FACULTY OF PHARMACY

M.S. RAMAIAH UNIVERSITY OF APPLIED SCIENCES

Department Pharmacology
Programme M. Pharm
Batch 2020 Semester I
Course Code MPL102T Course Title Advanced Pharmacology I
Course Leader(s) Mrs. Sathiya. R; Dr. Kesha Desai
Name of the
Sumit kumar Reg.No.
Student 20PHPG059013
Marks
Sections Marking Scheme Max. Marks Obtained
Marks
1.1 Introduction 02
1.2 Drug safety 04
1.3 Examples and reasoning 04
A Part-A Max Marks 10
2.1 Beneficial drug-drug interaction 05
2.2 Clinical importance 05
Part-B Max Marks 10
3.1 Selection of Recent advancements 02
3.2 Explanation 06
C
Part-C Max Marks 08
References 02
30
Total Marks

(Total Marks reduced to 15)

Signature of the Examiner:

Date:
Instructions to students:
1. The assignment consists of 3 questions.
2. Each question carries 10 marks
3. The maximum number of pages including Part A, Part B and Part C should be restricted to 25 A-4 size : font size
11, Spacing 1.5 including the references, diagrams, pictures, tables and equations
4. The assignment has to be neatly word processed as per the prescribed format.
5. Assignment should be checked for Similarity index and it must be less than 10%
6. The complete Similarity index checked assignment document must be submitted to Course leader
7. Submission Date: 21-03-21
8. Submission after the due date is not accepted.
9. Use only SI units.
10. IMPORTANT: It is essential that all the sources used in preparation of the assignment must be suitably
referenced in the text.
11. Marks will be awarded only to the sections and sub-sections clearly indicated as per the problem statement

Part A: 10 marks
Develop an essay on “Cardiovascular Drug Therapy in Geriatric
1.1 Introduction to Geriatric Cardiology
1.2 Cardiovascular Drug safety in elderly patients
1.3 Safe and unsafe cardiovascular drugs (5 each) examples and reasoning

Ans: Geriatric cardiology is also called as cardio-geriatrics, it can be defined as branch of cardiology and geriatric
medicine that treat the cardiovascular disorders in elderly people. The developing ground of geriatric cardiology
reveals the change in clinical practice as the distinctive cardiovascular patients grown old and not same he was
in past. the approach of a geriatric cardiologists involves in taking assumptions not only on age alone but on the
medical, physical and mental profile of the patients in order to achieve a sort of individualization, not just on a
given cardiovascular analysis, but with respect to each patient's aging capability. As it modifies the
pharmacokinetics and the idea of fragility that ought to guarantee to acknowledge a treatment that considers
for age-related changes, These progressions may incorporate an intricate blend of psychological overdue debts,
adjusted pharmacokinetics, and pharmacodynamics, incontinence, torment, wooziness, and weariness which
may unequivocally influence the principle need and the helpful methodology. Also, perspectives concerning the
administration of a geriatric patient ought to be likewise viewed as like function decrements, just as visual and
hear-able impediments. cardiovascular sickness likewise shows various non-cardiac diseases that make the
utilization of customary cardiology testing. Quite possibly the most well-known cases are identified with the
connection between meds that are recommended for different conditions that may rise the dangers of
antagonistic effects in more established grown-ups. drug security is the pharmacological science identifying with
identification, appraisal, observing, and anticipation of unfavorable effects with drug items. As maturing
prompts deteriorate the absorption, digestion, and discharge of various medications.

In elderly patients, it’s been seen to have diminished gastric acid secretion and blood flow which can lead to
diminished retention of various drugs. Somehow there is an affiliated decrease in gastrointestinal motility which
can increase absorption due to longer transit times. as these can be further complicated by the concurrent
widespread use of antacids that interfere with drug absorption. Aging also affects the pharmacokinetics of drug
distribution. Elderly patients have lower total body water content. Lipophilic drugs have an increased volume of
distribution with an extended half-life and hydrophilic drugs tend to have a smaller distribution volume in the
elderly. This prompts expanded groupings of water solvent medications that can prompt harmfulness.
Moreover, lower serum protein levels in this populace lead to expanded non-protein bound convergences of
medications that elevate drug harmfulness for a given measurement, as indigestion prompts diminished hepatic
reduction of the medication and diminished phase I digestion because of decline in liver mass, hepatic blood
stream and metabolic movement As the hepatic first-pass impact decreased, the bioavailability of specific
medications can be expansion in the older, Hepatic medication leeway of specific medications can be
diminished. Getting old prompts diminished renal blood stream and decline in the all-out number of successful
nephrons. This can potentiate diligence of different medications and metabolites in the dissemination. In
addition to cardiac arrhythmia which includes atrial fibrillation, ventricular arrhythmia, and sudden cardiac
death increases with age

