Introduction to Pharmacology PDF Notes

Introduction to Pharmacology  Basic definitions Drug , Drug Nomenclature, Pharmacy Pharmacology Pharmacodynamics Pharmacokinetics Toxicology Clinical pharmacology Pharmacotherapeutics Drug Nomenclature Stimulation, Inhibition, Replacement Routes of drug administration  What is DRU...

Introduction to Pharmacology  Basic definitions Drug , Drug Nomenclature, Pharmacy Pharmacology Pharmacodynamics Pharmacokinetics Toxicology Clinical pharmacology Pharmacotherapeutics Drug Nomenclature Stimulation, Inhibition, Replacement Routes of drug administration  What is DRUG? Medicine? Drug? DRUG A drug is defined as any substance used for the purpose of: Diagnosis Prevention Relief or cure of a disease in human or animals.  DRUG  Legal definition Any agent approved by the Drug Control Authority for the treatment or prevention of disease  Social definition Any agent taken that is disapproved/illegal Drug is often associated with addictive, narcotic or mind-altering substances  WHEN DO WE NEED DRUG? Disease state Physiology Pathophysiology Drugs http://www.wisegeek.com/what-is-human-physiology.htm Can you guess from where and how the drugs are obtained or derived from?  Sources of drugs A drug may be: Synthetic chemicals Natural sources – Plants: Alkaloids (Morphine) – Microbes: Antibiotics (Penicillin, streptomycin) – Animal tissues: Hormones (Growth hormone, insulin) – Minerals: Lithium (Psychotherapy)  Plant-Based Drugs DIGOXIN from Digitalis lanata (foxglove) ASPIRIN: WONDER DRUG Vincristine & Vinblastine from Catharanthus roseus (Madagascar periwinkle)  Drug Nomenclature Trade names Manufacturer’s Brand name/proprietary name – Panadol®, Tylenol®, Uphamol® Chemical name The drug’s chemical composition and molecular structure - N-Acetyl-p-aminophenol Generic name (non-proprietary name) Official name, international non-proprietary name – Paracetamol, acetaminophen You will probably use only generic or trade names. Trade names Drug Nomenclature Viagra Chemical name 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1- methyl-3-propyl-4H-pyrazolo[4,3-d]pyrimidin-7-one (formula C22H30N6O4S) Generic name Sildenafil Brand Name Generic Name Uses Pain relief and fever Tylenol Acetaminophen reduction Pain relief, fever reduction, Advil Ibuprofen and inflammation Zocor Simvastatin Reduces cholesterol levels For depression, anxiety Prozac Fluoxetine disorders, and other mental health conditions For attention deficit (Amphetamine/dextroamp Adderall hyperactivity disorder hetamine) (ADHD) Treats gastroesophageal reflux disease (GERD) and Prilosec Omeprazole other acid-related conditions For the relief of allergy symptoms such as Zyrtec Cetirizine sneezing, itching, runny nose, and watery eyes Manages type 2 diabetes Glucophage Metformin and controls blood sugar levels  Drug Classification: How do you usually Classify drugs ? Therapeutic usage Mechanism of action Site of action Chemical Structure Pharmacokinetic sub-classification  Therapeutic usage Therapeutic usage – Antidiabetics, antihypertensives, anticancer agents etc Conventional antidiabetic drugs https://www.ezmedlearning.com/blog/antihypertensive-medication-drug-list Mechanism of action Mechanism of action – e.g. Beta-blocker (Propranolol) ; opioid agonist (morphine) Site of action e.g. loop diuretic ,at loop of Henle, (Furosemide) Chemical Structure Chemical Structure – Glycosides; steroids; alkaloids – Benzodiazepines; dihydropyridines Pharmacokinetic sub-classification Pharmacokinetic sub-classification – short-acting; long-acting; – slow-release  Pharmacy Pharmacy is the art and science of compounding and dispensing drugs or preparing suitable dosage forms for administration of drugs to man or animals. It includes: collection, identification, purification, isolation, synthesis, standardization and quality control of medicinal substances. The large scale manufacture of drugs is called Pharmaceutics. It is primarily a technological science.  Pharmacology  ‘Pharmacology’ is the science of drugs (Came from Greek: Pharmakon—drug or poison).  It deals with interaction between drugs and living organisms including human being and animals)  It encompasses all aspects of knowledge about drugs that are related to effectiveness and safety. Components of Pharmacology  The two main divisions of pharmacology are : pharmacodynamics & pharmacokinetics. 1- What the drug does to body :is called Pharmacodynamics 2- What the body does to drug : is called Pharmacokinetics Does the drug actually reach its site of action?? This is governed by these factors: ADME 1. Absorption - Uptake of the drug from the application site into the systemic blood circulation 2. Distribution -Transport between the blood and the rest of the organism 3. Metabolism - How much is broken down in the liver 4. Elimination - Filtration and secretion in the kidneys  Pharmacotherapeutics It is the application of pharmacological information together with knowledge of the disease for its prevention, mitigation or cure. Pharmacotherapeutics It includes the selection of the most appropriate drug, dosage and duration of treatment.  