Lipid Lowering + CHF + ACS + Anticoags
Lipid Lowering + CHF + ACS + Anticoags
Urates + Tumour Lysis Syndrome
Malaria + Immunosuppres
Psychomimetic + nausea
100

Define HDL, LDL and VLDL and their primary function?

  • Very Low-Density Lipoprotein (VLDL):
    Transports triglycerides from the liver to peripheral tissues.
  • Low-Density Lipoprotein (LDL) Cholesterol:
    Transports cholesterol to body tissues. Often referred to as “bad cholesterol” because elevated levels contribute to atherosclerosis and plaque formation.
  • High-Density Lipoprotein (HDL) Cholesterol:
    Transports cholesterol to some tissues and also carries excess cholesterol from peripheral tissues back to the liver for breakdown and excretion (e.g. conversion into bile acids). Often referred to as “good cholesterol.”
100

What is haemostasis? What are the 3 stages? At what stages do antiplatelet and anticoagulant drugs work at?

Haemostasis refers to the stopping of bleeding. 

1. Vascular spasm

2. Platelet aggregation and plug formation --> targeted by antiplatelet drugs

3. Coagulation (thrombus, clot) --> targeted by anticoagulant drugs 

100

What is the pathway of purine metabolism in humans? What enzyme are humans missing with respect to other animals?

Purines --> Hypoxanthine --> Xanthine --> Uric Acid 

Xanthine oxidase (the enzyme that converts the substrates)

Missing urate oxidase (uricase) which breaks down the uric acid into allantoin. 

100

Which cytokine increases the growth and activity of T and B lymphocytes and promotes the differentiation of T cells into cytotoxic and memory cells?

IL-2 

100

What are the receptors located in the chemoreceptor trigger zone (5) ?


Contains the 5HT3 (serotonin) receptors, Dopamine D2 receptors, neurokinin-1 (NK1) receptors, opioid and cannabinoid receptors. 

200

What are the 5 classes of lipid-lowering drugs? Provide an example of each. 

Statins (simvastatin)

Ezetimibe 

PCSK9 inhibitors (alirocumab, evolocumab)

Fibrates (gemfibrozil, fenofibrate)

Ion exchange resins (cholestyramine, colestipol)

200

Name 4 anticoagulants. What are their mechanisms of action?

Anticoagulants = heparin, warfarin, dabigatran, rivaroxaban, apixaban

Heparin - combines with antithrombin III and enhances the rate at which antithrombin III inhibits thrombin (IIa) and activated factor X (Xa)

Warfarin - inhibits the synthesis of vitamin-k dependent clotting factors by inhibiting the enzyme vitamin K epoxide reductase (2,7,9,10)

DOACs (direct oral anticoagulants) 

- Dabigatran = competitive, reversible direct inibitor of thrombin 

- Apixaban and Rivaroxaban = are direct, reversible inhibitors of activated factor X (factor Xa)

200

What is one precipitating and one protective factor with respect to Gout?

Precipitating: Testosterone increases the renal reabsorption of uric acid by an effect on URAT1. Peak incidence of an initial acute attack of gout is in the 40-60 age group, males >> females. 

Protective: Oestrogen increases the renal excretion of uric acid by reducing the tubular reabsorption of uric acid by an effect on URAT1 and GLUT9 --> gout it uncommen in premenopausal women and incidence increases in women after menopause. 

200

What are bDMARDS? What are their MOA? Provide an example. 

Biological disease modifying antirhematic drugs. 

bDMARDS are biological agents which act more specifically on the immune system and primarily inhibit the actions of TNFa 

Infliximab = chimeric human marine MAB that binds to TNFa

200

What is the MOA of Aprepitant?

  • Substance P is a neuropeptide involved in the vomiting pathway, especially at the chemoreceptor trigger zone (CTZ).
  • It causes vomiting by binding to neurokinin-1 (NK1) receptors.

Aprepitant

  • Aprepitant blocks NK1 receptors in the CNS.
  • This prevents the action of substance P and helps reduce vomiting.

Uses of Aprepitant

  • Prevention of postoperative nausea and vomiting (PONV)
  • Prevention of chemotherapy-induced nausea and vomiting (CINV), usually combined with other antiemetics.
300

Which enzyme is responsible for metabolising simvastatin or atorvastatin? What are 2 inhibitors and 1 inducers of this enzyme. 

CYP3A4


Inhibitors - Clarithromycin, Erythromycin, Itraconazole, Ketoconazole


Inducers - St John's wort + Carbamazepine

300

What are the antidotes to Dabigatran and factor Xa inhibitors (apixaban/rivaroxaban)?

