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Q49: Why are hormones important?

Q49:  Why are hormones important?

Hormones are the  substance, usually a peptide or steroid, produced by one tissue and conveyed by the bloodstream to another to effect physiological activity, such as growth or metabolism.

The role of hormones

The major endocrine glands are the pituitary, the thyroid, the four parathyroids, the pancreas, the two adrenals, and the paired testes or ovaries (See endocrine). Hormones are also produced by organs or tissues whose function is not primarily an endocrine one: the digestive tract, the heart, and the kidneys all produce hormones. Even nerve cells produce them. For example, the hormones controlling secretion from the anterior lobe of the pituitary gland are synthesized in the hypothalamus, but they are released into the local blood supply to the anterior pituitary, rather than entering the general circulation. These cells are said to have a neuroendocrine function. Furthermore, it is now recognized that hormones need not even be released into blood vessels. The hormonal products of some nerve cells stimulate adjacent neurones and thus act as neuromodulators, while in the digestive tract hormones act on surrounding cells and are said to have a paracrine function (para: Greek for beside). Finally, some hormones, such as growth factors, can act on the originating cell itself; in this case they are described as exhibiting autocrine control. The classical definition has therefore been extended to include chemical messengers which are secreted by certain cells, and which reach and act upon cells which are receptive to them, whether local or distant.

Chemical nature of hormones

Chemically, most hormones belong to one of three major groups: proteins and peptidessteroids (fat-soluble molecules whose basic structure is a skeleton of four carbon rings), or derivatives of the amino acid tyrosine, characterized by a 6-carbon, or benzene, ring. There are some hormones, such as melatonin from the pineal gland and the locally actingprostaglandins, which cannot be included in any of these groups, but may share a number of their characteristics. The glands which produce protein and peptide hormones are the pituitary, certain cells of the thyroid, the parathyroids, and the pancreas. Steroids are produced by the cortex or outer layer of the adrenal gland and by the ovaries and testes. The tyrosine derivatives are the thyroid hormones, and the catecholamines (adrenaline and noradrenaline) which are produced in the medulla of the adrenal glands.

Knowledge of the chemical nature of a hormone is important as it enables one to predict how the hormone is produced, how rapidly it can be released in response to a stimulus, in what form it circulates in the blood, how it acts, the time course of its effect, and the route of administration therapeutically.

The chemical nature of the hormone also affects the mechanism of action. All hormones act on cells by way of their ‘receptors’. Each hormone has its own receptor to which it binds, matching rather like a lock and key. This is why hormones circulating throughout the body in the blood may leave capillaries to enter the extracellular fluid of many tissues, but act only on those cells which possess the appropriate receptor. Proteins and peptides cannot enter the cell and so act via cell membrane receptors, producing their effects by ‘second messengers’, which are activated in the cell as soon as the hormone binds to the receptor. Thus peptide hormones can produce quite rapid responses. Steroid and thyroid hormones, by contrast, can enter the cell and bind to intracellular receptors, producing their effects by stimulating the production of new proteins. There is therefore a relatively long lag period before the response to these hormones is seen.

Hormones produce a variety of responses throughout the body and may be grouped according to their actions, although there is overlap between the groups.
First there are the metabolic hormones which control the digestion of food, its storage and use. Such hormones include those produced by the digestive tract, which control secretion of digestive juices and activity of the muscle in the wall of the tract; also the hormones which regulate blood glucose, namely insulin, (which lowers it), and glucagon, growth hormone, the thyroid hormones, and cortisol, which all raise it.

Second are the hormones which regulate the composition of the blood, and hence of all the body fluids. Excluding those that regulate the glucose content, these are: aldosterone and atrial natriuretic hormone (produced in the heart), which control the amount of sodium in the blood; vasopressin or antidiuretic hormone, which controls the amount of water; parathyroid hormone and vitamin D, which raise blood calcium; and calcitonin, which lowers blood calcium. It is perhaps surprising to learn that a vitamin can also be a hormone, but it is similar in many ways to the steroid hormones, and the active form is produced in one part of the body for action an another. The vitamin D taken in the diet or formed in the skin under the action of UV light is not the active form: this is produced after modification takes place first in the liver and then the kidney.

