PED2006 EXAM PRACTICE Flashcards
What is bacterial conjugation
genetic transfer between bacteria that involves direct cell-to-cell contact
how does antibiotic resistance spread
transfer of genetic material through bacterial conjugation
what are the four steps in the conjugation process
formation of pilus
mating pair formation
transfer of plasmid DNA
separation
what happens during the formation of pilus
the donor bacterium, which contains a conjugative plasmid, extends a hair like appendage called a pilus
the pilus attaches to the surface of the recipient bacterium, forming a connection between the two cells
what happens during mating pair formation
the pilus retracts, bringing the two bacteria into close contact
a mating bridge forms between the cells, allowing the transfer of genetic material
what happens during the transfer of plasmid DNA
the conjugative plasmid in the donor cells is nicked at a specific site called the origin of transfer
one strand of the plasmid DNA is transferred to the recipient cell through the mating bridge
the single stranded DNA in both the donor and recipient cells is replicated to form double stranded plasmids
what happens during separation
after the transfer is complex, the mating bridge dissassembles, and the two bacteria separation
both the donor and recipient cells now contain the plasmid
what is required for antimicrobial resistance spread
presence of resistance genes
horizontal gene transfer
proliferation of resistance bacteria
what is horizontal gene transfer
conjugations allows for the horizontal transfer of R plasmids between bacteria, which can occur when between different species
this means that a non-resistant bacterium can quickly acquire resistance genes from a resistant donor
how does proliferation of resistant bacteria occur
once a bacterium acquire a resistance plasmid, it can survive and proliferate in the presence of antibiotics
these bacteria can further transfer the plasmid to other bacteria, spreading the resistance genes within and between bacterial populations
what are the clinical implications of the spread of antimicrobial resistance
the spread to antibiotic resistance genes through conjugations can lead to the emergence of multi-drug resistant bacterial strain
this poses a significant challenge for treating bacterial infections, as standard antibiotics become ineffective, necessitating the use of more potent and often more toxic alternatives
what are fluoroquinolone
a class of broad-spectrum antibiotics that are effective against a variety of gram positive and gram negative bacteria. they exert their antibacterial effects by targeting bacterial DNA replication and transcription
what is the mechanism of actions of fluoroquinolone
inhibitions of DNA gyrase
inhibition of topoisomerase 4
what is the functions of DNA gyrase
in bacteria, DNA gyrase is an essential enzyme that introduces negative supercoils into DNA. this is critical for the replication and transcription processes as it prevents the DNA helix from becoming overall tangles and allows it to unwind
what is the action of fluoroquinolone
bind to the DNA gyrase-DNA complex, stabilising the enzyme-DNA interaction. this prevents the enzymes from resealing the DNA double strands after they have been cut to relieve the torsional strain
why is the inhibition of DNA gyrase important
the interruption of this process leads to the accumulation of double stranded DNA breaks, which ultimately results in bacterial cell death
what is the function of topoisomerase 4
this enzyme is involved in the separation of interlinked daughter DNA molecules following DNA replication. it is crucial for proper cell division
how do fluoroquinolone impact toposimerase 4
fluoroquinolone interferes with the activity of topoisomerase 4 by stabilising the cleavage complex that the enzyme forms with DNA
why is inhibition of topoisomerase 4 beneficial
this action prevents the segregation of replicated chromosomal DNA into daughter cells, thereby inhibition of bacterial cell division and leading to cell death
what are the benefits of fluoroquinolone
broad spectrum so effective against a wide range of bacteria
bactericidal effect - they kill bacteria due to irreversible damage they cause to bacterial DNA
drawback of fluoroquinolone
resistant mutations can develop in the genes encoding DNA gyrase and toposimerase 4, which are prevent in various bacterial species
what is the posterior lobe of the pituitary gland
the posterior lobe of the pituitary gland plays a crucial role in the regulation of various physiological processes
what is the location of the posterior lobe
the posterior lobes is located at the base of the brain, attached to the hypothalamus by the pituitary stalk
what is the hypothalamic hypophyseal tract
the axons of neurone from the supraoptic and paraventricular nuclei of the hypothalamus extend down through the pituitary stalk into the posterior lobe. these neuron’s synthesise hormone and transport them along their axons to be stored and released from the posterior pituitary
what is the function of the posterior pituitary
store and release ADH and oxytocin produced by the hypothalamus
where is ADH synthesised
synthesised by the supraoptic nuclei of the hypothalamus
