Pharmacology Flashcards
hazards/risks associated with giving medicine
death - allergy to drug - toxicity of the drug drug interactions - effect on absorption or metabolism of other essential medicines, such as: warfarin (anticogulant), carbamazepeine (anticonvulsant)
5 drug classes
- local anesthetics
- antimicrobials e.g. antibiotics
- drugs in pain and inflammation (analgesics)
- drugs in sedation
- emergency medical drugs
local anaesthetics use
to reduce awareness of Pain
local anaesthetics action
LA act on nerve ion channels to block propagation
- stop signals passing to a nerve
4 types of local anaesthtics
- lignocaine (lidocaine)
- prilocaine
- bupivicaine
- mepivicaine
all pH sensitive in tissues
what is often added to local anesthetics?
vasoconstrictor to prolong duration of action by keeping blood flow to a minimum so LA stays longer - reduced clearance
patient can have extra distressing reaction to LA - e.g. pulse racing
what do vasodilators do?
open blood flow - lowering time of effect
3 types of antimicrobials
- antibiotics
- antivirals
- antifungals
commonly prescribed antibiotics
- Amoxycillin
- Metronidazole
- Doxicycline
- Clindamycin
antibiotics method of action
varies
what is the most commonly prescribed antiviral drug in dentistry?
aciclovir
- can be systemic (tablet to all tissues) or topical (apply to area where problem is e.g. cold sore cream)
2 antifungal drugs
nystatin (topical)
fluconazole (systemic - oral)
what increases incidence of oral fungal infections?
use of inhalers, dentures or orthodontics
analgesics are
drugs in pain and inflammtion
what are non-steroidal anti-inflammatory drugs? (NSAID)
drugs used to reduce the inflammatory mediators
what are corticosteroids?
drugs used to reduce the inflammation process
what is paracetamol’s mechanism of action?
its uncertain
- unknown is peripherally or central (in brain or where pain is)
reduces temperature via thermoregulation in the brain
what type of drug is paracetamol?
anti-pyretic and analgesic
- little to no anti-inflammatory action
few side effects
co-codamol
paracetamol and codeine
paracetamol is often combine with other drugs to make more potetn
3 types of anti-inflammatory analgesics (NSAID)
salicylates
- aspirin
propionic acid derivatives
- ibuprofen
phenylacetic acid derivatives
- diclofenac (prescription only)
what is a dental prescription for diclofnec?
very effective analgesic for inflammtion based pain e.g. wisdom teeth
(phenylacetic acid derivative)
what do non-steroidal anti-inflammatory drugs do?
inhibit prostaglandin synthesis
(true action unknown)
- change the balance of PGE1 and PGE2
- cyclo-ocygenase (COX 1 & 2) enzyme inhibitor
both large mediators of pain in body - so prohibit feeling
how do non-steroidal inflammatory drugs work?
Work by inhibiting Arachidonic Acid
All come from same precursor
- Prostaglandins lead to thromboxane – cause platelets stick together
Side effect of non-steroidal anti-inflammatory can cause more bleeding as less platelet adhesion e.g. if tooth removed
reason why you can’t have aspirin
if have kidney issue
either lower dose or none (300-600mg up to 4 times a day)
pharmacokinetics of aspirin q
Rapid absorption from GIT
- Elimination by 1st order kinetics – easy to eliminate
Unless overdose (enzyme saturation) - Toxic effects - acidosis
action of aspirin
Inhibits COX 1
- Reduced synthesis of prostaglandins
- Reduced production of inflammatory mediators
Anti-pyrexic
important characteristic of aspirin
can be taken BEFORE inflammatory process starts
- Pre-emptive analgesia
any non-steroidal taken in anticipation of inflammation (e.g. extraction) is more effective
what are potential side effects of any non-steroidal anti-inflammatory drug? (5)
Gastric irritation
- Erosions, ulceration
- Worse with alcohol
Inhibition of platelet function
- Enhanced bleeding
Bronchospasm
- Exacerbate asthma
Allergic reactions (rash)
Drug interactions
- Significant protein binding – WARFARIN (anti-coagulant) potentiation
what is ibuprofen?
