Exam Flashcards
Describe Neutrophils
First line defenders
Move rapidly to site of infection in large numbers
Most abundant but die fighting
Become phagocytic on exposure to infectious material
Describe Macrophages
Develop from monocytes, chief phagocytic cells, robust cells
Free and fixed
Describe Eosinophils
Mildly phagocytic
Defence against parasites and regulation of vascular mediators
Describe Natural Killer Cells
Function = recognise and eliminate cells infected with viruses and eliminating cancer cells
Non-phagocytic large granular lymphocytes
Attack cells that lack “self” cell-surface receptors
Induce apoptosis in cancer cells and virus-infected cells
Secrete potent chemicals that enhance inflammatory response
Purpose of Interleukins
Produced by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation
Purpose of Interferons
Protect against viral infections
Released by viral infected cells and protect neighbouring cells; activate NK cells and macrophages.
What line of defence is innate immunity?
1 and 2
What line of defence is adaptive immunity?
3
Outline innate immunity
Natural resistance
Epithelial barriers Mucous membranes Phagocytes NKC Chemical mediators (cytokines) Inflammation
Outline adaptive immunity
Gained after birth Involves memory Specific ID of pathogens Recognition of self and non self Lag between exposure and response
Antigens
Immune cells (lymphocytes, antigen presenting cells, effector cells)
Humoral response
Cell-mediated response
Outline primary response
Initial exposure
Has latent period or lag phase when B cell differentiation occurs
After 5-7 days an IgM antibody for specific antigen is detected
An IgG response equal or slightly less follows IgM response
Outline secondary response
More rapid
Larger amounts of antibodies are produced from memory cells
Mature T cells already present
IgM produced in similar quantities to primary response byt IgG is significantly higher
What is an allergy?
Exaggerated hypersensitivity response to environmental antigens
What is hypersensitivity?
Exaggerated or inappropriate immunologic response to an antigen that results in disease or damage to the host
What is autoimmunity?
Body defences are misdirected against the body’s tissues
Autoimmune disease occurs when autoantibodies and cytotoxic T cells start to damage the persons own tissue
What is immunodeficiency?
Body defences are insufficient to protect the host
Categories of transplant rejection
Hyperacute
Acute
Chronic
Outline Hyperacute transplant rejection
Immediate and rare
Pre-existing antibody to the antigens of the graft
Outline Acute transplant rejection
Takes days to months
Cell-mediated immune response against unmatched HLA antigens
Biopsy demonstrates infiltration of lymphocytes and macrophages characteristic of type IV reactions.
Outline Chronic transplant rejection
Months or years after period of normal function
Slow, progressive organ failure
Inflammatory damage as a result of a weak cell-mediated reaction against minor HLAs
What is Systemic lupus erythematosus
Chronic multisystem inflammatory disease
Autoantibodies against: nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc.
Deposition of circulating immune complexes containing antibody against host DNA
Excessive levels of autoantibodies react with circulating antigens and form immune complexes, causes reactions in kidneys, brain, heart, spleen, lungs, GI tract, peritoneum and skin.
More common in females (10:1), esp 20-40 yrs
CM of Systemic lupus erythematosus
Arthralgias or arthritis (90% of individuals) Vasculitis and rash (70–80%) Renal disease (40–50%) Haematologic changes (50%) Cardiovascular disease (30–50%)
Tx of Systemic lupus erythematosus
No cure (as for most autoimmune diseases)
Aim to treat symptoms and suppress the autoimmune response
NSAIDS
Corticosteroids for serious active disease
Immunosuppressive drugs, e.g. methotrexate
Avoid UV exposure to reduce “flares”
Potential Rx with stem cell treatments
Why doesn’t the body clear the HIV virus totally?
It has a high replication rate - main reason for lack to total clearance
Provirus can be hidden where it is not detectable by the immune system
High mutation rate - antigens to antibodies and CD8s have mutated so cannot recognise and destroy.
Mutation is continual.
