Editing File

1st Lecture Antiemetics

Pathophysiology:The vomiting center is in the brainstem.its afferent input is as following:

Out
side
BBB

Drugs list:

5-HT3 antagonists Ondansetron , Granisetron

NK1 antagonists Aprepitant

Glucocorticoids Dexamethasone , Methylprednisolone

Prokinetics: Domperidone, Metoclopramide

D2 antagonists
Antipsychotics:Chlorpromazine,droperidol

H1 antagonists Diphenhydramine , Promethazine , Meclizine , Cyclizine

M1 antagonists Hyoscine (scopolamine)

Drugs uses

-Cytotoxic drugs vomiting

-CINV
-Motion sickness
-Vomiting with pregnancy
-Drug- induced vomiting
-Uremia
-Gastritis
2nd Lecture
Drugs in peptic ulcer

What its complications in long term use H2 receptor blockers?

1-vitamin B12 deficiency 2-increase risk of hip joint fractures

What are the side effects that specific of Cemitidine?

1-CYT-P450 inhiption 2-glactorrhea 3-gynecomastesia&impotence

What should we give in condition of NSAID-indused peptic ulcer?

Prostaglandin analogues ( not used in pregnancy)

Drug group Drug names Mechanism of action NOTES

Proton pump inhibitors Omeprazole, Irreversible inhibition -Most potent inhibitors of

lansoprazole, of (H+/K+ atpase) acid secretion.
Pantoprazole, proton pump.
Raprozaole -Hypersecretory
conditionsas Zollinger
Ellison syndrome and
gastrinoma. (first choice.)

H2 receptor blockers Cimetidine, Rantidine, Reversible & Famotidine is the most

Famotidine, competitive blocking potent drug.
Nizatidine at H2 receptors on Nizatidine has the greatest
parietal cells bioavailability.

Prostaglandin analogues Misprostol -Decreases HCL -

secretion
-Increase protective
measures.

Antacids Inorganic salts acts by direct -

checmical
neutralization of HCL.
3rd Lecture
Treatment Of dysentery and amoebiasis

The two most common cause are:

Amebic dysentery: protozoal infection mainly by Entameba Histolytica
Bacillary dysentery (or shigellosis):bacterial infection mainly by shigella

Name two lumenal and two tissue (systemic) anti-Amebic drugs?

Luminal amebicides : (Treatment of asymptomatic amebiasis)
❏ Diloxanide furoate ❏ Iodoquinol ❏ Paromomycin

Tissue or systemic amebicides :(Treatment of systemic form of the disease)

❏ Metronidazole/ tinidazole ❏ Emetine / dehydroemetine ❏ Chloroquine

What is the MOA of Mitronidazole? ❏ Metronidazole inhibits DNA replication.

What are the ADRs of mitronidazole?

1- GIT disturbance 2- CNS involvement 3- dark urine 4-Disulfiram-like effect if taken with alcohol
What is the major side effect that is caused by emetine dihydroemetine? cardiotoxicity
What is the only use of chloroquine and its ADRs?
use : amebic liver diseases
ADRs:pruritus , blurred vision ,hemolysis
What are the side effects of iodoquinol?
1- optic neuritis 2- enlarged thyroid gland 3- iodine sensitivity
What are the signs of iodine toxicity? dermatitis,urticaria, pruritus, fever

Bacillary dysentery caused by shigella

Treated by :
Fluoroquinolones such as ciprofloxacin (can cause Arthropathy )
Cotrimoxazole in traveller’s diarrhea
Oral cefixime or parenteral ceftriaxone are safe and effective.(They are 3rd generation cephalosporin)
4th Lecture
Constipation and IBS

What are the General Measures in treatment of Constipation?

1. Adequate fluid intake. 2. High fiber contents in diet. 3. Regular exercise
4. Regulation of bowel habit. 5. Avoid drugs causing constipation. 6. Use drugs (laxatives or purgatives)

How are laxatives classified and mention the mechanism of each?

These drugs are generally classified by simplified mechanism of action, that is,
- as stimulants Act by direct stimulation of nerve endings in colonic mucosa → peristalsis & purgation
- osmotic: water content in large intestine.
- Bulking: volume of non-absorbable solid residue bulk of intestinal contents by water retention.
- stool softeners Alter the consistency of feces → easier to pass

Give some examples of stimulant laxatives.

