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Questions and Answers
What is the study of substances that interact with living systems to activate or inhibit normal body processes called?
What is the study of substances that interact with living systems to activate or inhibit normal body processes called?
Pharmacology
Simple diffusion depends on the concentration gradient, molecular size, lipid solubility, and degree of ionization.
Simple diffusion depends on the concentration gradient, molecular size, lipid solubility, and degree of ionization.
True
Which process involves the passage of drugs across cell membranes by any of the following methods?
Which process involves the passage of drugs across cell membranes by any of the following methods?
______ of drugs are determined by factors related to the drug and the patient.
______ of drugs are determined by factors related to the drug and the patient.
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What does Vd stand for in pharmacokinetics?
What does Vd stand for in pharmacokinetics?
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Which of the following is a result of Phase I reactions in drug metabolism?
Which of the following is a result of Phase I reactions in drug metabolism?
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Enzyme inducers decrease the effects of other drugs.
Enzyme inducers decrease the effects of other drugs.
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Enzyme inhibition can cause ________ drug interactions.
Enzyme inhibition can cause ________ drug interactions.
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Match the drug excretion route with the example drug:
Match the drug excretion route with the example drug:
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Cefoperazone belongs to which generation of cephalosporins? It is known for being less effective on gram +ve cocci but more active on gram-ve bacilli. It has the unique characteristic of not passing through the ________.
Cefoperazone belongs to which generation of cephalosporins? It is known for being less effective on gram +ve cocci but more active on gram-ve bacilli. It has the unique characteristic of not passing through the ________.
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Which antibiotic is extremely toxic and is used only topically in skin and gut infections?
Which antibiotic is extremely toxic and is used only topically in skin and gut infections?
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Tetracyclines have a bacteriostatic effect by binding to the 50s subunit of bacterial ribosomes.
Tetracyclines have a bacteriostatic effect by binding to the 50s subunit of bacterial ribosomes.
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What is the common adverse effect associated with fluoroquinolones due to their interaction with sunlight?
What is the common adverse effect associated with fluoroquinolones due to their interaction with sunlight?
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Match the antibiotic with its mechanism of action:
- Clindamycin
- Rifampicin
Match the antibiotic with its mechanism of action:
- Clindamycin
- Rifampicin
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What is the formula for plasma half-life of a drug (t ½)?
What is the formula for plasma half-life of a drug (t ½)?
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Which type of drug kinetics is directly proportional to dose and has a constant t ½?
Which type of drug kinetics is directly proportional to dose and has a constant t ½?
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Drug tolerance can be either congenital or acquired.
Drug tolerance can be either congenital or acquired.
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Match the adverse drug effect with the correct description:
Match the adverse drug effect with the correct description:
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Idiosyncrasy is also known as _________.
Idiosyncrasy is also known as _________.
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Study Notes
Compartmental Distribution
- The interstitial compartment holds 12-14 liters of fluid.
- The plasma compartment holds 4 liters of fluid.
- The volume of distribution (Vd) is the apparent volume of fluid required to distribute a drug evenly throughout the body.
- Phenytoin has a Vd of 3-4 liters.
- Aspirin has a Vd of 4 liters.
Selective Distribution
- Iodide is selectively distributed in the thyroid gland.
- Tetracycline is selectively distributed in bone and teeth.
- Calcium is selectively distributed in bones.
- Aminoglycosides (e.g., streptomycin) are selectively distributed in the kidney and vestibular system.
Clinical Importance of Vd
- Vd indicates whether a drug is concentrated intra-vascularly or extra-vascularly.
- Vd is constant for each drug and changes in Vd can indicate disease states (e.g., liver cirrhosis or edematous conditions).
- Dialysis is not useful for drugs with high Vd (extensive tissue distribution).
- Vd helps in estimating the total amount of drug in the body at any time.
- Vd is important for determining the loading dose.
Protein Binding
- There are two forms of a drug: bound and free.
- The bound form is inert, non-diffusible, and not available for metabolism or excretion.
- The free form is active, diffusible, and available for biotransformation and excretion.
- Significance of protein binding:
- Affects drug interactions.
- Hypoalbuminemia (e.g., in starvation and malnutrition) can lead to increased free drug concentration.
- Drugs with high binding capacity persist in the body longer and are less available for dialysis.
- The rate of injection of a highly bound drug affects the concentration of the free form.
Biotransformation
- Phases of biotransformation:
- Phase I (non-synthetic) reactions: oxidation, reduction, and hydrolysis.