Next are the stress hormones, primarily adrenaline and noradrenaline, which are under the control of the autonomic nervous system: cortisol and a number of the pituitary hormones are also involved in the response to stress.

A further group are those responsible for growth, development, and reproduction. These include growth hormone itself, and the hormones controlling ovarian and testicular function (luteinizing hormone, LH, and follicular stimulating hormone, FSH) — all of which come from the pituitary — and the hypothalamic hormones, which in turn control these pituitary secretions. Included also are the steroid hormones, produced by the ovaries (oestrogens and progesterone) and testes (testosterone), and those hormones involved in birth and lactation, chiefly oxytocin and prolactin.

The final major group includes those hormones that control other endocrine systems, and therefore interact with the other groups. The pituitary hormones adrenocorticotrophic hormone(ACTH), thyroid stimulating hormone (TSH), and the gonadotrophic hormones LH and FSH control the release of some of the metabolic and stress hormones and of the reproductive hormones, whilst hypothalamic hormones in turn control pituitary function.

Hormone effects

Hormone effects vary widely, but can include:

In many cases, one hormone may regulate the production and release of other hormones

Many of the responses to hormone signals can be described as serving to regulate metabolic activity of an organ or tissue.

 

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Q48: Please describe the action of cardiac glycosides?

Q48: Please describe the action of cardiac glycosides?

Answer:

CARDIAC GLYCOSIDES

The cardiac glycosides are an important class of naturally occurring drugs whose actions include both beneficial and toxic effects on the heart. Plants containing cardiac steroids have been used as poisons and heart drugs at least since 1500 B.C. Throughout history these plants or their extracts have been variously used as arrow poisons, emetics, diuretics, and heart tonics. Cardiac steroids are widely used in the modern treatment of congestive heart failure and for treatment of atrial fibrillation and flutter. Yet their toxicity remains a serious problem.

 

 Mode of action

All cardiac glycosides are highly selective inhibitors of the active transport of Na and K across cell membranes, by binding to specific site of Na-K-ATPase, the enzymatic equivalent of the cellular Na-“pump”. This inhibition causes activation of Na-Ca-exchanger and increase of intracellular Ca levels, which interact with contractile proteins of myocardial cells and increasing the contractility of cardiac muscle.

 

Effects

1)     Positive inotropic effect – increasing of the heart velocity and contractility.

2)     Negative chronotropic effect – decreasing of heart automatisity and increasing maximal diastolic resting membrane potential in sino-atrial and atrio-ventricular nodes, causing in this way decreased heart conduction.

3)     Vasoconstriction in rapid IV administration –  transient effect, via inhibition of Na-K-ATPase and increasing of Ca entry cause effect on vascular smooth muscles.

 

Pharmacokinetics and dosing

Digoxin’s half-life is 48 hours, this permits a once-a-day dosing; then the drug is started, during first week loading dose is given (“digitalisation”), then the treatment is continued with maintenance doses.

Digoxin excreted mainly with urine (most part is unchanged). Tissue reservoir of digoxin is skeletal muscles, so dosing should be based on estimated lean body mass. Monitoring is required during administration (target serum concentration is about 1.0 nanogramm/ml).

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Q47: Cytotoxic drugs used in skin diseases?

Q47: Please find, on the Internet, articles about Cytotoxic drugs used in skin diseases?

Answer: Following are the article I have found on internet regarding Cytotoxic drugs used in skin diseases.