1- Castor oil 2- Anthraquinone derivatives (senna, cascara, aloes) 3- Bisacodyl

What are the side effects of stimulant laxatives?

Prolonged use → dependence & destruction of myenteric plexus leading to atonic colon.

Name some members of Bulking group?

These agents, which are usually insoluble during the digestive process, include:
- From indigestible parts of fruits and vegetables)
- Hydrophilic colloids ( Methylcellulose, Bran powder , Psyllium seed Carboxymethyl cellulose (CMC))

List some osmotic Laxatives?

1.Sugars : e.g. lactulose 2.Salts (Saline laxatives) → • Mg sulphate or hydroxide •Na or K phosphate.
3.Polyethylene glycol (PEG)

What is the mechanism of lactulose ? and why is commonly used in liver cirrhosis?
- mechanism: increases the H+ concentration in the gut, This favors the formation of the non-absorbable NH4+
from NH3, trapping NH3 in the colon and reducing its back diffusion into blood.
- because Lactulose → Lactic acid + Acetic Acid acidification of the colon ammonia absorption (NH4+)

Stool Softeners . How do these agents work and Name some ?

By emulsification stool, these agents soften it and make its passage easier.
include mineral oil, glycerin suppositories, and detergents such as dioctyl sodium sulfosuccinate (docusate)

Mention some Symptomatic treatment of IBS.

1- Antispasmodics e.g. mebeverine 2- Alosetron (IBS-D) 3-Tegaserod (IBS-C)

What are the mechanism of Alosetron and Tegaserod ?

Aloserton:Selective 5HT3 antagonist of the enteric nervous system of the GIT
Tegaserod : 5HT4 agonist. Stimulation of 5HT4 of enteric nervous system of GIT → increases peristalsis

What is the main side effect of Aloserton that make it used in limited emergency situation?
Constipation and ischemic colitis.
5th Lecture
Cytochrome system and drug metabolism

What is the rate limting oxidase cytochrome system? CYTP450

Where can we found the CYT P450?

1/ attached to the smooth endoplasmic reticulum of hepatocytes
2/ nterocytes of the small intestine have the principal extra-hepatic source.
3/ Very small quantities in kidneys, lungs, & brain

What is the structure of CYT P450? They are heme-containing isoenzyme

What are the function of CYT P450?

1. Endogenous substances : steroid hormones, prostaglandins, lipids.
2. Exogenous compounds : diet (food & beverages) / Drugs / environmental xenobiotics

How the regulation of CYT P450 occures?

1. Directly : through the enzyme itself.*drug activate cyt-p450 direct*
2. Indirectly : by expression or repression of its relevant genes by activation or inhibition of the
responsible transcription factors

What are the type of regulation by drugs?

Enzyme Inducer : if activate the enzyme.
Enzyme inhibitor : if inactivate the enzyme

Polymorphism in CYP2C19 showes - Warfarin, phenytoin, &

increased & prolonged action of its tolbutamide are examples of drugs
substrates as omeprazole. - This has with narrow therapeutic index that
been an advantage as in those are metabolized by CYP2C9.
variants cure rates in peptic ulcer - Clearance of these drugs is
patient with Helicobacter pylori. impaired in genetic variation of the
Genetic enzyme

CYTP2C19 CYP2C9
5th Lecture

Substrates Inhibitors= toxicity Inducers= no response

Immunosuppressants: •Protease Inhibitors: •Rifampicin

Cyclosporine Ritonavir • Phenytoin
• Carbamazepine
• Cimetidine • Barbiturates CYT P450
Azole Antifungals: • Chloramphenicol • Dexamethazone
• Nefazadone • Progestins
“3A4”
Fluconazole
• Grape Fruits

Antibiotics: Erythromycin,
Clarithromycin

Ca channel blockers:
Amlodepine, Verapamil

Statins: Atorvastatin

Antiarrhythmic:
Amidarone

Cancer Chemotherapy:
Cyclophosphamide,
Tamoxifen

Non-Sedating
Antihistaminics:
Astamizole

Benzodiazipines:
Midazolam, Clonazepam

Metabolism of some drugs The pro-drugs

neuroleptics, tricyclic cannot be converted to their

Neuropathy antidepressants, antianginals therapeutically active metabolite;
after
agent ( perihexiline), e.g poor analgesia with codeine
therapeutic
doses antiarrhythmics (propafenone & & tramadole because they are
metoprolol) is suppressed → so not transformed into active forms.
side effects & toxicity develop
Severe brady
arrhythmias →
heart block on
therapeutic CYP2D6
dose
6th Lecture
Hepatotoxic drugs

Why is the liver considred the major site of ADRs is ?

