Lecture 2 - Drug target interactions and clinical effects Flashcards
describe pharmacokinetics vs pharmacodynamics
pharmacokinetics is what the body does to the drugs - ADME
pharmacodynamics is the effect of the drug on the body - targets
describe absorption of the body on the drug.
drugs characteristics that affect drug absorption
- molecular weight, ionisation, solubility, and formulation
- liberation (pharmacology)
factors that affect drug absorption related to the patient
- gastric pH, route of administration and contents of the GI tract
treatment
- onset of acute
- acute symptoms vs chronic condition
dosage regime
- solubility and elimination
describe distribution of a drug in the body
membrane permeability
- cross the membrane to the site of action
protein plasma binding
- bound drugs cannot cross the membrane
- malnutrition = decreased albumin which increases free drug
Lipohilicity of the drug
- lipophilic rugs accumulate in adipose tissue
- volume of distribution: large volume of distribution = extensive in tissues
Describe digoxin and its distribution in the body
digoxin in a Na-K ATPase inhibitor
it is a cardiac glycosides (used to treat heart failure and irregular heartbeat)
70 to 80% of oral dose is absorbed
half-life is 26-45 hours
digoxin is extensively distributed in tissues which is reflected by its large volume of distribution
describe metabolism of a drug in body
liver - the main routeof drug metabolism
the liver can also be used to convert pro-drug(inactive) to an active state
two types of reactions
- Phase I (cytochrome p450)
-Phase II
describe statins and their metabolism in the body
some are prodrugs
CYP3A4 metabolism
grapefruit interactions with warfarin/ coumarins
interactions with certain antimycotics
describe ADME or PK considerations
steady state: drug that is administered is equal to the amount of drug eliminated in one dosing interval resulting in a plate or constant serum drug levels
drugs with a shorter half life reach steady state faster. drugs with a long half life can take days to weeks to reach steady state
loading dose: allows rapid achievement of therapeutic serum levels
describe enzyme kinetics
follows linear kinetics until enzymes become saturated
enzymes that are responsible for metabolism/ elimination become saturated resulting in a non-proportional increase in drug levels
describe the pharmacodynamics: efficacy and potency
efficacy is the degree to which a drug is able to produce the desired effect
potency is the amount of drug required to produce 50% of the maximal response the drug is capable of inducing
- used to compare compounds within classes of drugs
describe the other pharmacodynamics
effective concentration 50% - this is the concentration that specifically induced for a clinical response in 50% of subjects
lethal dose 50% - this is the concentration of drug which causes death in 50% of subjects
therapeutic index - this is a measure of the safety of the drug - LD50 / ED50
margin - this is the margin between the therapeutic effect and the lethal doses of a drug
what do most drugs bind to?
most drugs bind to cellular receptors
- a ligand that binds and activates a receptor is an agonist
neurotransmitters and hormones are endogenous ligands
drugs are exogenous
pharmacological effects are due to alteration of an intrinsic physiological pathway and not the creation of a new process
- with side effects
how do other drugs work?
some drugs work without any direct innervation within the cell
example: mannitol interferes osmotically with water reabsorption by the kidneys
what are cell surface receptors?
proteins and glycoproteins
- found in the cell surface, on an organelle within the cell or in the cytoplasm
finite number of receptors in a given cell
- receptor mediate responses upon saturation of all receptors
what are drug receptors?
action occur when a drug binds to a receptor and the action may be:
- ion channel open or closes
- second messenger is activated
cAMP, cGMP, inositol phosphate and ca2+
initiates a series of chemical reactions
- cellular functions can be ‘turned off’ or ‘turned on’
what types of drugs causes contraction?
agonists
- noradrenaline
histamine
angiotensin
calcium Channel blockers
what drugs causes relaxation?
potassium channel activators
agonist
adenose
beta agonists
prostaglandins
PDE inhibitors
what is CVD pharmacology?
basis of therapeutics
homeostasis of blood pressure
treatment
- manipulation of cardiac output, peripheral vascular resistance and blood volume
prevention
- reduce platelet adhesion and reduce cholesterol
name ace inhibitors, arbs and aldosterone antagonists
ACE inhibitors
- lisinopril, ramipril and enalapril
arbs
- losartan, irbesartan
Aldosterone antagonists
- spironolactone, eplerone
what it the treatment of heart failure?
heart failure
- increase in cardiac efficiency
- reduce cardiac oxygen demand
- diuretics
vasodilators
positive inotropic drugs
negative inotropic drugs
what is CVD pharmacology in reducing atherosclerosis?
reduce platelet adhesion
reduce cholesterol
what drugs reduce platelet adhesion ?
irreversibel cyclocygenase
- aspirin
adenosine diphosphate inhibit
- clopidogrel
how is cholesterol reduced?
HMG - CoA reductase inhibitors
bile acid sequestrate
fibrates
choelsterol absorption inhibitors
describe elimination of drug in the body
pulmonary = expired in air
bile acid excreted in faces
- enterohepatic circualtion
renal
- glomerular filtration
- tubular secretion
- tubular reabsorption