how is ADH released
ADH is transported down the axons of the hypothalamic neurone to the posterior pituitary, where it is stored in vesicles and released into the bloodstream in response to specific physiological triggers
what is the functions of ADH
ADH primarily acts on the kidneys to promote water reabsorption in the collecting ducts, which helps to regulate the body’s water balance and maintain blood pressure. it also has vasoconstrictive effects on blood vessels, contributing to the blood pressure regulation
where is oxytocin synthesised
oxytocin is synthesised in the paraventricular nuclei of the hypothalamus
how is oxytocin released
oxytocin is transported along the axons to the posterior pituitary where it is stored and released into the bloodstream upon appropriate stimulation
what is the function of oxytocin
labor and deliver - it stimulate uterine contractions during childbirth
lactation - it triggers milk ejections from the mammory glands in response to suckling
social and emotional bonding - oxytocin is also involved in behaviours related to bonding, social recognitions and emotional regulation
what is an ADH agonist, such as desmopressin
mimics the action of natural ADH and are primary used to treat conditions like diabetes insipdus and nocturnal enuresis by promoting water reabsorption in the kidneys. their action is particularly significant in the juxtamedullary nephrons, which play a crucial role in the concentration of urine
what is the anatomy of juxtamedullary nephrons
juxtamedullary nephrons are located near the border of the renal cortex and medulla. they have long loops of hence that extend deep into the medulla, which is essential for concentrating urine
what is the functions of juxtamedullary nephrons
these nephrons are key in creating the osmotic gradient in the medulla necessary for water reabsorption
what is desmopressin
is a synthetic analogue of ADH with a longer duration of action and selective V2 receptor activity, which enhances its antiduiretic effects with minimal vasoconstrictive effects
what is the relationship between V2 receptors and desmopressin
desmopressin selectively binds to V2 receptors located on the basolateral membrane of the principal cells in the collecting ducts and distal convoluted tubules of the nephrons
what is the relationship between juxtamedullary nephrons and desmopressin
juxtamedullary nephrons have a high density of V2 receptors, making them particularly response to ADH and its agonists
how does desmopressin activate the cAMP pathway
upon binding to V2 receptors, desmopressin activate adenylate cyclase, increasing the intracellular concentration of cyclic adenosine monophosphate
cAMP acts as a second messenger to activate protein kinase A
how does desmopressin trigger the insertion of aquaporin 2 channels
PKA phosphorylation targets proteins that facilitate the translocation of aqauporin 2 water channels to the apical membrane of the principal cells
what are aquaporin 2 channels
the channels allow water to move from the lumen of the collecting ducts into the cells
how do aquaporin2 channels affect water reabsorption
water is reabsorbed from the filtrate in the collecting ducts back into the surrounding interstitial space and then into the bloodstream, effectively reducing urine volume and concentrating the urine
how do the juxtamedullary nephrons affect the medullary osmotic gradients
the juxtamedullary nephrons long loops of henle maintain a high osmolarity in the renal medullar, which facilitates water reabsorption
how does desmopressin affect the medullary osmotic gradient
desmopressin enhances the ability of the kidneys to reabsorb water by increasing the osmotic gradient
what are the clinical applications of desmopressin
diabetes inspidus
nocturnal enuresis
haemophilia A and von willebrands disease
how can desmopressin be used to treat diabetes insipid
desmopressin is used to manage central diabetes inspidus by replacing deficient ADH, thus reducing excessive urination and thirst
how can desmopressin help nocturnal enuresis
it helps manage bedwetting by reducing nighttime urine production
how can desmopressin help haemophilia A and von willebrands disease
desmopressin is also used to increase the levels of clotting factors in these bleeding disorders
what are the side effects of desmopressin
hyponatremia - due to increase water reabsorption, there is a risk of dilution hyponatremia, where the blood sodium levels become too low
headache - caused due to changes in water balance
nausea and abdominal pain
state the hormones released by the posterior pituitary
ADH
oxytocin
what is the functions of ADH
ADH primarily regulates water balance in the body by increase water reabsorption in the kidneys, thereby reducing urine output. it also has vasoconstrictive properties, which help to increase blood pressure
how is ADH regulated
ADH release is stimulated by increased plasma osmolarity and by a decrease in blood volume or blood pressure
what is the role of oxytocin
oxytocin plays a crucial role in childbirth and lactation. it stimulates uterine contractions during labor and helps with milk ejections reflex during breastfeeding. additional, oxytocin is involved in social bonding and emotional responses
