Introduction Flashcards
Define pharmacology
Study of interactions of exogenously administered drugs with living system
Define drug
Any substance that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient
Pharmacotherapuetics
Application of pharmacological info with knowledge of disease for prevention mitigation and cure
Clinical pharmacology
Scientific study of drugged in man
Chemotherapy
Treatment of systemic infection/ malignancy with specific drugs that have selective toxicity
Drugs divided into
Pharmacodynamic agents
Chemotherapeutic agents
Pharmacology divided into
Pharmacodynamics - what drug does to the body
Pharmacokinetics - what body does to the drug
Four major routes of drug administration
enteral
parentral
pulmonary
topical
Commonly used routes:
Commonly used routes: oral(po), intravenous(iv), intramuscular(im), and subcutaneous(sc)
Weak acids exist more in non-ionized form in
Weak acids exist more in non-ionized form in the stomach, more in ionized form in the intestine
ion trapping
Non-ionized form of acidic drug which crosses the gastric mucosal membrane, reverts into ionized form(pH 7.0) and then slowly passes into ECF
Bioavailability (F)
Bioavailability (F)is the term used to indicate the fraction of the administered dose reaching systemic circulation
Rate of absorption must be at least …. times greater than rate of elimination to achieve meaningful plasma concentration
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Distribution of drugs-
Distribution of drugs-is the process of dissemination of drug molecules from the blood stream to body tissues and fluids
Four basic patterns of drug distribution:
1) Drugs with relatively high molecular weight e.g. dextran are confined to plasma water
2) Drugs that can pass capillary wall but can not pass across cell membranes e.g mannitol
3) Drugs that can pass freely across cell membranes but do not have a special affinity for a specific tissue e.g. alcohol
4) Drugs that concentrate specifically in one or more tissues of the body e.g. chloroquine in the liver
Apparent volume of distribution(Vd ) can be calculated by
Apparent volume of distribution(Vd ) can be calculated by dividing the administered dose with plasma concentration
Vd implications
Drugs extensively bound to plasma proteins are largely restricted to vascular compartment and have low Vd values,e.g. warfarin(99% bound) has a Vd 0.15L/kg
Drugs sequestered in other tissues have values much greater than the total body water or body mass,e.g. chloroquine Vd approx. 13000L
PPs that bind acidic drugs
PPs that bind basic drugs:
PPs that bind acidic drugs: albumins (mol. wt 66000);
PPs that bind basic drugs: alpha1 –acid glycoproteins
Drug metabolism (biotransformation):
Drug metabolism (biotransformation): irreversible chemical alteration of the drug in the body to another compound(metabolite
Biotransformation reactions are classified into two:
Biotransformation reactions are classified into two: phase I and phase II reactions
phase 1
Phase I introduce or unmask functional groups(-OH, -NH2, -SH)
Reactions involve oxidation, reduction and hydrolysis
phase 2
endogenous substrates such as glucuronic acid, sulphate, acetic acid or an amino acid combine with newly incorporated functional groups to form a highly polar conjugate
microsomal enzymes
These are located on
smooth endoplasmic reticulum
monooxygenases, cytochrome P450, UGTs,
epoxide hydrolases
They catalyse most of the oxidations, reductions, hydrolysis and glucuronide conjugation.
non microsomal enzymes
Present in the cytoplasm and mitochondria of hepatic cells as well as plasma. The
esterases, amidases, some flavoprotein oxidases and most conjugases are nonmicrosomal.
Reactions catalysed are:
Some oxidations and reductions, many hydrolytic reactions and all conjugations except glucuronidation.
Microsomal drug oxidations require
cytochrome P450, P450 reductase, NADPH and molecular oxygen
Drug+O2 +NADPH+H+ =Drug-OH +H2O+NADP+
Enzyme induction
process by which the expression and activity of an enzyme is increased in response to a specific stimulus, typically a molecule or compound that the enzyme is capable of metabolizing.
consequences of inducers
results in accelerated metabolism of the inducer(autoinduction) and other co-administered drugs
decreased efficacy of drugs(e.g. failure of contraception with oral contraceptives);
tolerance development
Prodrug’s effect is increased with inducers
Possible uses of enzyme induction:
Possible uses of enzyme induction:
Congenital nonhemolytic jaundice(due to deficient glucuronidation of bilirubin) ; phenobarbitone hastens clearance of bilirubin
Cushings syndrome; phenytoin reduces manifestations by enhancing degradation of adrenal steroids
Chronic poisoning; by faster metabolism of accumulated poisonous substance
Liver disease
Enzyme inducers include
Enzyme inducers include barbiturates, carbamazepine, rifampin, phenytoin, etc.
Enzyme inhibition: and inhibitor-
Enzyme inhibition: Some drug substrates inhibit CYP enzymes
Inhibitors: cimetidine, erythromycin, ketoconazole, etc.
Clinical consequences of enzyme inhibition:
increased concentration of the inhibitors or co-administered drugs which increases the effect, with likelihood of toxicity
Prodrugs effect can be decreased
Excretion of drugs and metabolites by kidney involves three processes:
Excretion of drugs and metabolites by kidney involves three processes:
Glomerular filtration
Active tubular secretion and
Passive tubular reabsorption(urinary pH plays a key role)
Drug elimination is the sum total of
Drug elimination is the sum total of metabolic inactivation and excretion
Kinetics of elimination:
Kinetics of elimination:
First order (exponential)kinetics
Zero order(linear) kinetics
first order
zero order
half life
t1/2= 0.7xVd /CL
maintainance dose
F
loading dose
F
cpss max
Cp,ss max =F x Dose / Vd / fraction lost in a dosing interval
cpss min
cpss max x fraction remaining
Revised dose rate
Revised dose rate = Previous dose rate x Target Cpss/ Measured Cpss
