Untitled Quiz

Vaccine Types

• Live Attenuated
  • Cannot cause disease
  • Virus or bacteria is alive but weakened
  • Usually single exposure is sufficient for lifelong immunity
  • Can cause more mild side effects than other vaccines
  • Cannot be used in immunocompromised people
  • E.g. Measles, Mumps, Yellow Fever, Tuberculosis, Typhoid
• Inactivated
  • Often require multiple doses to establish lifelong immunity
  • Use booster doses at varying time intervals
  • No symptoms of the disease are possible
  • Safe & encouraged in immunocompromised patients
  • Contain complete or parts of virus or bacteria
    • Inactivation with chemicals or heat
  • Include Polio, Influenza, & Hepatitis A
• Toxoid
  • Inactivated toxins that are secreted by pathogens
  • Inactivated with heat or chemicals
  • Recognises entire bacterium
  • Diphtheria & Botulism
• Subunit
  • Certain parts of the virus
  • Usually proteins of the virus
  • Faster & more safely than eggs
  • Tend to be recombinant
• Conjugated
  • Part of a pathogen not recognised to a carrier protein that is recognised

Special Populations

• Should receive yearly influenza, pneumonia, varicella zoster
• Pregnant women should receive yearly influenza, pertussis (before pregnancy or 3rd trimester)

Immunisation Issues

• Must be studied & proven to not cause disease or death
  • May show a few symptoms but no disease
• Needs to be stored correctly

Immunisation Failure

• Don't maintain refrigeration
• Not always 100% guaranteed effective
• Incorrect injection site

Antigenic Shift

• Mutation & evolving to create new forms & types
• Change of antigens

Asthma

• 1/10 have asthma at one stage in their life
  • 1 death per 21 hours
• Chronic airway inflammatory stimulated by antibodies
  • When mast cells activated they release inflammatory mediators
• Inflammatory mediators can result in;
  • Increased mucous
  • Wheeze
  • Thickened bronchial walls
  • SOB
  • Chest tightness
  • Cough
  • Expiratory airflow limitation (inability to breathe out) - no CO2 and O2 exchange
• Can be;
  • Exercise
  • Stress
  • Chemicals and medications
  • Predisposing genetics
  • Allergens
• Mast cells begin to degranulate due to IgE antibodies
• An attack is a flare of asthma
  • Acute (immediate)
  • Over days, weeks or months

Other Key Asthma Information

• Increased releases of;
  • Prostaglandins
  • Cytokines
  • leukotrienes
  • All lead to chronic inflammation
• Bronchospasm happens
  • Air cannot flow through
• Can have;
  • Acute (bronchospasms)
  • Chronic inflammation (non-specific hyperreactivity) - worsening of symptoms
  • Airway remodelling (constant bronchial restriction)
• Goal is control!!!- No limitation of activity
  • Daytime symptoms 160/100mmHg
• Choice of therapy;
  • Consideration for a patient's pre-existing comorbidities
  • Stepwise approach
    • Adding drugs on if not bettering
    • Majority require 2 or more drugs
  • Following drug classes;
    • Angiotensin converting enzyme (ACE) inhibitor
    • Angiotensin receptor blockers (ARBs)
    • Calcium channel blocker
    • Thiazide diuretics
    • Beta blockers

Angiotensin Converting Enzyme (ACE) Inhibitors

• Ramipril, Perindopril, Lisinopril, Enalapril
• Inhibit angiotensin converting enzyme (cannot raise MAP)
• Cannot convert angiotensin I to angiotensin II
• Reduce vasoconstriction, reduce everything in RAAS
• Reduces stroke volume, HR and SVR
• Often the first-line selection
  • So effective at reducing MAP
• Adverse effects;
  • Hypotension
  • Hyperkalaemia (increase in plasma potassium)
    • Stopping sodium and water retention
    • Potassium is kept in the blood because sodium and water are staying in the urine
  • Persistent dry cough
• Triple whammy interaction (results in acute renal failure)
• Should NOT be used in combo with ARBs

Angiotensin Receptor Blockers (ARBs)

• Candesartan, Telmisartan, Olmesartan, Irbesartan
• Antagonise the angiotensin type-1 receptor
  • Prevents angiotensin II from binding & causing downstream effects
• Sit in the receptor preventing binding
• Block out RAAS
• ADRs;
  • Hypotension
  • Hyperkalaemia
• Often reversed if you don't tolerate an ACE inhibitor
• Involved with triple whammy
• NO use with ACE inhibitors
  • Doing the same thing
  • Can cause lots of harm

