Pharmacology Overview

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Questions and Answers

What is the primary role of pharmacology?

To create new cell functions within the body.

To investigate drugs and their effects on existing cell functions. (correct)

To study how to synthesize drugs for commercial use.

To explore the historical applications of medicinal plants.

Which source of drugs does Heparin belong to?

Mineral sources

Plant sources

Synthetic sources

Animal sources (correct)

Which process in drug therapy involves the mechanism of action and pharmacological actions?

Pharmacokinetic process

Pharmacodynamic process (correct)

Pharmaceutical process

Pharmacotherapeutic process

What describes 'reflex or remote action' in pharmacodynamics?

The indirect stimulation of distant body functions via nerve pathways. Signup and view all the answers

What is the primary function of receptors in pharmacodynamics?

To serve as sites for drug, neurotransmitter, or hormone binding. Signup and view all the answers

What characterizes a hypersensitivity reaction to a drug?

Can act as an antigen Signup and view all the answers

Which of the following is an example of a secondary effect?

Superinfection from long-term antibiotics Signup and view all the answers

What defines supersensitivity in drug response?

Enhanced response to a standard dosage Signup and view all the answers

Which of the following best describes the response due to idiosyncrasy?

Abnormal reactions based on genetic makeup Signup and view all the answers

What is the primary reason for dose adjustment in instances of drug intolerance?

The actions of the drug are exaggerated Signup and view all the answers

What is a characteristic of active transport in drug absorption?

It requires a carrier protein. Signup and view all the answers

Which factor does NOT influence the binding of drugs to plasma proteins?

Body temperature. Signup and view all the answers

What defines facilitated diffusion in the context of drug absorption?

It requires a carrier but is similar to simple diffusion. Signup and view all the answers

Which of the following is an example of a drug affected by binding to plasma proteins?

Bilirubin Signup and view all the answers

What is a critical aspect of drug absorption for amphetamines in relation to urine pH?

Weak bases absorb better in acidic urine. Signup and view all the answers

What type of antagonism does succinylcholine exhibit?

Competitive reversible Signup and view all the answers

Which factors affect simple (lipid) diffusion of drugs across cell membranes?

Concentration gradient and molecular size Signup and view all the answers

What does a low lipid/water partition coefficient indicate about a drug?

The drug is likely to be ionized Signup and view all the answers

How does urinary pH affect the excretion of drugs?

Alkaline urine increases drug excretion Signup and view all the answers

In an alkaline medium, how does acetyl salicylic acid (aspirin) behave?

It becomes ionized and less lipid soluble Signup and view all the answers

What characteristic of the endothelial cells in brain capillaries allows certain substances to pass through?

Presence of tight intercellular pores Signup and view all the answers

Which of the following statements about the passage of drugs through the blood-placental barrier is true?

Only lipid-soluble drugs can pass through Signup and view all the answers

In Phase I biotransformation reactions, which process is classified as a reduction?

Reduction of chloral hydrate Signup and view all the answers

What is one effect of aging on hepatic microsomal enzyme activity?

Decreased activity resulting in reduced drug metabolism Signup and view all the answers

Which of the following correctly describes the outcome of Phase II biotransformation reactions?

They result in drug deactivation Signup and view all the answers

What occurs as a result of enzyme inducers in drug metabolism?

They lead to a tolerance effect with certain drugs. Signup and view all the answers

Which statement best describes the first-pass effect?

It describes the process where drugs are extensively metabolized in the liver after oral administration. Signup and view all the answers

Which route is considered the major site of drug excretion?

Renal through the kidneys. Signup and view all the answers

What is true about enzyme inhibitors in drug metabolism?

They increase the overall effects of drugs. Signup and view all the answers

Which process is NOT involved in renal drug excretion?

Conjugation processes. Signup and view all the answers

What does the lock-and-key model specifically represent in enzyme function?

The structure and role of a substrate Signup and view all the answers

What occurs when an incorrect substrate attempts to bind to an enzyme's active site?

No reaction occurs due to a poor fit Signup and view all the answers

How does a poison molecule affect enzyme activity?

By blocking the enzyme's active site Signup and view all the answers

What is the role of the active site in enzyme activity?

To facilitate substrate binding and reaction Signup and view all the answers

What happens to an enzyme after the reaction has occurred?

The enzyme returns to its original shape Signup and view all the answers

What does the fluid-mosaic model suggest about the structure of a cell membrane?

It is a bilayer structure with embedded proteins. Signup and view all the answers

In osmosis through a cell membrane, where does water move when comparing hypotonic and hypertonic solutions?