Idarucizumab (Praxbind) is an antidote to dabigatran = it is a humanised monoclonal antibody fragment that binds to dabigatran and neutralises its effect. Has a x300 more greater affinity for dabigatran than thrombin. 

Andexanet Alfa is an antidote to factor Xa inhibitors. Apixaban/Rivaroxaban bind to andexanet alfa with a higher affinity than they bind to factor Xa 

300

What are the medications used in the treatment of an acute attack of gout? Provide the MOA of Colchicine.

NSAIDS + Colchicine + Corticosteroids 


Colchicine - binds to tubulin and inhibits microtubule polymerisation which inhibits the activation and migration of neutrophils to the joint. this reduces phagocytosis and reduces pro-inflammatory pain mediators.

300

What is the life-cycle of the Malaria parasite?

Life Cycle of the Malaria Parasite 


  • The parasite has:
    • A sexual cycle in the female Anopheles mosquito
    • An asexual cycle in humans

Infection Begins

  • An infected female mosquito bites a human and injects sporozoites into the bloodstream.

Liver Stage

  • Sporozoites travel to the liver and infect liver cells.
  • They develop into schizonts, which burst and release merozoites.

Blood Stage

  • Merozoites infect red blood cells.
  • Inside red blood cells, they become trophozoites and multiply.
  • The red blood cells burst, releasing more merozoites to infect other cells.

Haemoglobin Breakdown

  • The parasite digests haemoglobin for nutrients.
  • Toxic free haem is produced but converted into harmless haemozoin by the parasite.

Sexual Forms

  • Some parasites develop into gametocytes (sexual forms).
  • When another mosquito bites the infected person, it takes up these gametocytes and the cycle continues.


300

Provide two serious adverse effects of Ecstasy intake?

Ecstasy (MDMA)

Mechanism of Action (MOA)

  • Blocks serotonin reuptake via the serotonin transporter (SERT)
  • Enters the nerve terminal through SERT
  • Causes large release of serotonin (5HT) into the synapse
  • Also increases:
    • Dopamine (DAT)
    • Noradrenaline (NET)

Main Effects

  • Euphoria
  • Increased energy
  • Mood elevation

Adverse Effects of Ecstasy

Serotonin Syndrome

Due to excess serotonin stimulation.

Features

  • Agitation, confusion
  • Tremor, myoclonus
  • Sweating, hyperthermia
  • Tachycardia, hypertension
  • Seizures, coma

Hyperthermia

  • Increased body temperature
  • Worse with dancing and hot environments
  • Can cause:
    • Muscle breakdown
    • Renal failure

Hyponatraemia

Usually due to:

  • SIADH (↑ ADH → water retention)
  • Excessive water intake

Features

  • Headache
  • Confusion
  • Muscle cramps
  • Seizures
  • Coma 
400

What are the four NYHA HF Classifications?

  • Class I:
    Cardiac disease is present, but there is no limitation of physical activity. Ordinary physical activity does not cause symptoms such as fatigue, palpitations, dyspnoea, or angina.
  • Class II:
    Cardiac disease results in a slight limitation of physical activity. Patients are comfortable at rest, but ordinary physical activity causes symptoms.
  • Class III:
    Cardiac disease causes a marked limitation of physical activity. Patients are comfortable at rest, but less-than-ordinary activity results in symptoms.
  • Class IV:
    Cardiac disease results in an inability to perform any physical activity without symptoms. Symptoms may even be present at rest and worsen with physical activity.
400

In the treatment of stable angina, what is used for treatment of acute attacks vs prevenetion (prophylaxis) vs treatment of the underlying condition?

Provide one example of each. 

Treatment of acute attacks = organic nitrates (glyceryl nitrate)

Prevention = organic nitrates, CCBs (amlodipine), BBs (propanolol (ns), metoprololol (s)

Treatment of underlying condition = antiplatelet medication (low-dose aspirin), ACEI (blood pressure control), lipid control (statins. 

400

Provide two examples of Xanthine Oxidase inhibitors? What can they precipitate and what should they be administered with?

Allopurinol = metabolite is oxypurinol works to inhibit xanthine oxidase

Febuxostat = works to inhibit xanthine oxidase

Initiation of the above can precipitate an acute attack of gout due to the initial change in plasma uric acid levels and mobilisation of urate from the tissue deposits. 

Always administered with either an NSAID or colchicine - dual therapy for 3 months. 

400

Provide treatment use for (1) Uncomplicated Malaria and (2) Malaria Prophylaxis.

Bonus: When should the prophylactic ones be given?