how is oxytocin regulated
oxytocin release is triggered by the distension of the cervix and vagina during labor and by suckling at the breast during breastfeeding. it can be influenced by emotional and social stimuli
give an example of a beta 2 adrenergic agonists
albuterol
how does albuterol work
albuterol binds to and activates beta2 adrenergic receptors on the smooth muscle cells lining in the airways
activation of these receptors stimulates the enzyme adenylate cyclase, which converts ATP to cyclic AMP
increased levels of cAMP activates protein kinase A, which in turns phosphorylates and inactivates myosin light chain kinase. this leads to relaxation of the smooth muscle cells and bronchodilator
what is the effect of albuterol
the rapid relaxation of bronchial smooth muscle results in the widening of the airways, making it easier to breathe and providing quick relief from acute asthma symptoms
when to use albuterol
used as a first line treatment for acute asthma attacks due to their rapid onset of action
what are the side effects of albuterol
tremors
tachycardia
palpitations
nervousness
hypokalaemia
give an example of anticholinergics
ipratropium bromide
how does ipratropium bromide work
ipratropium bromide competitively inhibits muscarinic cholinergic receptors on bronchial smooth muscle
by blocking these receptors, ipratropium prevents acetylcholine from binding to them
the inhibitions of acetylcholine binding reduces the intracellular levels of calcium, which is necessary for smooth muscle contractions
this leads to the relaxation of the bronchial smooth muscle and bronchodilation
what is the effects of ipratropium bromide
ipratropium provides bronchodilator and helps in reducing mucus secretion, improving airflow and reducing the symptoms of an acute asthma attack
what is ipratropium bromide used for
often used in combination with beta2 agonists during acute asthma attacks for a synergistic effect, especially in patients who do not respond adequately to beta2 agonists alone
what are the side effects of ipratropium bromide
dry mouth
throat irritations
cough
urinary retention and increase intraocular pressure
what is pain
pain is a subjective, unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms such as damage
what are the types of pain
acute or chronic
somatic
visceral
neuropathic
psychogenic
what is the function of pain
protective mechanism, pain serves as a warning signal for potential or actual damage, prompting individuals to withdraw from harmful situations and seek treatment
what is nociceptions
is the neural process of encoding and processing noxious stimuli. it involves the detections of harmful stimuli and the transmission of signals to the central nervous system
what are nociceptors
specialised sensory receptors that respond to potentially damaging mechanical, thermal and chemical stimuli
what is the transmission pathway of nociception
transduction - noxious stimuli are converted into electrical signals by nociceptors
transmission - these elctrical signals are transmitted via peripheral nerves to the spinal cord and then to the brain
perception and modulation - once the signals reach the brain, they are processed and can result in the perception of pain. the brain can also modulate the signals, altering the perception of pain through various mechanisms
what is the function of nociception
is essential for detecting harmful stimuli and initiating protective reflexes, such as withdrawal from the source of harm
what are opioid receptors
opioid receptors are a group of g-protein coupled receptors that mediate the effects of opioid drugs. there are 3 primary types of opioid receptors: mu, kappa and delta receptors. each receptor type has distinct roles and is involved in various physiological effects of opioids
what is the role of mu opioid receptors
analgesia, euphoria and reward, respiratory depression, sedation, gastrointestinal effects, physical dependence
what are the examples of mu opioid receptor drugs
morphine
fentanyl
methadone
oxycodone
heroin
what is the role of kappa opioid receptors
analgesia
dysphoria and hallucinations
diuresis
sedation
what are the examples of kappa opioid receptor drugs
butorphanol
nalbuphine
pentazocine
dynorphins
what is the role of delta opioid receptor
analgesia
mood regulation
neuroprotections
respiratory function
what are the examples of delta opioid receptor drugs
deltorphins
enkephalins
what is morphine
is a potent opioid analgesic that is widely used for the management of moderate to severe pain. it acts primarily on the central nervous system and the gastrointestinal tract
how does morphine induce analgesia
morphine exerts its analgesic effects by binding to and activating mu opioid receptors in the CNS, particularly in the brain and spinal cord. this activation inhibits the release of neurotransmission such as substance p and glutamate, which are involved in the transmission of pain signals
how does morphine induce sedation
by activating mu opioid receptors in the brains reward pathways, morphine induces a feeling of euphoria. it also depresses the central nervous system, leading to sedation
how does morphine induce respiratory depression
