Wks 8-14 SDLPs

Question 1

Why are antiretroviral drugs often used in combination for the treatment of HIV?

Answer 1

To stop the virus (agent) from becoming RESISTANT to one particular medication (agent). to decrease rate of RESISTANCE, maximally suppress the virus, and STOP its progression

Question 2

list the 8 steps that result in cancerous growth within the body.

Answer 2

1 - Exposure of a cell to a MUTAGEN or INHERITANCE of a mutated gene
LEADS TO
2 - alteration of the cellular DNA
WHICH
3 - changes a proto-oncogene into an oncogene OR inactivates tumour supression genes
SO THAT
4 - the transformed cell (clone) is no longer subject to the cell cycle control
THUS
5 - has growth advantages (over non-transformed cells & proliferates)
WHICH
6 - activates other proto-oncogenes
AND
7- produces more growth factors and tumour specific proteins
LEADING TO
8 - uncontrolled cancer growth

Question 3

Approximately how many cancer cells are present before clinical symptoms begin to appear?

Answer 3

10_9 cells are usually the smallest that are physically detectable (palpable) in a solid tumour. (about 1 million cells) size of a small grape and weighs approx 1g. if left untreated, can cont. to grow until fatal.

Question 4

Discuss the following principles of cancer chemotherapy that are important to consider when determining the best course of treatment for a patient:

Selective Toxicity

Answer 4

Finding & Exploiting the difference in biochemical pathways between normal cells and neoplastic/host cells; thus minimizing any adverse effects on normal cells.

Question 5

Drug Delivery

Answer 5

Specialised Techniques used to deliver drugs directly to the cancer site; such as Intra-Arterial or through the use of pro-drugs that are activated preferentially in neoplastic cells.
chemo is the most effective against small tumours due to the efficient blood supply.

Question 6

Cell-Kill Fraction

Answer 6

Chemo drugs given in adequate/therapeutic doses that tend to kill a certain proportion rather than a specific number of cancer cells.

Question 7

Growth Fraction

Answer 7

Term that distinguishes the cell POPULATION in the tumour that are actively engaged in cell cycling from the fraction that are not.

Question 8

Courses of Treatment

Answer 8

Removing LRG localised tumours via surgery to decrease the tumour cell burden.
Subsequent courses of chemo or radiation will hopefully decrease/help eliminate residual cancer cells that can then be controlled by the pts own immune system.

Question 9

Adjuvant Therapy

Answer 9

additional treatment given after the primary treatment, this includes immunotherapy to enhance the immune response against neoplastic cells

Question 10

Cell Cycle Specificity

Answer 10

Cytotoxic agents generally inhibit all cell replication and are thus considered anti-proliferative. But they can have different sites of action on the dividing cell cycle

Question 11

List some of the precautions that maybe necessary when handling this type of medication.

Answer 11

1 - Drugs should be adequalty labelled, and prepared/dispensed in a cytotoxic drug safety cabinet with the exhaust air being filtered before being vented into the atmosphere.
2 - Safe handling should be ensured via the use of PPE and resp protective equipment.
3 - Techniques must be developed/maintained to avoid inhaling droplets/powders/spilling solutions.
4 - Health of staff should be monitored by blood and liver/kidney function tests
5 - Excess drug/any waste/contaminated equipment should be disposed appropriately and incinerated
6 - pt body fluids after admin should be considered mutagenic.

Question 12

Discuss the possible treatment options available using either breast or prostate cancer as an example.

Answer 12

Prostate - surgical removal of the prostate &/or the testes.
Radiation administration of anti-androgenic drugs plus Oestrogenic hormones (have anti-androgenic effects)
PLUS
gonadtropin-releasing hormone analogues and antagonists (GnRH)
PLUS
cytotoxic agents

Question 13

Infection

Answer 13

The Invasion & Multiplication of pathogenic microorganisms in the body tissues. they secrete a toxin that then causes an antigen-antibody reaction in the host; can be classed as either local or systemic.

Question 14

Local Infection

Answer 14

An infection specifically involving the skin or internal organs. can progress into a systemic infection

Question 15

Systemic Infection

Answer 15

Involves the whole body via the bloodstream.

Question 16

Colonisation

Answer 16

is the localized presence of microorganisms in the body tissues/organs. can be pathogenic or part of the normal flora.

