Clinical Pharmacology - Science topic

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Because older adults are under-represented in clinical trials, doctors can’t be certain that approved cancer drugs will work as intended in this age group. In the absence of high-quality evidence, researchers are looking for ways to improve medical decision-making and better predict outcomes based on age...

Please compare Croatian per capita GDP & PPP with countries such as Sweden, Finland, Norway, Austria etc ! Democracy & progressive society are always directly proportional to per capita GDP & PPP !

AMPs(antimicrobial peptides) will be greatly promoted because ARGs and anti-biotics resulted in more and more anxiety in people.

I would rather ask, why you want to combine it? MAOIs are very potent Antidepressant, in adequate dose and duration, i think will be sufficient for your patient. I also hold the same opinion like others who opined , better to avoid adventurous practice rather play safe.

hello mr Abhishek Raj how about your long term stability ? and what kind of primary packaging did you use for HQ cream. i have this problem too, but before this case, i dont have any complain about turning brown

based on a double-blind, multicenter, RCT comparing 1,000 mg tabs vs 500 mg tabs (same daily dose) in acute hemorrhoid, the authors concluded that "We have been demonstrated that the new single MPFF 1000 mg tablet has clinical acceptability and a good safety profile, comparable to that of MPFF 500 mg tablets. MPFF 1000 mg was as effective as MPFF 500 mg in reducing anal pain and bleeding. The new dose regimen should lead to better treatment adherence and consequently to better management of hemorrhoidal disease."

This is what I would call a very risky and stupid design. Get books on research ethics and clinical trials and try hard to understand what they are telling you. David Booth

All the reasons are possible, especially the inheritance factor.

The first is the sample size issue, a predictive model are trained and built with limited imaging data from a particular hospital or region; this has to face bias caused by various factors when dealing with a wider range of diagnoses; it may not be adaptable when making diagnostic decisions for images from other regions.

The second is the inability to balance the patient's treatment intentions, the patient's financial situation, and different regional customs when making treatment decisions.

I am a clinical Pharmacy Specialist with about 4 years of experience. Mostafa Elsersy

To get this straight, the treatment goal is addressed under pharmacotherapy one area of clinical pharmacy. Unless you have a measurable goal or pre-defined goals (sign or symptoms improvements) it is difficult to assess whether the treatment is adequate or not. Specific to your question, the main goal of Glaucoma treatment is to halt or slow down the disease progression or to prevent further deterioration of the vision. Lowering IOP help to decrease the disease progression or prevents glaucoma in patients with ocular hypertension (without optic nerve damage). If you want to dig more you can read standard textbooks such as Pharmacotherapy: A pathophysiologic approach (Joseph T. Dipiro) or Applied Therapeutics: The Clinical Use of Drugs (Caroline S. Zeind)

Agreed with dear Arvind Singh

Awareness can be increased if everyone is involved, the task of making people aware of COVID-19 prevention should not be left to the government alone. Let all stake holders be involved: that is civic leaders, the church, the education bodies, traditional leaders NGOs and the others.

Superoxide dismutase, glutathione peroxidase and total antioxidant are antioxidant parameters but malondialdehyde are oxidant markers. The values of these factors are different in the articles. Different laboratory kits, different animal tissues as well as measurement methods can be the cause of this difference. Last but not least is the unit of measurement that should be considered.

I think it would be helpful to search for articles with similar measurement methods to your own work and to compare control groups.

Best regards

Goranka Glad Scherr Please check your message. Thanks.

Actually, factors affecting self medication practice among university students can be identified with only research. Therefore, as per findings from different studies I have seen, the following are the major once.

1.knowledge of students about self medication

2.Attitude of students about self medication among university students

3.age of students

4.sex of students

5.Economic status of students

6. religion of students

7.year of study of students

8. Type of department of students who are attending

9.distance of health institution or pharmacy to university

10. Availability of clinics in the university or around

11.Accessability of health professionals around

etc

Dear researcher, besides these, you can better search others from different literatures.

1,4-dideoxy-1,4-imino-D-Arabinitol (DAB) is soluble in DMSO. For obtaining a higher solubility ,it is necessary to warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.

Regardless if you have a psychiatric diagnosis and not, you can have infections and other p0hysical disorders. My experience is that too little focus is put on these patients' physical disorders. In the early years alcohol and penicillin was recommended not to be taken together. This was not due to any interaction between alcohol and penicillin but it was a precaution that sailors and others with sexually transmitted disorders could forget to take their antibiotics when drunk.

Two important challenges - pin pointed vaccine and social distancing during the unlock phase

Micro-nutrients, which include many vitamins, and minerals are imperative to maintain good health. I am of the opinion that micro-nutrients that boost the immunity should be included in our diet. The person with strong immune system can hardly get infection.