morphien depresses the brainstems respiratory centres by reducing the responsiveness of these centres to carbon dioxides. this action is mediated by mu opioid receptors. this can lead to decreased respiratory rate and volume
how does morphine cause antitussive effects
morphine suppresses the cough reflex by acting on the cough centre in the medulla
how does morphine cause gastrointestinal effects
morphine increases the tone of the smooth muscle in the GI tract while decreasing peristalsis by binding to opioid receptors in the enteric nervous system
how does morphine cause miosis
morphine stimulates the parasympathetic nervous system, resulting in the constriction of the pupils
how does morphine cause cardiovascular effects
morphine can cause peripheral vasodilation by releasing histamine and depressing the vasomotor centre in the brain. this can lead to decreased systemic vascular resistance and a drop in blood pressure
what are the effects of morphine inducing histamine release
morphine can induce the release of histamine from mast cells. this can cause pruritic, urticaria, and in some cases bronchoconstriction and vasodilation, leading to hypotension
what is schizophrenia
schizophrenia is a complex and multifactorial psychiatric disorder characterised by a range of symptoms, including delusions, hallucinations, disorganised thinking and impaired social functioning
what is the dopamine hypothesis for schizophrenia
overactivity in mesolimbic pathway -
under activity of the mesocortial pathway
what is the effect of overactivity in the mesolimbic pathway
excessive dopamine activity in the mesolimbic pathway is associated with positive symptoms e.g. hallucinations and delusions
what is the effects of under activity in mesocortiyal pathway
reduced dopamine activity in the mesocortical pathway is linked to negative symptoms e.g. anhedonia, social withdrawal and cognitive deficits
what is the glutamate hypothesis for schizophrenia
NMDA receptor hypofunction - dysfunction of the NMDA-type glutamate receptors contribute to symptoms of schizophrenia. reducing glutamate signalling can affect various neural circuits, leading to both positive and negative symptoms
what is the serotonin hypothesis for schizophrenia
5-HT2A receptor involvement - altered serotonin activity, particularly through 5-HT2A receptors, plays a role in modulating dopamine release and can contribute to the symptoms of schizophrenia
what are the structural brain abnormalities associated with schizophrenia
enlarged ventricles - indicating loss of brain tissue
cortical thinning - reducing in grey matter volume
hippocampal abnormalities - associated with cognitive impairments and memory deficits
what are the functional brain abnormalities associated with schizophrenia
hypofrontality - reduced activity in the prefrontal cortex during tasks requiring executive function and working memory
default mode network dysregulation - abnormal connectivity and activity in the DMN, which is involved in self-referential thought and resting state in the brain
what are the genetic and environmental factors associated with schizophrenia
genetic predisposition - schizophrenia has a significant genetic components, with a higher risk among first degree relatives
environmental triggers - prenatal exposure to infections, malnutrition, stress and psychological factors
what are neuroleptics
neuroleptics are the main stay of pharmacological treatment for schizophrenia. they are primarily classified into two categories - typical and atypical
what is the mechanism of action of typical antipyschotics
dopamine D2 receptor antagonism - these drugs primarily block dopamine D2 receptors, reducing dopamine activity in the brain, particularly in the mesolimbic pathway
what are the examples of typical antipsychotics
haloperidol, chlorpromazine
what are the effects of typical antipsychotics
reduction of positive symptoms - effective in alleviating hallucinations and delusions
what are the side effects of typical antipsychotics
extrapyramidal symptoms such as dystonia, parkinsonism, and tardive dyskinesia due to dopamine blockage
what is the mechanism of action of atypical antipsychotics
these drugs block both dopamine D2 and serotonin 5-HT2A receptors, providing a more balanced effect on neurotransmitters
what are the examples of atypical antipsychotics
risperidone, olanzapine, quetiapine, clozapine
what are the effects of atypical antipsychotics
reducing of positive and negative symptoms - more than typical
what are the side effects of atypical antipsychotics
lower risk of EPS but may cause metabolic side effects such as weight gain, diabetes and dyslipidaemia
what are glucocorticoid receptors
type of nuclear receptor that upon binding with glucocorticoids, acts as a transcription factor to regulate gene expression
what in the resting state of glucocorticoids
in the absence of glucocorticoids, the GR resides in the cytoplasm in an inactive state, bound to chaperone proteins such as heat shock proteins including HSP90 and HSP70
How do glucocorticoids bind
glucocorticoids diffuse through the cell membrane and bind to the GR. this binding induces a conformational change in the receptor, causing the release of the chaperone proteins
what happens during nuclear translocation of GR