Question 17

Inflammation

Answer 17

A protective mechanism of the body tissues in response to an invasion or toxins produced by colonising microorganisms

Question 18

Bacteraemia

Answer 18

presence of viable bacterial in the circulatory system

Question 19

Septicaemia

Answer 19

a systemic infection caused by microorganism multiplication in the circulation

Question 20

Sepsis

Answer 20

syndrome with multiple organ involvement that is a result of microorganisms and their toxins circulating the blood

Question 21

Gram Stain

Answer 21

sequential procedure involving crystal violate and iodine solutions (followed by alcohol) that allows rapid classification or organisms into groups (gram -/+)

Question 22

Bacteriostatic agents

Answer 22

Inhibit bacterial growth

thus allowing intact host defense systems time to remove the invading organisms

Question 23

Bactericidal agents

Answer 23

Cause bacterial cell deaths and lysis plus eradicate infection.
Which is important in situations of impaired host defenses.

Question 24

Intrinsic Resistance

Answer 24

Refers to the organisms “innate chromosomal/genetic make-up” that predicts its specific resistance.
i.e. ability to resist particular agents through inherited structures/functions.

Question 25

Acquired Resistance

Answer 25

response that occurs following an earlier, localized exposure to an agent.
arises due to a change in its genetic make-up due to the acquisition of new genetic info specifying a new MOA of resistance that the organism did not previously posses.

Question 26

Discuss three distinct mechanisms by which bacteria can develop drug resistance.

Answer 26

1 - the microorganism produces an ENZYME that Modifies/Destroys the antibiotic structure = renders it inactive.

2 - through target site alteration so that the drug can no longer bind and activate its effects.

3 - via being pumped out by an “efflux pump” by the organism before the drug can exert its effects.

Question 27

Define and give examples of each class

Inhibitors of Bacterial Cell Wall Synthesis
     Penicillins 
     Cephalosporins 
     Carbapenems 
     Glycopeptides

Answer 27

Penicillins
weakens/destroy the cell wall by binding to the
Penicillin Binding Proteins (PBP); thus inhibiting
the transpeptidase activity responsible for cross
linking = cell lysis and death.
C = Broad/Extended, Moderate, Narrow
Spectrum agents plus narrow spectrum
penicillinase resistant agents.

Cephalosporins
inhibit cell wall synthesis and are also bactericidal.
Inhibit cell division and growth.
C = 1st, 2nd, 3rd and 4th gen (cephazolin,
cephalexin, cefaclor, ceftazidime and
cefepime)

Carbapenems
inhibit bacterial cell wall synthesis by binding to
PBP.
C = Ertapenem, Doripenem, Imipenem and
Meropenem.

Glycopeptides
Inhibit bacterial wall synthesis and are primarily
active against gram + bacteria.
C = vancomycin and teiroplanin

Question 28

Define and give examples of each class

Bacterial Protein Synthesis Inhibitors
     Macrolide Antibiotics 
     Lincosamides 
     Aminoglycosides 
     Tetracyclines

Answer 28

Macrolide Antibiotics
inhibit bacterial RNA dependent protein synthesis
by binding to the 5OS ribosomal subunits. Thus
inhibiting growth of microorganisms.
C = erythromycin, clarithromycin and
roxithromycin.

Lincosamides
Inhibits protein synthesis by binding to the 5OS
ribosomal subunit and preventing peptide bond
formation. Primarily bacteriostatic.
C = Lincomycin, Clindomycin, erythromycin

Aminoglycosides
are potent bacteriocidal antibiotics usually
reserved for serious life threatening infections.
Very effective againts gram - bacteria.
C = Amikacin, Gentamicin, Tobramycin and
Neomycin

Tetracyclines
Bacteriostatic. inhibit protein synthesis by
reversibly blocking the 3OS subunit of the
ribosome and preventing access of tRNA to the
mRNA-ribosome complex.
C = Doxycycline and Minocycline

Question 29

Define and give examples of each class

Inhibitors of DNA Synthesis

Fluoroquinolones

Answer 29

Fluoroquinolones
(broad spectrum) interferes with the enzyme
involved in the supercoiling of DNA that is
necessary for the duplication, transcription and
repair of bacterial DNA.
C = Ciprofloxacin, Moxifloxacin, Norfloxacin and
Ofloxacin

Question 30

Define and give examples of each class

Miscellaneous
Metronidazole
Trimethoprim -
sulfamethoxazole

Answer 30

Metronidazole
these interact with DNA, inhibit bacterial
synthesis and causes cell death. selectively toxic
to anaerobic bacteria and protozoa.
C = metronidazole