1-It is the first organ to come in contact with the drug after absorption from the GIT.
2-Being the metabolic clearing house of the body it expresses the highest levels of drug metabolizing
enzymes that converts some drugs( PROTOXINS) into intermediate (TOXINS) before being conjugated
for elimination

Mention 3 diffrences between intrinsic hepatotoxin and idiosyncratic hepatotoxin ?

1- Direct while Indirect
2--SUPERTHERAPEUTIC or CUMULATIVE dose while Normal dose
3-Predictable while Unpredictable / bizzar

Mention the two main types of intrinsic hepatotoxin ?

A. Immunoallergic Idiosyncratic Hepatotoxicity : A drug or its metabolite binds to hepatic membranes or
proteins act as hapten to induce a variety of immune reactions
B. Metabolic Idiosyncratic Hepatotoxicity :The metabolite of the offending drug interferes with hepatic
metabolism as that of bilirubin or protein synthesis

Mention two drugs the have viral hepatits like pattern , inflammotory cholestasis, interfre with
bilirubin metabolism and interfere with protien synthesis ?
1- Viral hepatits like pattern : isoniazed and phenytoin
2-Inflammtory cholithesis : Chlorpropamide. Erythromycin.
3-interfere with bilirubin metabolism : Erythromycin and Rifampicin
4- Interfere with protien synthesis : Corticosteroids and Tetracycline

Patient is taking drug A, after 6 months from taking this drug he developed pruritus, what is drug
A?
Oral contraceptives ,Chlorpropamide ,Erythromycin or Rifamycin ((Cholestatic type))

Mention the drugs that cause hepatoceullar type of injury ?

Acetaminophen ,NSAIDs ,Isoniazid or Amiodarone

Mention the line of treatment ?

1-Immediate withdrawal : of any suspected drug ( If it cause an injury u immediately stop it )
2-Symptomatic : 1-severe allergic reaction USE Corticosteroids 2- pruritus USE Cholestyramine 3-
cholestatic liver injury USE Ursodeoxycholic acid (Ursodiol) 4-coagulopathy or encephalopathy develop
USE High carbohydrate, moderate protein diet .
3-Specific antidotes :1-acetaminophen toxicity : use N- acetylcysteine ( if a child took overdose or
someone commit suicide 2-valproate toxicity : use L-carnitine
4- Emergency liver transplantation : for drug induced liver falure
7th Lecture Drugs used in IBD and biological and immune therapy

Symptoms: Abdominal pain, Vomiting, Diarrhea, Rectal bleeding, Weight loss

Complications: Anemia, Abdominal obstruction (Crohn’s disease), Mega colon, Colon cancer
Treatment:
Stepwise therapy:
1. 5-amino salicylic acid compounds (5-ASA) or aminosalicylates.
2. Glucocorticoids
3. Immunomodulators
4. Biological therapy (TNF-α inhibitors).
5. Surgery in severe condition.
1. 5-amino salicylic acid compounds (5-ASA) or aminosalicylates.
unformulated 5-ASA are 80% absorbed in small intestine So different formulations of aminosalicylates are made:
*Azo compounds (N=N) -Sulfasalazine: 5-ASA + Sulphapyridine note: Sulphapyridine is the part that causes the
side effects
*Mesalamines ((Beter than Sulfasalazine, Sulfa free)) (Oral : Asacol , Pentasa) , (Rectal:Canasa , Rowasa )
The major differences are in mechanism and site of delivery. The bond will break in the terminal ileum and colon