Define drug abuse
using a drug in a fashion inconsistent with medical or social norms
Define drug addiction
chronic, relapsing brain disease process characterized by compulsive seeking and use of a specific psychoactive substance despite harmful consequences
Define drug tolerance
regular drug doses elicit a smaller response than initially, requiring higher and higher doses to elicit desired effects
Define psychological dependence
an intense, subjective need for a particular drug
Define physical dependence
a state where an abstinence syndrome will occur if drug use is discontinued
Define withdrawal syndrome
S&S that occur in physically dependent people when they discontinue drug use
Define cross tolerance
tolerance to one drug confers tolerance to another drug, usually same group
Define cross dependence
same for dependence
Diagnostic criteria for substance use disorder
Maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by 2 or more of the following, occurring within a 12 month period:
- Recurrent use resulting in failure to fulfill role obligations - - Recurrent use in situations where physically hazardous
- Continued use despite problems
- Tolerance
- Withdrawal
- Taken in larger amounts and longer than intended
- Persistent desire and unsuccessful quitting/controlling
- Time spent on activities relating to substance abuse
- Giving up other activities
- Continued despite knowing harmful effects
- Craving
Substance abuse involves which drugs
Schedule 8 or 9
What are schedule 8 drugs
Controlled drugs
Available for use but require restriction to reduce misuse or dependence
What are schedule 9 drugs
Prohibited substances
Substances which may be abused or misused
Neurobiology of Addiction
Voluntary users can become compulsive users as a result of molecular changes in the brain
Reward circuit is activated
Major transmitter is dopamine: regardless of what initiates the reward pathway, the end is the same
Factors that Contribute to Drug Abuse
Reinforcing properties of the drug Physical dependence Psychological dependence Social factors Drug availability Vulnerability of the individual
Therapeutic use of alcohol
Antidote for antifreeze and methanol poisoning
Antiseptic (alcowipes)
Nerve blocks
Benefits from moderate consumption of alcohol
Prolongs life
Reduces risk of dementia, diabetes and cardiovascular disorders
Contributes to the joy of living
Cognitive effects of alcohol
Acute effects
- General depression of CNS function
- Enhances GABA-mediated inhibition
- Dose-dependent
- Activation of the reward circuit
- Binds with 5-HT3 receptors
Chronic effects
- Encephalopathy
- Effect on sleep
Physical effects of alcohol
- Cardiovascular system
- ↓respiration
- Liver damage
- Stomach
- Kidney
- Pancreas
- ↓blood glucose levels by inhibiting hepatic glucose output → risk for hypoglycaemia, masks signs (diabetics!)
- Sexual function
- Cancer: breast and colorectal cancer
- Pregnancy and lactation
What is Fatty Liver
Large amounts of fat accumulate in hepatocytes (steatosis)
Liver enlarges and becomes yellow
Damage reversible once alcohol is discontinued
What is Alcoholic Hepatitis
Often due to binge drinking
Inflammation and necrosis
Stimulates irreversible fibrosis
What is cirrhosis
Irreversible fibrosis of the liver Fat deposits, ↑connective tissue Loss of liver function - Loss of hepatocytes - Obstruction of biliary duct system
Cessation of alcohol reverses the fatty deposits but not the fibrosis or hepatocyte damage
CM of ALD
Tenderness/pain in Rt upper quadrant Portal hypertension Coagulation disturbance Hepatic encephalopathy Jaundice, pruritus Feminisation Weight loss, anorexia Weakness Diarrhoea, nausea
DX of ALD
History (social, work)
Questionnaires (AUDIT) and DSM-5 criteria
S & S
Liver US or biopsy
Bloods
- liver enzymes (ALT, AST, γ-GT)s and bilirubin
- serum albumin
- prothrombin time
- U & Es, FBC
TX alcohol use disorder
Reduce or stop alcohol intake (CBT, drugs)
Reduce portal hypertension (beta blockers)
Varices (balloon tamponade, vasopressin)
Bleeding (administration of clotting factors)
Ascites (diuretics, abdominal paracentesis)
Dietary intake (low protein, high carbohydrate, vitamin supplements)
Correct electrolyte and fluid imbalance and hypoglycaemia
Transplant in severe cirrhosis?
Drugs which facilitate alcohol withdrawal
Benzodiazepines
- Diazepam (drug of choice, tapered dosage over 6 days)
- Oxazepam, lorazepam (in severe liver disease)
Adjuncts to benzodiazepines
- Antipsychotics (haloperidol)
- Antiepileptics (carbamazepine)
- Antiemetics (metoclopramide)
- Thiamine (IM/IV and oral) and multivitamins
- Beta blockers (atenolol, propanolol)
- Review/cease drugs that ↑seizure risk (SSRIs)
Drugs used to Maintain Abstinence
Acamprosate (Campral)
- Structure similar to GABA
- Administered orally
- Adverse effects (diarrhoea, rash, nausea)
Naltrexone
- Pure opioid antagonist
- Administered orally, implants are being tested
- Adverse effects (nausea, headache, anxiety, sedation)
- Hepatotoxic
Disulfiram (Antabuse)
- Causes irreversible inhibition of aldehyde dehydrogenase
- Acetaldehyde syndrome (nausea, flushing, vomiting, headache, palpitations, chest pain)
Effects of Nicotine
Cardiovascular effects
- SNS and adrenal gland
- Arrhythmias
- Tachycardia
- Vasoconstriction
GI effects
- PNS, vomiting
- ↑gastric acid and motility
CNS effects
- Pregnancy and lactation
- Low birth weight
- Pre-term labour
- SIDS?
