Pharmacokinetics Flashcards
(26 cards)
What is pharmacokinetics
It is the branch of pharmacology tht deals with absorption distribution metabolism and excretion of drugs
Plasma half life t1/2
It is the time taken by a drug to become half of its previous concentration in plasma
Depends on volume of distribution (Vd) and clearance
T1/2 = 0.693× Vd / CL
Why half life is imp
Construction of dosing schedule
To maintain steady state concentration
Estimation of time tk eliminate the drug
Guideline for duration for drug action
Drugs with long half life
Diazepam
Digoxin
Digitoxin
Azithromycin
Ceftrioxone
Doxycycline
Drugs with intermediate half life
Atenolol
Drugs with short half life
Benzyl penicillin
Dobutamine
Factors affecting absorption of drug
- Drug factors
- Solubility
Lipid soluble drug: more absorbed
Water soluble drug: less absorbed - Ionization of drug or polarity
Unionized or non polar drug is more absorbed
Ionized or polar drug is less absorbed
3.pka of drug and ph of environment
Basic drug; more absorbed in basic and less abs in acidic env
Acidic drug: more absorbed in acidic and less absorbed in basic env.
4.Molecular wt and size:
Drugs with smaller molecular wt absorbs more easily than drugs with high molecular wt. - Formulation factors:
Solid formulation: Delays absorption
Liquid formulation: fast absorption
Suspension of fine particles
: better abs than solid formulation - Disintegration and dissolution time
Tablet and capsule : disintegration and dissolution time
Granules and powder: dissolution
Liquid : bypass both - First pass metabolism
B. Host factors
1. blood flow to the absorption site . Inc blood flow inc absorption
2. Total surf Area available for absorption. Highest abs in intestines
3. Presence or absence of food in stomach
Inc abs in presence of food in case of : griseofulvin; propranolol, hydralazine ; riboflavin
Decreased abs in presence of food: ampixillin , aspirin, doxycycline ,tetracycline
4. Rate of gastric emptying
Inc gastric emptying time: increased absorption and vice versa
5. Intestinal motility
Increased motility decreased absorption and vice versa
6.contact time at absorption surface. Inc contact time Inc absorption
7. Efflux transporter.
Transport mechanism for drug
- Passive transport
.Simple diffusion
Eg. Aspirin , barbiturates, morphine
.Filtration
Eg .aminoglycosides pass through glomerular filtration
Bulk flow
Eg.
- Specialized transport
Active transport
Iron , levodopa, alpha methyl dopa, amino acid
Facilitated diffusion
Eg. Vit b12 and tetracycline
Endocytosis
Pinocytosis
Ion pair transport
Which is the most common transport mechanism and why
Drugs move from higher conc to lower conc
No carrier needed
No energy needed
Pressure gradient acts as a driving force
Process is not saturable
Lipid soluble drugs are mostly absorbed.
Eg. Aspirin, barbiturates, morphine, sulphonamide
Criteria of active transport
Drug molecule moves from lower conc ti higher conc
Carrier is needed
Energy is needed
Highly specific
Saturable process
Eg. Iron, levodopa, alpha methyl dopa
Define bioavailability
Bioavailability is defined as the unchanged fraction of a drug reaching the systemic circulation following administration by any route.
Bioavailability (F)= 1 means 100%
F=100% when administered through IV route
F<100% when given by other route
Bioavailability is estimated from AUC
Formula: AUC/AUCiv ×100
Factors affecting bioavailability
A. Factors affecting absorption
1. Drug factors
1. Solubility
Lipid soluble drug: more absorbed
Water soluble drug: less absorbed
2. Ionization of drug or polarity
Unionized or non polar drug is more absorbed
Ionized or polar drug is less absorbed
3.pka of drug and ph of environment
Basic drug; more absorbed in basic and less abs in acidic env
Acidic drug: more absorbed in acidic and less absorbed in basic env.
4.Molecular wt and size:
Drugs with smaller molecular wt absorbs more easily than drugs with high molecular wt.
5. Formulation factors:
Solid formulation: Delays absorption
Liquid formulation: fast absorption
Suspension of fine particles
: better abs than solid formulation
6. Disintegration and dissolution time
Tablet and capsule : disintegration and dissolution time
Granules and powder: dissolution
Liquid : bypass both
7. First pass metabolism
- Host factors
- blood flow to the absorption site . Inc blood flow inc absorption
- Total surf Area available for absorption. Highest abs in intestines
- Presence or absence of food in stomach
Inc abs in presence of food in case of : griseofulvin; propranolol, hydralazine ; riboflavin
Decreased abs in presence of food: ampixillin , aspirin, doxycycline ,tetracycline - Rate of gastric emptying
Inc gastric emptying time: increased absorption and vice versa - Intestinal motility
Increased motility decreased absorption and vice versa
6.contact time at absorption surface. Inc contact time Inc absorption - Efflux transporter
B. Factors affecting first pass metabolism
1. Routes of drug administration
2. Hepatic circulation
3. Hepatic biotransforming enzyme activity
4. Hepatic diseases
What is first pass metabolism
It is the metabolism of a drug during its passage from the site of absorption to the systemic circulation.
Sites of fpm
Liver
Lungs
Intestinal wall
Stomach
Drugs with high first pass metabolism
Nitroglycerin
Propranolol
Salbutamol
Define volume of distribution of drug
Vd volume of distribution is the volume of fluid in the body in which a drug is distributed at the same concentration as in plasma
Vd= total amt of drug/ plasma conc of drug
Factors affecting volume of distribution of drug
- polarity of drug: non polar= less distribution
2.degree of plasma protein binding :more= less distribution - Solubility: more lipid soluble= more distribution
- Cellular or tissue binding:
More binding= more distribution - Pathological conditions such as chr. Heart failure, uremia, liver cirrhosis
- Special barriers;
Blood brain barrier
Placental barrier - Molecular wt: high= less distribution
Plasma proteins
- Albumin
- a1 acid glycoprotein
- Globulin
Significance of plasma protein binding
- Drug transport
- Prolongs half life
- Creates higher concentration in blood than in ICF
- Slows down metabolism
- Drug reservoir: provides depot
6.drug interactions
Drugs with high plasma protein binding
Warfarin
Carbamezipine
Salicylate
Tolbutamide
Diazepam
Valproic acid
Phenytoin
Different types of drug doses
1.Suppository: inserted into rectum
2.ointment: greasy preparation
3. Paste: semisolid preparation
For external application
4. Cream: miscible with skin secretion
5. Solution: homogenous preparation
6. Suspension: heterogenous system of liquid dosage
7. Emulsion
8. Parenteral preparations
9. Topical preparation
10. Inhaler
11. Nasal prep
12. Ear prep
14. Eye preparation
15. Rectal preparation
16. Vaginal preparation
Fixed dose combination
When two or more drugs are combined to be given as a single preparation.
Eg. Rifampicin+ isoniazid+ pyrazinamide+ ethambutol in tb
Oestrogen + progesterone as ocp
Cotrimoxazole(trimethoprime + sulphamethoxazole)
Adv: synergistic effect that increases efficacy
Reduces adverse effects
Prevents drug resistance
Reduces drug cost
Disadv
Reduced flexibility in dose adjustment
Difficult to assess side effects
Increased risk of toxic effects