Calcium Channel Blockers

• Calcium is required for muscle contraction
  • INCLUDES THE HEART
• 2 subclasses;
  • Dihydropyridine
  • Stable angina
• Post-MI
• Heart failure
• Stable Angina;
  • Retrosternal chest discomfort
  • Commonly triggered by stress or physical activity
  • Typically goes away with rest
  • Myocardial O2 demand exceeds supply
  • Short-acting nitrates for treatment
  • Beta blockers, non-dihydro and nitrates for prophylaxis of acute episodes
    • All meds reduce the amount of O2 that the myocardium requires

Nitrates

• GTN, Isosorbide mononitrate
• Produce vaso and venodilation
• Reduction in venous return and preload
• Post-MI
  • Most patients benefit from long-term combination therapy
  • MI-5;
    • Ace inhibitors (decrease cardiovascular mortality)
    • Beta blockers (decrease myocardial O2 requirements)
    • Statins
    • P2Y12 inhibitors
    • Aspirin
• Heart failure
  • Most patients benefit from long-term combo therapy
  • Include;
    • Ace inhibitors (increase all cause survival, decrease hospitalisations)
    • Beta blockers (increase all cause survival, decrease hospitalisations)
    • Aldosterone antagonists
    • ARN inhibitors
    • Digoxin
    • Loop Diuretics (reduce the symptoms of heart failure - breathlessness/oedema)

Loop Diuretics

• Furosemide
• Do the same thing as thiazides
• Only do it in the Loop of Henle instead of the distal portion
• Very very effective diuretics
• Can see dehydration, hypotension, electrolyte disturbances
• Need to be mindful of diuresis & adherence

Nitrates

• Glyceryl trinitrate, Isosorbide mononitrate
• Produce vasodilation & veno dilation
  • Reduction in venous return therefore reduce preload
  • Therefore reduce stroke volume
• ADRs;
  • Vasodilatory
  • Headaches
  • Dizziness
  • Hypotension
• Short acting (spray) or long acting (patch)
• Nitrate tolerance develops if there is no nitrate-free period for 24 hours
  • For long acting
• Very serious interaction with PDE-5 inhibitors e.g sildenafil (viagra)
• Reducing the O2 demand of the heart
• Triple whammy
  • Happens for many reasons
  • Especially when combining particular drugs

Hyperthyroidism

• Characterized by an excess of thyroid hormones in the body
• Common signs and symptoms include:
  • Exophthalmos: Bulging of the eyes
  • Thyroid Dermopathy: Swelling and lumpiness under the skin, accompanied by itching and redness
  • Thyroid Acropachy: Clubbing of fingers and toes, and inflammation around connective tissue

Diagnosis

• Usually relies on blood tests
• Parameters:
  • Hyperthyroidism: Low free TSH, high levels of T4
  • Subclinical: Low free TSH, normal T4
  • Hyperthyroidism Secondary to Tumors: High TSH, high T4

Treatment

• Three main options:
  • Pharmacotherapy:
    • Beta-1 selective or non-selective blockers: Control symptoms by targeting the beta cells
    • Carbimazole: Thiourea that inhibits the biosynthesis of thyroid hormones
    • Propylthiouracil (PTU): Thiourea with additional mechanism of action, inhibiting the activated form of thyroid hormones in the periphery
  • Surgery: Removal of thyroid tissue
  • Radioactive Iodine: Destroys thyroid tissue, usually in a single dose

Carbimazole and PTU

• Both medications are thioureas that inhibit thyroid hormone biosynthesis
• Mechanism:
  • Divert iodine away from iodination sites
  • Stop MIT and DIT from coupling to form T3 and T4
  • Prevent iodine molecules from incorporating into tyrosine
  • PTU has an additional mechanism, inhibiting the activated form in the periphery
• Contraindications:
  • PTU: Avoid in children (requires specialist monitoring), preferred in pregnancy (only in the first trimester, switched to carbimazole in the second and third), watch for agranulocytosis (fever, mouth ulcers, sore throat, rash, abdominal pain, jaundice), can cause hepatotoxicity
  • Carbimazole: Avoid in children, monitor carefully if patient has poor hepatic function, watch for agranulocytosis

Radioactive Iodine

• Typically only a single dose is needed
• Mechanism:
  • Taken up by thyroglobulin
  • Biologically inactive due to being a radioactive isotope
  • Damaged tissue can no longer produce and secrete thyroid hormones