- Phase II (synthetic) reactions: conjugation with glucuronic acid, glutathione, glycine, sulfate, and acetic acid.
- Phase I reactions result in:
- Drug inactivation.
- Inactive to active metabolite.
- Active to active metabolite.
- Toxic metabolite.
- Phase II reactions result in:
- Inactivation (with few exceptions).
- Most drugs pass through both phase I and phase II reactions.
Sites of Biotransformation
- Microsomal enzymes: responsible for most oxidative reactions, affected by age, and inducible by drugs.
- Non-microsomal enzymes: present in liver, kidney, plasma, skin, and GIT, and are not inducible by drugs.
Factors Affecting Drug Metabolism
- Drugs:
- Induction: increases enzyme synthesis.
- Inhibition: decreases enzyme activity.
- Genetics:
- Genetically determined polymorphisms affect enzyme activity.
- Nutritional state:
- Conjugating agents (e.g., sulphate, glycine) are affected by body nutrient level.
- Age:
- Drug metabolism is reduced in extremes of age.
- Gender:
- Metabolism is faster in men for certain drugs (e.g., diazepam, caffeine) and faster in women for certain drugs (e.g., propranolol, lidocaine).
- Disease state:
- Liver disease: reduces drug metabolism.
- Heart failure: reduces hepatic flow and affects rapidly metabolized drugs.
- Kidney disease: affects the excretion of drugs.
Renal Excretion
- Factors affecting renal excretion:
- Glomerular filtration rate.
- Change in urinary pH: affects the excretion of weak acid and weak base drugs.
Other Routes of Excretion
- Bile: eliminates certain drugs (e.g., ampicillin, rifampicin) through enterohepatic circulation.
- Sweat: eliminates certain drugs (e.g., rifampicin, vitamin B1).
- Lungs: eliminates gases and volatile anesthetics.
- Milk: eliminates certain drugs (e.g., morphine, amphetamine, chloramphenicol, oral anticoagulants).
Pharmacodynamics
- What the drug does to the body:
- Physical action: e.g., kaolin adsorbs toxins.
- Chemical action: e.g., HCl + NaHCO3.
- Cytotoxic action: e.g., anticancer drugs.
- Interference with selective passage of ions: e.g., local anesthetics.
- Interference with normal metabolic pathway: e.g., sulphonamides.
- Action on specific receptors: e.g., hormone, neurotransmitter.
Affinity and Potency
- Affinity: the tendency of a drug to bind to receptors.
- Potency: the amount of ligand required to elicit a response.### Classification of Cephalosporins
- First generation:
- Oral: cephalexin, cephradine, cefadroxil
- IV/IM: cefazolin, cephlothin, cephaporin
- Activity: Gram +ve cocci (pneumococci, streptococci, staphylococci) and Gram -ve (Proteus, E. coli, Klebsiella)
- Not effective against CSF
- Second generation:
- Oral: cefaclor, cefuroxime
- IV: cephmandole, cefoxitin, cefoncid
- Activity: As 1st generation + H. influenzae, Neisseria
- Not effective against CSF
- Third generation:
- Oral: cefixime, cefpodoxime
- IV: cefoperazone, cefotaxime, moxalactam, ceftriaxone
- Activity: Less effect on Gram +ve cocci, more active on Gram -ve bacilli
- Effective against CSF (except cefoperazone)
- Fourth generation:
- IV: cefipime
- Activity: As 3rd generation, more resistant to beta-lactamase
- Effective against CSF
Kinetics of Cephalosporins
- Absorption and passage to CSF related to generation
- Pass placenta
- Excreted by kidney (except cefoperazone and ceftriaxone, which are excreted in bile)
Uses of Cephalosporins
- Infections by Klebsiella, Enterobacter, Hemophilus
- Gonorrhea (ceftriaxone)
- Meningitis (3rd and 4th generation)
- Anaerobic infection (cefoxitin)
- Typhoid fever
Toxicity of Cephalosporins
- Allergy, cross allergy
- Nephrotoxicity (cephaloridine) especially with loop diuretics and aminoglycosides
- Thrombophlebitis (IV)
- Pain (IM)
- Anti-vitamin K effect (cefamandole, cefoperazone, moxalactam)
- Disulfram-like action (moxalactam)
Mechanism of Action of Cephalosporins
- Bactericidal, binds to 30S subunit of microbial 70S ribosome, misses mRNA message, and produces non-functional protein
Aminoglycosides
- Mechanism of action: Irreversible binding to 30S subunit of microbial 70S ribosome, misses mRNA message, and produces non-functional protein
