PHARMACOLOGY IMPORTANT
LONG QUESTIONS (15 MARKS)
(PART 3: QUESTION NO. 15-21)
PREPARED
BY MR. ABHIJIT DAS
1.
What do you mean by parenteral route?
What are advantages of parenteral routes over oral route? Classify parenteral
route.
2. Define
absorption of drugs. Give a note on different processes of absorption of drugs
and factors affecting the absorption process.
3. Define
biotransformation of a drug. Describe various processes of drug metabolism.
4. Explain
the various factors affecting the dose and action of drugs.
5. Define
cholinergic drugs. Classify it with suitable suitable examples. Give a note on
pharmacological action of acetylcholine.
6. What
do you mean by sympathomimetics and parasympathomimetics? Classify
anti-cholinergic drugs. Discuss pharmacological action of atropine on eye, CVS,
glands and smooth muscles.
7. Define
adrenergic drugs & classify them. Describe about pharmacological action,
adverse effect and use of adrenaline.
8. Write
down the definition, classification, mechanism of action, pharmacological action
and use of local anaesthetics.
9. Explain
general anaesthetics. Briefly describe the different stages of general
anaesthesia. Write a note on barbiturates.
10.
What are NSAIDS? Classify them. Write
the mechanism of action, pharmacological action and uses of aspirin.
11.
what is the difference between narcotic
and non-narcotic analgesics? Classify opiod
analgesics. Give a note on pharmacological actions, ADME, side effects
and therapeutic effects of morphine.
12.
Define epilepsy. Describe shortly
different types of epilepsy. Classify anti epileptic drugs. Write the mechanism
of action and adverse effects of phenytoin.
13.
What is sedative? Classify the drugs
used as sedative-hypnotics. Give an account of pharmacological action, ADME,
adverse reactions and therapeutic uses of barbiturates.
14.
Define diuretics. Classify it. Write
down the pharmacological action, adverse effect and use of furosemide.
15.
What do you mean by cardiac glycosides?
Write the mechanism of action, pharmacological action, adverse effects and uses
of digoxin.
16.
Enumerate the drugs used for the
treatment of peptic ulcer and describe pharmacological action, toxicities of H2
blockers.
17.
What is purgative? Classify it with
example. Give a note on irritant purgatives.
18.
Define chemotherapeutic agents and
antibiotics. Write the mechanism of action of penicillins and a note on
semi-synthetic penicillins. Or Classify penicillins and describe their method
of action, toxicity and therapeutic uses.
19.
What is tuberculosis? Classify anti
tubercular drugs with examples. Give a note on firstline anti tubercular drugs.
20.
What is amoebiasis? Classify antiamoebic
drugs. Discuss about the mechanism of action, pharmacokinetics, side effects
and uses of metronidazole.
21.
What is cancer? Classify anti cancer
drugs. Discuss shortly the mechanism of action of anti metabolites and
alkylating agents.
15.
WHAT DO YOU MEAN BY
CARDIAC GLYCOSIDES? WRITE THE MECHANISM OF ACTION, PHARMACOLOGICAL ACTION,
ADVERSE EFFECTS AND USES OF DIGOXIN.
ANS:
CARDIAC GLYCOSIDES
Cardiac glycosides are
medicines that increase the cardiac output and rate of contraction of heart.
They are used for
treating heart failure and certain irregular heart beats.
Cardiac glycosides are
found in several plants, including the leaves of the digitalis plant. This
plant is the original source of this medicine.
DIGOXIN
Digoxin is one of the
oldest medications used in the field of cardiology.
It is taken through
oral route or by injection into vein.
MECHANISM OF ACTION OF
DIGOXIN
Digoxin is a potent
inhibitor of Na+/K+-ATPase.
This inhibition
promotes sodium-calcium exchange, which increases the intracellular calcium
concentration, resulting in an increase in the force of myocardial contraction.
Calcium particles bind
to cell that helps the cell to contract, which makes the heart to pump blood.
PHARMACOLOGICAL ACTIONS
HEART
Digoxin increases
myocardial contractility in the failing heart. It also increases cardiac
output.
Digoxin helps to
increase the heart rate.
BLOOD VESSELS
Digoxin has mild direct
vasoconstriction action. Systolic blood pressure may increase and diastolic
blood pressure may fall in CHF patients.