Article number one:

Toxic epidermal necrolysis: Effector cells are drug-specific cytotoxic T cells

A Nassif, A Bensussan, L Boumsell, A Deniaud, H … – The Journal of Allergy and Clinical Immunology, 2004 – Elsevier
 Immunostaining for granzyme B used 5 μL phycoerythrin-labeled antigranzyme B monoclonal
antibody  Determination of drug-specific cytotoxic activity in 

Article number two:

Drug Specific Cytotoxic T-Cells in the Skin Lesions of a Patient with Toxic Epidermal Necrolysis

A Nassif, A Bensussan, G Dorothée, F Mami-Chouaib … – Journal of Investigative Dermatology, 2002 – nature.com
 Then, we used these stimulated cells to evaluate the molecular basis of target cell
killing. The drug-related cytotoxic effect was not inhibited by a 

Article number three

Treatment of Psoriasis

MW Greaves, GD Weinstein – New England Journal of Medicine, 1995 – content.nejm.org
 etretinate and PUVA has also been used in chronic  Stern RS, Lange R. Non-melanoma skin cancer occurring  The action of cytotoxic drugs on cell proliferation in 

Article number Four

Cytotoxic drugs in the treatment of skin disease.

RP Rapini – Int J Dermatol, 1991 – ncbi.nlm.nih.gov
Int J Dermatol. 1991 May;30(5):313-22. Cytotoxic drugs in the treatment of skin
disease. Rapini RP. Department of Dermatology, University 

Article Number Five

The skin biopsy in the diagnosis of acute graft-versus-host disease in man

GE Sale, KG Lerner, EA Barker, HM Shulman, ED … – American Journal of Pathology, 1977 – ASIP
 of acute graft-versus-host disease (GVHD) using  results of “blind” studies of skin
biopsy specimens  Large doses of cytotoxic drugs and irradiation given before  

Article Number Six

Drug-Induced Skin Pigmentation: Epidemiology, Diagnosis and Treatment.
O Dereure – American Journal of Clinical Dermatology, 2001 – dermatology.adisonline.com
 9] Corneal pigmentation is often associated with skin changes and  Cytotoxic Drugs
TOP.  is a very common adverse effect of chemotherapeutic agents used in cancer 

Article Number Seven

Immunosuppressive and cytotoxic drugs in dermatology.
PI Dantzig – Arch Dermatol, 1974 – ncbi.nlm.nih.gov
Immunosuppressive and cytotoxic drugs in dermatology. Dantzig PI.  Methotrexate/
therapeutic use; Procarbazine/therapeutic use; Skin Diseases/drug therapy*; 

Article Number Eight

Rituximab for the treatment of type II mixed cryoglobulinemia
II MC – ARTHRITIS & RHEUMATISM, 2002 – doi.wiley.com
 on systemic autoimmune manifestations, we used the drug  with diffuse purpura, ulcerative
skin lesions on  associated with use of steroids and cytotoxic drugs

Article Number Nine

Cytotoxic agents for use in dermatology. I.
CJ McDonald – J Am Acad Dermatol, 1985 – ncbi.nlm.nih.gov
 improved quality of life for patients who have diseases such as  of circumstances,
in the properly monitored patient cytotoxic drugs may be used safely and 

Article Number ten

Management of ‘refractory’skin disease in patients with lupus erythematosus
JP Callen – Best Practice & Research Clinical Rheumatology, 2005 – Elsevier
 have both been used in doses similar to those used for acne  In addition, each of
these drugs is associated with possible  Immunosuppressive and cytotoxic agents. 

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Q46: Define the term “cholinergic drugs”?

Q46: Define the term “cholinergic drugs”?

Answer: Cholinergic means related to the neurotransmitter acetylcholine, and is typically used in a neurological perspective. The parasympathetic nervous system is entirely cholinergic. Neuromuscular junctions, preganglionic neurons of the sympathetic nervous system, the basal forebrain, and brain stem complexes are also cholinergic. In addition, the receptor for the merocrine sweat glands are also cholingergic since acetylocholine is released from post ganglionic symapathic neurons.

A substance is cholinergic if it is capable of producing, altering, or releasing acetylcholine (“indirect-acting”) or mimicking its behaviour at one or more of the body’s acetylcholine receptortypes (“direct-acting”).

Cholinergic drugs are the medications that mimics or enhances the action of the neurotransmitter acetylcholine. Cholinergic drugs are used for urinary retention, myasthenia gravis, glaucoma.

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Q45: What kind of the new drug against cancer would win the market?

Q45: What kind of the new drug against cancer would win the market?

