
o At this they report no improvement of sxs, next step:
Antibacterial ointment: chloramphenicol (broad spectrum anti-bacterial) 2x daily
Still no improvement: IP: oral tetracycline: doxycycline (100mg), once daily - No option in UK for topical anti-biotic at moment, just oral if IP qualified
Describe oral vs topical (ocular) administration?
- E.g. corneal abrasion
o Artificial tears: Clinitas gel (carbomer (long chain polymer that increases viscosity of artificial tears)), every 3 hours – choose artificial tear that has doesn’t drain too quickly from eye
o Lubricant: Hylo-Night (liquid paraffin (waxy, thick substance)), once at night – to prevent recurrent corneal erosion syndrome
o Prophylactic antibacterial? chloramphenicol (1%) ointment TDS (3x a day) - Antimicrobial Stewardship:
o Use ONLY when clinically indicated
o Don’t give every px with corneal abrasion an antimicrobial – consider each px individually – is px immunocompromised? Consider depth of abrasion – deeper, more risk of infection? What caused the abrasion – risk of contaminated material coming into contact with eye (e.g. gardening injury)? - For painful eyes:
o Corticosteroids – powerful anti-inflammatory drugs – impair immune response (so contra-indicated in this case) could increase risk for opportunistic bacteria to invade abrasion
o Non-Steroidal Anti-Inflammatory Drug (NSAID):
Oral: ibuprofen – 400mg, 3 times a day in adult (same as for headache)
IP ONLY: Topical: diclofenac sodium (0.1%) (Voltarol Ophtha) QDS
What are the advantages of using topical NSAID administration?
- Direct delivery to target site (Eye) – if used oral then px has to swallow it, be processed by stomach acid, into digestive tract, passed through liver, into systemic circulation then be past to eye
- Increase availability at target receptor sites – less distribution
- Improved therapeutic effect at lower doses
- Rapidity of therapeutic effect
- Significantly reduced risk of Adverse Drug Reactions (ADRs)
o ADRs associated with oral NSAIDs: gastric ulceration, peptic bleeding – less risk of these with topical NSAIDs
Describe pharmacokinetic of topical (ocular) administration?
- Initial rapid wash-out – how much is lost
o Tearfilm: 7-10µl
o Eyedrop: 30-40µl
Not enough room for eyedrop in tearfilm so it: - Spills over lid margin & peri-ocular skin
- Drains through punctum (like plug-hole) – drug draining down here is rapidly lost
o Drug that remains on eye & is not lost during wash-out is absorbed across corneal epithelium & conjunctival epithelium (then available for absorption by network of conjunctival BVs) - Once eyedrop passed through punctum:
o Drains into canaliculi (superior puncta towards nose & inferior puncta towards nose
o Superior & inferior canaliculi meet and become common canaliculus
o After passing out of common canaliculus, eyedrop drains into lacrimal sac
o Then moves down into nasolacrimal duct due to gravity
o Eyedrop then passes through Valve of Hassner, into nasal cavity (large space at back of nose). Nasal cavity lined by nasal mucous epithelium (nasal-mucosa contains network of small, fine BVs – drug is available to be absorbed across BV walls of that network of small fine BVs
o Once drug been absorbed across BVs, it has entered body’s systemic circulation & then can be carried elsewhere in body
Describe systemic absorption of topically applied drugs?
- Every time drug is applied to ocular surface, unintended absorption (via nasal mucosa) into systemic circulation is inevitable
- No first pass metabolism; drug passes directly into systemic circulation
- Increased risk of significant ADRs – can be carried throughout body by circulation system – no liver to filter it
- Topical Beta Blockers:
o Sympathetic ANS: increase heart rate – if beta blocker reaches heart it will decrease heart rate & could cause Bradycardia (<60BPM)
In some pxs who have used beta-blockers to treat glaucoma have had clinically significant reduction in heart rate
o Sympathetic ANS: dilation of airways (Bronchial dilation) – breathe more air into lungs – if beta blocker reaches here may see constriction/ narrowing of airways obstructive airway disease/asthma - Effect of topical phenylephrine on systemic blood pressure:
o Mimics action of noradrenaline (sympathetic) at iris dilator receptors stimulating muscle to contract pupil dilation
o Increases blood pressure
Time-dependent response – rise in blood pressure seen in time of effect of phenylephrine
Dose-dependent effect - Both graphs show that administering phenylephrine as eye drop has significant effect on pxs blood pressure (increase)