Week 11 - Pharmacology Flashcards
What are agonists?
What are antagonists?
Activate receptors
Block receptors
What are the types of drug actions?
- Interact with ion channels
- Activate / inhibit enzymes (statins, penicillin)
- Inhibition of transporters / pumps
- Interact with DNA (anticancer)
What are the sries of events for the action of salbutamol?
Binds to receptors
Receptor is activated
Receptor couples to G-protein
Association of alpha subunit
GDP-GTP
Activation of adenylyl cyclase
AMP-cAMP
Relaxation
What happens during modality?
- Receptors respond to specific energy / modality
- Specific sensation from type of receptor activated
- Concentrate on simple somatosensory system
What is the role of the pacinian corpuscle?
Vibration and rapid movements
What are the properties of transduction?
Stimulation - touch / vibration –> sensory AP
Occurs at naked nerve terminal
Involves changes in ion channel activity
Non-propagated potential
What happens during encoding?
What is an adaptation of encoding?
Sensitivity = ability to encode and detect stimuli of wide range of strengths –> increase sensitivity = use neurons with different AP thresholds and population encoding (use large no. of neurons for small stimuli detection, + chance of detection)
Temporal change in output in response to a stimulus –> + sensitivity and + cellular efficiency
What is involved in pain?
What are the 2 types of pain?
Nerve response to noxious stimuli –> above normal range, can cause damage, withdrawal behaviour
Specialised nerve fibres –> myelinated = fast, sharp pricking acute pain (Aδ), mechanical mainly, unmyelinated = slow, dull ache (C fibres), polymodal (mechanical + thermal for example)
TRPV1s = burning, heat
Meissner’s Corpuscles = tingling, numbness
What are the properties of the autonomic nervous system?
Smooth + cardiac muscle –> sympathetic (positive heart inotropy and chronotropy, gut vasoconstriction, skeletal muscle vasodilation, + sensory awareness, sweat secretion) or parasympathetic
What happens during sympathetic flight or flight response?
Heart inotropy and chronotropy
Vasoconstriction in gut
Vasodilation in skeletal muscle
Sensory awareness – eg vision
Sweat secretion
What are the prevertebral ganglia?
Celiac ganglion
Superior cervical ganglion
Superior mesenteric ganglia
What is the sympathetic outflow from spinal cord III (cervical region)?
Follow blood vessel and enter skull
What is the sympathetic outflow from spinal cord IV?
Midline plecuses
What is included in the parasympathetic nervouse system?
Cranio-sacral outflow
Long-pre and short-post ganglionic fibres
Cranial nerves III (occulomotor), VII (facial), IX (glossopharyngeal), X (vagus)
Where do the parasympathetic cranial and sacral nerves lead to?
What tissues only have parasympathetic innervation?
Ciliary muscle
Constrictor pupillae
(eyes)
Which nerves are radial and circular eye ,muscles supplied by?
Radial = sympathetic
Circular = parasympathetic
What are the effects of parasympathomimetic drugs?
Agonists of parasympathetic systems (Miosis (pupil constriction), decrease in near point, decrease in intraocular pressure)
What are the effects of parasympatholytic drugs?
Blockers of parasympathetic systems (mydriasis (dilation of pupil), cycloplegia, increased intraocular pressure)
What are the effects of sympathomimetic drugs?
Agonists of sympathetic systems (mydriasis, increased IOP)
What are the effects of sympatholytic drugs?
Blockers of sympathetic systems (miosis)
What are the 4 adrenoceptor subtypes and their functions / properties?
What type of agonist is adrenaline and how does it work?
Directly acting sympathomimetics adrenoceptor agonist:
Used for cardiac arrest, sepsis and septic shock
Delivered intravenously
Stimulation of b1 starts / increases heart rate
Used for anaphylactic shock
What type of agonist is salbutamol and how does it work?
Directly acting sympathomimetics adrenoceptor agonist:
Beta-2 adrenoceptor agonist
Bronchodilation
Bronchial asthma
What type of drug are NA reuptake inhibtors and how do they work?
Indirectly acting sympathomimetic drugs:
TCAs for depression treatment –> enhances NA function and 5-HT, block reuptake by varicosity
Other effects enhanced
What type of drug are cocaine and amphetamine and how do they work?
Indirectly acting sympathomimetic drugs:
CNS stimulant and NA reuptake inhibitor
+ sympathetic excitation
Amphetamine = causes exocytotic NA from neuronal uptake
What are propranolol and prazosin and how do they work?
