This document discusses drug elimination kinetics. It describes the main routes of drug excretion from the body, including hepatic excretion through bile and renal excretion through glomerular filtration and tubular secretion/reabsorption. The kinetics of drug elimination are explained, including plasma half-life, repeated dosing to achieve steady state concentrations, and target level strategies using loading and maintenance doses. The principles of first-order and zero-order elimination, as well as therapeutic drug monitoring, are also outlined.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
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Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
A power point presentation on general aspects of Pharmacokinetics suitable for undergraduate medical students beginning to study Pharmacology. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
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Lecture Presentation in Basic Intravenous Therapy Seminar talks on Basic Pharmacology, the pharmacodynamics and pharmacokinetics, the common IV medications used, precautions and interactions of medications
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3. ROUTES OF DRUG EXCRETION
Hydrophilic compounds can be easily
excreted
Liver
Kidney
Sweat and saliva
Milk
Pulmonary
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4. HEPATIC EXCRETION
Drugs can be excreted in bile, especially when the are
conjugated with – glucuronic Acid
Portal
vein
Bile duct
Intestines
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5. ENTEROHEPATIC CYCLING
Eg. steroid hormones, rifampicin, amoxycillin,
contraceptives
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Drug is absorbed
glucuronidated or sulfatated in the liver
and secreted through the bile
glucuronic acid/sulfate is cleaved off by
bacteria in GI tract
drug is reabsorbed
6. RENAL EXCRETION
Glomerular Filtration
Depends on their plasma protein binding and renal
blood flow
Tubular Reabsorption
Back diffusion of Drugs (99%) – lipid soluble drugs
Depends on pH of urine, ionization
Tubular Secretion
Energy dependent
Utilized clinically – penicillin Vs probenecid, probenecid
Vs uric acid (salicylate)
Quinidine decreases renal and biliary clearance of
digoxin by inhibiting efflux carrier P-gp
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7. KINETICS OF ELIMINATION
Pharmacokinetics - F, V, CL, t1/2
Clearance: volume of plasma from which drug
is completely removed in unit time
CL = Rate of elimination /C
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8. PLASMA HALF-LIFE
Defined as time taken for its plasma concentration
to be reduced to half of its original value –
t1/2 = In2/k
In2 = natural logarithm of 2 (0.693)
k = elimination rate constant
Elimination rate constant = CL / V
t1/2 = 0.693 x V / CL
CL = RoE/C
V = dose IV/C
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10. REPEATED DOSING
At steady state, elimination = input
Dose Rate = target Cpss x CL
Oral administration
Dose rate = target Cpss x CL/F
Zero order kinetics: Michaelis Menten kinetics
RoE = (Vmax) (C) / Km + C
Vmax = max. rate of drug elimination
Km = Plasma conc at which elimination rate is half maximal
CL = Roe/C
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11. THE PLATUE PRINCIPLE
Repeated dosing:
• When constant dose of
a drug is repeated before
the expiry of 4 half-life –
peak concentration is
achieved after certain
interval
• Balances between dose
administered and dose
interval
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16. KINETICS OF ELIMINATION
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FIRST ORDER ZERO ORDER
Drug eliminated in
unit time
Constant fraction Constant amount
Nature Elimination proportional to
drug concentration
Elimination saturates at
higher concentration
Plasma
concentration – time
curve
Exponential decay Linear decay
On log scale linear Non- linear
kinetics Linear kinetics Non linear kinetics
Drugs Most drugs(95%) Alcohol, aspirin, warfarin,
theophylline
17. TARGET LEVEL STRATEGY
Low safety margin drugs (anticonvulsants, antidepressants,
Lithium, Theophylline – maintained at certain concentration
within therapeutic range
Drugs with short half-life (2-3 Hrs) –administered at conventional
intervals (6-12 Hrs) – fluctuations are therapeutically acceptable
Long acting drugs:
Loading dose: Single dose or repeated dose in quick succession –
to attain target conc. Quickly
Loading dose = target Cp X V/F
Maintenance dose: dose to be repeated at specific intervals
Maintanace dose = ssPC X Clearance/F
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18. THERAPEUTIC DRUG MONITORING(TDM)
Useful in
Narrow safety margin drugs – digoxin, anticonvulsants,
antiarrhythmics and aminoglycosides
Large individual variation – lithium and antidepressants
Renal failure cases
Poisoning cases
Not useful in
Response measurable drugs – antihypertensives
Drugs activated in body – levodopa
Hit and run drugs – Reseprpine, MAO inhibitors
Irreversible action drugs – Organophosphorous compounds
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Faeces: Liver actively transport drugs and its metabolites into bile (Glucoronides). OATP – orgnic acids and OCT – organic bases. Other lipophillic drugs – by P-gp. Most lucoronides are deconjugated by bacteria and reabsorbed in intestine – enterohepatic circulation. Drugs – erythromycin, rifmpicin and tetracycline etc. Ultimate excretion occurs in urine
Milk – not importnt for mother but for fetus. Basic drugs can pass to milk as it has slightly lower pH Drugs –
Saliva – Lithium, KI, heavy metals and rifampicin
Although Cpss cn be calculated, its real value actually varies with individuls – deviation from averge ptients