NSAID
benefit of ibuprofen over aspirin
fewer side effects - less common
how can you get diclofenac?
prescription only
results of diclofenac being more potent than ibuprofen
more potent = more side effects = more effective
how to corticosteroids reduce inflammation?
by inhibiting
- Capillary permeability
- Formation of bradykinin
- Migration of white blood cells
- Reduce eicosanoid synthesis
Suppress features of inflammation – do not address the cause!
how do topical drugs work?
on the surface of the desired tissue
examples of topical drugs
- Steroid inhalers in asthma
- Hydrocortisone cream – eczema
- Steroid treatments for mouth ulcers e.g. Beclomethasone inhalers; Hydrocortisone adhesive tablets; Betamethasone solutions (mouthwashes)
how to systemic drugs work/
given to the whole organism?
do dentists get encouraged to use systemic drugs?
generally, no
mainly used for chronic immunological diseases
(in hospitals)
examples of systemic drugs
Prednisolone (tablets)
- Prevent transplant rejection
- Treat immunological diseases
Dexamethasone (injection)
- To reduce swelling after surgery
- e.g. Wisdom tooth removal
systemic steroid side effects
- High blood pressure
- Weight gain (fluid)
- Fat distribution change (Centripital obesity + ‘buffalo hump’)
- Gastric ulceration
- Adrenal suppression
- Osteoporosis
- Diabetes
what drugs are used to reduce anxiety?
anxiolytics
Benzodiazepines – diazepam, midazolam
- Forget what happened – no short to long term memory
Gas – Nitrous Oxide
after effect of benzodiazepines is
Forget what happened – no short to long term memory
benzodiazepines action
Stick to GABA receptors - Change ion flow into cells - Can affect GABA receptors Pain modifier Analgesics Anxiolytic
Habituate
- Longer taking become less effective
Stop taking cause rebound - increased anxiety
benzodiazepines metabolism
Metabolise to metabolites that do the same job
- Still sticks to receptor
Different lasts for different lengths of time
Diazepam has 24hrs approx. length of action
- reflexes impaired
long half life
describe the drug nitrous oxide
inhalation sedation
positives of nitrous oxide
- amount of effect can be adjusted during procedure
- no organ metabolism issues - excreted unchanged as a gas
downside of nitrous oxide
intereferes with folic acid metabolism
- avoid in pregnancy for both patients and staff
instances where medical emergency drugs used
- asthsma
- heart attacks
- diabetic emergencies
- seizures
definition of a drug
“external substance that acts on living tissue to produce a measurable change in the function of that tissue”
what does the term side effect of drug mean?
unwanted effect
- same action in every person sometimes unwanted results
what do you need to balance when prescribing a drug?
benefits against unwanted effects
what are the 3 general mechanisms of drug actions?
- stimulate normal body communications
- interrupt normal body communications
- act on non-host organisms to aid body defences
what are the 2 main types of host communications?
- hormone messages
- neural messages
describe hormone messages
general information to all tissues
describe neural messages
targeted information for Specific tissues
similarities between hormones and nerve messengers
both chemical messengers
both can be stimulated or interrupted
role of thyroid hormones
balance’s body’s metabolism
- control metabolism and function of tissue - whole range of responses altered
- Large physiological change
what condition is too much thyroid hormone?
hyperthyroidism
Sweaty, hot, anxious Eyeball pushed forward in socket • Proliferation of fat in socket • Problem with antibody in thyroid gland Proptosis - u Sweaty, hot, anxious Staring Eyeball pushed forward in socket
what condition is too little thyroid hormone?
hypothyroidism o Cold intolerant o Slow mental activity o Hair loss o Slow pulse & low Blood pressure
what does thyroxine tablet replace?
missing T3 and T4
- dose adjusted to correct level gradually to normal metabolism
where does thyroxone tablet work?
directly in the tissues - no direct effect on thyroid gland
sympathetic nerve communication
adrenaline
part of autonomic nervous system
parasympathetic nerve communication
acetylcholine
(muscarininc cholinergic)
(part of autonomic nervous system)
sympathetic control of heart rate
adrenergic stimulation
- speeds up heart rate via beta-receptors
parasympathetic control of heart rate
cholinergic stimulation
- slows the heart rate via cholinergic receptors
what does anticholinergic drugs do?
stops saliva production in the mouth
4 ‘autonomic’ drugs
adrenaline
atenolol
pilocarpine
atropine
what is adrenaline?
beta agonist
- speed up heart rate
‘autonomic’ drug
what is atenolol?
beta blocker
- slow down heart rate
- blocks adrenaline receptor so stopping action
reduce arrythmias, lower BP
‘autonomic’ drug
what is pilocarpine?
cholinergic agonist
‘autonomic’ drug
what is atropine?
cholinergic blocker
take away effect on heart
HR is kept artificially low at rest by cholinergic system
‘autonomic’ drug
3 ways drugs can interact with tissues
- receptors
- enzymes
- ion channels
how do receptors for drugs work?