- Poorly absorbed orally, do not penetrate CSF, more active in alkaline medium
- Include: Streptomycin, Neumycin, Kanamycin, Tobramycin, Amikacin, Paromamycin
- General adverse effects: Ototoxic, Nephrotoxic, Neuromuscular blocking effects
Tetracycline
- Mechanism of action: Bacteriostatic, binds to 30S subunit of bacterial ribosome, inhibits protein synthesis
- Spectrum: +ve, -ve bacteria, Rickettsia, Chlamydia
- Kinetics: Incomplete oral absorption, absorption decreased with food, excreted in bile and urine
- Uses: Gonorrhea, Syphilis, Bacillary dysentery, Cholera, Mycoplasma, Acne, Eye infection, Amoebiasis
- Toxicity: GIT upset, Chelation with Ca in bone and teeth, Teratogenic, Photosensitivity, Hepatic toxicity, IM injection pain, IV injection thrombosis
Erythromycin
- Mechanism of action: Irreversible binding to 50S subunit of bacterial ribosome, inhibits protein synthesis
- Activity: Bacteriostatic in low concentration, bactericidal in high concentration, affects Gram +ve as (Pneumococci, Streptococci, Staphylococci, Diphtheria, Corynebacterium) and Gram -ve (H. influenzae, Legionella) and Mycoplasma, Chlamydia, Treponema palladium
- Kinetics: Given orally in enteric coated form, destroyed by HCl, activity increased in alkaline medium, distributed to all tissues except CSF, metabolized in liver, excreted in urine and bile
- Uses: Diphtheria, Pneumonia, UTI with Chlamydia during pregnancy, Penicillin allergic patients
- Adverse effects: GIT upset, Cholestatic jaundice, Fever, Rash, Eosinophilia
- Interaction: Decrease cytochrome P450, increase warfarin
Quinolones
- Mechanism of action: Bactericidal, interferes with DNA gyrase enzyme, inhibits replication of bacterial DNA
- Activity: Mainly Gram -ve, less effect on Gram +ve
- Kinetics: Absorbed orally or injection, fluorinated form distributed to all tissues, metabolized in liver, excreted in urine, milk, and bile
- Uses: UTI, Infectious diarrhea, Soft tissue, Bone, and Joint infection, Respiratory infection, Resistant TB
- Adverse effects: Allergy, Photosensitivity, CNS: Headache, Dizziness, Confusion, Avoid driving, Seizures, Chondrolytic effect, Avoid in pregnancy, lactation, and children up to 18 years
- Contraindication: Pregnancy, patients below 18 years of age
Sulphonamides
- Mechanism of action: Bacteriostatic, competes with PABA, inhibits folic acid synthesis
- Spectrum: Gram +ve, Gram -ve (E. coli, H. influenzae) and Chlamydia
- Kinetics: Given orally, bound to plasma protein, metabolized by acetylation, excreted in urine
- Classification:
- Rapidly absorbed and excreted (e.g. sulphadiazine, sulphaisoxazole, sulphamethoxydiazine)
- Rapidly absorbed, slowly excreted (e.g. sulphamethoxazole)
- Poorly absorbed (e.g. sulphaguanidine, sulphasalazine)
- Topical use (e.g. sulphacetamide, mefenide)
- Uses: Coccal meningitis, UTI, Bacillary dysentery, Ulcerative colitis, Eye infection, Wound and burn, Prophylaxis of coccal meningitis, Prophylaxis of rheumatic fever
- Toxicity: Crystalluria, Allergic reaction, Blood dyscrasias, Diarrhea, Hepatic injury, Kernicterus
- Interaction: Potentiates sulphonylurea and oral anticoagulants### Pharmacology
Efficacy and Agonists
- Efficacy: biological response to a drug
- Agonists: bind to receptors, stimulate response, and initiate changes
- Characteristics of agonists:
- Affinity: binding to receptors
- Efficacy: ability to stimulate response
- Rapid dissociation rate
Partial Agonists
- Stimulate and block receptors
- Characteristics of partial agonists:
- Affinity: binding to receptors
- Efficacy: less than full agonists
- Moderate dissociation rate
Plasma Half-Life
- Definition: time required for the concentration of a drug to decrease by half
- Formula: t½ = 4 hours
- Importance: determines drug elimination and steady state
Clinical Significance of Plasma Half-Life
- Measure of drug elimination
- Indicates time required to attain steady state
- Depends on drug clearance
Types of Drug Elimination Kinetics
First Order Kinetics
- Constant proportion of drug is absorbed, metabolized, or eliminated depending on concentration