Please take a look at this useful link.

informative links Tze Tsung Tan hope Serena make use of them ..

No indication for an ocular surface condition like phlyctenular keratoconjunctivitis, which is a type-IV (cell-mediated) hypersensitivity reaction to high-MW bacterial (Staph, mycobacteria) capsule proteins. Phyctenular ulceration may occur, but it usually involves the gelatinous proliferative tissue on its apical portion, rather than the corneal epithelium. On the other hand, AC inflammatory reaction is not a common feature of the disease; therefore, ciliary spasm is not frequently present.

No, there is no cure for Sjogren's syndrome.

I think yes every formulation should be tested because excipients will be different in each formulation and may lead to increased or decreased bioavailability.

Regards

According to classic theory, a migraine attack is initiated by cerebrovascular spasm followed by extracranial vasodilatation. Results of recent studies support this theory and suggest that cerebral blood flow during the initial phase of migraine symptoms is, in fact, decreased and this decrease probably leads to ischemia and hypoxia. Cellular hypoxia, in turn, can cause an increase in the flow of calcium from the extracellular fluid to the intracellular space, resulting in calcium overload and cellular dysfunction. Because calcium-channel blockers selectively inhibit the intracellular influx of calcium ions, investigators have begun evaluating the efficacy of these agents for migraine prophylaxis. Nimodipine, a calcium-channel blocker that exhibits selective effects on cerebral vessels, seems to offer protection against the cerebral ischemia and hypoxia presumed to be operative during migraine attacks.

Hi Eran Assaraf , did you find info on the administration of Clozapine in drinking water and its efficacy in activating DREADDs?

Although there have not been any studies about intubation, a question I asked 4 years ago but we do have something about extubating a patient on vasoactive drugs.

Quasim T et al. (2018) Safety of Extubating Mechanically Ventilated Patients on Vasoactive Infusions: A Retrospective Cohort Study. Am J Respir Crit Care Med, Articles in Press. Published on 28 June 2018 as 10.1164/rccm.201712-2492LE 

This is both a medical and ethical question. Because the medications are not without side-effects, should we prescribe a drug in the absence of identifiable illness?

If you wanted to be expert in pharmacology, I recommended this reference :

1. Lippincott Illustrated Reviews: Pharmacology

2. pharmacotherapy a pathophysiologic approach 2017

They contain many core and simple concept of pharmacology, pathophysiology and also pharmacotherapy of disease. some guideline (algorithm) of disease that can be help. example if Hypertension the guideline is JNC or AHA. That can be very useful.

Please have a look at these useful links.

Welcome

Metabolomic factor is one out of 5 main factors influencing drug-body interactions and drug response.

The clinical value of metabolomics is that a drug may change hepatic and tissue metabolic activity that may influence physiology or coadminister drugs activity like macrolides and the risk of torade de pointes from metaclopromide. On the other hand metabolomic setup like racial differenxes may influence drug kinetics and response. From overall interactions drug order of kinetics and constants may be altered to be considered therapeutically like Cl, Vd, t1/2 and F

I have a major problem with i.p injection of the same compound. It's published to work at 100mg/kg via i.p. The drug appears to become insoluble once injected, it forms large encapsulated black 'bubbles' that are very hard. When I cut it open it's just the drug in a semi-powder form. Clearly the drug isn't be adsorbed... Does anyone have any idea why this would happen? Mice are treated every 2 days over a 2 week period.

Hi Ahmed

I think these books may help to find your queries

1. Drug-drug interactions in pharmaceutical development/ [edited by] Albert P. Li : Wiley,2008.

2.Drug-drug interactions /edited by A. David Rodrigues: Informa Healthcare,2008.

3. Drug-membrane interactions: analysis, drug distribution, modeling/ Joachim K. Seydel and Michael Wiese: Wiley,2002.

4. Meyler's side effects of drugs: the international encyclopedia of adverse drug reactions and interactions/ editor, J.K. Aronson: Elsevier,2016.

5. Drug facts and comparisons

6. Drug-Drug interactions with an emphasis on psychiatric medications / Sheldon H Preskorn: Professional Communications,2018.