Answer: Currently all the drugs that are used to treat cancer are not very compliant to patients and some have severe side effects so as far as my point of view is concern a cancer drug that could win the market should be the one that fights the disease by impeding the blood supply that tumours need to survive and also at the same time having less toxic effects with maximum compliance to patient.

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Q44: Why could regular antibiotics not be used as effective treatment of viral diseases?

Q44: Why could regular antibiotics not be used as effective treatment of viral diseases?

Answer: Antibiotics are totally worthless and ineffective for the treatment of flu or other viral diseases.

Viruses pose a considerable challenge to the body’s immune system because they hide inside cells. This makes it difficult for antibodies to reach them. However, special immune system cells, called T-lymphocytes, can recognise and kill cells containing viruses, since the surface of infected cells is changed when the virus begins to multiply. Many viruses, when released from infected cells, will be effectively knocked out by antibodies, produced in response to infection or previous immunisation.

Antibiotics kill bacteria by interfering with their metabolic processes, but viruses are so simple they use their host cells to perform their activities for them. This is why antibiotics are useless against viral infections. Antiviral drugs work by interfering with the viral enzymes. Antiviral drugs are currently only effective against a few viral diseases, such as influenza, herpes, hepatitis B and C and HIV, but research is ongoing. A naturally occurring protein, called interferon (which the body produces to help fight viral infections), can now be produced in the laboratory and is used to treat hepatitis C infections.

Viral diseases should never be treated with antibiotics. Sometimes a person with a viral disease will develop a bacterial disease as a complication of the initial viral disease. For example, children with chickenpox often scratch the skin sores caused by the viral infection. Bacteria such as staph can enter those lesions and cause a bacterial infection. The doctor may then prescribe an antibiotic to destroy the bacteria. The antibiotic, however, will not work on the chickenpox virus. It will work only against staph.

Antibiotics do not affect viruses, but many flu deaths are due to secondary bacterial infections such as pneumonia. Antibiotics would be used to treat these cases.

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Q43:What unique qualities should a new drug for the treatment of Alzheimer’s disease possess in order to become successful?

Q43:What unique qualities should a new drug for the treatment of Alzheimer’s disease possess  in order to become successful?

Answer:

Alzheimer Disease:

Defination:

Alzheimer-type dementia is a degenerative process, with a loss of cells from the basal forebrain, cerebral cortex, and other brain areas.

Causes: Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid, leading to generalised neuroinflammation.

In 1991, the amyloid hypothesis postulates that amyloid beta (Aβ) deposits are the fundamental cause of the disease. It is a compelling theory because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and people with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD by 40 years of age. Also APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD. Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology.An experimental vaccine was found to clear the amyloid plaques in early human trials, but it did not have any significant effect on dementia.

Deposition of amyloid plaques does not correlate well with neuron loss. This observation supports the tau hypothesis, the idea that tau protein abnormalities initiate the disease cascade. In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies.When this occurs, the microtubules disintegrate, collapsing the neuron’s transport system.This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.

The previous drugs like Tacrine(Cognex) – acridine derivative; acts by  treating  AchE, administrated orally.

The unique quality that a new drug should have for the treatment of alzheimer is thatit should breakup or dissolve the protein tangles that clogs victims brain and result in death of the brain cells and complete loss of memory or death.

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Q42:Why would the development of new drugs used in treatment of allergies, be very attractive for pharmaceutical companies?

Q42:Why would the development of new drugs used in treatment of allergies, be very attractive for pharmaceutical companies?