2. Glucocorticoids.
I)Oral preparation: e.g. prednisone, prednisolone
II)Parenteral preparation: e.g. hydrocortisone, methyl prednisolone
–Higher rate of absorption –More adverse effects compared to rectal administration
III) Rectal preparation e.g. Hydrocortisone
•As enema or suppository, give topical effect. •Less absorption rate than oral.
•Minimal side effects & maximum tissue effects
Budesonide: Is subject to extensive first pass metabolism
Mechanism of action of glucocorticoids
•Inhibits phospholipase A2
•Inhibits gene transcription of NO synthase, cyclo-oxygenase-2 (COX-2)
•Inhibit production of inflammatory cytokines
Uses of glucocorticoids not effective as prophylactic therapy

4. Monoclonal antibodies used in IBD (TNF-α

3. Immunomodulators
inhibitors)
include: •Infliximab
•Methotrexate: -given to Patients not responding to immunomodulators or
Used to induce and maintain remission glucocorticoids
used for Cancer important Side effect Severe hepatic failure
•Purine analogs: •Adalimumab
(azathioprine is pro-drug of 6-mercaptopurine) -humanized IgG antibody to TNF-α
-advantage subcutaneous injection
-drug of chouse fore Crohn’s disease ***
•Certolizumab
– Given subcutaneously for the treatment of Crohn's disease
& rheumatoid arthritis
 8th Lecture Anticoagulants

Parenteral anticoagulants: Oral anticoagulants:

Direct thrombin inhibitors: Lepirudin. Vitamin K antagonists: Warfarin

Indirect thrombin inhibitors: Heparin, LMWH, Fondaparinux. -

Name of Drug Heparin (UFH) LMWH (Fondaparinux),enoxaparin ,

Characteristic dalteparin)

IV ½ life 2 hours 4 hours

Bioavailability after SC injection 20% 90%

Antidote protamine sulphate none

Advantages / disdvantages Disadvantages Advantages

- Risk of HIT(Heparin Induced -Better bioavailability (Anticoagulant
Thrombocytopenia) response is predictable )
- NEEDED: aPTT - Binding to platelets & osteoblasts is
- frequent bleeding, reduced
- Allergic reaction ( chills, - can be given once a day
fever…) - for FondaparinuxLess likely to trigger
- Osteoporosis (HIT)
- Anticoagulant response is -less bleeding.
variable since it binds to -less ADR in general.
plasma proteins. - not needed for aPTT

Mechanism of action inhibits factors IIa & Xa inhibits Xa only

Warfarin

Mechanism of action Advantage Disadvantages

Inhibits synthesis of Bioavailability 1- slow onset and offset of action 2-narrow therapeutic window
Vitamin K-dependent 100% leading to increased risk of severe bleeding
coagulation factors II, 3- numerous interaction with foods (containing Vit. k) and drugs.
VII, IX, & X as (not use 4- need Monitoring by measuring PT , expressed International
in pregnancy) Normalized Ratio.

Why the mechanism of action in Warfarin takes 3-4 days until the effect is seen ?
because Does not have any effect on already-synthesized coagulation factors; therefore, the therapeutic effects are
not seen until these factors are depleted
Lepirudin: a direct thrombin inhibitor used as IV anticoagulant in patients with HIT.

Patient has got toxicity because of heparin overuse. Mention the management steps?
1- Stop the drug First 2- use Protamine sulfate
9th Lecture
Antiplatelet Drugs

What are the substance that inhibit the platelet aggregation ?

NO & prostacyclin
What is thrombosis ?
is the formation of unwanted clot within the blood vessel
What are the difference between anticoagulants & antiplatelet?
anticoagulants :drugs which prevent clotting by inhibiting clotting factors
antiplatelet :drugs which prevent and inhibit platelet activation and aggression

calssification of antiplatelet drugs

Arachidonic Phosphodiest ADP Glycoprotein

acid pathway erase inhibitors IIb/IIIa
inhibitors inhibitors inhibitors

Drugs Aspirin Dipyridamole Ticlopidine - Abciximab –

Clopidogrel Eptifibatide -
NEW: Tirofiban
Prasugrel
Ticagrelor

MOA Irreversible Inhibits Glycoprotein

These drugs
inhibition of phosphodiestr IIb/ IIIa
cyclooxygena ase thus specifically receptor is
se enzyme ( increases and required for
COX-1 ) via cAMP irreversibly platelet
acetylation causing inhibit ADP aggregation
decreased receptor of with each
synthesis of others and
subtype
thromboxane with
A2 and other P2Y12, which fibrinogen
platelet is required for and von
aggregating platelets Willbrand
factors activation factor
thus prevent
platelet
aggregation.
9th Lecture