the activate GR translocates from the cytoplasm to the nucleus
what is DNA binding involving GR
in the nucleus, the GR dimerises and binds to specific DNA sequences called glucocorticoid response elements located in the promoter regions of target genes
how is gene expression regulated
transactivation
transrepression
how is GR activity positively regulated through transactivation
GR binding to GREs can enhance the transcription of anti-inflammatory and immunosuppressive genes, such as lipocortins 1, which inhibits phospholipase A2, reducing the synthesis of pro-inflammatory molecules like prostaglandin and leukotrienes
what enzymes are involved in transactivation
tyrosine aminotransferanse, which plays a role in gluconeogenesis
how is gene expression negatively regulated through transrepression
GR can also interact with other transcription factors, such as NFkB and AP1, to repress the expression of pro-inflammatory cytokines, chemokine and adhesion molecules
how can GR interfere transrepression with transcription factors
GR can inhibit NFkB and AP1 by preventing their binding to DNA or by recruiting co-repressors, thus reducing the transcription of genes involved in inflammation and immune response
what are the drugs involved in anti-inflammatory and immunosuppressive therapies
prednisone
dexamethasone
hydrocortisone
when are glucocorticoids used
used to treat inflammatory and autoimmune conditions such as rheumatoid arthritis, asthma, inflammatory bowel disease and lupus
how are glucocorticoid drugs used
by mimicking endogenous glucocorticoids, these drugs bind to the GR, leading to the suppression of pro-inflammatory genes and up regulation of anti-inflammatory genes
what are the side effects of glucocortoid drugs
oestoporosis, muscle weakness, hypertension, hyperglycaemia, and increased risk of infections due to immunosuppression
which glucocorticoid drugs can be used in cancer treatment
dexamethasone, prednisone
when are glucocorticoids used in cancer therapy
used as part of chemotherapy regiments for certain lymphomas and leukemias
how do glucocorticoids treat cancer
these drugs induce apoptosis in lymphoid cells by up regulating pro-apoptotic genes and downregulating anti-apoptotic genes
which glucocorticoids are used in adrenal replacement therapy
hydrocortisone
cortisone acetate
how do glucocorticoids work in replacement therapy
used to replace deficient cortisol in conditions like Addisons disease and congenital adrenal hyperplasia
these synthetic glucocorticoids supplement or replace endogenous cortisol, helping to maintain metabolic and immunologic homeostasis
which glucocorticoids are used in immunosuppressive therapy
prednisone and methylprednisolone
how do glucocorticoids work in immunosuppressive therapy
glucocorticoids suppress the immune response, reducing the likelihood of the body attacking the transplated organ. used to prevent rejections in organ transplants
what is Parkinson’s disease
is a progressive neurodegenerative disorder characterised primarily by motor symptoms such as tremors, rigidity, bradykinesia and postural instability
what is the pathophysiological basis of Parkinsons Diases
dopaminergic neuro degeneration
neuroinflammatory and oxidative stress
genetic factors
non-dopaminergic systems
how does dopaminergic neuro degeneration leads to parkinsons
PD primarily involves the degeneration of dopaminergic neurone in the substantial nigra par compact, a region of the brain that is part of the basal ganglia. these neuron’s produce dopamine, a neurotransmitter essential for regulating movement
the loss of dopaminergic neurone leads to a significant reduction in dopamine levels in the striatum, a crucial component of the motor circuit in the brain
how does neuroinflammation and oxidative stress lead to PD
chronic neuroinflammations and increased oxidative stress have been implicated in the pathogenesis of PD. microglial activation and the production of pro-inflammatory cytokines can exacerbate neuronal damage
how do genetic factors leads to parkinsons
genetic mutations have been identified that increase the risk of developing the disease such as mutations in the SNCA, LRRK2 and PARK2 genes
how do non-dopaminergic systems contribute to PD
other neurotransmitter systems, including the cholinergic, serotonergic and noradrenergic systems, can also be affected in PD, contributing to non-motor symptoms such as cognitive decline, mood disorders and autonomic dysfunction
what are the different types of pharmacological approaches to treating PD
dopaminergic therapies
anticholinergic agents
amantadine
adenosine A2A receptor antagonists
what is included in dopaminergic therapies for PD
levodopa
dopamine agonists
MAO-B inhibitors
COMT inhibitors
why is levodopa used in treatment for PD
levodopa is a precursors to dopamine that can cross the BBB and is converted to dopamine in the brain. it is usually combined with a peripheral decarboxylase inhibitor to prevent its conversion to dopamine outside the brain, which reduces side effects and increases availability in the CNS
why are dopamine agonists used in the treatment for PD
these drugs directly stimulate dopamine receptors and can be used alone or in combination with levodopa
why are MAO-B inhibitors used in PD