KIDNEY
Diuresis is seen in CHF
patients. The retained salt and water is gradually excreted.
No diuresis occurs in
normal individuals due to other causes.
CNS
Digoxin has little
effect on CNS in therapeutic doses.
Higher doses causes
nausea and vomiting.
Still higher doses produce mental confusion, disorientation and visual disturbances.
ADVERSE EFFECTS OF
DIGOXIN
The adverse effects are
often grouped as cardiac and extra cardiac.
CARDIAC
Ø Delayed
AV conduction
Ø Ventricular
tachycardia
Ø Ventricular
fibrillation
EXTRA
CARDIAC
Ø Nausea
& vomiting
Ø Anorexia
(fear of being overweight)
Ø Head
ache
Ø Blurring
of vision
Ø Mental
confusion
THERAPEUTIC
USES
1.
Digoxin is used to treat heart failure.
2.
Digoxin is also used to treat cardiac
arrhythmias.
16.
ENUMERATE THE DRUGS USED
FOR THE TREATMENT OF PEPTIC ULCER AND DESCRIBE PHARMACOLOGICAL ACTION,
TOXICITIES OF H2 BLOCKERS.
ANS:
DRUGS USED FOR THE
TREATMENT OF PEPTIC ULCER
1.
REDUCTION OF GASTRIC ACID SECRETION
a. H2
BLOCKERS: Cimetidine, Ranitidine, Famotidine, Roxatidine
b. PROTON
PUMP INHIBITORS: Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole,
Esomeprazole
c. ANTICHOLINERGICS:
Pirenzepine, Propantheline, Oxyphenonium
d. PROSTAGLANDIN
ANALOGUE: Misoprostol
2.
NEUTRALIZATION OF GASTRIC ACIDS (ANTACIDS)
a. SYSTEMIC:
Sodium bicarbonate, Sodium citrate
b. NONSYSTEMIC:
Magnesium hydroxide, Magnesium trisilicate, Aluminium hydroxide gel,
Magaldrate, Calcium carbonate
3.
ULCER PROTECTIVES: Sucralfate, Colloidal
bismuth subcitrate (CBS)
4.
ANTI H.PYLORY DRUGS: Amoxicillin,
Clarithromycin, Metronidazole, Tinidazole, Tetracyclin
H2 BLOCKERS
These drugs are the
first class of highly effective drugs for peptic ulcer.
These drugs inhibit the
action of histamine on H2 receptors and thereby reduce gastric
secretion.
They
can cause 90% reduction in gastric secretion by a single dose.
Four
H2 blockers cimetidine, ranitidine, famotidine and roxatidine are
available in india.
MECHANISM
OF ACTION
All
four drugs have similar mechanism of action..
Combination
of histamine with H2 receptors present on the surface of gastric
parietal cell increases HCl secretion.
But
when H2 receptor blockers bind with the H2 receptor and
block the binding of histamine with H2 receptors, resulting in
inhibition of HCl secretion.
PHARMACOLOGICAL
ACTIONS
H2
BLOCKADE: H2 blockers block histamine induced gastric secretion.
BLOOD
VESSELS: They cause fall in blood pressure
LUNGS:
They cause bronchial relaxation. So H2 blockers are used in
histamine induced bronchospasm.
ADVERSE
EFFECTS
1. Diarrhoea
2. Muscle
pain
3. Dry
mouth
4. Rashes
5. Dizziness
6. Headache
THERAPEUTIC
USES
1. They
are used to treat duodenal ulcer and gastric ulcer
2. They
are used to treat Zolinger-Ellison Syndrome ( a rare digestive disorder that
results in too much gastric secretion).
3. They
are also used to treat GERD (gastro esophageal reflux disease).
17.
WHAT IS PURGATIVE?
CLASSIFY IT WITH EXAMPLE. GIVE A NOTE ON IRRITANT PURGATIVES.
ANS:
PURGATIVES
Purgatives are drugs
that promotes defecation. They are also called laxatives or cathartics.
Laxatives are milder evacuants while cathartics are more powerful evacuants.
CLASSIFICATION OF PURGATIVES
1.
BULK FORMING AGENTS
Dietary
fibre: Bran, Psyllium (Plantago), Ispaghula, Methylcellulose
2.
STOOL SOFTNER
Docusates
(DOSS), Liquid Paraffin
3.
