Introduction to clinical sciences Flashcards
What is atherosclerosis
Accumulation of fibrolipid plaques in systemic arteries
Risk factors for atherosclerosis
hypertension
hyperlipidaemia
cigarette smoking
poorly-controlled diabetes mellitus
Does atherosclerosis occur in low pressure arteries
No
Main lipid in atherosclerosis
Cholesterol
Things within an atherosclerosis
Lipids-Cholesterol
Lymphocytes
Can atherosclerosis’ kill organs
Yes, if the organ only has 1 source of blood flow
What causes atherosclerosis risk in cigarette smoking
Free radicals
Carbon monoxide
nicotine
How does hypertension cause risk of atherosclerosis
Shearing forces on endothelial cells
How does diabetes cause risk of atherosclerosis
superoxide anions
glycosylation products
How does hyperlipidaemia cause risk of atherosclerosis
Lipids cause direct damage to endothelial cells
What does accumulated endothelial damage cause
Atherosclerosis
What are caspases
Family of protease enzymes with essential roles in apoptosis regulation
What is apoptosis
Programmed cell death
Function of apoptosis
prevents cells with accumulated genetic damage from dividing and potentially becoming cancer cells
Function of p53 protein
Can detect DNA damage and can the trigger apoptosis
What is Necrosis
It is wholesale destruction of large numbers of cells by some external factor
Clinical examples of necrosis
Infarction e.g myocardial
Frostbite
Toxic venom
Pancreatitis
What cells phagocytose dead cells following necrosis and replace necrotic tissue
Macrophages
myelomeningocele
Nerves bulge out with meninges
What is an inherited disease caused by
An inherited genetic abnormality
Acquired disease is caused by
Non-genetic environmental factors
What is hypertrophy
Increase in size of a tissue caused by an increase in size of the constituent cells
What is hyperplasia
Increase in size of a tissue caused by an increase in the number of the constituent cells
What is a congenital disease
Disease present at birth
What is a meningocele
Outpouching of meninges
Polygenic inheritance is the inheritance of….
Many genes
benign prostate hyperplasia
muscle in prostate
What is mixed hypertrophy/hyperplasia
increase in the size of an organ due to increase in size and number of its constituents
Atrophy
Decrease in size of an organ due to decrease in size or number of its constituent cells or both
What is metaplasia
Change in cell differentiation from one fully differentiated type to another fully differentiated type
What is Dysplasia
Morphological changes that may be seen in cells (often epithelium) in the progression on to development of cancer(neoplasia)
Why would skin cells from older people divide less than those from younger people
The telomere region at the end of chromosomes shortens and eventually becomes so short that it is not possible for the chromosomes to divide and replicate so the cell can no longer divide.
Effects of ageing on skin
Wrinkling
Effects of ageing on eyes
Cataracts
Effects of ageing on osteoporosis
Loss of bone matrix
Effects of ageing on brain
Dementia (e.g Alzheimers)
Effects of ageing on muscle
Loss of muscle (sarcopaenia)
Effects of ageing on hearing
Causes deafness
What happens to growth hormone with age
decreased
What happens to testosterone with age
Decreased
What happens to catabolic cytokines with age
Increased
What are catabolic cytokines
Catabolic proinflammatory cytokines play a key role in mediating biochemical changes associated with many pathophysiological states
Where does a basal cell carcinoma invade/ spread to
only invades locally
Cure for basal cell carcinoma
Complete local excision
Cure for leukaemia
systemic chemotherapy
Where do carcinomas spread to
The lymph nodes that drain the site of the carcinoma
Can carcinomas spread through the blood to bone
Yes
Common cancers that commonly spread to the bone
Breast, prostate, lung, thyroid and kidney
What is adjuvant therapy
Extra treatment given after surgical excision
Can micro metastases be present even if a tumour is completely excised
Yes
What is a neoplasm
An abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should
What is the name of the main effector cell in acute inflammation
Neutrophil polymorph
What is the name of the cells that produce collagen in fibrous scarring
Fibroblasts
Example of acute inflammation
Appendicitis
Does granulomatous inflammation occur in Crohn’s disease
Yes
What is granulomatous inflammation
When immune cells clump together and create tiny nodules at the site of the infection or inflammation
Example of a process that is a chronic inflammatory process from its start
Infectious mononucleosis
Example of hyperplasia
Benign prostate enlargement
Examples of apoptosis
Loss of cells from tips of duodenal villi
Loss of cells during embryogenesis
Graft versus host disease
Is a loss of cells from tips of duodenal villi apoptosis
YES
Is a loss of cells during embryogenesis apoptosis
Yes
Is the brain in dementia atrophy?
Yes
Example of necrosis
Renal infarction
Drug that inhibits platelet aggregation
Aspirin
What process is defined by the formation of a solid mass of blood constituents within an intact vascular system during life?
Thrombosis
What is Carcinogenesis
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
What does oncogenesis consist of
Benign and malignant tumours
Does carcinogenesis apply to malignant neoplasms
Yes
What does carcinogenic mean
Cancer causing
What does oncogenic mean
Tumour causing
What is a carcinogen called when it acts on DNA
Mutagenic
What % of cancer risk is environmental
85%
5 Classes of carcinogens
Chemical
Viral
Ionising and non-ionising radiation
Hormones, parasites and mycotoxins
Miscellaneous
Do chemical carcinogens have any common structural features
No
Do chemical carcinogens require metabolic conversion
Yes, from pro-carcinogens to ultimate carcinogens
See Carcinogens PPt for examples of carcinogens
OK
Hormones that can cause cancer
Oestrogen
Anabolic steroids
miscellaneous carcinogens examples
Asbestos
Metals
Host factors for cancer
Ethnicity
Diet / Lifestyle
Constitutional factors - age, gender etc.