Diabetes

• Epidemiology:
  • 1 in 11 adults have diabetes (415 million people)
  • 1 person dies every 6 seconds from diabetes
  • 1 person develops it every 5 minutes
• Pathophysiology:
  • Normal Physiology: Glucose is the primary fuel for cellular energy, polysaccharides are broken down into monosaccharides (e.g., glucose), excess glucose is packaged as glycogen and stored in the liver and adipose tissue
  • Pancreas: Alpha cells secrete glucagon, beta cells secrete insulin
  • Homeostasis of Glucose: Essential for proper function, too high or too low can lead to complications
    • Hyperglycemia: Risk of microvascular and macrovascular complications
    • Hypoglycemia: Adrenergic (pallor, diaphoresis, anxiousness) and neuroglycopenic (confusion, agitation, altered level of consciousness) side effects
• Insulin Homeostasis:
  • When blood glucose levels rise: Insulin is released from pancreatic beta cells, triggers glycogenesis (glucose is stored as glycogen)
  • Glucose-Dependent Insulin Secretion:
    • Consuming food results in rising plasma glucose concentration
    • Consumption of food leads to the release of incretins (GIP)
    • Dipeptidyl peptidase-4 enzyme breaks down incretins
    • Both processes signal the pancreas to release insulin
  • Prandial Insulin Secretion: Large spikes in insulin occur after each meal, reflecting direct secretion of insulin in response to food, a baseline levels of insulin is maintained
• Glucagon Homeostasis:
  • When blood glucose levels are low: Alpha cells release glucagon, triggers glycogenolysis (glycogen is broken down to glucose)
• Types of Diabetes:
  • Type 1 Diabetes: Insulin deficiency, autoimmune destruction of beta cells, no insulin production
  • Type 2 Diabetes: Insulin insufficiency, progressive beta cell dysfunction and insulin resistance, reduced insulin effectiveness and function

Pharmacodynamic Management of Type 1 Diabetes

• Four main goals:
  • Manage hyperglycemia
  • Avoid acute complications of hyperglycemia
  • Reduce chronic implications of hyperglycemia
  • Avoid hypoglycemia
• Insulin:
  • Major therapy is reintroducing exogenous insulin
  • Insulin is a large protein, not orally bioavailable, must be injected
  • Various formulations available
• Formulations of Insulin:
  • Ultra-Short Acting: E.g., Insulin aspart, rapid spike and decline
  • Long Acting: E.g., Insulin glargine, smaller peak with sustained duration
• Pharmacotherapeutics of Insulin:
  • Basal-Bolus Regime: Most common approach, combines long-acting and ultra-short acting insulin
    • Basal Insulin: Long-acting, e.g., insulin glargine, provides background insulin
    • Bolus Insulin: Short-acting, e.g., insulin aspart, mimics glycogenesis effect, given before meals
• Adverse effects: Hypoglycemia
• Practice Points:
  • Hypoglycemia: Increased risk with recreational substances (e.g., alcohol), fasting, may compromise ability to recognize hypoglycemia
  • Temperature Sensitivity: Must be refrigerated
  • Delivery Options: Injection or insulin pumps
  • Monitoring: Regular blood glucose monitoring

Pharmacodynamic Management of Type 2 Diabetes

• Four main goals:
  • Manage hyperglycemia
  • Avoid acute complications of hyperglycemia
  • Reduce chronic complications of hyperglycemia
  • Avoid hypoglycemia

