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72 Cards in this Set
- Front
- Back
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What is pharmacology |
Study of substances that interact with living Systems through chemical processes by binding to regulatory molecules and by accelerating or inhibiting normal body processes. |
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What are the two methods of action of medicines? |
1. Achieve beneficial effects on therapeutic processes in the patient or 2. Toxic effects on regulatory processes in parasites that invade the patient. |
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What is toxicology |
Branch of pharmacology that deals with the undesirable toxic effects of chemicals on living systems from cells to humans to complex ecosystems |
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What is materia medica? |
The science of drug preparation and the medical uses of drugs |
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What is pharmacogenomics? |
The relation of an individual’s genetic make up to his or her response to specific drug |
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What are the actions of a drug on a target molecule? |
The drug is considered an agonist if it accelerates or an antagonist if it inhibits on a target molecule known as a receptor |
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What are chemical antagonists? |
Drugs that interact directly with other drugs |
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What are chemical antagonists? |
Drugs that interact directly with other drugs |
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What are osmotic agents? |
These are drugs that exclusively interacts with water molecules |
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What are chemical antagonists? |
Drugs that interact directly with other drugs |
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What are osmotic agents? |
These are drugs that exclusively interacts with water molecules |
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What are toxins? |
Poisons that are exclusively produced by plants and animals are known as toxins. |
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What is the ideal properties of a drug? |
A drug must have the appropriate size ,shape, Electrical charge and composition. A drug should have the property of getting transported from its site of administration to its site of action. Finally a drug should be metabolized and excreted from the body at a reasonable time So that it will have an appropriate duration of action |
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How does drug size influence its action in the human body? |
Normal range of drug molecular weight is between hundred to thousand. Anything below 100 will not be very specifically binding to its receptor and anything above 1000 will find it difficult to cross compartment barriers. Example of very small molecular weight is lithium while very large molecular weight is alteplase , a clot dissolving enzyme. |
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Main types of drug receptor bonds |
Covalent ,electro static and hydrophobic |
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What are the features of a covalent bond? |
They are the strongest bonds. In many cases ,they are not reversible under biological conditions. Example, Acetyl group of acetylsalicylic acid with cyclooxygenase of platelets. The platelet Agglutinating factor of aspirin last for several days and will go away only when new platelets with new enzymes are formed which may take several days. Other examples are DNA alkylating agents used in cancer chemotherapy of tumours. |
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What are pharmacodynamics? |
What the drug does to the body |
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What is pharmacokinetics? |
What the body does to the drug regarding absorption metabolism and excretion. Important in impaired renal function. |
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What are the types of drug receptor interaction? |
Agonist are drugs that bind to the receptor and cause a direct or indirect effect. Example opening of Ion channel or activation of enzyme activity.
Antagonist drugs bind to the receptor site and prevent the binding of agonist thereby blocking the effect of the agonist.
Example acetylcholine blocking by atropine.
Some of the blocking are reversible while others are Irreversible or pseudo reversible. Irreversible blocking action may prevent the action of the agonist even if the agonist concentration is increased. Reversible blocking can be unblocked by increasing the concentration of the agonist.
Allosterically binding drugs bind to the receptor site but do not prevent the binding of the agonist, their actions also cannot be prevented by increasing the concentration of the agonist.
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What is electrostatic bonding? |
They are weaker than covalent bonds but more common. Permanently charged ionic molecules have relatively strong bonds but there are weaker bonds like hydrogen bonds or dipole forces like Vanderwall bonds |
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What are hydrophobic bonds? |
Very weak bonds. Important in the interactions between lipid soluble molecules and the lipid layer of cell membrane |
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Which bonds are more selective for a receptor? |
Weaker Bonds like electrostatic bonds are more selective than covalent bonds. |
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How does drug shape influence receptor site binding? |
Chirality or stereoisomerism is common in more than half of all the useful drugs. Some molecules fit better than its enantiomer into the receptor sites. Example ketamine carvedilol Also drug metabolizing enzymes and drug transporters are also stereoselective which can influence the duration of action of a drug. |
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What is rational drug design? |
The ability to predict the approximate molecular structure of a drug based on the knowledge about it’s biologic receptor. A few modern drugs have been developed by designing The molecule based on the knowledge of three-dimensional structure of its receptor site. |
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Agonists that inhibit the binding molecules |
Some drugs inhibit the binding molecules that terminate the action of an Endogenous agonist. Example Acetylcholine esterase inhibitors. They slow the destruction of endogenous acetylcholine. They cause cholinomimetic effects but do not bind or passively bind to the molecules. They are usually more selective and less toxic |
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What is constitutive activity? |
Receptor maybe existing in the non functional ri form inactivated , or in the activated Ra form the small amount of Ra can induce agonist similar activity, this is called the constitutive activity of the receptor. |
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What are full agonist |
Most agonists, if given in sufficient concentration, can activate the receptor fully that is shifted completely to the Ra form showing maximum activity these agonists are called full agonist |
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What are partial agonist |
Some agonists activate the same receptors but do not shift all the receptors to the right to form a significant amount still exist in the Ri form and show the response shown is not complete even if the concentration is increased these types of agonist are called partial agonist.