Premalignant lesions
Transplacental exposure
Can a carcinoma in situ in a duct spread
No
Can an invasive carcinoma spread
Yes
What is a micro-invasive carcinoma
When the carcinoma only partially invades the basement membrane
What do cancer cells produce
Proteases-matrix metalloproteinases
Collegenase
Cathepsin D
urokinase-type plasminogen activator
Why do cancer cells contain collegenases
To break down collagen in Basement membrane
Cancer spread process
Invades intracellular matrix
Blood vessel
Lymph tissue
Through blood vessel
through more intracellular matrix
Into another cell
Specific process of cancer spread
Invasion of basement membrane
Tumour cell motility
Intravasation
Evasion of host immune defence
Extravasation
Growth at metastatic site
Angiogenesis
What is angiogenesis
Formation of new blood cells
What is intravasation
Entering blood vessel
Where does a tumour in the IVC end up and why
Lung, because blood vessels get smaller here
Where would a tumour of the colon metastasize to
Liver via portal venous system
Is conventional chemotherapy best for fast dividing or slow dividing tumours
Fast dividing
Is conventional chemotherapy selective for tumour cells
No
What is a granuloma
A macrophage collection
What is the name of a malignant tumour of a striated muscle?
rhabdo myo sarcoma
Does liposarcoma commonly metastasise to bone
No
what term describes a cancer that has not invaded through the basement membrane
Carcinoma in situ
What is the name of a benign tumour of glandular epithelium
Adenoma
What is the name of a benign tumour of fat cells
Lipoma
What is the name of a malignant tumour of glandular epithelium
adenocarcinoma
What is a neoplasm
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
What are neoplastic cells derived from
Nucleated cells
Functions of neoplasm stroma
Connective tissue framework
Mechanical support
Nutrition
Why do we classify neoplasms
To determine appropriate treatment
To provide prognostic information
Methods of classification for neoplasms
Behavioural:benign/borderline/malignant
Histogenetic:cell of origin
Features of benign Neoplasms
Localised, non-invasive
Slow growth rate
Low mitotic activity
Close resemblance to normal tissue
Circumscribed or encapsulated
Features of malignant neoplasms
Invasive
Metastases
Rapid growth rate
Variable resemblance to normal tissue
Poorly defined or irregular border
What can neoplasms arise from
Epithelial cells
Connective tissues
Lymphoid/haematopoietic organs
What is a papilloma
Benign tumour of non-glandular, non-secretory epithelium
What is an adenoma
Benign tumour of glandular or secretory epithelium
What is a carcinoma
Malignant tumour of epithelial cells
What does the suffix lipoma suggest
Adipocytes
What does the suffix chondroma suggest
Cartilage
What does the suffix osteoma suggest
Bone
What does the suffix angioma suggest
Vascular
What is rhabdomyoma to do with
Striated muscle
What is leiomyoma to do with
Smooth muscle
What is a neuroma to do with
Nerves
Does a basal cell carcinoma metastasize
Never
Malignant connective tissue neoplasms and their associated cell types
Liposarcoma adipose tissue
Rhabdomyosarcoma striated muscle
Leiomyosarcoma smooth muscle
Chondrosarcoma cartilage
Osteosarcoma bone
Angiosarcoma blood vessels
What does anaplastic mean
The cell-type is unknown
Are all -oma suffixes neoplasms
No
What is a melanoma
Malignant neoplasm of melanocytes
What is a mesothelioma
Malignant neoplasm of mesothelial cells
What is a lymphoma
Malignant neoplasm of lymphoid cells
What does the suffix -oma mean
Neoplasm
TNM classification system for staging of tumours
T = tumour size
N = node involvement
M = metastasis
PL = pleural involvement
R = resection, with R0 being the ideal = fully excised
What does tumour staging allow
allows decision making with regard to follow-up treatment, particularly if there is evidence of metastasis
Therapies for tumours
Biopsy + anti-tumour therapies (molecular signalling pathway inhibitors)
Chemotherapy
Radiotherapy
Surgery
Innate immunity
Instinctive, non-specific, does not depend on lymphocytes, present from birth
Adaptive immunity
Specific ‘Acquired/learned’ immunity, requires lymphocytes, antibodies
What is serum
Plasma without fibrinogen and other clotting factors
What type of immunity are T and B cells used in
Adaptive immunity
What are mast cells used in
Allergic reaction
WHat are natural killer cells used in
Viral + cancer reaction
What type of immunity are macrophages used in
Innate Immunity
What are leukocytes
White blood cells
Modes of action of complement
Direct lysis
Attract more Leukocytes to site of infection
Coat invading organism
What is complement
Group of ~20 serum proteins secreted by the liver that need to be activated during an immune response to be functional
Are immunoglobulins antibodies
YES
Most common immunoglobulin
IgG
What are cytokines
Proteins secreted by immune and non-immune cells controlling the growth and activity of other immune system cells and blood cells
Types of cytokines
Interferons
Interleukins
Colony stimulating factors
Tumour necrosis factors
Chemokines
Examples of physical barriers to disease
Lysozyme in tears
Mucus
cilia
Skin barrier
Fatty acids
Acid(stomach)
pH change
Inflammatory response
Stop bleeding (coagulation)
Acute inflammation (leukocyte recruitment)
Kill pathogens, neutralise toxins, limit pathogen spread
Clear pathogens/dead cells (phagocytosis)
Proliferation of cells to repair damage
Remove blood clot – remodel extracellular matrix
Re-establish normal structure/function of tissue
What is chronic inflammation
Persistent, un-resolved inflammation
Acute inflammation steps
Pathogen is fully eliminated
Resolution of damage
Disappearance of leukocytes
Full regeneration of tissue
What senses microbes in blood