monoamine oxidase B inhibitors e.g. selegiline and rasagiline, inhibit the breakdown of dopamine, thereby increasing its levels in the brain
why are COMT inhibits used in PD
catechol-O-methyltransferase inhibitors e.g. entacapone and tolcapone prevent the breakdown of levodopa, prolonging its effects
why are anticholinergic agents used in PD
these drugs help to reduce tremors and muscle rigidity by blocking acetylcholine, which is relatively overactive due to the loss of dopamine
why is amatadine used in PD
has both dopaminergic and anticholinergic properties and may help reduce symptoms, particularly dyskinesia associated with long term levodopa use
why is adenosine A2A receptor antagonists used in PD
istradefylline is an example of this class, which helps reduce motor symptoms by modulating the activity of the basal ganglia circuits
how can cognitive and psychiatric symptoms of PD be treated
cholinesterase inhibits can be used for cognitive impairment
antidepressants (SSRIs) and anxiolytics may be prescribed for mood disorders
how can sleep disorder be treated in PD
medications such as melatonin or clonazepam may be used to manage sleep disturbances
how can autonomic dysfunction be treated in PD
medications to manage blood pressure, urianry incontinence and gastrointestinal symptoms may be necessary
why is hormone replacement therapy used to target oestrogen receptors
used in menopausal women to alleviate symtpoms such as hot flushes, night sweats, vaginal dryness and oesteoporosis
how does hormone replacement therapy work
oesterogen is administered to compensate for the decreased endogenous production
what are the agents used in hormone replacement therapy
conjugated oestrogen, oestradiol patches, and oesteragens
when is selective oestrogen receptor therapy used
used in breast cancer treatment and prevention, oesteoporosis preventions, and other oestrogen related conditions
what is the mechanisms of selective oestrogen receptor modulators
SERMs act as oestrogen agonists in some tissues e.g. bone, cardiovascular systems, and antagonists in other e.g. breast and uterus
what are the agents used in selective oestrogen receptor modulators
tamoxifens - antagonist in breast, agonist in bone and uterus
raloxifene - antagonist in great and uterus, agonist in bone
when are oestrogen receptor down regulators used
used in the treatment of hormone receptor-positive breast cancer
what is the mechanism of oestrogen receptor down regulators
ERDs bind to the oestrogen receptors, blocking its actions and promoting its degradation
what is the agent used as oestrogen receptor down regulators
fluvestrant
when is hormone replacement therapy used to target progesterone receptors
combined with oestrogen in menopausal women with intact uterus to prevent endometrial hyperplasia and cancer
what is the mechanism of HRT in progesterone therapy
progesterone opposes the proliferative effects of oestrogen on the endometrium
what are the agents used in progesterone HRT
micronised progesterone, medroxyprogesterone acetate
when are progestins used in contraception
used in various forms of hormonal contraceptions
what is the mechanism of progestins in contraceptions
progestins prevent ovulations, thicken cervial mucus, and alter the endometrium to prevent fertilisation and implantations
what are the agents of progestins in contraception
levonorgestrel, norethindrone, etonogestrel, medroxyprogesterone acetate
when are selective progesterone receptor modulations used
used in emergency contraception, treatment of uterine fibroids and endometriosis
what is the mechanism of action of SPRMs
they exhibit both agonist and antagonistic effects on progesterone receptors depending on the tissue
what are the agents of SPRMs
ulipristal acetate (emergency contraception, uterine fibroids), mifepristone (used in combination with misoprostol for medical abortion
what treatments can be used in ER positive breast cancer
SERMs - tamoxifen
ERD - fluvestrant
aromatase inhibitors - anastrozole, letrozole
how does SERMs work in the treatment of ER positive breast cancer
block oestrogen receptors in breast tissue, reducing tumour growth
how does ERDs work in the treatment of ER positive breast cancer
promote the degradation of oestrogen receptors, further decreasing oestrogen signalling in cancer cells
how do aromatase inhibitors work in the treatment of ER positive breast cancer
reduce oestrogen production, indirectly lowering oestrogen receptor activation
what are the treatments for endometriosis and uterine fibroids
progestins - medroxyprogesterone
SPRMs - ulipristal
how do progestins treat endometriosis and uterine fibroids
suppress endometrial tissue growth and reduce symptoms
how do SPRMs treat endometriosis and uterine fibroids
reduce size of fibroids and control bleeding
how do progestins treat menstrual disorders
used to manage how heavy menstrual bleeding and irregular periods
what are combined oral contraceptives
contain both oestrogen and progestin to prevent ovulation and alter the uterine environment
what are progestin-only contraceptives
suitable for women who cannot take oestrogen, they prevent ovulation and increase cervical mucus viscosity
what are the treatments for osteoporosis
