MBChB III

Guidance for Pharmacology RE-Test 1

Pharmacokinetics and Pharmacodynamics:

 Counteracts of overdose
 Drug metabolism
 Factors increasing and decreasing half-life of a drug
 Tachyphylaxis
 Receptor affinity

Anticancer drugs:

 Classification of anticancer drugs

 Antimetabolites

MOA =DNA synthesis inhibitors

 Folate analogues = methotrexate, permetrexate

 Purine analogues = 6mercaptopurine, fludarabine, Tioguanine

 Pyrimidine analogues =fluorouracil, cytarabine, Capecitabine

 Cytotoxic antibiotics

 Actinomycin D = dactinomycin

 Anthracycline = Doxorubicin hydrochloride and Daunorubicin

hydrochloride

 Alkylating agents

 Nitrogen mustard analogues= Cyclophosphamide, Ifosfamide

 Alkyl sulphonates = carmustine, Dacarbazine

 Other = Temozolomide

 Microtubule inhibitors

 Vinca alkaloid = vinblastine, vincristine

1
  Taxanes = Docetaxel, Paclitaxel

 Corticosteroids

 Prednisone

 Selective Estrogen receptor modulator

 Tamoxifen

 Aromatase inhibitors

 Nonsteroidal = Anastrozole and letrozole

 Steroidal = exemestane

 Monoclonal Antibodies

 Trastuzumab, Rituximab, Bevacizumab, Cetuximab

 Topoisomerase Inhibitors

 Camptothecins, Etoposide

 Proteasome inhibitors

 Bortezomib • Carfilzomib
 Indications
 Methotrexate
 Acute lymphoblastic leukemia
 Lymphoma
 Choriocarcinoma
 Trophoblastic neoplasm
 Head, neck, breast and bone tumors
 Agents that produce myelosuppression
 Methotrexate
 Dactinomycin
 Temozolomide
 Carmustine

Chemotherapeutic drugs:

 Penicillins administered orally

 Phenoxymethylpenicillin (Pen V)

2
  Amoxicillin

 Ampicillin

 cloxacillin
 Antibacterials metabolized in the liver
 Macrolides
 Lincosamides
 Chloramphenicol
 Fluoroquinolones
 Penicillins
 Tetracyclines (partially)
 Dihydrofolate reductase inhibitors (pyrimethamine, trimethoprim)
 Classification of antibacterials
Cell Wall Synthesis Inhibitors:
 Beta-Lactams:
o Penicillins: e.g., Penicillin G, Penicillin V, Amoxicillin, Ampicillin, Cloxacillin.
o Cephalosporins: e.g., Ceftriaxone, Cefalexin, Cefepime.
o Carbapenems: e.g., Imipenem, Meropenem, Ertapenem.
o Monobactams: e.g., Aztreonam.
 Glycopeptides: e.g., Vancomycin, Teicoplanin.
Protein Synthesis Inhibitors:
 Aminoglycosides: e.g., Gentamicin, Tobramycin, Amikacin.
 Tetracyclines: e.g., Doxycycline, Tetracycline.
 Macrolides: e.g., Erythromycin, Azithromycin, Clarithromycin.
 Chloramphenicol: e.g., Chloramphenicol.
 Lincosamides: e.g., Clindamycin.
 Oxazolidinones: e.g., Linezolid.
Nucleic Acid Synthesis Inhibitors:
 Fluoroquinolones: e.g., Ciprofloxacin, Levofloxacin, Moxifloxacin.
 Rifamycins: e.g., Rifampin, Rifabutin.
 Metronidazole: e.g., Metronidazole.
Folate Synthesis Inhibitors:
 Sulfonamides: e.g., Sulfamethoxazole.
 Trimethoprim: Often used in combination with Sulfamethoxazole (e.g., Co-
trimoxazole).
Membrane Integrity Disruptors:
 Polymyxins: e.g., Polymyxin B, Colistin

3
 Mechanism of action
Doxycycline
 Doxycycline works by binding to the 30S ribosomal
subunit of bacterial ribosomes
Levofloxacin
 Inhibition of DNA Gyrase
 Binds to topoisomerase IV, which is necessary for cell
division, interferes with the separation of replicated
DNA into daughter cells
Streptomycin
 Binding to the 30S Ribosomal Subunit = Inhibition of
Protein Synthesis
Sulfamethoxazole
 competitively inhibits the bacterial enzyme
dihydropteroate synthase = inhibition of folate
synthesis
Chloramphenicol
 Binding to the 50S Ribosomal Subunit: inhibits protein
synthesis
Ampicillin
 Inhibition of Cell Wall Synthesis
 Adverse effects
Vancomycin
 Red man syndrome
 Ototoxicity and nephrotoxicity
 Pain and phlebitis at injection site
Doxycycline
 Gastric discomfort
 Teeth discoloration
 Stunted growth in children
 Phototoxicity 
 Vestibular disturbances
Chloramphenicol
 Gray baby syndrome
 Bone marrow suppression
 Candida superinfections
Sulphamethoxazole
 Crystalluria
4
  Hematopoietic disturbances
 Hypersensitivity= photosensitivity, Skin reactions – rashes  Angioedema
 Stevens-Johnson-syndrome
Amoxycillin
 Hypersensitivity
 anaphylaxis
Ciprofloxacin
 cartilage erosion
 photosensitivity and skin rashes
 Pain and inflammation in tendons