Monocytes
Neutrophils
What senses microbes in tissues
Macrophages
Dendritic cells
Antigen presenting cells examples
Macrophages
Dendritic cells
B cells
What membrane bound immunoglobulins do B cells normally express
IgM
IgD
What is APC
A type of immune cell that boosts immune responses by showing antigens on its surface to other cells of the immune system
Functions of antibodies
Neutralise toxin by binding to it
Increase opsonisation – phagocytosis
Activate complement
What is opsonisation
Marking for phagocytosis
What is pharmacodynamics
How the drug acts on the body
What is pharmacokinetics
What the body does to the drug
What is Physicochemical
How the drugs interact regardless of the condition
What is Physicochemical
How the drugs interact regardless of the condition
Summation
Drugs used together produce the expected result
Synergism
Two drugs together have a greater effect than expected
Antagonism
One drug has a negative effect on the other
Potentiation
One drug is made more potent than the other drug without any alterations to the other drug
Pharmacokinetics acronym:ADME
Adsorption
Distribution
Metabolism
Excretion
What is bioavailability
How much of a drug is available over a period of time
What drug is given in a paracetamol overdose
Activated charcoal
How does activated charcoal help a paracetamol overdose
Paracetamol binds to the charcoal to be excreted
What does INR stand for
International normalised ratio
What does a high INR mean
Blood clots more slowly than desired
Definition of drug
A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body
Pharmacology definition
The branch of medicine concerned with the uses, effects and modes of action of drugs
What is druggability
It describes a biological target that is known to or is predicted to bind with high affinity to a drug
Examples of drug targets
Receptors
Enzymes
Transporters
Ion channels
What is a receptor
A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects
Example of exogenous ligand
Drugs
Example of endogenous ligands
Hormones
Neurotransmitter
Examples of autacoids
Cytokines
Histamine
What is an autacoid
Physiologically active substance (such as serotonin, bradykinin, or angiotensin) that is produced by the body
Types of receptors
Ligand-gated ion channels
G protein coupled receptors
Kinase-linked receptors
Cytosolic/nuclear receptors
Example of cytosolic/nuclear receptor
Steroid receptors
What are ion channels?
Ion channelsare pore-formingmembrane proteinsthat allowionsto pass through the channel pore so that the cell undergoes a shift inelectric chargedistribution
What is the largest and most diverse membrane receptor
G protein coupled receptors (GPCRs)
Alternative name for G proteins
Guanine nucleotide-binding proteins
What are Kinases
Enzymes that catalyse the transfer of phosphate groups between proteins-phosphorylation
How do nuclear receptors work
By modifying gene transcription
Can imbalance of chemical/receptors lead to pathology
Yes
Examples of chemical imbalance leading to pathology
allergy-increased histamine
Parkinson’s-reduced dopamine
Examples of Receptor imbalance leading to pathology
myasthenia gravis; loss of ACh receptors
mastocytosis; increased c-kit receptor
What is an agonist
A compound that binds to a receptor and activates it
What is an antagonist
A compound that reduces the effect of an agonist
What is the two-state model of receptor activation
Describes how drugs activate receptors by inducing or supporting a conformational change in the receptor from “off” to “on”.
What is intrinsic activity/efficiacy
The ability of a drug receptor complex to produce a maximum functional response
What is affinity
Describes how well a ligand binds to the receptor
Do both agonists and antagonists show affinity
Yes
What is efficacy
How well a ligand activates the recptor
What is efficacy
How well a ligand activates the receptor
Do antagonists have efficacy
No
What is receptor reserve
The idea that some agonists needs to activate only a small fraction of the existingreceptors to produce the maximal system response.
Is any receptor response seen for a partial agonist
No
Receptor related factors that govern drug action
Affinity
Efficiacy
Tissue related factors that govern drug action
Receptor number
Signal amplification
What is inverse agonism
When a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist
What is tolerance
Reduction in agonist effect over time due to continuously high concentrations
Is any compound truly ever specific
NO
What is an enzyme inhibitor
A molecule that binds to an enzyme and (normally) decreases its activity
What are the two types of enzyme inhibitors
Irreversible inhibitors
Reversible inhibitors
How do irreversible inhibitors work
Usually react with the enzyme and change it chemically e.g covalent bond formation
How do reversible inhibitors work
Bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme, enzyme substrate complex or both
What is streptokinase
A clot buster
Function of statins
Block the rate limiting step in the cholesterol pathway
What does inhibiting Angiotensin converting enzyme (ACE) do
Reduces ATII production and therefore causes a reduction in blood pressure
Reason for xenobiotic metabolism
generates compounds that are more readily excreted by the body
What are xenobiotics
Are compounds foreign to an organism’s normal biochemistry, such any drug or poison
What does pharmacokinetics give us
Gives us information about how drugs will function at certain doses and for how long
What is bioavailability
The fraction (%) of an administered drug that reaches the systemic circulation
What are CYPs(Cytochrome P450)
Major enzymes involved in drug metabolism
What percentage of metabolism do CYPs account for
75%
Which antigen presenting cell is the best at activating lymphocytes