Adrenoceptor antagonists:
Prazosin = selectively blocks alpha receptor
Propranolol = selectively blocks beta receptor (B2 agonist so stop salbutamol effects) - is used for:
Ischaemic heart disease
Reduce cardiac load during heartbeat
Beta blockers
Is administered orally
How are muscarinic receptors characterised?
Activated by muscarine
Act via metabotropic events
Neural, cardiac and glandular are family members
Utilise different 2nd messengers
Act on different target proteins
When are muscarinic receptor agonists used theraputically?
What are some side effects?
Oxybutynin:
Used for incontinence
–Non-selective parasympatholytic or anti-muscarinic
–Prevents unwanted bladder contractions
–Side-effects same as atropine which include: blurred vision,
tachycardia, dry mouth
What are ophthalmic uses of muscarinic agonists?
How do they work?
Pilocarpine:
Glaucoma
- Constriction of circular muscle
- Opens up drainage channel
- + aqueous humour drainage
- intraocular pressure.
When is the muscarinic antagonist tropicamide used ophthalmically?
For ocular examination:
Mydriasis
- Relaxation of circular muscle of iris
- Relaxation of ciliary muscle
What are the actions of anticholinesterases?
Examples of drugs used?
- Reversible
- Competitive inhibitors
Physostigmine (used for glaucome, bladder stimulation and treatment for atropine poisoning)
Neostigmine (treatment for myasthenia graves)
What are the proeprties of irreversible anticholinesterases?
- Non-competitive inhibitors
- Insecticides
- Covalently modify AChE organophosphorous compounds
What are the symptoms of organophospho anticholinesterase poisoning?
Muscarinic effects =
- Miosis
- Salivation
- Sweating
- Bradycardia
Nicotinic effects =
- Twitching
- Paralysis
CNS effects =
- Anxiety
- Restlessness
- Dizziness
How do you treat anticholinesterase poisoning?
Anti-muscarinic:
- Alleviate muscarinic symptoms by decreaseing mAChR availability
- Use atropine to block mAChR
Dephosphorylate acetylcholinesterase
What is the health belief model?
What is the health belief model used for?
- Help to predict, understand and address non-adherence to treatment
- Better at predicting initiation of health protective behaviours (screening) than reducing health risk behaviour (smoking)
- Useful framework for health promotion, for example increasing vaccination coverage
What is the theory of planned behaviour?
What is the concept of the theory of planned behaviour?
- The idea of perceived behaviour control
- Suggests what might be stopping someone from doing a behaviour
- Judgments are based on if you have resources or opportunities to do behaviour
What is the transtheoretical model (stages of change)?
What is motivational interviewing and its properties?
Counselling which is patient centred and explores and resolves ambivalence about behaviour change
Useful = for peoplke unmotivated and unprepared for change
Not useful = for people motivated for change
It increases motivation and makes commitment to the change
What are the function and properties of receptors?
Respond to messengers by initiating a signal
- Selective binding site for endogenous hormone / transmitter
- Act as molecular switches
What are the 4 main receptor superfamilies?
- Ligand gated ion channels
- G protein coupled receptors
- Catalytic receptors
- Nuclear receptors
What is drug affinity?
What is drug efficacy?
Ability of drug to bind to receptor
Ability of drug to activate receptor by conformational change, when bound
What is an agonist?
What is an antagonist?
Has affinity and efficacy as it binds and activates receptor
Has only affinity as it binds but doesn’t activate receptor, instead blocks it
What is KON?
What is KOFF?
What is KD and how do you work it out?
Forward rate of reaction
Reverse rate of reaction
Concentration of drug required to occupy 50% of receptors
KON / KOFF
What does a low KD indicate?
High affinity
What is EC50?
What is Rmax?
Effective concentration of agonist for 50% of its maximal response (Rmax)
Maximum response of a drug
What does the presence of an antagonist do the agonist potency and maximum response?
Reduces EC50
Rmax is unchanged
What are the properties of competitive antagonists?
What are the properties of uncompetitive antagonists?
- Bind at same 3D site on target receptor as agonist
- Have structural similarities
- Bind to different binding site on target receptor
- Have non-surmountable effects
What is a xenobiotic?
What is intoxication?
What is toxic syndrome?
Foreign substance to our body
When compound reaches above safe maximum dose value
Toxic effects comprising a set of clinical fingerprints for a group of toxic chemicals
How are xenobiotics classified?