Up-regulation of receptors
- Tolerance
- Dependence
Acute poisoning
- 40mg can be fatal
- No specific antidote – activated charcoal can be given
- Monitor for respiratory depression and supportive treatment
Chronic toxicity from smoking
- Cancers
- Cardiovascular diseases
- COPD
Symptoms of withdrawal from nicotine
Craving Irritability, restlesness Frustration, anger Anxiety Sleep disturbances Difficulty concentrating ↓heart rate ↑appetite, weight gain
“5 As” Model for treatment of tobacco addiction
Ask (screen all patients for tobacco use)
Advise tobacco users to quit
Assess willingness to make a quit attempt
Assist with quitting (offer medication and provide or refer to counseling)
Arrange follow-up contacts, beginning within the first week after the quit date
TX of tobacco addiction
Nicotine replacement therapy
- Chewing gum
- Lozenges and sublingual tablets
- Transdermal patches
- Mouth spray
- Inhaler
Other non-nicotine drug treatments
- Bupropion (Zyban)
- Varenicline (Chantix)
What is nicotine replacement therapy
High dose and combination therapy safe for heavy smokers
Smoking rate or serum cotinine
Assess adequacy of nicotine replacement by patient response or percent replacement
More complete nicotine replacement improves withdrawal symptom relief
Adverse effects usually minor and transient
Withdrawal symptoms
Nicotine overdose (tachycardia, palpitations, arrythmias)
Adverse reactions to NRT
Indigestion Irritation of mouth and throat Sinusitis Irritation of mouth and throat Take care if patient has dentures Local site reactions Insomnia, dizziness, agitation, lack of concentration Fever, rash, nausea, dry mouth
What is nociception
perception of pain
What are neuromodulators
substances that alter pain transmission
Located in pathways of nervous system
Triggered by tissue injury and or inflammation
What is the endorphin response
Endorphins interact with the opiate receptors in the brain to reduce our perception of pain and act similarly to drugs such as morphine and codeine
What are opioid receptors
3 main classes of opioid receptors have been identified:
Mu (μ)
Kappa (К)
Delta (δ)
Analgesic drugs stimulate μ receptors with some action on К
Classic triad of acute toxicity
Respiratory depression
Coma
Pinpoint pupils
Immediate effects of heroin
Lower abdominal sensation similar to sexual orgasm
Euphoria
Long term effects of heroin
Intense sadness Irregular periods and infertility No sex drive Constipation Damaged heart, lungs, liver and brain Vein damage Skin, heart and lung infections from injecting Tolerance and dependence on heroin Financial, work or social problems
Effects of first time heroin use
nausea
vomiting
dysphoria
Routes of administration of heroin
High lipid solubility
IV route preferred, but also smoking, nasal inhalation
Overdose
Signs of heroin overdose
Cognitive (sleepy, LOC) Urinary retention Itchiness Arrhythmias ↓resps Death
Rx: Naloxone, ventilation
Heroin withdrawal symptoms
Cravings for heroin
Restlessness, irritability, depression, crying
Diarrhoea, vomiting
↑HR
Why is Pethidine the choice of health professionals
Highly effective in oral route
Minimal effect on smooth muscle: fewer problems with constipation and urinary retention
Don’t get tell-tale signs of repeated injections
Routes of administration of oxycodone
Abusers crush tablet, snort powder or dissolve in water for IV
Controlled-release drug
Entire dose absorbed immediately with high risk of death
Immediate effects of oxycodone
Euphoria
Dental problems
Mood swings
Signs of oxycodone overdose
respiratory depression
arrhythmias
LOC
Treatment of acute toxicity / overdose
Naloxone
- pure opioid antagonist used to counter the effects of opioid, especially in overdose
- extremely high affinity for μ-opioid receptors in CNS
- reverse depression of CNS, respiratory system, and hypotension
- Naloxone may be combined with other opioids so when taken orally the opioid has effect but if misused the naloxone blocks the effect of the opioid
Naltrexone - structurally similar but has increased affinity for κ-opioid receptors over naloxone, can be administered orally, and has a longer duration of action.
Nalmefene - opioid receptor antagonist used in management of alcohol dependence.
Methods of opioid detoxification
Methadone:
Substitute methadone for dependent opioid to prevent abstinence syndrome as has cross-dependence.
Gradually reduce doses
Abstinence syndrome is mild (moderate influenza)
10 days
Clonidine:
Used for physically dependent person on opioids
Suppresses symptoms of abstinence (nausea, vomiting, diarrhoea, muscle aches, restlessness, anxiety and insomnia)
Doesn’t diminish opioid craving
Rapid and ultra-rapid withdrawal:
Given opioid antagonist to precipitate immediate withdrawal and accelerate withdrawal process
Done under GA or heavily sedated
Social/family support
Counselling
Rehabilitation
Long-term opioid addiction management
Three groups of medications:
1) opioid agonists
2) opioid agonist-antagonists
3) opioid antagonists
Methadone (opioid agonist)
Maintenance and suppressive therapy
Aim = avoid withdrawal symptoms, prevent addiction
Buprenorphine (opioid agonist-antagonist)
Maintenance therapy and detox facilitation
Aim = alleviate cravings, reduce drug use
Naltrexone (opioid antagonist)
Discourages renewed opioid abuse by blocking euphoria and other effects