Dendritic cells
What can monocytes differentiate into
Macrophages
Dendritic cells
What does adrenergic relate to
Adrenaline or noradrenaline and their receptors
What does cholinergic relate to
Acetylcholine and its receptor
Afferent definition
Carries signals towards brain or spinal cord
Efferent definition
Carries signals away from the brain or spinal cord
How many neurons between CNS and skeletal muscle in somatic NS
Single neuron
What does the somatic NS innervate
Skeletal muscle
Does the somatic NS excite or inhibit
Excite
How many neurons are there in the autonomic NS chain
Two
What does the autonomic NS innervate
Smooth muscle
Cardiac muscle
Glands
GI neurons
Does the autonomic NS lead to excitation or inhibition
Both
Is fight or flight sympathetic or parasympathetic
Sympathetic
Is rest or digest parasympathetic or sympathetic
Parasympathetic
What separates the two neurons in the ANS
The autonomic ganglion
Where is the autonomic ganglion in the parasympathetic system
Close to the effector organ
Where is the autonomic ganglion in the sympathetic system
Within a chain adjacent to the spinal cord
Preganglionic neurotransmitter
Acetylcholine
Postganglionic neurotransmitters
Acetylcholine (parasympathetic)
Noradrenaline (sympathetic)
What receptor does acetylcholine act on preganglionic
Nicotinic receptor (sympathetic and parasympathetic)
What receptor does acetylcholine act on postganglionic
Muscarinic receptors (parasympathetic)
What receptors does noradrenaline act on postganglionic
Alpha and beta receptors (sympathetic)
Are muscarinic receptors receptive to drug targeting
Yes
What are the 5 types of muscarinic receptors
M1: Brain
M2: Heart
M3: All organs with parasympathetic innervation
M4: Mainly CNS
M5: Mainly CNS
How do muscarinic receptors activate intracellular processes
Through G-proteins
What does activation of M2 receptors on heart SA node cause
Decrease in heart rate
What does activation of M2 receptors on heart AV node cause
Decrease in conduction velocity
Induces AV node block (Increases PR interval)
M3 Receptors stimulation in respiratory system effects
Produces mucus
Induces smooth muscle contraction (bronchoconstriction)
M3 Receptors stimulation in GI tract effects
Increase saliva production
Increases gut motility
Stimulates biliary secretion
M3 Receptors stimulation in Skin effect
Sweating
Where is the only place the sympathetic system releases ACh
Skin
M3 Receptors stimulation in urinary system effects
Contracts detrusor muscle
Relaxation of internal urethral sphincter
M3 Receptors stimulation in Eye effects
Causes myosis
Increases drainage of aqueous humour
Secretion of tears
What is myosis
Excessive constricting of pupil
What does blockage of normal transmission of ACh lead to
Skeletal muscle weakness-myaesthenia Gravis
What is the precursor of adrenaline and noradrenaline
Dopamine
See Cholinergic and adrenergic PPt for alpha and beta receptor info
OK
What does alpha 1 receptor activation cause
Vasoconstriction (mainly in the skin)
Alpha 2 receptor activation causes..
Mixed effects on vascular smooth muscle
What do alpha 1 blockers do
Lower blood pressure
Where are beta 1 receptors usually found
Heart
Kidney
Fat cells
What does agonism of beta 1 receptors cause
Tachycardia
Increase in stroke volume
Renin release (increase in vascular tone)
Lipolysis and hyperglycaemia
Beta blockers effects
Reduce heart rate
Reduce stroke volume
Reduce myocardial oxygen demand and help remodelling in heart failure or post-myocardial infarction
Examples of naturally occurring opioids
Morphine
Codeine
Opioid antagonist
Naloxone
Synthetic partial agonists for opioids
Buprenorphine
How long does a single dose of morphine last for
3-4 hours
Routes of administration for opioids
Sub-cutaneous
IV
IM (intra-muscular)
What is opium made up of
Morphine and codeine
What drug class are opioids
Class A drugs
How do opioids work
Inhibit the release of pain transmitters at spinal cord and midbrain and modulate pain perception in higher centres
Changes the emotional perception of pain
What does sustained activation by opioids lead to
Tolerance and addiction
What is potency
Whether a drug is ‘strong’ or ‘weak’ relates to how well the drug binds to the receptor,
the binding affinity
What is efficacy
Looking at if it is possible to get a maximal response with the drug or not
Biological definition of tolerance
Down regulation of the receptors with prolonged use
Need higher doses to achieve the same effect
Side effects of opioids
Respiratory Depression
Sedation
Nausea and Vomiting
Constipation
Itching
Immune Suppression
Endocrine Effects
What is morphine metabolised to
Morphine 6 glucuronide
What happens in renal failure (morphine related)
Morphine 6 glucuronide builds up as it isn’t cleared and may cause respiratory distress
What is tramadol
A weak opioid agonist, stronger than codeine
Oral availability for morphine
50%
Type 1 hypersensitivity reaction
Allergy
Primarily IgE dependent
Type 2 hypersensitivity reaction
Primarily IgG-dependent cytotoxicity
Type 3 hypersensitivity reaction
IgG/IgM-dependent immune complex formation
Type 4 hypersensitivity reaction
Delayed type hypersensitivity (DTH)
Cell dependent (Th1/ cytotoxic T cells/macrophages)
Which hypersensitivity reactions are antibody mediated
Type 1-3
What does IgE in type 1 hypersensitivity reaction induce
Mast cell activation
Which hypersensitivity reactions are directed against soluble antigens
1 and 3
Which hypersensitivity reaction is directed at a cell or matrix associated antigen
Type 2
Clinical allergy indications for skin
Swelling
Itching
Reddening
Clinical allergy indications for airways
Anaphylaxis
Excessive mucus production
Bronchoconstriction
Clinical allergy indications for GI
Abdominal bloating
Vomiting
Diarrhoea