Target organ classification
Use in the public domain (i.e. food colourings)
According to source
According to effects
According the physical state
According to biochemical properties
What are the routes of eposure of xenobiotics?
- Oral
- Intranasal
- Inhalation
- Parenteral (non-GI tract)
What are the duration and frequency of xenobiotics?
Acute = < 24 hours
- One exposure or low dose continual exposure until 72 hours
- Subacute = repeated exposure > 72 hours < 1 month
Chronic = > 3 months
- Continuous or intermittent exposure
- Subchronic = 1 - 3 months
What are the 4 chemical interactions of toxic agents?
Agonistic
Antagonistic
Potentiation / Synergistic
Additive
What are the harmful effects of toxins?
- Asphyxiant (simple / chemical)
- Irritant
- Corrosive
- Narcotic
- Sensitiser
- Toxic
- Carcinogenic
- Mutagen
- Teratogen
What is graded dose response?
Relationship of individual test subject or system to increasing / continuous dose of a chemical
What is quantal dose response?
All-or-nothing response
Determined by distribution of responses to increasing doses in a population of test subjects
What is theraputic dose ED50?
What is toxic dose TD50?
What is lethal does LD50?
Median effective dose - dose that produces effective dose in 50% of population taking it
Median toxic dose - dose which toxicity occurs in 50% of population taking it
Dose that causes death in 50% of animals tested
What is IC50?
Inhibitory concentration:
Concentration necessary to inhibit 50% of a measured response in an in-vitro system
What is the threshold dose?
What is NOAEL?
Point where toxicity first appears
No observed adverse effect level
What is toxicokinetics?
What is toxicodynamics?
Considers rate chemical enters the body, the storage and metabolism and sebsequent excretion
Concerns dynamic interaction of a toxicant with a biological target and its biological effects
What is pharmacokinetics?
What is ADME?
Time course of a drug from absorption to elimination, determining dose and how often
Absorption
Distribution
Metabolism
Excretion
What are the 5 different drug frequency acronyms?
o. d. = once daily
b. d. = twice daily
t. d.s. = thrice daily
q. d.s. = four times daily
p. r.n. = as required
What are the 5 different drug routes and their acronyms?
po = oral
im = intramuscular
iv = intravenous
sc = subcutaneous
neb = nebuliser
What are the benefits of IV?
Rapid effects
Absorption circumvented
Good for emergency use
Permits dosage titration
Suitable for large volumes and irritating substances when diluted
What are the disadvantages of IV?
+ risk of adverse effects
Risk from embolism
Not for oily or insoluble substances
Requires IV access
What are the properties of the subcutaneous drug route?
Prompt from aqueous solutions
Slow and sustained
Suitable for insoluble suspensions and pellet implantations
Not suitable for large volumes
Possible pain or necrosis from irritating substances
What are the properties of the intramuscular drug route?
Prompt from aqueous solution
Slow and sustained
Suitable for moderate volumes, oily vehicles and irritating substances
Painful
Danger from incorrect site of injection
What are the 2 drug systemics?
When are IV used?
When are subcutaneous routes used?
Enteral (via GI tract) and parenteral (avoids GI tract)
Antibiotics, general anaesthetic
Insulin, heparin of low molecular weight
What are the properties of oral drugs?
Solutions, suspensions, tablets, capsules
Interpatient variation
Variable bioavailability
Most convenient
Requires patient cooperation
What are other drug routes?
Topical (eye drops)
Transdermal (patches)
Inhalation
Rectal
Sublingual
What is the magnitude of drugg effect proportional to and other properties?
Concentration at site of action (plasma concentrations)
Needs to be within theraputic window so is effective but not toxic
What are the properties of drug absorption?
What is zero order and first order in pharmacokinetics?
Zero-order = rate independent of concentration –> occur when system is saturated
First-order = rate dependent on concentration
What are the properties of IV injection?
What is salt factor?
?
Proportion of a dose of a drug that is actually the drug
What is bioavailability?
How do you work out amount of drug?
Amount of administered drug that reaches systemic circulation / volume absorbed
Amount needed / F (bioavailability)
What is volume of distribution?
Apparent volume in which drug is absorbed into the body
Vd = amount in body / concentration
In L or L/Kg
What are the properties of drug elimination?
Metabolism and excretion
What is clearance in pharmacokinetics?
Volume of plasma cleared of a drug per unit time
L/h
What is k in pharmacokinetics?
What is t1/2 in pharmacokinetics?
Fraction eliminated per unit time
k = clearance / Vd
Time for concentration to decrease by 50%