Answer: It has proved to be very difficult to develop new classes of antiasthma therapy, partly because existing drugs, and particularly inhaled corticosteroids are so effective. The only new class of drug developed in 25 years have been the antileukotrienes which are less effective than inhaled corticosteroids. There is a need to develop new treatments for asthma, since patients with severe asthma are not well controlled on doses of corticosteroids that are safe, and there is a problem of poor compliance with existing inhaler therapy. Several drugs are now in development for asthma. New bronchodilators have been difficult to develop as new drugs are less effective than β2-agonists and have more side effects. Mediator antagonists have proved disappointing as so many mediators are involved in asthma. Inhibitors of cytokines, such as interleukin (IL)-5, IL-4 and eotaxin, which may inhibit eosinophilic inflammation, are now in clinical development. Other approaches include more selective immunomodulation, anti-IgE antibodies, adhesion molecule blockers and kinase inhibitors. Preventive treatments in the future may include drugs that alter the immune abnormalities in atopy by stimulating a protective Th1 immunity. A cure for asthma does not seem likely in the near future instead of that development of new drugs used in the treatment of allergy are attractive because of their compliance and less toxic effects.

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Q41: You are reviewing the results of a clinical research study on a new compound with action similar to Warfarin (Coumadin). What would be the most dangerous side effect of such a drug?

Q41: You are reviewing the results of a clinical research study on a new compound with action similar to Warfarin (Coumadin). What would be the most dangerous side effect of such a drug?

Answer:Following are the expected dangerous side effects of a drug that is similar in action with warfarin:

Severe bleeding

Bleeding from the rectum or black stool

Skin conditions such as hives, a rash or itching

Swelling of the face, throat, mouth, legs, feet or hands

Bruising that comes about without an injury you remember

Chest pain or pressure

Nausea or vomiting

Fever or flu-like symptoms

Joint or muscle aches

Diarrhea

Difficulty moving

Numbness of tingling in any part of your body

Painful erections

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Q40: Why do you think development of new antibiotics is not very attractive venture for the pharmaceutical companies? How are antibiotics different from other “life-time” drugs?

Q40: Why do you think development of new antibiotics is not very attractive venture for the pharmaceutical companies? How are antibiotics different from other “life-time” drugs?

Answer3:

 

Development of new antibiotics no longer attractive for pharma industry

 

Bacteria become pathogenic under varied circumstances especially when the host defenses become weak due to whatever reasons e.g. poor nutrition. Louis Pasteur, Joseph Lister and others began linking these bacteria to disease and today the discipline of infectious disease has become the greatest ever challenge facing the scientific world. Discovery of Penicillin by Sir Alexander Flemming – its impact and value – was realized as a great breakthrough in the world of life sciences during and after World War II. Advances in medical technology increased our success in combating the bacterial diseases with the manufacture of a variety of antibiotics – tetracycline, streptomycin, ampicillin, amoxicillin etc. and so on – indeed once labelled as the wonder drugs. But today these wonder drugs and their development is no longer an attractive venture for the pharmaceutical companies – why?
Due to ever changing environment – external and/or internal – these bacteria evolved their own mechanism of defense that helps them survive the adversaries of the environment. One theory that shook the entire scientific world and stood the test of the time is the so called ‘Theory of natural selection’ by Charles Darwin with the core concept that struggle for existence leads to origin of new species and strains. Such species and strains become well equipped to handle the disturbances in their environment including the milieu interior of the human body. During their struggle for existence, these organisms – prokaryotes as well as eukaryotes acquire ever emerging newer mechanisms of resistance that help them overcome the adversaries in environmental conditions by evolving through the process of adaptation – a process of acquiring or developing newer characters which help them survive the adverse environment conditions, and, indeed this ‘survival of the fittest’, then, leading to emergence of newer species and strains.

By analogy, whenever an antibiotic is administered to eradicate the disease producing pathogenic bacteria, it tends to eliminate not only the pathogenic bacteria but also in the process inflicts damage to the non-pathogenic bacteria, especially ‘commensals’ that leads to serious disturbances in the milieu interior. At this stage comes struggle for existence for these microbes. Every living being on the planet earth, be it a microbe or human being is, hitherto, provided with defense mechanisms exclusive to the ‘one life’ itself. This defense arsenal, in microbes exists in the form of resistance mechanisms that lead to microevolution at a fairly rapid rate. Of these, the R-plasmids are the most significant. Exposure of a bacterial population to a specific antibiotic, in the laboratory designed system or within a living system, kills the antibiotic sensitive bacteria but not those that possess R-plasmids or resistance mechanisms. Theory of natural selection predicts that under these circumstances an increasing number of bacteria inherit genes for the antibiotic resistance (microevolution). This resistance, in turn, must spread for the benefit and survival of the entire affected bacterial population to maintain its population dynamics and equilibrium in the given ecosystem.