What is allergy
Abnormal response to harmless foreign material (allergens)
What is atopy
Tendency to develop allergies
Examples of allergic diseases
Anaphylaxis
Allergic asthma
Allergic rhinitis (hay fever)
Atopic dermatitis
Allergic conjunctivitis
Oral allergy syndrome (food allergy)
Angioedema (not idiopathic)
Cells involved in allergic diseases
Mast cells, eosinophil, basophil
Lymphocytes, dendritic
Epithelial cells
Smooth muscle, fibroblast
Mediators of allergic diseases
Cytokines
Chemokines
Lipids
Small molecules
Low affinity Ige receptor
FceRII
CD23
Function of FceRII, CD23
Regulation of IgE synthesis
Triggering of cytokine release by monocytes
Antigen presentation by cells
3 major cell types that express a high affinity IgE receptor
Eosinophil
Mast cell
Basophil
What is CD117 (c-kit)
Cell surface receptor for Stem Cell Factor
What is the function of stem cell factor
Causes Stem blood cells to change into different types of blood cells
What does histamine cause
Arteriolar dilation
Capillary leakage
How do T cells work
T cells ‘polarise’ according to the threat detected and this determines the nature of the adaptive immune response
What does mast cell activation cause
Production of modulators of IgE synthesis
Anaphylaxis pneumonic (ABCDE)
Airway
Breathing
Circulation
Disability
Exposure
Anaphylaxis cardiovascular effects
Vasodilation
Increased vascular permeability
Lowered BP
Slow Anaphylaxis response
Pain
Vomiting
Gi related etc
Anaphylaxis respiratory effects
Bronchial smooth muscle contraction
Mucus
Anaphylaxis SKin effects
Rash
Swelling
Anaphylaxis biological effect
Mast cell or basophil activation
IgE or direct activation
Serum tryptase and histamine elevated
What is serum tryptase
A marker of mast cell degranulation
Chronic asthma
Non Th2 T cell mechanisms
CD8 (regulatory) T cell eosinophil responses
Function of Xolair(Omalizumab)
Inhibits binding of IgE to High- affinity IgE receptor (FcεRI)
What is omalizumab
Monoclonal antibody
What is IL-5
An interleukin produced by type-2 T helper cells and mast cells
Function of Glucocorticoids
Inhibit gene transcription
What is pavementing
Adhesion of neutrophils to vascular endothelium at site of acute inflammation
What is an adverse drug reaction
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use
What does an adverse drug reaction have to be
Noxious and unintended
What is a side effect
Unintended effect of a drug related to its pharmacological properties and can include unexpected benefits of treatment
What is nephrotoxicity
Damaging or destructive to the kidneys
What is ototoxicity
Has a toxic effect on the ear or its nerve supply
What is dysarthria
A speech disorder
What is ataxia
A lack of muscle coordination
What causes toxic effects of drugs
If the dose is too high
Or if drug excretion is reduced by impaired renal or hepatic function
By interacting with other drugs
patient risk factors for adverse drug reactions
Gender (F>M)
Elderly
Neonates
Polypharmacy (21% 5 or more drugs)
Genetic predisposition
Hypersensitivity/allergies
Hepatic/renal impairment
Adherence problems
Drug risk factors for adverse drug reactions
Steep dose-response curve
Low therapeutic index
Commonly causes ADR’s
Causes for adverse drug reactions
Pharmaceutical variation
Receptor abnormality
Abnormal biological system unmasked by drug
Abnormalities in drug metabolism
Immunological
Drug-drug interactions
Multifactorial
Adverse drug reactions (ABCDEF)
Type A (Augmented pharmacological)
Type B (Bizarre or idiosyncratic)
Type C (Chronic)
Type D (Delayed)
Type E (End of treatment)
Type F (Failure of therapy)
Most common drugs to have ADR
Antibiotics
Anti-neoplastics
Cardiovascular drugs
Hypoglycaemics
NSAIDS
CNS drugs
Common ADRs
Confusion
Nausea
Balance problems
Diarrhoea
Constipation
Hypotension
What does the yellow card scheme do
Collects spontaneous reports of ADRs
Collects suspected adverse drug reactions
Is the yellow card scheme a voluntary reporting scheme
Yes
What does the black triangle mean on a yellow card scheme
It indicates that a medicine is undergoing additional monitoring
Information that must be included on a yellow card report
Suspected drug(s)
Suspect reaction(s)
Patient details
Reporter details
Additional useful information
Is hypersensitivity caused by immunologic or non-immunologic mechansism
Both
What is cytopenia
When one or more of your blood cell types is lower than it should be
What is angioedema
Swelling underneath the skin
What happens in a type 2 hypersensitivity reaction
Drug or metabolite combines with a protein
Protein gets treated as foreign and the body forms antibodies (IgG, IgM)
Antibodies combine with antigen and complement activation damages the cells
Type 3 hypersensitivity process
Antigen and antibody form large complexes and activate complement
Small blood vessels are damaged or blocked
Leucocytes attracted to the site of reaction and release pharmacologically active substances leading to an inflammatory process
Type 4 hypersensitivity process
Antigen specific receptors develop on T-lymphocytes
Subsequent admin, adminstration leads to local or tissue allergic reaction
What are the effects of adrenaline
Vasoconstriction
Stimulation of Beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart
Reduces oedema and bronchodilates via beta2-adrenoceptors
Attenuates further release of mediators from mast cells and basophils by increasing intracellular c-AMP and so reducing the release of inflammatory mediators
Function of vasoconstriction
Vasoconstriction- increase in peripheral vascular resistance, increased BP and coronary perfusion via alpha1-adrenoceptors
What is a commensal
An organism which colonises the host but causes no disease in normal circumstances
What is an opportunist pathogen