Safe drugs Reasons

1. Direct acting oral anticoagulants DOACs have fewer drug and food interactions, quick
(dabigatran, rivaroxaban) onset, and ease of use that require no routine

monitoring compared to vitamin k antagonist

2. Chlorthalidone in low doses

(thiazide diuretics)

3. Satins at low dose decrease LDL levels

4.Asprin also used at low dose

5. Dabigatran oral coagulant

Unsafe drugs Reasons

1.alpha adrenergic blockers they can induce orthostatic hypotension and increase the
. risk of fall and injuries

2. minoxidil and hydralazine it can cause fluid retension reflux,tachycardia,artrial

. arrhytmia

3.clonidine  can cause sedation, bradycardia, and rebound

hypertension . if stopped abruptly

4.nitrates can not be used for long term in hypotension due to tolerance

5.flecainide can not be used frequently due to increases in pro-arrhythmia

Reference:

1. Dodson, J.A., Matlock, D.D. and Forman, D.E., 2016. Geriatric cardiology: an emerging discipline. Canadian

Journal of Cardiology, 32(9), pp.1056-1064.

2 Tsilimingras, D., Rosen, A.K. and Berlowitz, D.R., 2003. Patient safety in geriatrics: a call for action. The
Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 58(9), pp.M813-M819.

3. Malavolta, M., Caraceni, D., Olivieri, F. and Antonicelli, R., 2017. New challenges of geriatric cardiology: from
clinical to preclinical research. Journal of geriatric cardiology: JGC, 14(4), p.223.

4. Ayan, M., Pothineni, N.V., Siraj, A. and Mehta, J.L., 2016. Cardiac drug therapy—considerations in the
elderly. Journal of geriatric cardiology: JGC, 13(12), p.992.

Part B: 10 marks
Your discussion should include the following:

1.1 Drug drug interaction with emphasis on beneficial effect

1.2 Clinical importance of beneficial drug interactions

 1.1 Ans: A Drug interaction is an interaction between a drug and some other substance, such as another drug or
a certain type of food, which leads to interaction that could manifest as an increase or decrease in the
effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can
be severe enough to alter the clinical outcome, As pharmacokinetic drug communications incorporate tweak of
certain dynamic carriers and metabolic pathways by co-directed substances may prompt bothersome results. At
the point when efflux carriers and metabolic chemicals are incited, this may prompt fulfillment of sub-
restorative medication plasma levels that are connected with pharmacological inadequacy. As efflux carriers and
metabolic chemicals are repressed, it might prompt improved bioavailability and powerful restorative results if
the medication plasma level is inside the helpful window. In any case, an accomplishment of supra-restorative
medication plasma levels is related to unfavorable impacts and perhaps at the same time harmfulness. it is very
well might be utilized in a controlled way to the helpful advantage of patients, drug connections have both a
pharmacodynamic or pharmacokinetic premise. The previous might be simpler to expect and evade since added
substance impacts are unsurprising when medications having comparative pharmacologic action are taken
together. For instance, hyperkalemia is an expected result of the utilization of both ACE inhibitors and
potassium-saving diuretics. It was discovered that patients treated with ACE inhibitors and conceded to the
emergency clinic with a conclusion of hyperkalemia were multiple times bound to have gotten a potassium-
saving diuretic. Pharmacokinetic drug cooperations happen because of an adjustment in the openness to a given
portion of one medication when given with another. This is best surveyed by estimating the zone under the
plasma fixation/time bend however can be assessed in patients by estimating at least one plasma focuses under
consistent state conditions Drug associations are Mostly bothersome or Rarely alluring or helpful for instance,
uplifting of movement of penicillins when controlled with probenecid. The Net Impact of a Drug Interaction
either increments or diminishes the impact. For the most part for example fast or more slow impact.
Elements adding to medicate associations are by and large Multiple medication treatments, Multiple
prescribers, Multiple pharmacological impacts of medication. These medication drug connections may make you
experience an unforeseen result. For instance, blending a medication you take to help you rest which is calming
and the medication you take for sensitivities is an antihistamine as it can moderate your responses and make
driving a vehicle or working apparatus risky. Connections between medications might be valuable or hurtful.
Harmful medication drug communications are significant as they cause 10–20% of the antagonistic medication
responses that may require hospitalization and they can be kept away from. Old patients are particularly open
to a solid connection between expanding age, the number of medications recommended, and the recurrence of
potential medication drug communications. A few medications have inadequate oral bioavailability due to either
systemic extraction or digestion in the liver prior to arriving at the foundational dissemination. Conceivable
outcomes to build ingestion rely upon comprehending the system of helpless bioavailability, which is to realize
that is it a decent substrate for CYP3A/a carrier, for example, ketoconazole can heighten the bioavailability of
midazolam by a factor of 15 when midazolam is directed orally, yet simply by a factor of 5 when it is controlled
intravenously. This information can be utilized to assess the measure of the association is because of liver
digestion and gastrointestinal extraction. recognize that drug associations can cause numerous antagonistic
impacts and it is likewise vital to bring up that there are various restoratively helpful medication collaborations.
For instance, thiazide diuretics can cooperate with different diuretics that cause potassium maintenance so that
the mix fundamentally affects body potassium. In Cancer chemotherapeutic specialists are frequently given in
blend on the grounds that cell communications, for example, repressing cell replication and empowering
apoptosis among the medications cause more disease cell passing. Antihypertensive medications are regularly
given in mix since a portion of the results delivered by one medication is overwhelmed by the activities of the
other. These are only a couple of the numerous instances of helpful medication connections.

