pharmacology Flashcards
drug definition
external substance that acts on living tissue to produce a measurable change in the fct of that tissue
2 ways drugs work
stimulate/interrupt normal body communications
OR
act on non-host organisms to aid body defences
autonomic drugs
epinephrine - B agonist
atenolol - B blocker
pilocarpine - cholinergic agonist
atropine - cholinergic blocker
3 components drugs act on
receptors
enzymes
ion channels
what do drugs have their effects on?
proteins
receptors
transmembrane protein
coupled to ion channels, G proteins, enzymes, gene transcription
drug receptor interaction
agonist stimulates receptor, G-protein interacts directly with and changes the open probability of the ion channel
agonist stimulates receptor - G-protein activates or inhibits enzyme that gives rise to 2nd messengers
affinity
attraction of drug to receptor
occupancy
time drug stays stuck to receptor for
efficacy
how well combination of drug and receptor works
law of mass action
more drugs in vicinity of receptor = likely to get more efficacy
types of drug actions
agonists
partial agonists
antagonists
competitive/non-competitive
reversible/irreversible
agonists
bind to receptor and produce effect
partial agonists
more difficult to produce effect
increased conc might improve efficacy
antagonists
binds to receptor but nothing happens
drug phases
absorption
clinical effect
metabolism
excretion
routes of administration
enteral - oral
parenteral
enteral - oral advantages
socially acceptable
enteral - oral disadvantages
slow onset variable absorption gastric acid FPM also: lipid solubility and ionisation, drug formulation, GI motility, interactions with other substances in gut, GIT disease
parenteral routes of administration
IV IM SC inhalation intra-osseous topical sublingual/buccal rectal
parenteral advantages
predictable plasma levels
no FPM
parenteral disadvantages
more severe allergic reactions
access difficulties
drug cost higher
FPM
GIT (except sublingual and rectal)
HPV
liver
metabolises - inactivates/activates
abnormal liver fct causes
extremes of life
drug interactions
disease
bioavailability
proportion of an ingested drug that is available for clinical effect
FREE not bound
what affects bioavailability?
dosage form
destruction in gut
poor absorption
FPM
causes of poor absorption
molecule size
lipid solubility (easy absorbed)
degree of ionisation (very ionised not as easily absorbed)
3 aspects of drug distribution
compartments - dilution
lipid binding - slow release from accumulation
drug binding to plasma proteins
drug distribution - compartments
dilution
vascular, tissues, CNS
drug distribution - lipid binding
slow release from accumulation
drug distribution - drug binding to plasma proteins
bound = inactive = reservoir
interactions by competitive binding
e.g. aspirin higher affinity than Warfarin
excretion
renal, liver (bile), lungs, sweat, saliva
what organ can modify drug excretion secretions?
kidney
drug metabolism
phase 1 - inactivation
phase 2 - conjugation
drug metabolism phase 1
inactivation
change shape - doesn’t bind to receptor
oxidation, reduction, hydrolysis
drug metabolism phase 2
conjugation
glucuronidation, sulphation, methylation, acetylation, glutathione
where does drug metabolism happen?
liver
factors affecting drug metabolism
liver/kidney disease
interactions
some drugs increase activity of liver enzymes - increase rate
age - extremes have slower metabolisms and less plasma proteins
genetic factors
pharmacokinetics
what body does to drug - drugs don’t distribute evenly
pharmacokinetics - “body compartments”
single - behaves as if evenly distributed
2 compartment model - in equilibrium with different tissues in body
pharmacokinetics - more blood flow
tissue exposed to bigger doses
eventually - distribution equilibrium
drug clearance
removal of a drug from plasma
depends on 1/2 life
plasma half life
period of time required for conc/amount of drug in body to be reduced by half
what is the most common type of drug clearance?
1st order
1st order clearance
elimination/absorption by passive diffusion
drug removal proportional to drug conc
higher conc - moves quicker into urine/bile
curved graph
0 order clearance
active process - can be saturated by high drug conc
linear graph - straight line
enzyme system
think - ice cream scoop - fixed rate
2 examples of 0 order clearance
blood-alcohol elimination
paracetamol toxicity
drug accumulation
how plasma conc build if repeated doses of a drug are given
drug trial - dosing schedule
hazards of drug use
death - allergy/toxicity of drug
interactions - effect on absorption/metabolism of other essential meds
paracetamol
mechanism of action? anti-pyretic analgesic little anti-inflammatory action few SEs 1g x4 daily
LAs mechanism of action
1 - membrane expansion - forces pore closed
2 - acts on 2 gates- binds just under halt gate reversibly - stops Na+ getting in
esters metabolised in?
plasma
amides metabolised in?
liver
pH and LAs
pH sensitive in tissues
aspirin dose
300-600mg up to x4
aspirin kinetics
rapid absorption from GIT
1st order kinetics - unless overdose - enzyme saturation
aspirin mechanism of action
inhibits COX 1 prostaglandins
quick acting
anti-pyretic
analgesic
aspirin SEs
gastric irritation inhibits platelet fct bronchospasm (exacerbate asthma) allergic reactions drug interactions: significant protein binding, Warfarin potentiation association with problems in children
what can aspirin be used to reduce the risk of?