Microbe that only causes disease if host defences are compromised
What is virulence/pathogenicity
The degree to which a given organism is pathogenic
What is asymptomatic carriage
When a pathogen is carried harmlessly at a tissue site where it causes no disease
What is a pathogen
Organism that causes or is capable of causing disease
What are small round bacteria called
Cocci
What are rod shaped bacteria called
Bacilli
What are bacteria if they stain red
Gram negative
What are bacteria if they stain blue
Gram positive
Example of bacteria that don’t stain with Gram stain
Tb which is mycobacteria
What stain stains Tb
Ziehl-Neelsen stain
What structure do gram negative bacteria have that isnt in gram positive bacteria
Lipopolysaccharide(endotoxin)
What does Lipopolysaccharide(endotoxin) contain
Terminal sugars
O antigen
Lipid A
BActeria environment (temp, Ph)
-80C to 80C
Ph:4-9
What is an endotoxin
Component of the outer membrane of bacteria, eg lipopolysaccharide in Gram negative bacteria
What is exotoxin
Secreted proteins of Gram positive and Gram-negative bacteria
See endotoxin and exotoxin table in bacteria as causes PPT
OK
Typical bacterial chromosome base number
Typically 2-4 x 10*3 kb
Can plasmids be transferred between bacteria
Yes
Mutation causes for genetic variation in bacteria
Base substitution
Deletion
Insertion
Gene transfer causes for genetic variation in bacteria
Transformation eg via plasmid
Transduction eg via phage
Conjugation eg via sex pilus
What is conjugation
The process by which one bacterium transfers genetic material to another through direct contact
What is transduction
The process by which a virus transfers genetic material from one bacterium to another
What is transformation
The process by which an organism acquires exogenous DNA from its natural environment
Examples of Gram positive cocci
Streptococci
Staphylococcci
Features of gram positive cocci
Thick cell wall
What is staphylococcus aureus
Gram positive cocci in clusters
What is coagulase
An enzyme produced by bacteria that clots blood plasma
Is Staphylococcus aureus coagulase positive
Yes
Why is coagulase important
Forms a fibrin clot around bacteria and may protect it from phagocytosis
Example of coagulase negative bacteria
Staphylococcus epidermis
S.saprophyticus
Normal habitat of staphylococcus
Nose and skin
Main virulence factor of s.epidermis
Ability to form persistent biofilms
What is alpha haemolysis due to
Due to the production of hydrogen peroxide, which reacts with haemoglobin to form the green compound met-haemoglobin
What is beta haemolysis due to
It is due to the production of two pore-forming toxins – streptolysin O and S. Streptolysin O which is oxygen sensitive and is very antigenic
Function of streptokinase
Breaks down clots
Function of Streptolysins O&S
binds cholesterol
Function of M protein
Surface protein that encourages complement degredation
What is a pathogen’s ability to infect or damage its host tissues determined by
Virulence factors
What are virulence factors
The molecules that assist the bacterium to colonize the host at the cellular level
What does C.tetani cause
Tetanus
What does c.botulinum cause
Botulism
What does C.difficile cause
antibiotic associated diarrhea
pseudomembranous colitis
Examples of anaerobic Gram positive bacilli
C.tetani
C.Botulinum
C.Difficile
Examples of aerobic Gram positive bacilli
Listeria monocytogenes
Bacillus anthracis
Corynebacterium diphtheriae
What is an epitope
The part of an antigen to which the antibody attaches itself
2 main examples of mycobacteria
TB
Leprosy
What is mycobacteria
Aerobic, non-spore forming, non-mobile bacilli
What stain is used for mycobacteria
Ziehl-Neelsen stain
Acid fast bacteria stain red
Non-acid fast stains blue
Why is Mycobacteria resistant to Gram stain
Its cell wall has a high lipid content with mycolic acids
Are mycobacteria fast or slow growing
Slow growing
Primary tuberculosis
Initial contact made by alveolar macrophages
Bacilli taken in lymphatics to hilar lymph nodes
Latent tuberculosis info
Cell mediated immune response from T-cells
Primary infection is contained but Cell mediated immunity persistss
What happens in pulmonary tuberculosis
Granuloma forms around Bacilli that have settled in the apex
In apex of the lung there is more air and less blood supply so less white blood cells
Necrosis results in abscess forming and caseous material coughed up
What does miliary mean
Accompanied by a rash with lesions
How does TB affect us
Aerosol transmission
Primary TB in lung
Latent TB can remain for decades
Can spread beyond lungs
What is a virus
An infectious, obligate intracellular parasite comprising genetic material (DNA or RNA) surrounded by a protein coat and/or a membrane
What does obligate intracellular mean
Totally dependent on living cells for their replication and existence
Shapes of viruses
Helical
Icosahedral
Complex
Enveloped
Non-enveloped
What are viruses called when not insde an infected cell
Virions
Examples of non enveloped viruses
Adenovirus
Parvovirus
Examples of enveloped viruses
Influenza
HIV
How do viruses replicate
Attachment to specific receptor
Cell entry(uncoating of virion within cell)
Host cell interaction + replication
Assembly of virion
Release of new virus particles
What happens in host cell interaction+ replication
Migration of genome to cell nucleus
Transcription to mRNA using host materials
Translation of viral mRNA to produce structural proteins, viral genome and non-structural proteins e.g enzymes
How do viruses cause disease
Direct destruction of host cells
Modification of host cell
Over reactivity of immune system
Damage through cell proliferation (when viruses burst out of cell)
Evasion of host defences
Example of a virus that causes direct destruction of host cells
Poliovirus