OSMOTIC PURGATIVES
Magnesium
Sulfate, Magnesium Hydroxide, Sodium Sulfate, Sodium Phosphate, Lactulose
4.
STIMULANT PURGATIVES/IRRITANT
PURGATIVES
A. DIPHENYLMETHANES:
Phenolphthalein, Bisacodyl, Sodium Picosulfate
B. ANTHRAQUINONES
(EMODINS): Senna, Cascara Sagrada
C. 5-HT4
AGONIST: Tegaserod
D. FIXED
OIL: Castor Oil
STIMULANT PURGATIVES/IRRITANT PURGATIVES
These are powerful
purgatives. They produce peristalsis in the small or large intestine which
helps in purgation.
They may cause
abdominal cramps.
Larger doses of stimulant purgatives can cause excess purgation resulting in fluid and electrolyte inbalance.
1. BISACODYL
MECHANISM OF ACTION
Bisacodyl is converted to active
metabolite in the intestines.It irritates colonic mucosa to increase fluid
secretion as well as stimulates enteric neurons to promote peristaltic
movements.
ADVERSE AFFECTS
Ø Nausea
Ø Diarrhea
Ø Stomach
pain or cramps
2. SODIUM
PICOSULFATE
MECHANISM OF ACTION
It is hydrolysed by colonic bacteria to
the active form, which then acts locally to irritate the mucosa and activate
the enteric neurons, resulting in peristalsis.
ADVERSE EFFECTS
Ø Nausea
Ø Diarrhea
Ø Headache
Ø Stomach
pain
3. SENNA
MECHANISM OF ACTION
They are activated into their active
form in the intestines and stimulate the enteric neurons in the colon,
resulting in peristalsis.
ADVERSE EFFECTS
Ø Nausea
Ø Diarrhea
Ø Stomach
pain
Ø Excessive
bowel activity
4. CASTOR
OIL
MECHANISM OF ACTION
Castor oil is hydrolysed in the upper
small intestine to ricinoleic acid, a local irritant that increases intestinal
motility.
ADVERSE EFFECTS
Ø Nausea
Ø Diarrhea
Ø Stomach
pain
Ø Electrolyte
disturbance
18.
DEFINE CHEMOTHERAPEUTIC
AGENTS AND ANTIBIOTICS. WRITE THE MECHANISM OF ACTION OF PENICILLINS AND A NOTE
ON SEMI-SYNTHETIC PENICILLINS. OR CLASSIFY PENICILLINS AND DESCRIBE THEIR
METHOD OF ACTION, TOXICITY AND THERAPEUTIC USES.
ANS:
Penicillins are a type
of antibiotic derived from penicillium fungi (Penicillium
notatum & Penicillium chrysogenum).
Most penicillins in
clinical use are chemically synthesized from naturally produced penicillins.
These penicillin
antibiotics have a beta-lactam ring. The
beta-lactam antibiotics act by inhibiting the cell wall
synthesis in the bacteria.
CHEMOTHERAPEUTIC AGENTS
These are synthetic
compounds which suppress the growth or kill microorganisms. These drugs also
inhibit the growth of malignant cells (cancer cells).
ANTIBIOTICS
These are substances
produced by microorganisms which suppress the growth or kill bacteria.
CLASSIFICATION
A. NATURAL:
Penicillin G
B. SEMISYNTHETIC:
1.
ACID RESISTANT PENICILLINS: Penoxymethyl
Penicillin (Penicillin V)
2.
PENICILLINASE RESISTANT PENICILLINS:
Methicillin, Cloxacillin
3.
EXTENDED SPECTRUM PENICILLINS
a. Aminopenicillins:
Ampicillin, Bacampicillin, Amoxicillin
b. Carboxypenicillins:
Carbenicillin, Ticarcillin
c. Ureidopenicillins:
Piperacillin, Mezlocillin
4. BETA-LACTAMASE INHIBITORS: Clavulanic acid, Sulbsctsm, Tazobactam
MECHANISM OF ACTION
The beta-lactam
antibiotics act by inhibiting the cell wall synthesis in
the bacteria.
The cell wall of the
bacteria protects it from lysis. Peptidoglycan,
a complex polymer, is an important component of the cell wall.
Peptidoglycan consists
of glycan chains which are cross-linked by peptide
chains.