From hypotonic to hypertonic solutions. Signup and view all the answers

What role do glycoproteins play in the fluid-mosaic model of membranes?

They serve as receptors for signaling molecules. Signup and view all the answers

What is the primary function of carrier proteins in the membrane structure?

To facilitate the transport of specific molecules. Signup and view all the answers

Which statement correctly describes the arrangement of lipids in the fluid-mosaic model?

Lipids are arranged in a bilayer with hydrophilic heads facing outward. Signup and view all the answers

What does it mean when a patient shows tolerance to a drug?

The normal dose of the drug no longer produces the expected effect. Signup and view all the answers

Which of the following describes psychological dependence on a drug?

There is a strong psychological craving for the drug. Signup and view all the answers

Which of these drugs is primarily associated with causing Parkinsonism due to its iatrogenic effects?

Chlorpromazine Signup and view all the answers

What is an example of a drug interaction that shows antagonistic effects?

Adrenaline and histamine Signup and view all the answers

Which of the following would indicate a cytotoxic effect of a drug?

Ototoxicity from streptomycin Signup and view all the answers

What is the key characteristic of a synergistic drug interaction?

The combined effect is greater than the sum of individual effects. Signup and view all the answers

Which of the following drugs is associated with teratogenic effects?

Alcohol Signup and view all the answers

What does the term 'habituation' in drug dependence refer to?

The body becoming used to the drug's effects. Signup and view all the answers

Which of the following describes an additive drug interaction?

The combined effect is equal to the individual effects summed up. Signup and view all the answers

What physical condition can result from prolonged usage of some antibiotics like chloramphenicol?

Bone marrow depression Signup and view all the answers

Study Notes

Pharmacology

The study of drugs and their effects on living organisms.
Drugs are chemical agents that stimulate or inhibit existing cell functions but do not create new ones.

Sources of Drugs

Plant sources: Atropine, belladonna leaves
Animal sources: Heparin, Insulin
Mineral sources: MgSO4
Microorganisms: Penicillin
Synthetic: Sulphonamides
Biotechnology: Human insulin, tissue plasminogen activator (t-PA)

Uses of Drugs

Therapeutic agents in treating diseases
Prevention of diseases (prophylaxis)
Diagnosis of diseases
Prevention of normal biological function

Processes Involved in Drug Therapy

Pharmaceutical process: particle size, lipid solubility, coating materials
Pharmacokinetic process: ADME (Absorption, Distribution, Metabolism, and Excretion)
Pharmacodynamic process: mechanism of action, pharmacological actions, and adverse effects of drugs
Pharmacotherapeutic process: use of drugs in diagnosis, treatment, and prevention of diseases.

Pharmacodynamics

The study of the effect of drugs on the body.

Types of Pharmacodynamic Effects

Local or topical action: Eye drops, mouth wash
Systemic or general action: Aspirin
Reflex or remote action: Subcutaneous camphor irritation and reflex stimulation of respiratory center

Action on Specific Receptors

Receptors are chemically reactive macromolecular proteins with a special binding site.
Drugs, neurotransmitters, or hormones bind to receptors to initiate an effect.
D-R interaction: Drug-Receptor interaction
DR: Drug
Response: Outcome

Agonists

Drugs of high affinity, efficacy, and rapid dissociation rate.
Drugs that block receptors (competitive/non-competitive)

Partial agonists

Drugs that stimulate and block receptors.
They have affinity, efficacy, and slow dissociation.
Example: β-blockers (oxprenolol)
Example: Mixed agonist & antagonist opioids (pentazocine)

Adverse Effects of Drugs

Unpredictable abnormal response
Predictable adverse effects

Unpredictable Abnormal Response

Hypersensitivity (allergic) reaction
The drug may act as an antigen.
Hypersensitivity reaction does not occur on first exposure.
It is not dose-dependent.

Predictable Adverse Effects

Side effects: Undesirable normal actions of a drug
- Example: Atropine (antispasmodic) - dry mouth
Secondary effects:
- Example: Long use of oral broad-spectrum antibiotics - superinfection
Overdose: Exaggerated normal action of a drug
- By a single large dose, or accumulation of several small doses
Supersensitivity (drug intolerance):
- Exaggerated action to a normal dose of a drug
- Due to decreased clearance of the drug, or upregulation of receptors.
- Therefore, the dose should be reduced.