Example of virus that causes modification of the host cell
Rotavirus (atrophies villi and flattens epithelial cells)
Example of viruses that causes over-reactivity of immune system
Hepatitis B
SARS-CoV-2
Example of virus that causes damage through cell proliferation
Human papillomavirus (causes cervical cancer)
why do viruses vary wildly in the range of clinical syndromes they can cause
Due to different host cells and tissues that they can infect
Different methods of interaction with the host cell
Two types of immunity
Active
Passive
Two types of active immunity
Cell-mediated immunity
Antibody-mediated immunity
What are the 5 types of immunoglobulin
G,M,A,D and E
Is passive immunity temporary
Yes
What is passive immunity
Protection provided from the transfer of antibodies from immune individuals
Examples of passive immunity
Cross-placental transfer of antibodies from mother to child
Transfusion of blood or blood products including immunoglobulin
What are vaccines made from
Inactivated (killed) (e.g. pertussis, inactivated polio)
Attenuated live organisms (e.g. yellow fever, MMR, polio, BCG)
Secreted products (e.g. tetanus, diphtheria toxoids)
The constituents of cell walls/subunits (e.g. Hep B) or
Recombinant components (experimental)
Function of vaccination
Stimulates immune response and memory to a specific antigen/infection
What is primary vaccine failure
When a person does not develop immunity from the vaccine
What is secondary vaccine failure
When a person’s immune system initially responds but protection wanes over time
5 major groups of protazoa
Flagellates
Amoebae
Microsporidia
Sporozoa
Cilliates
Example of flagellate protazoa diseases
African Trypanosomiasis (AKA sleeping sickness)
American Trypanosomiasis (Chagas disease)
Leishmaniasis
Giardiasis
Trichomonas vaginalis
African trypanosomiasis symptoms
Chancre
Flu like symptoms
CNS involvement(sleepy, confusion, personality change)
Coma and death
How is African trypanosomiasis diagnosed
On blood film or CSF
Acute symptom of American Trypanosomiasis
Flu like symptoms
Chronic symptoms of American Trypanosomiasis
Cardiomyopathy
Megaoesophagus
Megacolon
3 clinical pictures of Leishmaniasis
Cutaneous
Mucocutaneous
Visceral
What does Cutaneous and mucocutaneous Leishmaniasis cause
Ulceration and destruction
Symptoms of visceral Leishmaniasis
Fever
Weight loss
Massive splenomegaly
Hepatomegaly
Anaemia
High fatality without treatment
Symptoms of giardasis
Diarrhoea
Cramps
Bloating
Flatulence
How is giardasis treated
metronidazole
Examples of amoebae diseases
Amoebiasis
Symptoms of amoebiasis
Dysentry
Colitis
Liver and lung abcesses
How is Amoebiais spread
Faeco-oral
How is amoebiasis treated
Metronidazole
Examples of sporozoa diseases
Cryptosporidiosis
Toxoplasmosis
Malaria
If someone has a fever and has travelled recently what disease are they likely to have
Malaria
Symptoms of Cryptosporidiosis
Diarrhoea (Watery, no blood)
Vomiting
Fever
Weight loss
When is Cryptosporidiosis severe
In the immunocompromised
5 species of anopheles mosquitos that cause malaria
Plasmodium falciparum
Plasmodium ovale
Plasmodium vivax
Plasmodium malariae
Plasmodium knowlesi
How do you test for malaria
Blood film!!
Signs of malaria
Anaemia
Jaundice
Hepatosplenomegaly
‘Black Water Fever’
Fever symptoms
Stages of malaria
Mosquito bite
Abdominal pain
Cyclical fever
Hameolysis
What does haemolysis cause
Anaemia
Jaundice
Haemoglobinuria
What does P.Falciparum cause
Obstructed microcirculation> complicated malaria
Cerebral malaria symptoms
Drowsy
Increased intracranial pressure
Seizures
Coma
What is complicated malaria
When particular organs are seen to be compromised
What is acute respiratory distress syndrome
A life-threatening condition where the lungs cannot provide the body’s vital organs with enough oxygen
Symptoms of complicated malaria
Cerebral malaria
ARDS
Renal failure
Bleeding
Shock
Malaria treatment
IV artesunate
IV quinine + doxycycline
Supportive measures for different aspects of complicated malaria
Cerebral: antiepileptics
ARDS: oxygen, diuretics, ventilation
Renal failure: fluids, dialysis
Sepsis: broad spectrum antibiotics
Bleeding/Anaemia: blood products
Exchange transfusion if huge parasite burden
What is used to treat acute infection
Broad spectrum antibiotics
Chloroquine
Primiquine to kill hypnozoites
What happens in malaria relapse
P. ovale and vivax can form hypnozoites in the liver
How to eliminate hypnozoites
Primiquine
Key attributes of pathogens
Infectivity
Virulence
Invasiveness
What is infectivity
The ability to become established in host, can involve adherence and immune escape
What is virulence
The ability to cause disease once established
What is invasiveness
The capacity to penetrate mucosal surfaces to reach normally sterile sites
Four stages of pathogenesis
Exposure (contact)
Adhesion (colonisation)
Invasion
Infection
5 groups of agents that cause infectious disease
Viruses
Bacteria
Fungi
Protozoa
Helminths (worms)
Do viral infections need rapid cell entry
Yes
What response do viral infections elicit
Humoral (antibody mediated) response
And cell mediated response
Viral infection humoral response
Antibodies (IgG, A, M) -Block binding, Block virus host cell fusion, are involved in opsonisation
IgM-Agglutinates particles
Complement-Opsonisation, lysis
What cells does influenza/RSV virus affect
Respiratory epithelium
What cells does Varicella Zoster virus affect
Skin cells
What cells does Yellow Fever virus affect
Liver cells
What cells does HIV affect
T helper cells
What is viral evasion
The process by whichviruses evadethe immune system and interferes with specific or non-specific defence
What is antigenic drift
Spontaneous mutations, occur gradually giving minor changes in HA (haemagglutinin) and NA (neuraminidase). Epidemics.