The synthesis of this
peptidoglycan requires enzymes called transpeptidases.
Beta-lactam
antibiotics inhibit these transpeptidases enzyme and thus inhibit
the synthesis of the peptidoglycan, resulting in the formation of cell wall
deficient bacteria. So bacteria undergo lysis.
That’s why penicillins
are bactericidal.
PENICILLIN G
Penicillin G is a
narrow spectrum antibiotic.
ADVERSE EFFECTS
1.
Hypersensitivity: skin rashes,
urticarial, fever, bronchospasm and rarely anaphylaxis.
2.
Local pain at the site of injection,
thrombophlebitis on IV injection.
3.
Large doses of penicillin G may produce
confusion, muscle twitching, convulsion and coma.
USES
Penicillin G is the
antibiotic of choice for several infections unless the patient is allergic to
it.
1.
Orodental infection
2.
Pneumococcal infection
3.
Streptococcal infection
4.
Meningococcal infection
5.
Staphylococcal infection
6.
Diptheria
SEMISYNTHETIC
PENICILLINS
Semisynthetic
penicillins are produced by chemically combining specific side chains in place
of benzyl side chain of penicillin G.
The aim of producing
semisynthetic penicillins has been to overcome disadvantages of penicillin G
such as:
1.
Poor oral efficacy
2.
Susceptibility to penicillinase
3.
Narrow spectrum of activity etc.
1. ACID
RESISTANT PENICILLINS
It differs from
penicillin G because it is acid stable.
PHENOXYMETHYL
PENICILLIN (PENICILLIN V)
It is administered
orally.
It should not be
preferred for more serious infections and is occasionally used for
·
Streptococcal pharyngitis
·
Sinusitis
·
Otitis media (ear infection)
·
Less serious pneumococcal infections
·
Trench mouth etc (gum infection)
2. PENICILLINASE-RESISTANT
PENICILLINS
These drugs have side
chains that protect the beta-lactam ring from attack by penicillinase.
They are only used in
infections caused by penicillinase producing staphylococci.
METHICILLIN
Methicillin is highly
penicillinase resistant but not acid resistant.
Methicillin can be
destroyed by gastric juice, hence given parenterally.
CLOXACILLIN
It is highly penicillinase
as well as acid resistant.
It is given orally.
It is more active than
methicillin against penicillinase producing bacteria.
3. EXTENDED
SPECTRUM PENICILLINS
These semisynthetic
penicillins are active against a wide variety of bacteria.
AMPICILLIN
It is active against
all organisms sensitive to penicillin G.
But due to wide spread
use, many bacteria have developed resistance against amphicillin.
Ampicillin is not
degraded by gastric acid. So oral route is adequate.
ADVERSE EFFECTS
1. Diarrhea
2. Intestinal
irritation
3. Hypersensitivity
reaction
USES
1.
Urinary tract infections
2.
Respiratory tract infection
3.
Meningitis
4.
Gonorrhea
5.
Endocarditis
CARBENICILLIN
Carbenicillin is
neither penicillinase-resistant nor acid-resiatant.
It is inactive orally
and is excreted rapidly in urine.
ADVERSE EFFECT:
Bleeding
USE: It is used to treat infections caused by pseudomonas (UTI, Septicaemia).
4. BETA-LACTAMASE
INHIBITORS
Beta-lactamase are a
family of enzymes produced by many bacteria that inactivate beta-lactam
antibiotics by opening the beta-lactam ring.
CLAVULANIC ACID
It inhibits a wide
variety of beta-lactamases produced by many bacteria.
It is administered
orally.
USE:
It is used against beta-lactamase producing bacteria (E.coli, Salmonella,
Shigella etc).
19.
WHAT IS TUBERCULOSIS?
CLASSIFY ANTI TUBERCULAR DRUGS WITH EXAMPLES. GIVE A NOTE ON FIRSTLINE ANTI
TUBERCULAR DRUGS.
ANS:
TUBERCULOSIS
Tuberculosis is a
serious infectious bacterial disease, caused by mycobacterium tuberculosis,
which mainly affects the lungs.
TB spreads from person
to person through air.
When a person develops
active TB disease, symptoms (such as cough, fever, night sweats or weight loss)
may be mild for many months.