Trimethoprim-sulfamethoxazole
Bacteriostatic. They competitively inhobit a
bacterial enzyme necessary for incorporating
TMP and SMX which involve the synthesis of
tetrahydrofolic acid. (it decreases synthesis =
interferes in other agent synthesis such as DNA.)
C = Trimethopin and sulfamethoxazole

Question 31

Explain why the plasma drug concentration of the aminoglycoside gentamicin is monitored

Answer 31

monitoring is generally not done if the course of treatment if shorter than 48hrs.
If longer, both plasma concentration and renal function are monitored to DETERMINE THE DOSAGE REGIMEN.
Done to ensure therapeutic concentrations are achieved without risks of adverse reactions (increased plasma concentrations).
They exhibit significant post antibiotic effects = inhibiting organism growth after the plasma concentration has decreased below the minimal inhibitory concentration.

Question 32

Acute Pain

Answer 32

Sensation of severe discomfort.
has a sudden onset with an obvious cause r/t an injury, surgery or disease.
often a protective function that is short lived and subsides w/ treatment.
(broken limbs, MI, burns, appendicitis or kidney stones)

Question 33

Chronic Pain

Answer 33

Persistant/reacurring pain that continues for more than 3 months or after complete healing and may be difficult to relieve w/ simple pain treatments (cancer, osteo/rheumatoid arthritis)

Question 34

Nociceptive Pain

Answer 34

physiological pain arising from stimulation of superficial/deep nociceptors by noxious stimuli such as tissue injury/inflammation (burns, wounds, skin ulcers, bony metastases)

Question 35

Neuropathic Pain

Answer 35

form of primary lesion/dysfunction in the somatosensory NS pathways.
(nerve compression r/t prolapsed inter-vertebral discs, inflamm, trauma/degeneration & can occur post amputation)

Question 36

Psychogenic Pain

Answer 36

physical pain that is caused/increased/prolonged by mental or behavioral factors. (Headaches, back pain, stomach pain etc)

Question 37

Opioid receptors are found in both the central and peripheral tissues. List three central effects and three peripheral effects of opioids

Answer 37

C = produce analgesia effects, supress cough reflex and resp centre in medulla (can lead to toxicity), sedation & sleep (narcotic properties), euphoria, hallucinations, pupil constriction (pin points) and N+V, tolerance and dependance

P = act on the gut - decrease motility, increase smooth muscle tone, cause constipation, spasms of sphincter muscles, decrease gastric emptying and cause urinary retention. suppress spinal reflexes and release histamine = bronchoconstriction and severe itching.

Question 38

Describe the action taken following an opioid overdose including the use of opioid antagonists

Answer 38

If resp depression evident - pts airway is established and may require 02 assistance.

an IV of Naloxone is administered to reverse opioid effects (depression and sedation) as its an antagonist that blocks opioid effects.
- can precipitate withdrawal symptoms/dependence; monotor and manage.

Can include aspiration/gastric lavage and activated charcoal.

Question 39

Paracetamol at normal doses is considered to be a safer over the counter analgesic than aspirin. List the reasons why

Answer 39

Because Adverse Effects and Allergic Reactions are rare (in therapeutic doses).

there is a decreased risk of gastric upset, peptic ulceration, bleeding, renal impairment etc in comparison to other NSAIDs or aspirin.

There is less ADRs meaning low doses can be taken alongside pts using anticoagulants, is considered safe during pregnancy and lactation and can be effective analgesics if taken regularly at low doses.

Question 40

There are four characteristics of inflammation name them and outline the three basic events that account for these characteristics

Answer 40

1 - Swelling (oedema)
        i,e blood vessel vasodilation 
             & increased capillary permeability
2 - Redness (erythema)
        i.e cellular infiltration
3 - Pain 
        i.e. tissue repair
4 - Heat

reaction due to localisation of phagocytic activity; plus destruction/removal of injured material, leading to repair/healing.

Question 41

Natural Immunity

Answer 41

(resistance passed down)

when the body inherits innate/natural abilities to resist/fight antigens

Question 42

Acquired Immunity

Answer 42

immunity acquired through both natural and artificial means (i.e actively or passively) such as through vaccines or infections

Question 43

Passive Immunity

Answer 43

When antibodies made by the mothers body are transferred by means of the placenta or breast milk to the fetus/infant.