Idiosyncrasy

Abnormal reaction to a drug due to a genetic/enzyme defect.
Example: Sulphonamide - G6-PD deficiency - hemolytic anemia
Example: Isoniazid - slow acetylator - peripheral neuritis

Tolerance

Failure of response: The usual dose of a drug no longer produces the expected effect.
Dose increase needed: Increasing the dose is required to achieve the desired effect.
Specific tolerance: Tolerance to pain relief (analgesia) and respiratory depression (from morphine) may occur, but not to pupil constriction (miosis) or constipation.

Drug Dependence

Habituation/Emotional/Psychological Dependence: This describes a state where the body and mind become accustomed to a drug, leading to emotional distress if the drug is stopped.
Distress period: A short period of emotional distress occurs when the drug is withdrawn.
Addiction/Psychic Craving: This involves a strong psychological craving for the drug and physical dependence on it.
Withdrawal Reaction: Severe withdrawal symptoms occur when the drug is stopped (including abstinence syndrome).
Example Drugs: Morphine and heroin.

Iatrogenic Drug

Induction of Disease
Example Drug: CPZ (Chlorpromazine)
Associated Disease: Parkinsonism

Carcinogenicity

Example Cause: Tobacco smoking

Teratogenicity

Example Drugs: Aspirin, thalidomide, and alcohol (FAS)

Cytotoxic Effect

Drug-induced cell damage: Some drugs can damage cells.
Examples of Drugs with Cytotoxic Effects:
- Streptomycin
- Halothane
- Chloramphenicol
- Sulphonamides
Specific Effects:
- Streptomycin causes ototoxicity.
- Halothane causes hepatic damage.
- Chloramphenicol and sulphonamides can cause bone marrow depression and nephrotoxicity.

Drug Interactions

Pharmacokinetic Interactions: Interactions related to how the body absorbs, metabolizes, and eliminates the drug.
Pharmacodynamic Interactions: Interactions related to how the drugs interact at the cellular level.

Pharmacodynamic Interactions

Additive Effect (1 + 1 = 2): The combined effect of two drugs is equal to the sum of their individual effects.
Synergistic Effect (1 + 1 > 2): The combined effect is greater than the sum of individual effects (e.g., isoniazid and rifampicin in tuberculosis treatment).
Antagonistic effect (1 + 0 > 2): The combined effect is less than the sum of individual effects (e.g., barbiturates and salicylates—an example of opposite actions).
Drugs with opposite actions: These drugs have opposing physiological effects (e.g., adrenaline and histamine on bronchial and blood pressure).
Actions can also be on a chemical level (eg.NaHCO3 and HCl or protamine sulphate and heparin).

Pharmacological Antagonism

Competitive reversible
Non competitive
- Reversible: succinylcholine
- Irreversible: organophosphorous anticholinesterase

Pharmacokinetics

The effect of the body on the drug.
ADME (Absorption, Distribution, Metabolism, and Excretion)

Drugs Can Pass Across Cell Membranes By

Simple (lipid) diffusion:
- The drug passes with a concentration gradient.
- No energy or carrier is required.
- It depends on: concentration gradient, lipid solubility, molecular size, and degree of ionization.

Lipid/Water Partition Coefficient

Ratio of drug concentration in lipid phase & water phase when shaken in one immiscible lipid/water system.
It measures lipid solubility.
Ionized drugs: low lipid/water partition coefficient (do not cross cell membrane).
Non-ionized drugs: high lipid/water partition coefficient (cross cell membrane).

Examples of Acidic Drug Behavior in Different Environments

Acidic Drug	Acidic Medium	Alkaline Medium
Acetyl salicylic acid (aspirin) & phenobarbitone	Non-ionized, absorbed in stomach	More ionized, less lipid soluble

Other Processes

Filtration: Reabsorbed from renal tubules (acidic urine).
Alkaline urine enhances drug excretion.

Drug Absorption Mechanisms

Filtration: It is of minor importance in absorption.
Facilitated Diffusion: Similar to simple diffusion.
- Requires a carrier.
Active Transport: Drugs move against the concentration gradient.
- Requires energy and a carrier protein.
- Examples include penicillin and uric acid secretion from renal tubules.
Binding to Plasma Proteins: Reversible and non-selective process.
- The amount of bound drug depends on: Free drug concentration, Binding site affinity, Protein concentration.
- Examples of drugs affected include sulfonamides and bilirubin.
- Defective conjugation can lead to hyperbilirubinemia in infants, potentially resulting in kernicterus.

Passage of Drugs to Brain and CSF

Endothelial cells of brain capillaries are characterized by the presence of tight intercellular pores.
Drugs must be lipid-soluble and non-ionized to pass to the brain.
Blood-brain barrier (BBB) isn't absolute; inflammation increases permeability.
Penicillin can pass in meningitis.