Please, see PLoS ONE September 11, 2018 it is a excellent review

Silva LS, Peruchetti DB, Silva-Aguiar RP, Abreu TP, Dal-Cheri BKA, Takiya CM, et al. (2018)

The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. PLoS ONE 13

(9): e0203836

Malaria-induced acute kidney injury (MAKI) is a life-threatening complication of severe

malaria. By activation of the sympathetic nervous system has been observed, due to vasodilation, which in turn leads to stimulation of RAS and a consequent increase in the level of angiotensin II (Ang II) . The effects of Ang II are mediated by specific receptors: AT1 and AT2 . The Ang II/ AT1 receptor pathway plays a central role in the development of the glomerular and tubular injuries observed in AKI from different causes. This effect has been associated with the induction of a pro-inflammatory phenotype promoting immune cell infiltration and cytokine secretion in renal tissue . It has been shown that pro-inflammatory cytokine production is strongly associated with severe malaria . Previously, the Ang II/AT1 receptor pathway was implicated in the modulation of immune cells such as CD4+ and CD8+ T cells and brain damage in experimental CM, modulating the secretion of pro-inflammatory cytokines . Therefore, it is possible to postulate that the Ang II/AT1 receptor pathway is involved in the development of MAKI. To test this hypothesis, in this work we used a well-known murine model of severe malaria, C57BL/6 mice infected by P. berghei ANKA (PbA-infected mice) , treated or not with losartan or captopril, blockers of the Ang II/AT1 receptor pathway. The authors observed that these compounds abolished the increase in secretion of pro-inflammatory cytokines, such as interferon gamma (IFN-γ), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-17, avoiding the development of glomerular and tubular injuries in MAKI. These data help us to better clarify the molecular mechanism of pathogenesis of MAKI and suggest a potential strategy for adjuvant treatment with RAS inhibitors in human malaria.

You might consider developing a PK/RO/PD model assuming that receptor occupancy (RO) is proportional to efficacy. As suggested previously, a joint PK/PD modeling approach linking PK of the drug to % RO using the equation: Cp/(Kd + Cp), and a suitable PD equation (e.g. direct effect, indirect response model) linking RO to an efficacy marker or endpoint can be performed. The model can may then be applied to find an optimal oral dose producing MEC and examine duration of efficacy. Hope this helps.

The biggest challenge with pvp centres in to get adrs from clinicians... there are two reasons for reluctance of clinicians to re adr:

1. Misconception that adr reporting can harm them .. they could be held responsible for occurrence of adr

2. They are busy and they dont think adr reporting is important

both these issues can be addressed by having frequent adr reporting sensitisation sessions.

other important thing that can help is to have good social repo witt clinicians

I agree with information shared by colleague Miyuru Chandradasa and include that SSRIs produce some anticholinergic activity, more precisely anti muscarinic activity

Hi,

After administration of one XL capsule, plasma flecainide concentrations gradually increase after a lag time of 2 to 3 hours to reach a peak between the 21st and 25th hour and remain at plateau levels until after the 30th hour.

ACE-inhibitor may have delayed response due to physiological intermediates (not only due to its long half-life). The physiological mediators of the blood pressure fall (due to angiotensin converting enzyme inhibition) are angiotensin (rapid effect) and sodium (slow effect). It can take at least a week to see the full blood pressure lowering effect because of the long half-life of sodium.

Clinical Pharmacist is an active member of healthcare team providing direct patient care. American College of Clinical Pharmacy describes role of a Clinical Pharmacist as working directly with physicians, other health professionals, and patients to ensure that the medications prescribed for patients contribute to the best possible health outcomes. This role provides opportunity for a Clinical Pharmacist to apply core of pharmacy in patient care.

I forgot to update this. We decided to follow the protocol outlined in the attached Powerpoint. See the methods section.

How we will calculate this sample

if you have frozen the liver enzymes in clean glass containers and kept for only 21 days and found loss in activity, remember it has nothing to do with glass as materials, it might have other reasons.

There is an interaction between Mebendazole and Metronidazole. Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole. So all the resources ( Product information leaflet, FDA website, Stockley’s interaction) says to avoid concomitant use of mebendazole and metronidazole.

A case control study was conducted in an attempt to identify risk factors associated with an outbreak of Stevens-Johnson syndrome/toxic epidermal necrolysis that occurred amongst Filipino workers in Taiwan. The risk of developing this serious condition was significantly higher in workers who had taken both metronidazole and mebendazole sometime in the preceding 6 weeks (odds ratio of 9.5). In addition, there was an increase in risk with higher doses of metronidazole.However, Stevens-Johnson syndrome/toxic epidermal necrolysis is a serious condition, and therefore, the manufacturer of mebendazole states that the concurrent use of mebendazole and metronidazole should be avoided .