- Characteristics:
- Rate of process is directly proportional to dose
- t½ is constant
- Linear disappearance curve if log dose is used
Zero Order Kinetics
- Constant number of moles are absorbed or eliminated regardless of total amount present
- Characteristics:
- Rate of process is not related to dose
- t½ increases with dose
- Non-linear disappearance curve if log dose is used
Factors Affecting Drug Response
Age
- Newborn infants are more susceptible to drugs due to:
- Underdevelopment of microsomal enzymes
- Low plasma protein and low binding capacity
- Reduced excretory function
- Immaturity of blood-brain barrier
Body Weight and Surface Area
- Larger body weight requires larger dose
- Surface area is a more accurate parameter for dose calculation
- In obese patients:
- Dose of fat-soluble drugs should be increased
- Dose of water-soluble drugs should be based on surface area
Sex
- Women may need smaller doses due to:
- Fat content
- Enzyme-inhibiting effect of female sex hormones
- Enzyme-inducing effect of male sex hormones
Route of Administration
- Affects dose and action:
- I.V dose is less than oral dose
- I.V administration is faster than other routes
- Examples of route-dependent effects:
- Magnesium sulphate: orally is a purgative, rectally is a dehydrating agent, I.V. is an anticonvulsant
Pharmacological Concepts
Drug Intolerance
- Exaggerated response to a normal dose of a drug
- Causes: decreased clearance of drug or upregulation of receptors
Tolerance
- Failure of response to a usual dose of a drug
- Types:
- Congenital
- Acquired
- Examples:
- Morphine, ethyl alcohol, nitrates, ephedrine
Hypersensitivity (Allergic) Reaction
- Immune response to a drug
- Characteristics:
- Does not occur on first exposure
- Not dependent on dose
- Can occur on reuse of the drug
- Can be cross-reactive between related drugs
Idiosyncrasy (Pharmacogenetics)
- Abnormal reaction to a drug due to genetic or enzyme defects
- Examples:
- Succinylcholine apnea
- Malignant hyperthermia with succinylcholine or halothane
- Anaemia and methemoglobinemia with G-6-PD deficiency
Drug Dependence
- Habituation: emotional or psychological dependence on the drug
- Addiction: physical dependence on the drug
Pathological State
- Effect of a drug on a specific disease state
- Example: aspirin lowering fever temperature to normal
Cumulation
- Rate of drug administration is greater than elimination
- Examples: digitalis and guanethidine
Emotional State (Placebo Effect)
- Psychological response to an inert substance
- Used in testing new drugs
Drug Combinations
- Types:
- Addition or summation
- Synergism
- Potentiation
- Antagonism
Adverse Drug Effects
Unpredictable Adverse Effects
- Allergy (hypersensitivity reaction)
- Idiosyncrasy (pharmacogenetics)
Predictable Adverse Effects
- Overdose toxicity
- Teratogenic effects
- Iatrogenic effects
- Long-acting sulphonamides can produce jaundice in premature babies
- Blood dyscrasias by chloramphenicol
- Carcinogenic effects
- Hepatic toxicity
- Nephrotoxicity
- Nerve damage
- Secondary effects
Types of Adverse Drug Reactions
Type A
- Predictable undesirable adverse effects
- Related to the normal pharmacological actions of the drug
- Examples:
- Side effects
- Supersensitivity (intolerance)
- Overdose
- Secondary effects
- Cytotoxic effects
Type B
- Unpredictable adverse effects
- Examples:
- Allergy (hypersensitivity reaction)
- Idiosyncrasy (pharmacogenetics)
Type C
- Chronic effects
- Examples:
- Tolerance
- Drug dependence
- Iatrogenic disease
Type D
- Delayed effects
- Examples:
- Teratogenicity
- Mutagenicity and carcinogenicity
Type E
- End of use effects
- Examples:
- Abstinence syndromes
- Worsening of existing disease
Type F
- Failure of therapy
- Examples:
- Primary failure
- Secondary failure
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Description
This quiz covers the basics of pharmacology, including the study of substances that interact with living systems, and the science of drugs used for treatment, prevention, and diagnostic purposes.