Because they occupy the receptor to prevent other full agonist from binding to the receptor and hence they act as antagonist in the presence of another full agonist. Eg pindolol, partial beta agonist in the presence of epinephrine. |
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What is neutral antagonism? |
Some drugs activate the receptor site in equal amounts there by keeping the r i and r a amounts equal hence there will be no activity seen but agonist cannot bind to the receptor site because of the presence of the antagonist so there will be no agonist action this is known as neutral antagonism. |
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What are inverse agonist |
Some agonists shift the receptor form to the r i, causing inhibitory action opposite to that of a normal full agonist, this is called as inverse agonist |
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What are the possible scenarios for duration of drug action |
In some cases the drug action may terminate as soon as the drug disassociates from the receptor site in other cases the action is prolonged because there is still coupling molecules present at the site. in covalent bonding the action will be prolonged until the receptor complex is destroyed or new receptor sites are formed as in aspirin |
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What are the ideal characteristics of a receptor? |
1. It should be selective in choosing to bind to ligands or drug molecules. 2. It must change its function upon binding in such a way that the function of the biologic system (cell, tissue) is altered. |
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What is an inert binding site? Significance? |
If a drug binds to a non regulatory molecule like plasma albumin, there will be no detectable change in function of the biologic system. This endogenous molecule is called an inert binding site. This binding affects the amount of free drug available in the circulation and also effects the drug distribution in the body. |
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What is a prodrug? |
An inactive precursor chemical that is readily absorbed and distributed in the body and gets activated to an active form by biological processes is sometimes needed in some drug systems. This is called a prodrug. |
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What is drug permeation? Different types? |
The diffusion of a drug in different compartments of the body is called drug permeation. 1. Aqueous diffusion 2. Lipid diffusion 3. Special carriers 4. Endocytosis and exocytosis |
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What is aqueous diffusion? |
Diffusion of a drug within the large aqueous compartments of the body (interstitial space, cytosol) and epithelial membrane tight junctions and endothelial lining of blood vessels through aqueous pores. |
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Where are sites in the body where aqueous diffusion is absent? |
Brain, testes, and some other tissues |
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What causes aqueous diffusion? |
It is driven by concentration gradient of the permeating drug based on the fick's law.
If the drug is bound to plasma albumin, it cannot permeate through vascular aqueous pores. If the drug is charged its flux is influenced by membrane potential or in the case of nephron, transtubular potential. |
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What are the principles of lipid diffusion? significance? |
Most important limiting factor of drug permeation because all the body compartments are lined by lipid molecule barriers. Because the lipid barriers separate aqueous compartments, the lipid : aqueous coefficient of diffusion of a drug determines the rate of permeation of a drug.
Weak acids or weak bases readily, gain or lose electrically charged protons depending on the pH. Charged molecules attract water molecules. So this influences the rate at which a drug permeates from lipid to aqueous or vice versa. |
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What does the Henderson Hasselbalch equation show? |
It shows the ratio of lipid soluble to water soluble form for a weak acid or weak base |
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What are special carriers in diffusion? |
Special carrier molecules exist to help facilitate diffusion through lipid membranes for substances that are important for cell function but too large or insoluble to pass through by passive diffusion. These are facilitated diffusion or active transport. They are saturable, selective and inhibitable. Many drugs resemble these substances and hence can cross using these carriers. |
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What are other types of special carriers for diffusion? |
A few not so selective carriers are specialized for expelling foreign molecules. Eg. ABC family (adenosine binding cassette) includes p glycoprotein, MDR1 ( multi drug resistance type 1) and MRP (multi drug resistance associated protein) please play an important role in the excretion of drugs are the metabolites into bile and urine and in the resistance of some tumors to chemotherapeutic drugs. These bind to ATP to excrete drugs but there are others which use Ion gradients. |
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Drug permeation by endocytosis and exocytosis |
Some substances are so large or so impermeable that they can be transported only by the method of endocytosis. Eg. Vitamin B12 with IF (intrinsic factor). Iron with transferrin into rbc. Exocytosis responsible for many secretions of substances from cells. Eg. neurotransmitter substances stored inside vesicles at nerve endings. |
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What is Fick's law of diffusion? |
Flux (molecules per unit time) = ( C1 - C2) * area * permeability coefficient /thickness C1 is higher concentration, C2 is lower concentration Area is the cross-sectional area of the diffusion path Thickness is the length of the diffusion path. Permeability coefficient is eg. Lipid:aqueous diffusion coefficient. |
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What does the Henderson Hasselbalch equation explain? |
The relation of the ratio of protonated to and protonated weak acid or weak base to the molecule's pka and the ph of the medium. |
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What is the henderson hasselbalch equation? |
Log protonated /unprotonated = pka - ph |
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Significance of the henderson hasselbalch equation? |
Applies to both acidic and basic drugs. The uncharged form or non polar is more lipid soluble. Hence, more of weak acid will be lipid soluble at acidic PH, more of a weak basic will be lipid soluble at basic PH |
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Where are drugs reabsorbed in the Kidney |
Glomerulus. Especially if it is lipid soluble. By simple passive diffusion |