Pain management and General-Local anaesthestics:

 Classification of drugs

 NSAIDs

 Salicylic acid- Aspirin • Proprionic acid – Ibuprofen • Acetic acid –

Diclofenac • Enolic Acid-Meloxicam • Acetic Acid-Diclofenac •
Fenamates-Mefenamic acid

 Selective COX-2 inhibitors = celecoxib

 OPIODS

 Ultra short acting = remifentanil

 Short acting = alfentanil

 Intermediate acting = fentanyl, sufentanyl

 Long acting = morphine, pethidine, tramadol

 Analgesics & antipyretics

 Paracetamol

 Anxiolytics = Benzodiazepines

 Ultra short acting = Midazolam • Triazolam

 Short acting = Lorazepam • Lormetazepam • Oxazepam •

Temazepam

 Intermediate acting = Bromazepam • Alprazolam • Lorazepam

5
  Long acting = Diazepam • Prazepam • Clobazam • Clonazepam •
Clorazepate • Chlordiazepoxide

 Benzodiazepine antagonist

 Flumazenil

 TCAs

 Amitriptyline

 Corticosteroids

 Glucocorticoids

 Short acting = hydrocortisone

 Intermediate acting = prednisolone, methyl prednisolone,

triamcinolone, deflazacort

 Long acting = dexamethasone, betamethasone

 Mineralocorticoids = aldosterone, fludrocortisone,

deoxycorticosterone acetate

 Selective serotonin reuptake inhibitors (SSRIs)

 Duloxetine; Fluoxetine, paroxetin, serotonin, and sertraline

 NMDA ANTAGONISTS (EXCITATORY AMINO ACID ANTAGONISTS)

 Ketamine

 Step 1 management of mild pain

 NSAIDs
 Indications for paracetamol
 Pyrexia
 Mild to moderate pain
 Therapeutic uses of morphine

 Analgesic ◎Antitussive ◎Antidiarrhoeal ◎Anaesthesia adjunct

6
  Contraindication and side effects of ketamine
 C/I
 Psychosis
 Uncontrolled severe hypertension
 Addiction
 Hepatic impairment
 Increase intracranial pressure
 Adverse effects
 Dissociation
 Hallucinations
 Confusion
 Nightmares
 Hypertension
 Bladder irritation
 Rash
 Respiratory depression

Antifungals, Antiprotozoals, Antimycobacterials, Antivirals/Immunosuppressants:

 Mechanism of action

Terbinafine

 an allylamine which acts as an inhibitor of fungal squalene epoxidase

enzyme

Rifampicin

 Rifampicin blocks mycobacterial RNA synthesis by binding to the β-

subunit of mycobacterial DNA-dependent RNA polymerase.

 Pharmacokinetics of amphotericin B
 IV
 Two formulations, conventional and liposomal
 Hepatic metabolism and renal excretion
 Does not cross BBB
7
  Mechanism of resistance to amphotericin B
 Efflux pumps
 Reduced ergosterol content
 Altered membrane properties
 Biofilms

 Amoebiasis therapy
 Metronidazole
 Tetracycline, doxycycline, or chloroquine (considered when metronidazole
is N/A)
 Iodoquinol
 Tinidazole
 Atovaquone-proguanil
 Cryptococcosis therapy
 Amphotericin B

 Adverse effects
Abacavir
 Lactic acidosis
 Hepatomegaly with steatosis
Efavirenz
 CNS or psychiatric side effects: vivid dreams, headache, impaired
concentration and insomnia
Tenofovir
 Nephrotoxicity
 Decreased bone mineral density
Lopinavir/ritonavir
 Metabolic disorders lipodystrophy and insulin resistance
Terizidone

Emtricitabine
 


The following statements is correct regarding tachyphylaxis:
1. There is a decreased receptor-mediated response to a drug
2. There is an increased risk of side effects occurring
8
3. Smaller doses cause an increased response to a drug
4. The rate of drug infusion equals the rate of excretion
5. The drug does not bind to receptors completely