CLASSIFICATION OF ANTITUBERCULAR
DRUGS
FIRST LINE DRUGS
1. Isoniazid
2. Rifampin
3. Pyrazinamide
4. Ethambutol
5. Streptomycin
SECOND
LINE DRUGS
1. Thiacetazone
2. Paraaminosalicylic
acid
3. Ethionamide
4. Cycloserine
5. Kanamycin
6. Amikacin
7. Capreomycin
FIRSTLINE DRUGS: These
drugs have high anti tubercular efficacy as well as low toxicity.
SECOND LINE DRUGS:
These drugs have low efficacy and high toxicity.
FIRST LINE ANTI TUBERCULAR DRUGS
ISONIAZIDE
(ISONICOTINIC ACID HYDRAZIDE)
Isoniazide is an
essential component of all anti tubercular resimens. It is primarily tuberculocidal.
It is one of the
cheapest anti tubercular drugs.
MECHANISM OF ACTION
Isoniazid inhibits the synthesis of mycolic acids which are
unique components of bacterial cell wall.
ADVERSE EFFECTS
1. Peripheral
neuritis
2. Mental
disturbances
3. Hepatitis
4. Arthralgia
(joint pain)
RIFAMPICIN
It
is a tuberculocidal as well.
MECHANISM
OF ACTION
Rifampicin
inhibits DNA dependent RNA synthesis.
ADVERSE
EFFECTS
1. Hepatitis
2. Breathlessness
3. Haemolysis
4. Rashes,
redness and watering of eyes.
ETHAMBUTOL
Ethambutol is tuberculostatic.
MECHANISM OF ACTION
It inhibits mycolic
acid incorporation in mycobacterial cell wall. So it works by inhibiting cell
wall synthesis.
ADVERSE EFFECTS
1. Rashes
2. Fever
3. Nausea
STREPTOMYCIN
It was the first
clinically useful antitubercular drug.
It is tuberculocidal, but less effective than isoniazid or
rifampin.
MECHANISM OF ACTION
Streptomycin blocks the
ability of ribosomes to make proteins.
ADVERSE EFFECTS
1. Stomach
upset
2. Lack
of appetite
3. Vertigo
4. Chest
pain
20.
WHAT IS AMOEBIASIS?
CLASSIFY ANTIAMOEBIC DRUGS. DISCUSS ABOUT THE MECHANISM OF ACTION,
PHARMACOKINETICS, SIDE EFFECTS AND USES OF METRONIDAZOLE.
ANS:
AMOEBIASIS
Amoebiasis is a
parasitic infection of the intestines caused by the amoeba Entamoeba
histolytica.
The symptoms of
amoebiasis include loose stool, abdominal cramping, stomach pain etc. However,
some people with amoebiasis won’t experience any symptom.
E. histolytica is a
protozoan than enters the human body through water or food contaminated with
stool.
The infection can also
spread through the bloodstream to the liver.
CLASSIFICATION OF
ANTIAMOEBIC DRUGS
1. TISSUE
AMOEBICIDES
a. FOR
BOTH INTESTINAL AND EXTRAINTESTINAL AMOEBIASIS:
NITROIMIDAZOLES: Metronidazole,
Tinidazole, Secnidazole, Ornidazole, satranidazole
ALKALOIDS: Emetine, Dehydroemetine
b. FOR
EXTRAINTESTINAL AMOEBIASIS: Chloroquine
2. LUMINAL
AMOEBICIDES
a. AMIDE:
Diloxanide furoate, Nitazoxanide
b. 8-HYDROXYQUINOLINES:
Quiniodochlor, Diiodohydroxyquin
c. ANTIBIOTICS: Tetracyclines
METRONIDAZOLE
Metronidazole is one of
the popular drugs for protozoal infections (E. histolytica).
MECHANISM OF ACTION
Metronidazole is
selectively toxic to anaerobic microorganisms (E. histolytica is an
anaerobic microorganism). E. histolytica reduces the nitro group of
metronidazole by nitroreductase and convert it to a cytotoxic derivative which
binds to DNA and inhibits protein synthesis.
PHARMACOKINETICS (ADME)
ABSORPTION:
Metronidazole is well absorbed from the small intestines.
DISTRIBUTION: It is
widely distributed in the body.
METABOLISM: It is
metabolized in the liver by oxidation and glucuronide conjugation.