Uncomplicated Malaria

Treatment options include:

  • Artemether + lumefantrine
  • Atovaquone + proguanil
  • Quinine + doxycycline
    • If pregnant or under 8 years old → use clindamycin instead of doxycycline

For Plasmodium vivax or Plasmodium ovale

  • Add primaquine to treat dormant liver forms (hypnozoites)
  • Must exclude G6PD deficiency before giving primaquine

Malaria Prophylaxis (Prevention)

Always check local malaria resistance patterns before travel.

Recommended Preventive Drugs

  • Atovaquone + proguanil
    • Start: 1–2 days before travel
    • Continue: 7 days after leaving
  • Doxycycline
    • Start: 1–2 days before travel
    • Continue: 4 weeks after leaving
  • Mefloquine
    • Start: 2–3 weeks before travel
    • Continue: 4 weeks after leaving
400

Compare the pharmacological actions of cannabis and LSD, including the neurotransmitter systems primarily involved and the major psychological effects produced.

Cannabis and LSD are both psychomimetic drugs, but they work through different neurotransmitter systems and produce different effects.

Cannabis mainly acts on the cannabinoid (CB1) receptors in the brain through THC. It also indirectly increases dopamine activity. Its effects include relaxation, euphoria, increased appetite, impaired memory and coordination, and altered perception of time. In high doses, it can cause anxiety, paranoia, or psychosis-like symptoms.

LSD mainly acts on serotonin receptors, especially 5-HT2A receptors. It produces strong hallucinations and sensory distortion. Effects include altered perception of colours, sounds, and time, as well as changes in mood and thinking. LSD may also cause panic, anxiety, or “bad trips.”

Overall, cannabis mainly causes relaxation and mild perceptual changes, while LSD causes intense hallucinations and major changes in perception and thought.

500
Name 3 pharmacological (name an example of each) and non-pharmacological treatments of HF?

Non-pharma = patient education, weight loss (if obese), regular exercise, fluid restriction, sodium restriction, no added salt and low salt foods, avoid smoking and alcohol restriction (0-2 per day)

Pharma = ACEI, ARBs, Neprilysin inhibitors (sacubirtril), Diuretics, BB, Digoxin, Ivabradine, Spironolactone. 


500

What drug is contraindicated with a neprilysin inhibitor? Why? How long should the washout period be?

Never administer with an ACE inhibitor due to the risk of angioedema. 36 hour washout period required. 

Angioedema may be caused by several stimuli including histamine and bradykinin. Bradykinin is broken down by both ACE and NEP. Increase in bradykinin = increase in the potential for angioedema 

500

What is tumour lysis syndrome? What can it result in? Explain why they present with those findings?

Tumour Lysis Syndrome (TLS)

  • Tumour Lysis Syndrome occurs when cancer cells break down rapidly, usually after cancer treatment begins.
  • The contents inside the cells are released into the blood.

Commonly Seen In

  • Acute leukaemia
  • Lymphoma

Main Problems Caused

  • Hyperkalaemia: release of potassium from broken cells
  • Hyperphosphataemia: release of phosphate from broken cells
  • Hypocalcaemia: phosphate binds calcium, lowering blood calcium levels
  • Hyperuricaemia: nucleic acids from cells are broken down into uric acid


500

What is the name of the drug used against liver hypnozoites? What forms and stage does this drug target? In which subgroup of people is this drug contraindicated in?

Primaquine or Tafenoquine = against exoerythrocytic stages of p.ovale and p.vivax. Exact mechanism is unknown but it inhibits the entry of the parasite into the liver cells. 

May cause severe haemolytic anaemia in individuals with G6PD deficiency. 

G6PD involves in the production of NADPH via the reduction of NADP. 

NADPH maintains glutathione in a reduced state which is essential to protect RBCs from oxidative stress. 

500

What is serotonin syndrome? What classes of medications may cause the serotonin syndrome? Provide an example of each class mentioned. 

Cause

  • Caused by excessive stimulation of serotonin receptors (5HT1A and 5HT2A) in the CNS and peripheral nervous system.
  • Can range from mild to severe and may rapidly become life-threatening.

Clinical Features

Mental

  • Confusion
  • Agitation
  • Disorientation
  • Mania

Autonomic

  • Hyperthermia
  • Sweating
  • Tachycardia
  • Hypertension
  • Diarrhoea

Neurological

  • Tremor
  • Myoclonus
  • Coma (severe cases)

Drugs That May Cause Serotonin Syndrome

  • Antidepressants: SSRIs, SNRIs, MAOIs, TCAs
  • Opioids: tramadol, fentanyl, pethidine
  • Cough suppressants: dextromethorphan
  • Other drugs/substances: cocaine, ecstasy, lithium, carbamazepine, sumatriptan, St John’s wort
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