HRT - oestrogen is used to prevent bone loss in postmenopausal womens
SERMs - preserves bone density by mimicking oestrogens effects on bone without stimulating breast and uterine tissues
what are the current strategies for treating antimicrobial resistances
antibiotic stewardship programs
combination therapy
newer antibiotics
optimising dosing regimens
vaccinations
what is the rationale for antibiotic stewardship programs
these programs promote appropriate use of antibiotics to minimise the development of resistance
how are ASPs implemented
ASPs involve guidelines for proper antibiotic selections, dosing, route of administration and duration of therapy. they emphasise de-escalation based on culture results and use of narrow spectrum antibiotics whenever possible
what is the rationale for combination therapy
using multiple antibiotics can prevent the emergence of resistance by attacking bacteria through different mechanisms
what are the examples of combination therapy
combining beta-lactams with beta lactamase inhibits e.g. amoxicillin-clavulanate or using dual antibiotics link vancomycin and rifampicin for certain reistant infections
what are the newer antibiotics used for combating antimicrobial resistance
linezolid
daptomycin
tigencycline
ceftraoline
what is the rationale for optimising dosing regiments
proper dosing can ensure effective eradications of bacteria and reduce the risk of resistance
how is optimising dosing regimens implemented
using pharmacokinetic/pharmacodynamic principles to guide dosing such as prolonged or continuous infusion of beta-lactams
what is the rationale for vaccinations
vaccines can reduce the incidence of infections and the need for antibiotics
what are the examples for vaccinations to prevent antimicrobial resistance
vaccines for streptococcus pneumonia and staphylococcus aureus
what are the future strategies for treating antimicrobial resistance
development of new antibiotics
anti-virulence strategies
bacteriophage therapy
CRISPR-cas systems
antibiotic adjuvants
host-directed therapies
nanotechnology
what are the examples of development of new antibiotics
oxazolidinone, lipoglycopeptides, and new beta-lactams with enhanced activity against resistant strains
what is the rationale for anti-virulence strategies
targeting bacterial virulence factors rather than killing bacteria directly can reduce selective pressure for resistance
what is the rationale for bacteriophage therapy
phages specifically target bacteria, including resistant strains, and can be tailored to individual infections
what is the rationale for CRISPR-cas systems
gene editing technology can be used to target and destroy resistance genes within bacterial populations
what is the rationale for antibiotic adjuvants
compounds that enhance the efficacy of existing antibiotics or inhibit resistance mechanism
what are the examples of antibiotic adjuvants
beta lactase inhibits, efflux pump inhibitors and compounds that disrupt cell wall synthesis
what is the rationale for host directed therapies
enhancing the hosts immune response to clear infections rather than directly targeting the bacteria
what are the examples of host directed therapies
immunomodulatory agents
cytokine therapies
vaccines
what is the rationale for nanotechnology in targeting antimicrobial resistance
nanoparticles can be used to deliver antibiotics more effectively or directly to infection sites, reducing the required dose and minimising side effects
what is emesis
emesis is a complex reflex that involves multiple systems and is regulated by the body through a coordinated response involved the central nervous system, gastrointestinal tract and various signalling molecules. these process ensures the expulsion of harmful substances from the stomach§
what is included in the central regulation of emesis
vomiting centre
chemoreceptor trigger zone
where is the vomiting centre found
located in the medulla oblongata of the brainstem
what is the function of the vomiting centre
it coordinates the acts of vomiting by integrating signals from various sources and triggering the necessary physiological responses
what is the location of the CTZ
located in the area postrema, on the floor of the fourth ventricle outside the blood brain barrier
what is the function of the CTZ
it detects circulating emetogenic substances in the blood cerebrospinal fluid and sends signals to the vomiting centre
what receptors are found in the CTZ
dopamine
serotonin
neurokinin
opioid
what is involved in the peripheral regulation of emesis
gastrointestinal tract
vestibular system
higher brain centre
what is in the gastrointestinal tract that is involved with emesis
mechanoreceptor and chemoreceptors - can detect distension, irritations, and the presence of toxins or pathogens
vagal afferents - send signals to the vomiting centre via the vagus nerve
what is the functions of the vestibular system in emesis
involved in motion sickness, it detects changes in balance and spatial orientation
what is the pathway in the vestibular system
signals from the vestibular apparatus are transmitted to the vomtiing centre through the vestibulocochlear nerve and are mediated by histamine and acetylcholine receptors
how is the higher brain centre involved in emesis
