pharmacology Flashcards
what are the 4 drug targets
enzyme
receptor
ion channel
transport protein
what are the 4 ways drug can react with receptors through chemical reactions
electrostatic interactions
hydrophobic interactions
covalent bonds
stereospecific interactions
what do u call full affinity but 0 efficacy drug
antagonist
what is the standard measure of potency
determine concentration or dose of a drug required to produce 50% tissue response
which is related to dose, potency or efficacy
potency
in ionised form, will the acid donate or accept protons
donate
in ionised form, will the base donate or accept protons
accept
what determines whether the drug is ionised or not
pH
pKa
what happens when pKa of drug and pH of tissue is equal
drug 50% ionised 50% unionised
for weak acid, when pH decreases which form will start to dominate
unionised form
for weak base, when pH increase, which form starts to dominate
unionised form
for weak base when pH decreases which form dominates
ionised form
different forms of drug administration
oral
inhalational
dermal(percutaneous)
intra-nasal
what affects diffusion of drug
lipid solubility
what influence tissue distribution
regional blood flow
plasma protein binding
capillary permeability
tissue localisation
factors affecting amount of drug that is bound
free drug conc
affinity of protein binding sites
plasma protein conc
what are the different types of capillary structure
continuous
fenestrated
discontinuous
BBB
which enzyme is responsible for drug metabolism
P450 enzymes
what are the phases of drug metabolism
phase 1 – introduce a reactive grp to a drug
phase 2 – add a conjugate to reactive grp
what are the main aims of the 2 stages in drug metabolism
decrease lipid solubility to aid excretion and elimination
what are the major excretion methods for drug via kidney
glomerular filtration
active tubular secretion (or reabsorption)
passive diffusion across tubular epithelium
what is the drug target if metformin
AMPK (5′-AMP-activated protein kinase (AMPK)
where is the primary site of metformin action
hepatocyte mitochondria
mechanism of action of metformin
inhibits gluconeogenesis and hence glucose output
metformin activates AMPK to inhibit ATP production to block gluconeogenesis, block adenylate cyclase to promote fat oxidation to restore insulin sensitivity
side effects of metformin
GI (abdominal pain, reduced appetite, diarrhoea, vomit)
why metformin can accumulate in liver and GIT
it’s high polar and need organic cation transporter-1 (OCT-1) to access tissue
when is metformin most effective in a patient
with presence of endogenous insulin / functioning pancreatic islet cells
example of DPP-4 inhibitors
sitagliptin
what is the primary site of DPP-4 inhibitors
vascular endothelium
main action of DPP-4 inhibitors
reduce break down of insulin / increase insulin production
mechanism of action of DPP-4 inhibitors
DPP-4 metabolise incretins in plasma which incretins help to stimulate production of insulin and reduce production of glucagon by liver
by inhibiting DPP-4, can let incretin remain to stimulate insulin production
side effects of DPP-4
upper respiratory tract infections (flu like symptoms)
allergic reaction
which patients shd avoid DPP-4 inhibitors
patients with pancreatitis
main benefit of DPP-4 inhibitors compared to other anti-diabetic drug
no weight gain
when is DPP-4 inhibitors effective
when residual pancreatic beta-cell activity is present
examples of sulphonylurea
gliclazide
target of sulphonylurea
ATP sensitive K+ channel
primary site of sulphonylurea
pancreatic Beta cells
main action of sulphonylurea
stimulate insulin production
mechanism of action of sulphonylurea
inhibit K+ ATP channel on pancreatic beta cell
cause depolarisation and stimulate Ca2+ influx and hence insulin vesicle exocytosis
side effects of sulphonylurea
wight gain
hypoglycaemia
when is sulphonylurea most effective
when residual pancreatic beta cell activity is present
risk of sulphonylurea
hypoglycaemia
examples of SGLT-2 transporter inhibitors
dapaglifozin
target site of SGLT-2 inhibitors
PCT
mechanism of action of SGLT-2 inhibitors
inhibit SGLT-2 in PCT to reduce glucose reabsorption and increase urinary glucose excretion
side effects of SGLT-2 inhibitors
uro-genital infections due to increase glucose load
decrease in bone formation
worsen diabetic ketoacidosis
physiological changes of SGLT-2 inhibitors
reduce weight
reduce BP
in which patients are SGLT-2 inhibitors less effective
renal impairment
what to administer when HbA1c > 48
standard release metformin
what to administer when HbA1c > 58
metformin + one of below
DPP-4 inhibitors
Pioglitazone
Sulphonylurea
SGLT-2 inhibitor
which transporter does metformin use
organic cation transporter -1 (OCT-1)
where is OCT-1 found in body
hepatocytes (liver) allow it to be absorbed
enterocytes (Small bowel) to be distributed to site of action
PCT (kidney) help excretion
risk of pioglitazone
heart failure
mechanism of pioglitazone
reduces peripheral insulin resistance, leading to a reduction of blood-glucose concentration.
why metformin may lead to lactic acidosis
accumulate metformin in bloodstream
block pyruvate carboxylase
inhibit gluconeogenesis and pyruvate build up
cause lactic acidosis