Question 44

Artificially Acquired Active Immunity

Answer 44

is evoked by the deliberate administration of antigens (may be live, partially modified, dead or just their toxins) which makes the body make antibodies in response, without acquiring the infection. (antibodies actively produced)

Question 45

Artificially Acquired Passive Immunity

Answer 45

Short term immunization achieved by the transfer of antibodies via a plasma.
doesn’t secure protection for a long duration of time like artificially acquired active immunity; may need boosters.

Question 46

Discuss the reasons why NSAIDs cause gastric ulceration and nephrotoxicity.

Answer 46

Because of its anti-inflammation effects; it inhibits an enzyme named COX1 in which its main function is to form 3 substances involved primarily in the inflammation process. Its present in most tissues (unlike COX2 which is only present at sites of inflamm) which has GI functions (maintaining normal mucosal lining in the stomach), and playing key roles in kidney and platelet function. Meaning, NSAIDs block the inflammatory effects but also interfere with its other abilities resulting in gastric ulcers and neprhrotoxicity.

(inhibits prosaglandin synthesis = increased gastric secretions due to COX inhibition = decrease in protective mechanisms of GIT = irritation

Question 47

Discuss the effect that histamine has on the systems and symptoms listed below to explain why anti-histamines are utilized as they are;

Vascular Effects 
Smooth Muscle Effects 
Exocrine Glandular Effects 
Central Nervous System Effects 
Inflammatory effects 
Urticaria
Atopy 
Food Allergies 
Bronchial Asthma 
Systemic Anaphylaxis

Answer 47

Vascular Effects
H stimulates both the H1 & H2 receptors
that dilate the capillaries & venules,
producing increased localized BF, increased
capillary permeability, erythema and oedema.
can also cause vasodilation in arterioles = low
BP.
Anti-H = reverse these effects but have the
potential to cause arrhythmia’s.

Smooth Muscle Effects
H produces a relaxing effect in the smooth
muscle of the arteriols, and a contractile action in
the smooth muscle of non-vascular organs (i.e.
Bronchi and GIT). The action of H1 receptors in
the lungs can result in bronchial contraction =
dyspnoea and airway obstruction.
Anti-H = used as an anti-inflammatory agent in
resp conditions to cause bronchi and bronchial
relaxation.

Exocrine Glandular Effects
H stimulates the gastric, salivary, pancreatic and
lacrimal (tear) glands. Stimulation of H2 receptors
in the stomach gastric glands increase
production of gastric acid secretions in which
can result in peptic ulcer formation.
Anti-H = therefore decreases H effects in GIT =
decreases risks of ulcer formation

Central Nervous System Effects
H effects involves both H1&2 receptor mediation.
Has effects in modulating neurotransmitters, and
is associated with maintaining wakefulness and
attention.
The activation of H1 receptors is associated with
motion sickness.
Anti-H = drowsiness, sedation, inhibition of N+V
and reduce motion sickness

Inflammatory effects
H specifically produces an anaphylactic reaction
associated with inflammation (body becoming
hypersensitive due to an exposure to a sensitive
allergen) resulting in the typical inflammatory s+s
Anti-H = regulate immune response in situations
where the response could be doing more harm
than good

Urticaria
H producing a vascular reaction of the skin
characterized by an immediate formation of a
red/swollen mark and area of redness
accompanied by severe itching due to exposure
to an external irritant.
Anti-H used to reverse effects/decrease reaction

Atopy (hay fever)
H is released due to exposure to irritant and
reaction manifests as an upper resp tract
disorder resulting in localized vascular dilation
and increased capillary permeability.
Anti-H acts to relax smooth muscle of the resp
tract and produce vascular constriction to
decrease the immune response to the area

Food Allergies
Involve IgE - a mast cell response to ingested
antigens. If the upper GIT is affected; vomiting
results. Lower GIT; cramps and diarrhoea. Can
result in systemic anaphylaxis after large
amounts are ingested.

Bronchial Asthma
Where the inhaled antigen combines with IgE,
stimulating the mast cells to trigger the release of
mediators in the lower resp tract (bronchi
bronchioles). H plays a role in the early asthma
response.
Anti-H = won’t completely combat the response
due to other chemical mediators involved.

Systemic Anaphylaxis
Generalized reaction manifested as a life
threatening systemic condition, where an Ag-IgE
mediator response involves the basophils in the
blood and mast cells in the connective tissue
releasing mass amounts of histamine into the
circulation causing widespread vasodilation and
a profound decrease in BP