1.2
A clinically applicable Drug-Drug Interactions occurs when the effectiveness or toxicity of one medication is
altered by the administration of another medicine or a substance that is administered for medical reason to be
distinguished from drug-food interactions. Adverse consequences of drug drug interaction may leads to either
reduced therapeutic action or toxicity. Among the various types of medical errors, the occurrence of adverse
drug-drug interactions is one that is usually avoidable. It is then essential that health experts be able to estimate
the potential for drug-drug Interactions and, when detected, to determine appropriate prevention or
management strategies. The potential for clinically important drug-drug Interactions can often be forecast based
on the drug properties, method of drug administration, and patient-specific parameters. Therefore, adverse
outcomes resulting from drug-drug interactions can be prevented by making patient- and situation-specific
assessments and, if appropriate, avoiding concomitant administration by implementing alternative therapeutic
strategies, or taking precautionary measures such as dosage adjustments and increased monitoring.
Some examples are
1.aminoglycosides and pencillins it will enhance aminoglycoside transport into cell and it’s bactericidal effect
2.aspirin and acetaminophen as acetaminophen lacks anti-inflamatory action but adds to the antipyretic and
analgesic effect
3.copper and penicillamine decreases harmful effect during copper poisioning
Reference:
1. Gerber, W., Steyn, J.D., Kotzé, A.F. and Hamman, J.H., 2018. Beneficial pharmacokinetic drug interactions: a

tool to improve the bioavailability of poorly permeable drugs. Pharmaceutics, 10(3), p.106.

2. Gerber, W., Steyn, J.D., Kotzé, A.F. and Hamman, J.H., 2018. Beneficial pharmacokinetic drug interactions: a
tool to improve the bioavailability of poorly permeable drugs. Pharmaceutics, 10(3), p.106.

Part C: 10 marks

Disorders of the Central Nervous System may involve vascular disorders, infections, structural disorders,
functional disorders, degeneration. In this context, discuss on any three recent advancements (new drugs and
techniques) in the treatment of CNS disorders.

Ans: 1. seizure is well-known as an epileptic seizure, it is a period of manifestations because of unpredictably

unnecessary or coordinated neuronal movement in the cerebrum. outside impacts fluctuate from uncontrolled
shaking developments of the body with loss of cognizance are tonic-clonic seizures, and the shaking progression
with variable degrees of cognizance are central seizure and to an unobtrusive fleeting loss of mindfulness
nonappearance seizure. More often than not these events last under few mins and it needs some investment to
move towards business as usual.

The US Food and Drug Administration(FAD) recently legalized XCOPRI, which are cenobamate pills, for the
treatment of the partial-onset seizures in adults. This is a promising approach for treating adults with partial-
onset seizures, which is a difficult-to-control disorder that can have a major impact on the patients' standard of
living. Patients can respond differently to the various seizure medications that are available. This acceptance
adds a much-needed recovery alternative for people suffering from this disease. The prescribed maintenance
dose of XCOPRI, the drug regulation time, is 200 mg daily; but, depending on their clinical reaction, certain
patients may require an extra titration to 400mg per day, based on their clinical response and tolerability, the
maximum prescribed dosage  However, multiple organ hypersensitivity, a drug interaction with systemic
symptoms and eosinophilia, has been documented between individuals taking the drug and later no issues of
hypersensitivity were reported in patients when cenobamate is given at 12.5 mg /day and attuned around 14
days