Chemotherapy is the treatment of systemic infection/malignancy with specific drugs that have selective toxicity for the infecting organism/ malignant cell with no/minimal effects on the host cells. Chemotherapy Chemotherapeutic agents are designed to inhibit/kill invading parasite/malignant cell.  The same substance can be a drug or a poison, depending on the dose. Toxicology is the study of poisonous effect of drugs ,with emphasis on detection, prevention and treatment of poisonings. It also includes the study of adverse Toxicology effects of drugs.  The thalidomide disaster heralded modern teratogenicity testing … In fact, thalidomide is a useful drug, used today to treat leprosy ‫ ﺟﺫﺍﻡ‬and multiple myeloma ‫ﻭﺭﻡ ﻧﻘﻳﻲ ﻣﺗﻌﺩﺩ‬ Thalidomide recommended as an anti-emetic to treat morning sickness in pregnant women 1961 - thalidomide was the best-selling sleeping pill in West Germany and the UK but later withdrawn However, thalidomide produced teratogenic effects in 100% of fetuses exposed between 3- 6 weeks gestation. An estimated 8-12,000 infants were born with deformities caused by thalidomide.  Thalidomide brought changes in the way drugs are tested, what type of drugs are used during pregnancy, and increased the awareness of potential side effects of drugs. Slowly new studies began being made regarding thalidomide treatments for diseases like cancer or leprosy. Was found useful in treating diseases such as lupus ‫ ﻣﺭﺽ ﺍﻟﺫﺋﺑﺔ‬, relieving symptoms of HIV patients, decreased risk of bone marrow transplant rejection and rheumatoid arthritis Toxicity tests done in animals How long it takes to develop a drug? What are the steps or phases of drug development?  Types of Pharmacology work 1- Experimental Pharmacology: Evaluation of drug action in animals 2- Clinical Pharmacology Evaluation of drug action in humans  Clinical Studies Done in four stages/phases: Phase I – Study in in very small group normal people – Pharmacology, efficacy, pharmacokinetic, side-effects Phase II – Study in small group of sick people – Dose determination for phase 3 Phase III – Study in large group of sick people – Large multicenter clinical trials Phase IV – Pharmacovigilance: Post-marketing evaluation & surveillance  Can you distinguish between the following terms: Pharmacology Drug Medicine Pharmacokinetics Pharmacodynamics Toxicology SO FAR… EVERYONE UNDERSTAND?  Types of drug action 1. Stimulation 2. Depression 3. Irritation 4. Replacement 5. Cytotoxic action  1. Stimulation Selective enhancement of the level of activity of specialized cells. Example:  Adrenaline has a stimulatory effect on the heart (used to manage cardiac arrest).  Pilocarpine has a stimulatory effect on the salivary glands (used to treat dryness of the mouth and throat caused by a decrease in the amount of saliva that may occur after radiation treatment for cancer ) 2. Inhibition Inhibition is a Selective diminution of activity of specialized cells. Example:  Barbiturates have an inhibitory effect on the CNS (sedative-hypnotics).  Quinidine has an inhibitory effect on the heart (antiarrhythmic medication) Some agents stimulate one type of cells and inhibit the other. Example :  Acetylcholine, a neurotransmitter: stimulates the intestinal smooth muscle but inhibits sinoatrial (SA) node in the heart which cause a reduction in the heart rate.  3. Irritation Non-selective often noxious effect – applied to less specialised cells (epithelium, connective tissue). Certain drugs on topical application cause irritation of the skin and adjacent tissues. These drugs are using for counter irritant. Example : drugs used in sprains‫ ﺍﻻﻟﺗﻭﺍء‬, joint pain, myalgia ‫ﺃﻟﻡ‬ ‫ ﻋﺿﻠﻲ‬such as  Eucalyptus oil  methyl salicylates  4. Replacement Sometimes we need to use some natural metabolites, or hormones to manage the deficiency states. Example:  Levodopa as a dopamine replacement agent in parkinsonism disease.  Iron in anaemia.  insulin in diabetes.  5. Cytotoxic effect For managing the invading bacteria, parasites, and cancer cells, without affecting the host cells. Example:  Penicillins (Antibiotics)  Chloroquine (antimalarial drug )  Zidovudine (used to treat HIV infection ),  Cyclophosphamide (anticancer)  1- Physical action 2- Chemical action 3- Interacting with target Mechanism biomolecules ( usually a protein) Enzymes of drug Ion channels action Transporters Receptors  1. Physical action  Bulk laxatives (methylcellulose, wheat bran) absorb liquid in the intestines.  