Pick up drug like an aerial on outside of cell
By themselves not enough!
- coupled to ion channels – cause to channel to open, allow to flow in
- coupled to G-proteins – change conformation to trigger cascade
- coupled to gene transcription
occupancy
the fraction of bound receptors
affinity
how avidly the drug binds to its receptor
efficacy
maximum response achievable and capacity for sufficient effect or beneficial change
higher affinity and occupancy
greater response of drug
2 ways drug can bind
Form bonds which cannot be broken
- drug cannot come away and receptor cannot be reused e.g. aspirin
Receptor binds to the drug but is dependent on the concentration of the drugs and affinity of drug.
- Eqm balance
- Normal state some activated receptors some not and some free drug in blood.
- The higher the affinity the longer the drug will be on the receptor activating it and more time change in cell
what is the ‘law of mass action’?
drug in vicinity of receptor
- increase concentration of drug around receptor more drug will bind
agonist
bind to receptor and cause an effect
- directly causes an effect inside the cell
partial agonist
more difficult to produce the drug/receptor effect than with an agonist
- causes part change and part response but not full response, dynamic process
increase partial agonist concentration will improve efficacy for some but not all
antagonist
no effect but block receptor action
competitive and non-competitive
competitive antagonist
Reversible
- Antagonist effect reduced by increasing the concentration of the agonist
- Competitive reversible antagonist removed from receptor means agonist can still bind
Example: atenolol (β1 blocker)
non-competitive antagonist
irreversible
- Binds and reduces available receptors for the agonist
- Non-competitive irreversible antagonist causes conformational change so substrate can no longer bind
Example: phenoxybenzamine (α1 blocker)
way enzymes work can be described as
substrate antagonism
types of enzyme modification
reversible modification or irreversible modification
how can drugs effect enzymes?
change the way it folds so changes enzyme effect - irreversible e.g. cholesterol forming
block receptor site or change way it folds
ion channels
disrupt cell ion balance
influence electrical activity and ion influx
examples of drugs which work on ion channels
- local anesthetics - prevent conduction of AP, communication
- anti-diabetic drugs
how do ion channels work?
- Agonist come along changes cell
- Changes transmembrane protein
- Allows pore to open so ion can flow through
- Specific to type of ion
pharmacokinetics
what body does to a drug
refers to the movement of drug into, through and out of the body
(the time course of its absorption, bioavailibilty, distribution, metabolism and excretion)
pharmacodynamics
study of the biochemical and physiological effects of drugs
how the drug effect the organism
4 phases of drug from intake
absorption
clinical effect
metabolism
excretion
advantage of oral drug administration
Socially acceptable
disadvantages of oral drug administration
- Slow onset – not useful in emergency
- Variable absorption – some maybe lost in stomach acid, gut
- Gastric acid may destroy drug
- ‘first-pass’ metabolism – liver metabolises before enters circulation
advantage of ‘first-pass’ liver metabolism
makes an active form of an inactive drug
less needed by oral rout
e.g. valavivlovie -> aciclovir
disadvantage of ‘first-pass- liver metabolism
more needed by oral route to get desired clinical effect
e.g. glceryl trinitrate
what is important to factor into dosage when prescribing a drug?
if it is ‘first-pass’ metabolised and liver functionability
when can you get abnormal liver function?
- extremes of life
- liver disease
- drug interactions changing drug metabolism
6 factors affecting oral absorption
- ‘first-pass’ liver metabolism
- lipid solubility and ionisation
- drug formulation
- gastrointestinal motility
- interactions with other substances in the gut
- GI tract disease`
5 forms of drug administration
- oral
- intravenous
- intramuscular
- subcutaneous
- inhalation
advantage of non-oral drug administration
- predictable plasma levels
- no first pass metabolism (good for emergencies)
disadvantages of non-oral administration
- allergic reactions more severe adn faster
- access difficulties/self-medication
- drug cost higher
bioavailbilty
proportion of an ingested drug that is available for clinical effect
4 things that modify bioavailability
- dosage form
- destruction in the gut
- poor absorption
- first pass metabolism
volume of distribution
amount of the body the drug diluted in
- compartments
3 things that impact drug distribution
Lipid binding
- Bound to lipids in plasma
- Slow release from accumulation
Drug binding to plasma proteins
- Bound drug is inactive
- Can act as a reservoir
Drug interactions possible by competitive binding
- Warfarin & aspirin
Warfarin binds to plasmin protein – top up what’s used already
However if start taking a drug with a higher affinity then less will bind meaning one drug will have an emphasised response
how many stages are in preparing drugs for elimination from body?