Drugs Aspirin Dipyridamole Ticlopidine - Abciximab –

Clopidogrel Eptifibatide -
NEW: Tirofiban
Prasugrel
Ticagrelor

Uses Secondary abciximab:is used

•Prophylaxis of •Adjunctive prevention of with heparin and
thromboembolism therapy for ischemic aspirin as adjunct
•Prevention of prophylaxis of complications after to PCI for the
ischemic events thromboembolism myocardial prevention of
in cardiac valve infarction, cardiac ischemic
ischemic stroke complications.
replacement (with
and unstable
warfarin).
angina Eptifibatide -
Tirofiban:
•Secondary
•( act as
prevention of
fibrinogen-
stroke and
mimetic agents ).
transient ischemic
attack (with •They are given
aspirin). intravenously for
the reduction of
incidence of
thrombotic
complications
during coronary
angioplasty (PCI)

Disadvantage •peptic ulcer. -

•Headache •Sever
•GIT bleeding neutropenia
•Postural
hypotension •Bleeding

•G.I.T
•Allergic reactions

What are the clinical use of clopidogrel?

For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral
arterial disease.
- For patients with acute coronary syndrome
what are the AVD of ticagrelor? dyspnea
10th Lecture
Antimalarial drugs

1-name the main 4 drugs that are used for malaria:

a-artemesinin b-chloroquine c-quinene d-primaquine

2-what is the MOA of artemesinin:

They have endoperoxide bridges → –cleaved by haem iron to yield carbon- centered free radicals, that will:
Alkylate membranes of parasite’s food vacuole and mitochondria–→ no energy.
Irreversibly bind & inhibit sarco-endoplasmic reticulum Ca2+-ATPase of the parasite→ – inhibiting its
growth.
Inhibiting formation of transport vesicles → –no food vacuoles

3-what are the uses of chloroquine:

•Active against all forms of the schizonts (except chloroquine-resistant P.f. & P.v.)
•Effect against all Gametoside species except falciparum
•No activity against liver shizonts
what are the main side effect of quinine ?
★ therapeutic dose → poor compliance → bitter taste
★ Higher doses :
● Cinchonism syndrome : (tinnitus, deafness, headaches, nausea & visual disturbances)
● Abdominal pain & diarrhea
● Hypotension & arrhythmias
● Rashes, fever, hypersensitivity reactions
● Blackwater fever (Most series effect ) , a fatal condition in which acute haemolytic anaemia is
associated with renal failure

4-what are the main adverse effects of primaquine ?

At regular doses:
-G6PD deficient patients→hemolytic anemia
At larger doses:
● Epigastric distress, Abdominal Cramps
● Mild Anemia, cyanosis, methemoglobinemia
● Severe Methemoglobinemia >> patients with deficiency of NADH methomoglobin reductase (rare)
● Granulocytopenia, agranulocytosis (rare)
10th Lecture

WHO treatment guidelines

Sensitive: Resistant:

● Chloroquine(3 days) ● ACT (3 days)

In P. Vivax ● followed by Primaquine ● followed by Primaquine
(14 days) (14 days)

Uncomplicated Complicated: Special Risk Groups:

:
Artesunate (IV for 24 -Quinine +
-ACT hours) followed by:- Clindamycin
(pregnancy 1st
In Falciparum (all *ACT or trimester)
show resistance) [Artemether/Quinine
]+ -ACT
[clindamycin/doxycyli (Pregnancy 2nd, 3rd
ne] trimesters, lactating
women, infants, and
young children)

Prophylaxis in travellers

Areas without resistant P.

Chloroquine
Falciparum
Begin 1-2 weeks before departure (except
Areas with chloroquine- doxycycline 2 days prior)
Mefloquine
resistant P. Falciparum continue for 4 weeks after leaving endemic
area
Areas with multidrug-
Doxycycline
resistant P. Falciparum
DONE BY:
Elham Alghamdi Ahmed Alsaleh
Abdulrahman Alarfaj Sarah nasser Aljasser
Abdulrahman Alkaff Asmaa Rusaies
Sarah AlSalman