I believe ibuprofen is best because its metabolism in the liver, not affected by NAFLD because their metabolism pathway occur by number of CYP isoforms for example S-IBU is predominantly via CYP2C9 whereas R-IBU is more via CYP2C8. A number of other CYPs are capable of metabolism at high concentrations of IBU: CYP3A4, CYP2C8, CYP2C19, CYP2D6, CYP2E1, and CYP2B6 for 2-hydroxylation and CYP2C19 for 3-hydroxylation. In addition it less drug - drug and drug - disease interaction than aspirin. While acetaminophen is hepatotoxic and not preferred here. Aspirin to be used for headache should be taken at high dose (300-500)mg or more and it has wide range of adverse effects and drug-drug or disease interaction.

Hi,

You could check this article

It seems that, after apoptosis, ROS can be mediated by caspases to promote a regeneration process.

Regards

Dear Yojet,

I suppose you have patch clamp rig to measure ionic currents, if yes, then you can simply patch NSC derived neuron and record inward I_Na and apply TTX. You shall see rapid and almost complete block of sodium currents (see attached pic) which will confirm the efficacy and potency of TTX stocks you have. You can refer to the following paper for internal external combination and protocol to be used for recording.

measuring

Ensure that you aliquote your TTX and store it at -20/80 to preserves its efficacy. I hope it helps!

Best,

Nand

Studies show that Enalapril and enalaprilat have been detected in human breast milk; because of potential for serious ADRs in breastfed infant, including hypotension, hyperkalemia and renal impairment, there it is preferred not to use enalapril while breast feeding.

Source: @Medscape

Gee, you'd best ask a clinician that. They get feedback from their patients as to onset of effects. Probably varies amongst the various anxiolytics and patients.

Mostafa,

Note that Css is the steady state level that is reached after several half-lives following regular multiple dosing. The therapeutic level is simply the blood concentration that will result in a therapeutic response which (for certain drugs) can be reached just from a single dose.

Half life is the time duration required by a drug to get reduced in plasma by half of its initial concentration. For example if the plasma concentration is 100mg now what time it will take to remain 50 mg then 25mg and so on. A drug needs 4-5 half life toget elliminated or excreted completely from body not to acheive a steady state . Actually steady state is an equlibrium mantained by frequent doses of drugs. A single dose may acheive a minimum effective concentration in plasma and effects will be observed but a single dose will not acheive the steady state concentration.

Minimal effective concentrations is obtained 5mg so the response will be produced but the magnitude of effects is dependent on receptor occupied whileincreasing the dose to 20mg will raise the plasmaconcentrationof the drug that will occupy most of the receptors so the magnitude of effects will be increased .

further you can read from the Katzung basicand clinical pharmacology or further elaborate your question.

It's time to change the way we approach coughs in community pharmacy

Firstly, I don't think you should disregard side effect profiles when comparing pharmaceutical agents for the same indication. Side effects are a very important factor to consider when selecting among different drugs. They can cause harm to the patient, or they can cause the patient to cease taking the drug.

To compare different otc analgesics, you will have to set up a double-blind trial with placebo control. You will have to decide on the most appropriate dose(s) of each drug. Then you will have to come up with a readout, which in the case of analgesics is the subjective experience of pain upon application of some painful but harmless stimulus. You will have to include enough subjects to achieve sufficient statistical power to detect a difference between the effectiveness of the drugs of the desired size.

After MI, Fb are activated throughout the LV, presumably through TGF-β1 in response to increased wall stress and/or inflammation. Additional regional specific signaling leads to interstitial fibrosis via collagen cross-linking in MIadjacent. Local LOX activity could be stimulated by higher mechanical load imposed by tethering to the infarct or signals could diffuse from the scar. Identifying specific signaling cues to maintain the mature state of MyoFb phenotype in the scar tissue may open new perspectives in targeting the MyoFb reversibility in interstitial fibrosis without damaging existing scar tissue.

The undesirable effects that may appear are those well described: digestive disorders (frequent), nervous system (rare) and immuno-allergic (rare). They are related to flavonoids.

The pharmacological effects are likely to be expressed in the healthy subject (AGRAWAL AD, 2011. Pharmaceutical activities of flavonoids: a review. International Journal f Pharmaceutical Sciences and nanotechnology). In my opinion, they will not have any clinical expression.

Yes, they are requested for the pre-clinical trials.