The absorption of the following drug from the gastrointestinal tract is reduced by
food containing milk products:
1. Chloramphenicol
2. Amoxicillin
3. Clarithromycin
4. Doxycycline
5. Metronidazole

Regarding penicillins:
1. Are bacteriostatic
2. Are all completely absorbed when administered orally
3. An example is trimethoprim
4. Are largely administered topically
5. Are cell wall synthesis inhibitors

9
The following are poorly absorbed from the gastrointestinal tract:
1. Phenoxymethylpenicillin
2. Sulphamethoxazole
3. Pyrimethamine
4. Vancomycin
5. Amoxycillin

Regarding fluoroquinolones:
1. Are hepatically metabolised
2. Are bacteriostatic
3. Bind with 30 S ribosomal subunit
4. Are cell wall synthesis inhibitors
5. Increase the metabolism of warfarin

The following drug may be used in the treatment of paracetamol overdose:

1. Acetylcysteine
2. Simvastatin
3. Aspirin
4. Tramadol
5. Metformin

The following drug may be used to facilitate endotracheal intubation:

1. Metformin
2. Diclofenac
3. Carbocisteine
4. Tramadol
5. Atracurium

The following agent may trigger malignant hyperthermia in patients undergoing

general anaesthesia:

1
0
1. Succinylcholine
2. Cloxacillin
3. Aspirin
4. Hydrocortisone
5. Paracetamol

The following anaesthetic agent can produce dissociative anaesthesia:

1. Propofol
2. Ketamine
3. Etomidate
4. Midazolam
5. Mivacurium

Inadvertent intravascular administration of a large dose of an amide local

anaesthetic can result in:
1. Gastritis
2. Hepatic damage
3. Weight loss
4. Renal failure
5. Seizures

Nitrous oxide reaches systemic circulation in high concentration due to:

1. High solubility
2. Low dissolution
3. Slow blood transportation
4. Rapid excretion
5. Rapid absorption

The following is recommended for patients taking isoniazid to prevent peripheral

neuropathy:
1. Pyrazinamide
2. Rifampicin

1
1
3. Ethambutol
4. Pyridoxine
5. Dapsone

Resistance to clotrimazole occurs by the following mechanism:

1. Point mutations in the cytochrome b gene
2. Mutations within the gene encoding for the integrase enzyme
3. Mutations in the gene encoding for the arabinosyl transferase enzyme
4. Mutations in the gene encoding 14-α-demethylase enzyme.
5. Mutation within the gene encoding for the enzyme catalase-peroxidase

The following statement is true concerning viral resistance to HIV protease

inhibitors:
1. High-level resistance occurs to the reverse transcriptase enzyme.
2. It occurs as an accumulation of stepwise mutations of the protease gene.
3. It occurs to prevent allosteric inhibition of the reverse transcriptase enzyme.
4. Resistance occurs as four specific substitutions of the integrase gene.
5. A single-point mutation occurs within the integrase gene.

Match the correct terms with their relevant descriptions.

A. Hydrogen bond
B. First order kinetics
C. Lock-key concept
D. Ion trapping
E. Induced fit model.
F. Steady state

 A constant fraction of the drug is metabolized per unit of time. = B

 The change in ionization of a drug when crossing a membrane to an area of a
different Ph = D
 The rate of drug administration is equal to the rate of drug elimination = F
 The receptor changing its structure in the presence of the drug until it fits the
drug = E
 A type of attractive (dipole-dipole) interaction = A

Match the following terms with the correct definition. Each answer may be used
more than once or not at all:

1
2
A. Tachyphylaxis
B. Bioequivalence
C. Downregulation
D. Quantal dose response
E. Loading dose
F. Bioinequivalence

 Initial higher dose of a drug given to rapidly achieve the desired drug
concentration. = E
 All or nothing response. = D
 Two or more drugs that share the same active pharmaceutical ingredient(s) with
comparable bioavailability and similar peak concentration at similar time
intervals. = B
 Rapid diminishing drug effects due to receptor. = A
 A decrease in the number of receptors on the surface of target cells, making the
cells less sensitive to a hormone or another agent. = C

Match the following drugs with the appropriate adverse effects below. Each
answer may be used more than once or not at all:
A. Pyrazinamide
B. Rifampicin
C. Ganciclovir
D. Isoniazid
E. Clofazimine
F. Ethambutol hydrochloride

 Peripheral neuropathy = D
 Hyperuricemias = A
 Darkening of leprosy lesions= E
 Colours body fluids orange to brown and may cause permanent staining of
contact lenses = B
 Ocular toxicity = F

1
3