EXCRETION:
Metronidazole is excreted in urine.
ADVERSE EFFECTS
1.
Anorexia (fear of being overweight)
2.
Metallic taste
3.
Abdominal cramps
4.
Dryness of mouth
5.
Rashes
6.
Seizures at high doses
THERAPEUTIC USES
1.
Metronidazole is used to treat amoebiasis.
2.
It is used to treat giardiasis (an intestinal infection caused by a
giardia parasite).
3.
It is used to treat peptic ulcer.
4.
It is also used to treat trench mouth (a severe gum infection).
5.
It is also used to treat anaerobic bacterial infections.
21.
WHAT IS CANCER? CLASSIFY
ANTI CANCER DRUGS. DISCUSS SHORTLY THE MECHANISM OF ACTION OF ANTI METABOLITES
AND ALKYLATING AGENTS.
ANS:
CANCER
Cancer is a large group
of diseases that can start in almost any organ or tissue of the body when
abnormal cells grow uncontrollably.
One defining feature of
cancer is the rapid creation of abnormal cells that grow beyond their usual
boundaries, and which can then invade adjoining parts of the body and spread to
other organs.
Cancer is the second
leading cause of death globally (9.6 million deaths in 2018).
Other terms used for
cancer are malignant tumours and neoplasm.
CLASSIFICATION OF
ANTICANCER DRUGS
1. ALKYLATING
AGENTS
Nitrogen mustards: Mechlorethamine
(Mustine HCL), Cyclophosphamide, Ifosfamide, Chlorambucil, Melphalan
Ethylenimine: Thio-Tepa
Alkyl sulfonate: Busulfan
Nitrosoureas: Carmustine, Lomustine
Triazine: Dacarbazine
2. ANTIMETABOLITES
Folate antagonist: Methotrexate (Mtx)
Purine antagonist: 6-Mercaptopurine,
6-Thioguanine, Azathioprine, Fludarabine.
Pyrimidine antagonist: 5-Fluorouracil,
Cytarabine
3. VINCA
ALKALOIDS: Vincristine, Vinblastine
4. TAXANES:
Paclitaxel, Docetaxel
5. EPIPODOPHYLLOTOXIN:
Etoposide
6. CAMPTOTHECIN
ANALOGUES: Topotecan, Irinotecan
7. ANTIBIOTICS:
Actinomycin D (Dactinomycin), Doxorubicin, Daunorubicin, Mitoxantrone,
Bleomycins, Mitomycin C
8. MISCELLANEOUS: Hydroxyurea, Procarbazine, L-Asparaginase, Cisplastin, Carboplatin, Imatinib
ANTIMETABOLITES
These drugs generally
inhibit purine or pyrimidine synthesis in the cancer cells.
So no nucleotide is
synthesized and no DNA or RNA is formed.
METHOTREXATE (MTX)
Methotrexate is the
most important antimetabolite anticancer drug. Methotrexate inhibits folic acid
synthesis.
MECHANISM OF ACTION
Mtx binds to
dihydrofolate reductase (DHFR) and prevents the formation of tetrahydrofolate.
This tetrahydrofolate
is essential in several reactions in DNA synthesis.
The deficiency results
in inhibition of DNA synthesis.
ADVERSE EFFECTS
1. Gastritis,
gastric erosion
2. Thrombocytopenia
3. Hair
loss
4. Meningitis
6-MERCAPTOPURINE (6-MP)
It is structurally
related to purine.
MECHANISM OF ACTION
6-MP enters the cancer
cell and becomes converted to 6-mercaptopurine ribose phosphate (6-MPRP).
This 6-MPRP inhibits
the synthesis of purine hence nucleic acid synthesis stops (DNA/RNA synthesis
stops). So death of cancer cell occurs.
ADVERSE EFFECTS
1. Joint
pain
2. Bone
marrow suppression
3. Liver
inflammation
4. Nausea,
vomiting
ALKYLATING AGENTS
These drugs cause
attachment of an alkyl group to the DNA strand of cancer cells and hence
damaging the DNA strand.
MECHLORETHAMINE
MECHANISM OF ACTION
It alkylates the DNA
strand leading to damage of the DNA strand.
ADVERSE EFFECTS
1. Severe
vomiting
2. Bone
marrow suppression
3. Immune-suppression