There are many reasons why a drug has low oral bioavailability. A major one is poor aqueous solubility. Hence if we can improve the solubility for example using a suitable salt form then we may be able to increase the bioavailability. Other methods include forming a more soluble complex for example with cyclodextrins, using a more soluble polymorphic form or amorphous form of the drug. Drugs in the form of liquids such as vitamin E has low and erratic bioavailability under fasted state and hence should be taken after a meal or formulated as a self emulsifying system which can mimic the intraluminal processing when taken with a meal. Certain compounds are not stable in the harsh gastric environment where the pH is near 1. In this case an enteric coat is useful. Also, some drugs are affected by the absorption barrier comprising P-gP and CYP3A4. The former is a counter transport protein that expels the drug back into the lumen of the GIT whereas CYP3A4 is a metabolizing enzyme that metabolizes a wide variety of drugs. Both act synergistically a s barrier to the absorption of many drugs but both are saturable. Hence if we administer 2 compounds which a substrates of both P-gP and CYP3A4, absorption of both can be enhance if the system is saturated. Piperine may also increase the absorption of certain compounds (mentioned by someone else above) but not helpful to others.

It also can be in situation when API have a long half-life period and expressed two-conpartment PK. In this case absorbtion time will strongly affect on Cmax, but not on AUC.

If you have two formulations with a differece in dissolution and this type of PK you can get same AUC and significant difference in Cmax.

Model in attached file.

The half life of furosemide is 2-3 hrs while that of torsemide is 4-6 hrs. when furosemide is used alone the effect lasts only for six hours and in the remaining 18 hours of the day the homeostatic mechanisms retain the water in the body lost initially. therefore it is advised usually that if u want to prescribe furosemide use it in two daily doses at least six hours apart to prevent the homeostatic mechanism of the body to operate. The other solution is to add a longer acting torsemide or thaizide. Toresamide also has an active metabolite which may increase its effect further.

No adverse effects are not enough to present bad profile of the drugs. Idiosyncriatic reactions and role of genetics, metabolism in short pharmacokinetics and dynamics both are important.

I suggest you take a look at the public protocols of institutions such as WHO or the European Union

Very nice topic to discuss and participate

1. Classification using A, B, C, D for other issue is not suit able as these are already adopted by FDA safety categories to use drugs in pregnancy.

2. Even if one uses such classification that will be much more complex because a single drug has multi system side effects .

3. If you consider nausea as class A, Diarrhoea B, Constipation C, Vomiting D, Gastric Ulcer E, Stomatitis F, Metalic test G, Anorexia H, Insomnia I, Dizziness J, Fits K, Vertigo L, Headache M, Treamors N,

3.I mean to say long list of side effects they not be classified as you suggest even it will further complicate pharmacology of drugs to learn and remember

Based on TACT trial...ACC recommended chelation therapy as class 2b indication for therapy of stable ischaemic heart disease.. In 2014.Further studies are needed in this aspect. 

Primaquine itself is not active, but must be metabolized to generate metabolites which are active. It is possible that something interfered with primaquine metabolism so that these active metabolites were not generated.

Thank you very much. I will study your suggested articles carefully. Best regards. Mercedes

Thank you

You may find few in the following article: Generally the natural products derived from Food  are safe and long lasting.

 I have worked on  Apigenin flavonoid which is a good alternate found in dried parsley leaves.

This is a known fact every body knows .I want some one to guide in bringing some chemical changes in quinine structure.Reducing toxicity and enhancing its specificity for insulin release. 

I don't know much about topical therapy, but it seems to me that it should simplify the problem of dosing, since pharmacokinetics and ADME properties should be largely irrelevant. You basically have a static concentration. You only have to make sure that the concentration of the liposomal vancomycin is above the MIC for the infecting strain at the site of infection. Another factor will be stability of the formulation, if free and liposomal vancomycin have different MICs.

 may give some hint

I  think to IC50  you can use in experiment

Thank you for this add-in information. You are absolutely right!

I don't know if this helps at all but recalled MHRA concerns about levothyroxine stability https://www.gov.uk/government/publications/levothyroxine-a-review-of-clinical-and-quality-considerations

We should warn about the ADR but also tell the percentage of people who might develop it in a layman language. We must safeguard ourselves first. In developing countries, doctors are getting abused physically almost every day.

Dose administration  of drug or any chemical test item in chicken is very simple comparing with other Lab animals. Test item can be suspended or dissolved in suitable vehicle and put directly in to the esophagus or in the mouth cavity with the help of catheter. Chicken has tendency to gulp whatever you put in the mouth. Only thing you have be cautious  about regurgitation  of dosed material .     

Hi,

2 cyclodextrins are mainly used via parenteral (iv) route: 2-hydroxypropyl betacyclodextrin and sulfobutylether betacyclodextrin, they are considered as safe excipients, used to solubilize poorly soluble drugs, thus giving a good alternative to the use of co-solvents or agressive surfactants. I agree with Amin, these products are excreted rapidly mainly unchanged through glomerular filtration (93-100%) after parenteral administration.

Best regards,

Thank you Dr  Menik, for your impressive and informative comments.