Management of Type 2 Diabetes

• No strict hierarchical approach to management
• Stepwise Therapy: Medications are added progressively
• Primary Choices:
  • Biguanides: Metformin
    • Mechanism: Reduces intestinal carbohydrate absorption, increases insulin sensitivity, increases glucose uptake into peripheral tissues, decreases hepatic glucose production
    • Adverse Effects: Nausea, vomiting, diarrhea
    • Practice Points: Reduces risk of microvascular and macrovascular complications, unlikely to cause hypoglycemia on its own, available in immediate or extended release formulations, mindful of potential lactic acidosis
  • Sulfonylureas: E.g., Gliclazide, Glipizide, Glibenclamide
    • Mechanism: Increases pancreatic insulin secretion (independent of food)
    • Adverse Effects: Weight gain, hypoglycemia
    • Practice Points: Must be taken with food, will cause hypoglycemia if not taken with food
  • DPP-4 Inhibitors: Linagliptin, Sitagliptin, Saxagliptin
    • Mechanism: Inhibit DPP-4, increase concentration of incretins, enhance glucose-dependent insulin secretion
    • Adverse Effects: Well-tolerated, may see musculoskeletal pain
    • Practice Points: Unlikely to cause hypoglycemia on their own
  • SGLT2 Inhibitors: Empagliflozin, Dapagliflozin, Ertugliflozin
    • Mechanism: Inhibit SGLT2 in the kidneys, reducing glucose reabsorption, resulting in increased urinary glucose excretion
    • Adverse Effects: Polyuria, genital infections, euglycemic ketoacidosis
    • Practice Points: Unlikely to cause hypoglycemia on its own, can cause mild blood pressure reductions, mindful of dehydration, and potential for renal impairment
  • GLP-1 Analogues: Exenatide, Liraglutide, Semaglutide
    • Mechanism: Mimic the action of GLP-1, increase insulin secretion, decrease glucagon secretion, delay gastric emptying, promote satiety
    • Adverse Effects: Nausea, vomiting, diarrhea, pancreatitis
    • Practice Points: Can cause weight loss, may improve cardiovascular outcomes
• Secondary Choices:
  • Acarbose: Alpha-glucosidase inhibitor that slows down carbohydrate absorption
  • Pioglitazone: Thiazolidinedione that enhances insulin sensitivity
  • Insulin: Used when other medications are insufficient to control blood sugar levels

Epilepsy

• Epilepsy: an umbrella term for categorising different diseases or syndromes of the brain.
• A seizure: Abnormal excessive or synchronous neuronal activity occurring in the brain.
• Can have seizures without epilepsy, but can't have epilepsy without a seizure.
• Epilepsy can be caused by a variety of factors, including genetics, birth defects, and head injuries.
• Epilepsy is characterized by recurrent seizures, meaning that two or more unprovoked seizures occur.
• Seizure threshold: The upper limit of neuronal activity the brain can handle.
• Threshold is lowered by various factors like substances, sleep deprivation, and physiological changes that can lead to seizures despite no prior predisposition.
• Antiepileptic drugs (AEDs) work by raising the seizure threshold, making it harder for neurons to fire excessively.

Seizure Classification

• Seizures are classified based on where they originate and the symptoms they cause.
• Focal Seizures: Seizures with a specific origin in one hemisphere, may spread to the rest of the brain.
  • Aware: Individual maintains awareness during the seizure.
  • Impaired Awareness: Individual loses awareness during the seizure.
  • Motor onset: Involves involuntary movements
  • Non-motor onset: Involves changes in sensations.
  • Focal to Bilateral Tonic-Clonic: Starts in one area of the brain and spreads throughout causing a tonic-clonic type.
• Generalized: Affects both hemispheres.
  • Generalized Onset: Seizures involving both hemispheres from the start.
  • Motor: Involuntary movement
  • Non-motor: Changes in awareness or consciousness
• Unknown Onset: Seizure's origin cannot be determined.
  • Motor: Involuntary movement
  • Non-motor: Changes in awareness or consciousness
  • Unclassified: Not categorized.

Treatment: Drug Therapy

• Goal of AED Therapy: Suppress seizures and manage adverse effects.
• AEDs are complex due to varying mechanisms, interactions, and adverse effects.
• Three Major pathways of AEDs:
  • Sodium Voltage-gated channel blockers: Prevent excessive communication by blocking sodium channels.
  • Calcium Voltage-gated channel blockers: Prevent excessive communication by blocking calcium channels.
  • GABA Agonists: Increase the inhibitory effects of GABA to reduce neuronal activity.
• Overall, these drugs reduce excessive excitation and synchronous firings of neurons, increasing the seizure threshold.

Voltage-gated Sodium Channel Blockers

• Carbamazepine: A sodium channel blocker with multiple uses (epilepsy, bipolar disorder, pain) but also various adverse effects.
  • Strong CYP inducer: Causes numerous drug, food, and herbal interactions, requiring careful monitoring.

Drugs Affecting GABA Receptor

• Benzodiazepines reduce neuronal activity by increasing the inhibitory effects of GABA.
  • Used as adjuncts for epilepsy management, especially for acute seizures.

Non-pharmacological Interventions

• Non-pharmacological interventions (diet, lifestyle changes, cognitive behavioral therapy) can play a role in managing epilepsy
• Some patients may require lifelong therapy with both pharmacological and non-pharmacological interventions.

Key Facts:

• Drug therapy is a complex aspect of epilepsy management.
• A thorough understanding of various AED mechanisms, interactions, and adverse effects is essential.
• Close monitoring and individualized care are crucial for epilepsy patients with long-term success.