Adsorpants (kaolin and pectin) that work by coating the walls of the GI tract and binding the causative bacteria or toxin for elimination from the GI tract through the stool.  Mannitol (diuretic) blocks tubular reabsorption of water and enhances the excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate.  Radioactive Iodine: used only for treatment of thyrotoxicosis ‫ﺍﻻﻧﺳﻣﺎﻡ‬ ‫ ﺍﻟﺩﺭﻗﻲ‬and some type of thyroid cancer because it emits beta rays, which destroys the thyroid gland.  2. Chemical action  Antacids (NaHCO3) : neutralizing gastric acidity.  Chelating agents ( EDTA) : forming complexes with heavy metals. 3. Interacting with target biomolecules ( usually a protein) Enzymes Ion channels Transporters Receptors  A. Enzymes Enzymes are important target for drug : most of biological reactions are done under enzyme action.  Enzyme stimulation  Enzyme inhibition Example:  Adrenaline: activates adenylyl cyclase, relaxing the airways smooth muscles.  NSAIDs : aspirin and naproxen inhibit cyclooxygenase, leading to a block of prostaglandin production  ACE inhibitors: Captopril and Enalapril inhibit angiotensin converting enzyme to decrease blood pressure  A. Enzymes The drug competes with the natural substrate for the enzyme  Reversible Neostigmine inhibits the hydrolysis of acetylcholine by reversibly competing with Ach for attachment to cholinesterase at sites of cholinergic transmission.  Irreversible Organophosphates irreversibly inhibits cholinesterase. B. Ion channel  Responsible for the influx or out- flux of ions through cell membranes along their concentration gradients.  They are activated by alteration in action potential and are controlled by gating machinery. https://slideplayer.com/slide/4651495/ Ion channel (cont.) Drugs bind to alter channel function by block or modulation  Local Anaesthetics block Na+ influx through Na+ channel in nerve fibers.  They are Na+ channel Blockers.  C. Transporters (Carrier molecule ) Responsible for transport of ions and small organic molecules between intracellular compartments.  Antiporters simultaneously transport two different molecules in opposite directions across the cell membrane. Antiporter  Symporters simultaneously transport two different molecules in the same direction across the cell membrane. Symporter https://slideplayer.com/slide/4651495/  The dopamine transporter (DAT) belongs to the family of neuro- transmitter: sodium symporters and controls dopamine (DA) homeostasis by mediating Na+ and Cl−-dependent reuptake of DA.  It mediates the reuptake of the neurotransmitter dopamine (DA) from the extracellular space into the presynaptic dopaminergic https://www.futuremedicine.com/doi/10.2217/fnl.09.76 neuron, thereby serving an important function in terminating dopaminergic signalling  C. Transporters (Carrier molecule ) The drug binds to such molecules altering their transport ability Cocaine blocks transporters (symporters) that are responsible for the removal of catecholamines (dopamine) from the at synaptic cleft. Dopamine then accumulates in the https://nida.nih.gov/publications/research-reports/cocaine/how-does-cocaine-produce- synapse to produce an amplified signal its-effects to the receiving neurons. This is what causes the euphoria commonly results from Cocaine  C. Transporters (Carrier molecule )  Digitalis blocks efflux of Na+ by Na+ pump  Note: Na+/ K+ ATPase is Antiporter in cardiac cells https://medizzy.com/feed/6066581  D. Receptors  Most drugs produce their inhibitory or stimulatory effects through interacting with receptors which are macromolecules(proteins).  Drugs interact with receptors to bring about their effects ( Response). L ig and is a molecule that binds to a receptor L egand might be endogenous (neurotrans mitter, hormone, antigen), or can be exogenous (drugs , chemicals ) It can als o bind/interac t with the drug https://www.khanacademy.org/science/ap-biology/cell-communication-and-cell- and mediates its pharmacological cycle/signal-transduction/a/signal-perception actions to produc e a res pons e.  Receptors are the specific molecules in a biologic system with which drugs interact to produce changes in the function of the system. Receptors must be selective in their ligand-binding characteristics (so as to RECEPTORS respond to the proper chemical signal and not to meaningless ones). The receptor site (also known as the recognition site) for a drug is the specific binding region of the receptor macromolecule and has a relatively high and selective affinity for the drug molecule. Most are proteins; a few are other macromolecules such as DNA. Where receptors are located? Cell membrane Cytoplasm Nucleus When drugs bind to receptors Initiate biochemical reactions Alter physiologic processes Thank you