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In a drug overdose, how can the kidney be manipulated to excrete more of the drug in the urine? |
To prevent reabsorption in the tubule, most of the drug should be in the ionized state. This is done by adjusting the pH of the urine. Thus weak acids are usually excreted faster in alkaline urine. Weak bases are excreted faster in acidic urine. |
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Importance of carbon atoms in lipid solubility |
Quartenerary amines are always weakly lipid soluble charged form because it has no free electron to bind to a reversibly charged proton. But primary, secondary and tertiary amines have free electrons to bind. Thus, these can vary their lipid solubility with ph. |
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What is the first step in drug development? |
It starts with the discovery or synthesis of a potential new drug compound Or the finding of a new drug target |
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What is drug screening? |
It involves a variety of essays at the molecular cellular organic or whole animal level to find out the pharmacological profile That is the activity and selectivity of the drug. The receptor binding capacity of the drug the accelerating or inhibiting action on liver enzymes, The drugs mechanism of action and selectivity is studied to reveal expected and not expected toxic effects. Cardiovascular and renal function studies are also carried out at the whole animal level. |
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What is the no effect dose ? |
The maximum dose at which is specified toxic effect is not seen |
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What is the minimum lethal dose? |
The smallest dose that is observed to kill any experimental animal |
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What is the median lethal dose? |
Dose that kills at least 50% of the animals in an experimental group. It is estimated from the smallest number of animals possible |
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What are the limitations of pre-clinical testing? |
1.Rare adverse events are difficult to detect 2. Toxicity testing is time consuming and expensive 3. Large number of animals maybe needed to collect data 4. Toxicity data of animals is usually the same for humans but sometimes can be wrong |
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What are the problems in clinical trials? |
1.Some diseases have variable history of progression ,remission or disappearance 2. Known and unknown other diseases and risk factors like lifestyle 3. The possible response due to caring medical personnel |
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What is single blind clinical trial? |
A placebo which is an inert material that resembles the actual form in size shape and weight and appearance is given in a crossover design or in a separate group of subjects in clinical trial to gouge the response and predict the placebo effect |
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What is double blind clinical trial? |
In this clinical trial the The identity of the placebo or the active form is hidden from both subjects and the medical personnel caring for them in third group of administrators holding the code or the key to the dose administered |
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What is the FDA? |
It is the administrative body in the USA that handles the evaluation of a drug production and marketing of a new drug. It also has a role in food safety |
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What is IND? |
It is a notice of claimed investigational exemption for a new drug. It is filed in the FDA by a company that decides that a new drug is ready for clinical trials in humans. 1.It should list out the source and composition of the drug. 2.Chemical and manufacturing information data of animal studies 3. Proposed plans for clinical trials 4.The names and credentials of physicians who will contact the trials 5.Compilation of data about the drug that has been provided to peers and review boards |
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What is IND? |
It is a notice of claimed investigational exemption for a new drug. It is filed in the FDA by a company that decides that a new drug is ready for clinical trials in humans. 1.It should list out the source and composition of the drug. 2.Chemical and manufacturing information data of animal studies 3. Proposed plans for clinical trials 4.The names and credentials of physicians who will contact the trials 5.Compilation of data about the drug that has been provided to peers and review boards |
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What are orphan drugs? |
Drugs made for rare diseases are called orphan drugs because the trials ,research , market maybe expensive . Drug safety and efficacy in small populations need to be established. Not for profit organizations and the orphan drug act are helping |
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What are phase 1 trials? |
The drug effects are tested as a function of dosage among about 100 healthy volunteers . This is to determine the safe dosage level limits. Pharmacokinetics like absorption , half life, distribution, excretion checked. In special diseases like aids or cancer , the actual volunteer patients are used. Single blind study maybe used |
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What are phase 2 trials? |
Done in actual target diseased subjects. Highest drug failures detected here. Single blind used. More toxicities discovered. |
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What are phase 3 trials? |
Drug tested in larger numbers (thousands) of target disease volunteers. Double blind and crossover studies used. Expensive trials. The dosage is as formulated for the market. Done by specialists. Immunologic toxic effects detected usually here. |
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What are fast track approvals? |
FDA allows phase 2 trials to be marketed in control trials to speed up their approvals in severe diseases. |
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What are breakthrough drugs? |
FDA allows phase 1 testing of a few drugs for extremely rare severe diseases like cystic fibrosis. |
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What is phase 4 trial? |
Monitoring the safety of a drug in actual use in large numbers of patients. |
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Lifetime of a patent in USA |
20 years |
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What is a trademark? |
A drug’s proprietary trade name that is usually registered. Maybe legally protected as long as it is used. |
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What is an ADE? ADR? |
Adverse drug event. Adverse drug reaction. May reduce by use of electronic health records |
