intro to pharmacology and therapeutics Flashcards
5 factors needed for prescribing
medicine, dose, route, frequency, duration
what is pharmacodynamics
the study of biochemical and physiological effects of drugs on the body
‘what the body does to the drug’
4 types of receptors
channel linked receptors
G protein coupled receptors
Enzyme-linked receptors
nuclear receptors (intracellular receptors)
different targets of drug action
receptors, ion channels, enzymes, transporters
4 drugs related to treatment of hypertension
atenolol - blocks response to noradrenaline
ramipril - prevents formation of vasoconstrictors
amlodipine - blocks calcium channels (important in vasoconstriction)
bendroflumethiazide - acts in kidneys reducing reabsorption of sodium
drug dose response curve?
work out maximum response - Emax
ED50 (effective dose 50) - produces 50% of Emax
what is therapeutic index?
gap between beneficial effects and adverse effects - difference between doses
competitive vs non competitive antagonsists
competitive - block receptors
non-competitive - interfere with signal transduction mechanism
what effects do antagonists have on dose response curves
increased dose for same effect - shift to right
what is efficacy
the extent to which a drug can have its effect (greater Emax - high efficacy)
what is potency
amount of drug required to have a specific effect (lower dose for same effect would have high potency)
what is selectivity
receptors slightly different in different areas- different areas more or less likely to respond to same drug dosage
desensitisation
response tails off over time
gradual desensitisation over longer period of time?
tolerance
rapid desensitisation over short period of time
tachyphylaxis
causes of desensitisation - pharmocodynamic
reduction in receptor number
changes in receptor structure or function
exhaustion of mediators
physiological adaption
reduced drug response other than pharmocodynamic reasons
altered physiology (eg gained weight)
disease progression
drug interactions
reduced adherence (bad drug giving by patients)
pharmacokinetics?
what a drug does to the body
what are the four stages of drug handling
absorption
distribution
metabolism
excretion
how is pharmacokinetic handling of a drug influenced
physiological factors - age, sex, body, height
external factors - food, other drugs
different oral routes?
swallowing
buccal - tablet between upper lip and gum
sublingual - tablet beneath tongue
buccan and sublingual involve drugs being absorbed into capillaries of oral circulation
non oral routes of drug administration
intravenous
intramuscular
subcutaneous
inhaled
rectal
transderm
pros and cons of intramuscular injection
rapid effect but rate of absorption highly dependent on muscle blood flow
skin as a route of absorption?
transdermal - adhesive skin patches
topical - lotions/creams/etc
what is bioavaliability
fraction of administered drug that reaches systemic circulation
what is the most important limitation on absorption
‘First pass’ metabolism by enzymes in intestinal wall and liver
gut enzymes?
monoamine oxidase
L-aromatic amino acid decarboxylase
cytochrome P450 isoform 3A4
phase 2 conjugating enzymes
membrane transporters
what system in the liver accounts for most first-pass metabolism of oral drugs
phase 1 metabolising enxymes of the cytochrome P450 system
when is rectal administration useful
drugs used to soften faeces in constipated patients
useful for patients who cannot swallow and there is no suitable injectable formulation
features of intravenous injection
most direct route of entry, entire dose is bioavailable
what is a low therapeutic index
narrow range between lowest effective dose and highest safe dose
differences of peak concentration of oral and intravenous injection
lower and delayed for oral
movement of drug molecules after absorption through different fluids
plasma to interstitial to intracellular fluid
equilibrium and drug administration?
equilibrium will eventually be reached between plasma/interstitial/intracellular fluid. drug will be eliminated from plasma (metabolism or excretion) causing gradient moving drug out of tissues - unless further drug administration occurs
what does distribution of drug molecules between compartments depend on
molecular size, lipid solubility, ionisation, binding to plasma proteins, rate of blood flow, special barriers, drug affinity for specific tissues
how does the vast majority of drugs cross membranes
simple diffusion
what does rate of transfer of drug molecules by diffusion depend on
concentration gradient, the molecule, the membrane
how do drugs move across cell membranes other than passive diffusion
pore-mediated diffusion, pinocytosis
what is pinocytosis
form of endocytosis. invagination of part of cell membrane, vesicle created which traps extracellular constituents within cell. contents released in cell or extruded by fusion with another membrane
drugs that bind to plasma proteins? pros and cons?
aspirin, diazepam, phenytoin, warfarin.
stay in body longer, less efficient distribution, lower therapeutic activity, less available for dialysis after toxic doses
two phases of metabolism
phase 1 - non-synthetic - oxidation/reduction/hydrolysis
phase 2 - synthetic - conjugation with natural endogenous constituent resulting in more soluble product easier to excrete
factors effecting drug metabolism
genetics, age, sex, nutrition, disease, drugs, dose, route
routes of drug excretion
faeces, bile, breath, sweat, urine, breast milk
what must a drug be to be excreted
water-soluble
mechanisms of renal excretion
glomerular filtration
tubular secretion
tubular reabsorption
what is the law of mass action
the rate of a chemical reaction or process is directly proportional to the concentrations of the reactants
first-order kinetics
constant fraction of remaining drug eliminated in a given time - usually 50% (half life)
zero-order/saturation kinetics? drug examples?
concentration/time graph forms a straight line
phenytoin, aspirin, paracetamol
what are modified-release versions of medicines
release of drug in small bowel delayed so absorption occurs over longer period of time, prolonged effects
hepatic extraction ratio?
high hepatic extraction ratio drugs will be extensively metabolised.
what is the determinant of the rate at which steady state is achieved
half-life (not dose interval)