bowel cancer
stroke
cardiac problems
salicylates
aspirin
propionic acid derivatives
ibuprofen
phenylacetic acid derivatives
diclofenac
mechanism of action of NSAIDs
reduce inflammatory mediators
- inhibit prostaglandin synthesis
COX enzyme inhibition
- converts arachidonic acid - prostaglandins
change PGE1 and PGE2 balance - anti-inflammatory
- COX1 inhibitors
- COX2 inhibitors - reduce 1 SEs (caution with heart issues) e.g. celecoxib
what can NSAIDs cause GIT?
peptic ulcers
ibuprofen
same actions as aspirin
less SEs - safer
diclofenac
POM - more powerful inhibitor of enzyme pathway
- higher risk of gastric problems, asthma triggering, allergic reactions (rash)
more effective anti-inflammatory
diclofenac dose
50mg x3 daily
ibuprofen dose
200-600mg x3 daily
CS structure
ring
how do CSs reduce inflammation?
they inhibit:
- capillary permeability
- formation of bradykinin
- migration of WBC
- reduce eicosanoid synthesis
suppress inflammation features not cause
- don’t inhibit COX pathways
topical steroid tx for mouth ulcers
beclomethasone inhalers
hydrocortisone adhesive tablets
betamethasone solutions
systemic steroids - prednisolone
prevent transplant rejection
tx immunological diseases
systemic steroids - dexamethasone
injection
reduce swelling after surgery
SEs of steroids
high bp weight gain (fluid) centripetal obesity and 'buffalo hump' gastric ulceration adrenal suppression osteoporosis diabetes
BZDs mechanism of action
GABA agonists
- inhibitory neurotransmitter in CNS
anxiolytics
advantages of nitrous oxide
metabolised as soon as stop
no needle
amount of effect can be adjusted during procedure
no organ metabolism issues - excreted unchanged as gas
disadvantage of nitrous oxide
interferes with folic acid metabolism - avoid in pregnancy
oral anxiolytic
diazepam
IV sedation drug
midazolam
BZD metabolism
phase 1 - convert to metabolites
phase 2 - conjugation, convert to inactive metabolites
medical emergencies - adrenaline
1ml ampoules or prefilled syringes of 0.5ml of 1:1000 solution for IM injection
medical emergencies - aspirin
300mg dispersible tablets
medical emergencies - glucagon
1mg IM
medical emergencies - GTN spray
sublingual
400mcg per metered dose
medical emergencies - midazolam
oromucosal solution 5mg/ml
topical buccal administration
medical emergencies - oral glucose
non-diet fizzy drinks
glucose gel
powdered glucose
sugar lumps
medical emergencies - O2 cylinder
15l/min, enough for 30min supply
2 size D/CD or 1 size E
medical emergencies - salbutamol
inhaler 100mcg per actuation
what determines whether excreted in liver or kidney?
size of molecule with metabolites attached
drug graphs - oral
upside down U
drug graphs - IV
curve from top
drug graphs - IM
increases a little then curve from top
what do drug graphs give info for?
repeated timed doses to keep at therapeutic levels
routes of administration - ABs
oral
topical
IM
IV
mechanisms of action of ABs
bactericidal - kill bacteria
bacteriostatic - stop them growing, then host defences kill
1 - inhibit cell wall synthesis
2 - interfere with nucleic acids/metabolites
3 - inhibits protein synthesis
4 - cell membrane
vertical resistance
mutation
passed on in reproduction/replication
horizontal resistance
one species becomes resistant
pass it on via plasmids to own/other species
mechanisms of resistance
1 - reduce permeability 2 - inactivate antibiotic 3 - alter receptor site 4 - develop different metabolic pathway that drug doesn't act on 6 - can increase elimination
combating resistance
overexposure
- sort, correct doses
- targeted specific antibiotics not broad spectrum ones
penicillin mechanism of action
bactericidal - inhibits final step in cell wall synthesis
narrow/broad range
penicillin resistance
penicillinase (bacteria can sometimes produce it, inactivates and increases elimination)
metronidazole mechanism of action
acts on DNA of bacteria - inhibits protein synthesis
peripherally acting analgesics
aspirin
paracetamol
central acting analgesics
receptors in CNS
codeine, morphine
where are NSAIDs mostly absorbed?
stomach and SI
where are NSAIDs mostly excreted and what can be a consequence of this?
urine
could damage kidney if not drinking much - not a lot of fluid
where are opioids metabolised?
liver
where are opioids excreted?
urine
groups affecting safety
liver/kidney disease v elderly/young immunocompromised pregnant lactation
reducing risk of interactions
MH, check BNF
WARFARIN
alcohol - up regulates liver enzymes up to a point then liver disease
some ABs affect OCP