2. Alzheimers disease is a neurodegenerative disease which is the reasons of cognitive and functional
impairment as well as the onset of neuropsychiatric indications . The genetics that underpins is that Alzheimer's
disease includes the aggregation of soluble amyloid particles into unsolvable amyloid plaques, tau hyper-
phosphorylation with the forming intra-cellular neurofibrillary twists and may cause death as well as a number
of several other processes such as synaptic and circuit malfunction, neuroinflammation, mitochondrial and bio-
energetic disturbances, genetic mutations, and vascular anomalies. Neurochemical defects result from neuronal
loss of transmitter system root nuclei, which contribute to psychological - behavioral effects. The FDA has
licenced cholinesterase inhibitors and one NMDA receptor antagonist to treat Alzheimer's disease. The
cholinesterase inhibitors are galantamine, rivastigmine, and donepezil. Memantine is an N-methyl-D aspertate
receptor antagonist. Memantine and cholinesterase inhibitors have similar effects, with increases in memory
and global activity over baseline and transient stabilisation in tasks of daily life. Following therapy with
symptomatic agents, several studies indicate an increase in existing neuropsychiatric symptoms and a decline in
the occurrence of new neuropsychiatric symptoms. In Alzheimer's disease, the lack of presynaptic cholinergic
cells in the nucleus basalis allows for active post-synaptic stimulation, leading in cholinergic augmentation and
cognitive growth. The nucleus basalis is the main acetylcholine source in the amygdala cerebral cortex. The most
cholinergic feedback is received from the paralimbic and limbic cortices in brain, which are both the primary
sites of mutual cortical projections back to the nucleus basalis. Following treatment with Cholinesterase
Inhibitors, imaging studies like functional magnetic resonance imaging and fluorodeoxyglucose  positron
emission tomography  usually display increased cortical circuit operation.

3. Intranasal conveyance is a straightforward, unobtrusive means of surpassing the BBB to carry medicinal
experts to the spinal cord and brain. Sedates which can’t cross BBB will now be sent to the focal sensory system
in a matter of seconds thanks to this breakthrough. It also directly delivers medications to the brain that do
cross the BBB, eliminating the need for basic organisation and its possible consequences. This is plausible given
the novel connections between the cerebrum and the environment that the trigeminal nerves and olfactory
have .Restorative experts do not recommend any changes to intranasal conveyance. The olfactory framework
and related memory areas affected by Alzheimer's disease can be treated with a broad range of therapeutics,
including both small particles and macromolecules. Utilizing the intranasal conveyance framework, In a
transgenic mouse model of Alzheimer's disease, researchers have reversed neurodegeneration and preserved
memory. Intra-nasal insulin like development factor-I, erythropoietin and deferoxamine, has appeared to secure
cerebrum alongside the stroke in creature model. Insulin improves memory in ordinary grown-ups and patients
with Alzheimer's sickness without adjusting blood sugar. Energy digestion in the CNS is reliant upon glucose
moiety take-up which is managed by insulin in main mind area Intra-nasal distribution of the neuro-protective
peptide  to the brain also been used to control neuro-degeneration. Neurogenesis in adults has been found to
be triggered by intranasal fibroblast growth factor-2 and epidermal development factor and has for quite some
time been realized that glucose take-up and usage are lacking in patients with Alzheimer's sickness. As of late,
the quality articulation levels of IGF-1, insulin and receptors were demonstrated are especially diminished in the
minds of patients with Alzheimer's sickness. Subsequently, the capacity to convey insulin to the CNS without
modifying blood glucose could give a compelling way to improve glucose take-up and usage and lessen
intellectual shortfalls in patients with memory issues. Intra-nasal insulin progresses memory, consideration,
working in the patient with Alzheimer sickness, and even improves memory and disposition in ordinary grown-
up people. This new technique for conveyance can upset the treatment handling of Alzheimer sickness, and
cerebrum issues.
Refrence:

1. Cummings, J., 2021. New approaches to symptomatic treatments for Alzheimer’s disease. Molecular
Neurodegeneration, 16(1), pp.1-13.

2. Hanson, L.R. and Frey, W.H., 2008. Intranasal delivery bypasses the blood-brain barrier to target therapeutic
agents to the central nervous system and treat neurodegenerative disease. BMC neuroscience, 9(3), pp.1-4.