To this spread of resistance far and wide across the globe at a very rapid rate, contribute the unique mechanisms of reproduction (which these tiny microbial microscopic lives are naturally endowed with) – such as transformation, transduction and conjugation processes. So, the new species or the strains are now well adapted ‘survival of the fittest’ and spreads rapidly to restore its own population equilibrium in the vast ecosystem – an ecosystem for these inhabitants of earth that recognize no man made regional demarcations or boundaries. What is the net result?

The antibiotic that triggered all these events now becomes less and less effective, virtually ineffective, undergoing its natural elimination from the market usage culminating into huge economic losses for the pharmaceutical industry, a loss that could run into billions of dollars. The cow gives no more milk – it is dry and dumping this cow (the ineffective antibiotic) needs more investment than the money spent on its manufacture. The problem gets further compounded by the fact that there exist no universally acceptable guidelines to affect the judicious use of antibiotics. The net result is indiscriminate use of these wonder drug – the plethora of antibiotics manufactured all across the globe with the hope that one day at least, it will help, if not eliminate but contain the spread of eradicable bacterial diseases.

Antibiotics different from other “Life-Time” Drugs

Lifetime drugs that humans use, of and on, for entire lifetime, for example paracetamol – in striking contrast – do not act against any life form. Such drugs interact with the cell(s) at a molecular level and bring about temporary changes in the functioning of the host cell which returns to normal when the effect of the drug is over or the drug is withdrawn. The cell damage even if it occurs – undergoes natural repair and physiological restoration leading to the return of the cells, the organ and the system to its normal structural and functional status – physiologically as well as anatomically. Lifetime drugs continue to be of use throughout life of an individual without inviting any resistance to its occasional or repeated use and effects. In fact, for a pharmaceutical company improvement in the design of the lifetime drugs is more fruitful – a new fancy preparation in the market under a new trade name. Therefore, manufacturing of life time drugs is like breeding and cloning cows that continues to give milk for ever – a functional asset with good marketable values for long times ahead when compared to antibiotic manufacturing whose future always remains in dole drums, not only because of the resistance phenomenon but also because of its indiscriminate use.

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Q39: You are participating in research and development of a new adrenergic agonist drug. What side effects of such a drug can you anticipate?

Q39: You are participating in research and development of a new adrenergic agonist drug. What side effects of such a drug can you anticipate?

Answer:  Side Effect of a new adrenergic Agonist Drug:

1)     Redness and stinging in the eyes.

2)     Allergic reaction in the eyes (itching).

3)     Dry mouth (very common with the newer medications but usually improves over time).

4)     Drowsiness, nervousness, and headaches.

5)     Fast or irregular heartbeat.

6)     Increased blood pressure.

7)     Adrenergic agonists may widen (dilate) the pupil. This may trigger  closed-angle glaucomain people who have narrow  drainage angles.

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Q38: Please find on the Internet information on 3 pairs of drugs with opposing pharmacological effects and 3 pairs of drugs with similar pharmacological effects?

Q38: Please find on the Internet information on 3 pairs of drugs with opposing pharmacological effects and 3 pairs of drugs with similar pharmacological effects?

Answer:

Three Pairs of drug wit opposing Pharmacological effect:

1-caffiene and ephedrine, actuall caffiene potentiates ephedrine.

2-LSD and Psilocybe mushrooms (Psilocybin and Psilocyn)

3-Mescaline and 5meoDipt(Foxy).

Three Pairs of drug withSimiliar  Pharmacological effect:

1) Alprazolam (Xanax), Chlordiazepoxide (Librium) both are used for treatment of anxiety

2) Amphetamine and Methamphetamine are both powerful stimulants of the central nervous system

3) Zaleplon and Zolpidem Both compounds reduced locomotor activity and produced motor deficits in the rotarod and loaded grid tests in mice.

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