2
phase 1 drug elimination reaction
Oxidation, reduction, hydrolysis – little changes to molecule, changes conformation, no longer bind to receptor, inactivate it
phase 2 drug elimination reaction
Conjugation for excretion
- Glucuronidation, sulphation, methylation, acetylation, glutathione
Tag with enzyme onto molecule which will be excreted so increased the amount excreted from body
5 methods of drug excretion
- renal (urine)
- liver (bile)
- lungs (exhale gas)
- sweat
- saliva
method of excretion for most drugs
renal excretion
how can renal excretion be modified?
changing urine pH - make more alkaline can get rid of excess acidic drug
2 disorders of excretion
renal disease
- chronic renal failure
- drug doses must be reduced
liver disease
- liver failure (drug doses must be reduced)
single compartment model
drug behaves as if it is evenly distributed throughout the body
- goes everywhere in same concentration
two compartment model
drug behaves as if it is in equilibrium with different tissues in the body
- blood flow dependent
- go to large blood flow compartments first then other areas
what mainly causes body compartments?
largely due to blood flow
more flow = more drug delivery
first order kinetics
Drug elimination or absorption is by PASSIVE DIFFUSION only
Drug removal is proportional to the drug concentration
- removed from the body at a rate that is proportional to the concentration
- Logarithmic graph of elimination is a straight line
most medicines
- Half-life of drug is constant so can predict how long it will be in body
zero order kinetics
Drug elimination is an ACTIVE process and can be saturated by high drug concentrations
Linear graph of drug elimination
- Zero order has a constant rate of drug elimination whereas first order is proportional to drug concentration
use of zero order kinetics
Useful for how long drug in body and how fast will be removed
- Need to know half-life, bioavailability
Can work out dosing schedule based on bioavailability and mechanism of excretion
- so what is the required stable level in patient
what is drug accumulation?
How the plasma concentration builds if repeated doses of a drug are given.
too frequent dosing schedule
toxic plasma levels
too infrequent dosing schedule
result in sub-therapeutic plasma levels and no clinical effect
Injections Vs Creams as routes of administration
injection
- can get to site quicker
- know volume absorbed
- higher plasma peak level
cream
- can be more slow release (effects felt for longer; lower peak plasma level)
injections are more expensive as more HCP time needed
what method of administration is best for an infection?
injection
- higher peak plasma level faster
what method of administration is best for morphine?
what lot of pain relief for prolonged time
- transdermal patch
what is the only method of administration that involves first pass metabolism?
oral
not injection, absorption under tongue, path or cream
subcutaneous Vs transdermal method of administration
subcutaneous is already in connective tissue
- quicker action but shorter duration
e. g. insulin
how does blood flow effect duration of action of a drug?
higher blood flow = rapid rise in plasma level but short duration
e.g. muscle
what is bioavailability/
portion of ingested drug available for clinical effect
can be lost by
- First pass metabolism – lose proportion
- GI disease – not absorbed
- Destroyed by gastric acid
phase 1 in drug inactivation and excretion
adds or takes away sections so cannot bind to receptor (in liver)
- can go round multiple times with multiple modifications before make a sufficient change to prevent drug working
e. g. diazepam
phase 2 in drug inactivation and excretion
conjugate with other molecules so it can be removed by kidney and gut
bound and free drug relationship
Some will dissolve in plasma some will be bound to plasma proteins. Until concentration drops so that equilibrium from bound to free acting drug move towards more needing to be free so can be used
- Binidng to plasma means the duration of drug can be prolonged as circulate until eqm shift
albumin role
can bind to drugs
Determines oncotic pressure of keeping fluid in blood stream and not released into tissues
Made in liver
how can excess free drug occur and consequence of this?
not enough plasma proteins for drug binding
some drug may not be used efficiently and list
what is preferential binding in plasma and how can it be used?
preferential binding of one drug to the other if stronger affinity for that drug to the site
can change the amount of drug available in plasma
e. g. warfarin only works when free in plasma
- can increase by introducing a drug with stronger affinity so more free Warfarin