What is antigenic shift
Sudden emergence of new subtype different to that of preceding virus. Pandemics.
How does a bacterial infection enter a host
Respiratory tract
Gastrointestinal tract
Genitourinary tract
Skin/mucous membrane break
What response does a bacterial infection elicit
An antibody response unless intracellular bacteria which causes cell-mediated immunity response
Function of ahesins
Help bacteria bind to mucosal surfaces
Types of adhesins
Fimbriae and pili filamentous proteins e.g. Neisseria gonorrhoeae
Non fimbrial proteins e.g. Fibronectin binding protein of Treponema pallidum
Lipid e.g. lipid teichoic acid of Streptococcus pyogenes
Glycosaminoglycans of Chalmydia sp.
Complement function in bacterial infection
Cell lysis
Prevents proliferation
What is delayed type hypersensitivity
An immune response that occurs through direct action of sensitized Tcellswhen stimulated by contact with antigen
What is an antibiotic
A molecule that works by binding to a target site on a bacteria
Examples of beta lactams
Penicillins
Cephalosporins
Carbapenems
Monobactams
What do penicillin drugs end in
-illin
Function of beta lactam antibiotics
Disrupt peptidoglycan production by binding covalently to penicillin binding proteins
Cell wall is disrupted and lysis occurs
What type of bacteria is more succeptible to beta lactams
Gram positive
What causes the difference in activity of beta lactam antibiotics
Due to different affinities for different penicillin binding proteins
Are penicillins ineffective in the treatment of intracellular pathogens
Yes
What is the minimum inhibitory concentration
The amount of antibiotic needed to inhibit bacterial growth
What are the two major determinants of antibacterial effects
Concentration and the time the antibiotic remains on the binding sites
Antibiotics use in the body
Its release from the dosage form;
Its absorption from the site of administration into the bloodstream;
Its distribution to various parts of the body, including the site of action
Its rate of elimination from the body via metabolism (LIVER) or excretion (KIDNEY) of unchanged drug.
What enzyme hydrolyses the beta lactam ring of penicillins and cephalosproins
Beta lactamase
What is MRSA
Methicillin resistant Staphylococcus aureus
What is MRSA resistant to
B-lactam antibiotics
Methicillin=flucloxacillin
What are the two main ways antibiotics can be administered
Intravenously
Orally
What factors are considered when deciding if an antibiotic is safe to prescribe
Intolerance, allergy and anaphylaxis
Side effects
Age
Renal and Liver function
Pregnancy and breast feeding
Drug interactions
Risk of Clostridium difficile
What is the cell wall also known as
Peptidoglycan
Why are cephalosporins usually used
Good for people with penicillin allergy
Work against some resistant bacteria
Get into different parts of the body e.g. meningitis
What is known as a simple cell wall weapon
Beta-lactams
When are IV Vancomycin and Teicoplanin used
For gram positive bacteria resistant to beta-lactams
Or due to a penicillin allergy
Examples of gram-positive bacteria resistant to beta lactams
MRSA
Enterococci
Some coagulation negative staph
5 types of bacteria weapons
Inhibitors of cell wall synthesis
Inhibitors of protein synthesis
Inhibitors of nucleic acid synthesis
Anti-metabolites
Inhibitors of membrane function
What do Macrolides affect
Protein synthesis
Mainly for gram positive bacteria(S. aureus, β haemolytic strep)
Examples of Macrolides
Clarithromycin
Erythromycin
Both oral and IV
What drugs affect bacteria protein synthesis
Macrolides
Lincosamides
Tetracyclines
Example of Lincosamide
Clindamycin (oral & IV)
Example of tetracycline
Doxycycline(oral)
Do gram positive bacteria have a thick or thin cell wall
Thick cell wall
Do gram negative bacteria have a thick or thin wall
Thin cell wall
Chickenpox virus name
Varicella Zoster virus
What is prmary infection of varicella zoster virus called
Varicella (chickenpox)
What is secondary reactivation of varicella zoster virus called
Herpes zoster (shingles)
Who is chickenpox serious in
Immunocompromised and patients who have had transplants
Adults
Pregnant women
Smokers
Infants
Who is shingles most common in
The elderly
Process of aquiring sihingles
Primary infection-widespread chickenpox
Viral dormancy in dorsal root or cerebral ganglion
Localised reactivation-shingles
What are the two forms of fungi
Yeast-single cell that divide via budding
Moulds- form multicellular hyphae or spores
What is the cell wall of fungi made up of
Chitin and glucan
What do antifungal drugs target
Cell wall
Plasma membrane
What is the suffix for drugs used generally to treat fungi
-azole drugs
Two common fungal infections
Candida albicans
Aspergillus fumigatus
What does Candida albicans cause
Vaginal and oral infections
Sepsis(candidiasis)
Line/catheter infections
Does candida albicans kill quickly or slowly
Rapidly
What does Aspergillus fumigatus cause
Mainly lung infections
Allergic disease
Does aspergillus fumigatus kill quickly or slowly
Slowly
What type of virus is HIV
A retrovirus (RNA virus)
How does HIV get its DNA into an infected cell
It uses reverse transcriptase to make a DNA copy that becomes integrated into the DNA of the infected cell
What does HIV infect
CD4+ T cells and macrophages
How is HIV transmitted
Via bodily fluids
What are Highly acting anti-retroviral therapies (HAART) used for
HIV infection
What are direct acting antivirals (DAA) used for
Hepatitis C infection
What does HIV being a retrovirus mean
It encodes a reverse transcriptase for an extra life cycle step where RNA is transcribed into DNA, a protease and integrase
Slow dividing tumours
Lung
Colon
Breast