Passage of Drugs to Placenta

Blood placental barrier (BPB).
Placenta as cell membrane.
Drugs passing placental barrier can cause congenital malformations, especially in the first trimester.
Thalidomide, diphenylhydantoin, tetracyclines, corticosteroids, and antithyroid drugs & aspirin.

Biotransformation Reactions

Biotransformation reactions occur in 2 phases:

Phase I (Non-synthetic) Reactions

Oxidation: phenacetin & phenobarbital
Reduction: chloral hydrate
Hydrolysis: acetyl choline & procaine

Phase II (Synthetic) Reactions

Conjugation of the parent compound or its metabolite with:
- Glucuronic acid: chloramphenicol, morphine sulfate
- Acetic acid: sulphonamides, hydralazine & isoniazid
- Glycine: salicylates
- Catecholamines & histamine
Phase II (synthetic) reactions result in drug deactivation.

Biotransformation Reactions Carried By

Hepatic microsomal enzymes (HME):
- Catalyze most of oxidative reactions by cytochrome P-450.
- Glucuronide conjugation, reduction & hydrolysis.
HME Activity is Affected by Age:
- Neonates (premature): can't conjugate chloramphenicol (gray syndrome).
- Elderly, starvation, burns, cancer & liver diseases: low activity.
- Drugs may induce or inhibit HME.
Drugs may pass in one phase only or in both phases.

Drug Metabolism and Excretion

Enzyme activators, enzyme inhibitors, and the first-pass effect in drug metabolism
Routes of drug excretion

Enzyme Activators (Inducers)

Rate of enzyme synthesis: Increases the rate at which enzymes are produced.
Rate of degradation: Decreases the rate at which enzymes are broken down.
Example: Some drugs (oral anticoagulants, oral contraceptives, corticosteroids) have their activity decreased by enzyme inducers, leading to a tolerance effect, particularly with barbiturates.

Enzyme Inhibitors

Enzyme inhibitors increase the effect of drugs.

First-Pass Effect

Drugs taken orally must travel through the stomach and intestines first to reach the liver.
This effect can take place in: - The gut (through juices or enzymes in the lumen/epithelium). - The Liver (through acid-labile substances or enzymes, which extensively metabolize many drugs).
Note: Because of extensive liver metabolism, oral doses must often be higher than parenteral (non-oral) doses.

Drug Excretion Routes

Renal (major site): Drugs can be excreted through the kidneys.
- Major processes: - Glomerular filtration - Active tubular secretion (e.g., penicillin, probenecid) - Passive tubular reabsorption
Gastrointestinal Tract: Drugs can be excreted through other parts of the digestive system.
- Possible sites: - Salivary glands - Stomach - Large intestine - Liver (via bile)
- Liver role: Conjugation processes, enterohepatic circulation, with specific examples of Morphine and pH-dependent forms.

Enzyme Function and Inhibitors

Lock and key model of enzyme specificity
Poison molecules can block enzyme activity.

Lock and Key Analogy

Key: Represents the substrate.
Lock: Represents the enzyme.
Correct Fit: The correct substrate fits into the enzyme, allowing a reaction to occur.
Incorrect Substrate: An incorrect substrate does not fit into the enzyme, so no reaction occurs.

Lock & Key Model Of Enzyme Specificity

The diagram shows how a substrate fits into the active site of an enzyme.
The substrate enters the active site of the enzyme.
Bonds in the substrate are weakened
The enzyme and substrate form an enzyme-substrate complex.
Products are released.
The enzyme returns to its original shape, ready for another reaction

Active Site Of Enzyme Blocked By Poison Molecule

The diagram in this section illustrates how a poison molecule (alkaloid) can block an enzyme's active site, preventing the substrate from binding and initiating a reaction.
The poison molecule (alkaloid) fits into the active site of the enzyme.
This prevents the substrate from binding.
No reaction occurs.

Additional Information

Sweat: Item 3
Lungs: Item 4
Milk: Basic drugs are trapped & excreted in acidic milk (Item 5)

Fluid-Mosaic Model of Membrane Structure

Diagram of Osmosis Through a Cell Membrane
Fluid-Mosaic Model of Membrane Structure

Diagram of Osmosis Through a Cell Membrane

The membrane separates two compartments containing circles that represent solute particles.
One side (hypotonic) has more solute particles (darker circles).
One side (hypertonic) has fewer solute particles (lighter circles).
An arrow indicates the movement of water molecules across the membrane.
Water moves from the hypotonic solution to the hypertonic solution.