cortex and limbic system - emotional and sensory stimuli, such as disgust, fear, pain and certain smells or sights, can trigger vomiting
what is the pathway in the higher brain centre
these signals are processed in higher brain centres and then sent to the vomiting centre
which receptors are involved in emesis
serotonin
dopamine
neurokinin
histamine
acetylcholine
what is the location and role of serotonin receptors in emesis
found in the CTZ, GI tract and vagus nerve
activation of these receptors by serotonin leads to the initiation of the vomiting reflex
what is the location and role of dopamine receptors in emesis
prominently present in the CTZ
dopamine agonists can induce vomiting, while antagonists can prevent it
what is the location and role of neurokinin receptors in emesis
found in the CTZ and vomiting centre
substance P binds to NK1 receptors, playing a crucial role in the vomiting pathway
what is the location and role of histamine receptors in emesis
in the vestibular nuclei
involved in the vomiting reflex associated with motion sickness
what is the location and role of acetylcholine receptors in emesis
in the vestibular system and vomiting centre
activation can induce vomiting; anticholinergics can be used to prevent motion sickness
what are the phases of emesis
nausea - reduced gastric motility and increased tone in the small intestine
retching - contraction of abdominal muscles, diaphragm and intercostal muscles
vomiting - coordinated contraction of the diaphragm and abdominal muscles, relaxation of the oesophageal sphincter, and reverse peristalsis in the stomach and oesophagus
what are antiemetics
antiemetic drugs target various subtypes to prevent or alleviate nausea and vomiting
which antiemetic drugs target serotonin receptors
ondansetron, granisetron, palonserton, dolasetron
these drugs block serotonin receptors, preventing the initiation of the vomiting reflex
which antiemetic drugs target dopamine receptors
metoclopramide, prochlorperazine, promethazine, droperidol
these drugs inhibit receptors, which are involved in the vomiting pathway
which antiemetic drugs target neuokinin-1 receptors
aprepitant, fosaprepitant, rolapitant, netupitant
these drugs block NK1, preventing the action of substance P a key player in the emetic pathway
which antiemetic drugs target histamine receptors
diphenhydramine, meclisine, cyclizin, promethazine
these drugs block histamine receptors, particularly used in treating motion sickness and vestibular-related nausea
which antiemetic drugs target muscarinic receptors
scopolamine
this drug blocks muscarinic receptors, preventing acetylcholine from triggering the vomiting reflex, especially effective for motion sickness
which antiemetic drugs target cannabinoid receptors
dronabinol, nabilone
these drugs activate cannabinoid receptors, which can inhibit the vomiting reflex, particularly useful in chemotherapy-induced nausea and vomiting
which antiemetic drugs target glucocorticoid receptors
dexamethasone
believed to exert anti-inflammatory effects and modulate neurotransmitter activity, enhancing the efficacy of other antiemetics
when are serotonin receptor antagonists used
chemotherapy-induced nausea and vomiting
postoperative nausea and vomiting
radiation-induced nausea and vomiting
what are the side effects of serotonin receptor antagonists
headache
constipation or diarrhoae
dizziness
QT interval prolongation
serotonin syndrome
what are the central targets for antiemetic action of serotonin receptor antagonists
chemoreceptor trigger zone
nucleus tractus solitarus
vagal afferents in the gastrointestinal tract
when are dopamine receptor antagonists used
CINV
PONV
gastroesophageal reflux disease related nausea
gastroparesis-related nausea
general nausea and vomiting
what are the side effects of dopamine receptor antagonists
extrapyramidal symptoms, such as dystonia and tar dive dyskinesia
sedation
hypotension
anticholinergic effects
prolonged QT interval
what are the central targets for antiemetic action of dopamine receptor antagonists
chemoreceptor trigger zone
gastrointestinal tract
area postrema
when are NK1 receptor antagonists used
CINV
PONV
what are the side effects of NK1 receptor antagonists
fatigue
diarrhoea
hiccups
elevations in liver enzymes
what are the central targets for antiemetic action of NK1 receptor antagonists
chemoreceptor trigger zone
vomiting centre
what are the central targets for antiemetic action of histamine receptor antagonists
vestibula nuclei
vomiting centre
when are histamine receptor antagonists used
motion sickness
vertigo
general nausea and vomiting
PONV
when are muscarinic receptor antagonists used
motion sickness
PONV
when are cannabinoid receptor antagonists used
CINV
appetite stimulation in AIDs and cancer
when are glucocorticoid receptor antagonists used
CINV
PONV
what are the side effects of histamine receptor antagonists
sedation
drowsiness
dry mouth
blurred vision
urinary retention
constipation
what are the side effects of muscarinic receptor antagonists
dry mouth
blurred vision
drowsiness
constipation
urinary retention
confusion
what are the side effects of cannabinoid receptor antagonists
dizziness
euphoria or dysphoria
sedation
dry mouth
increased appetite
potential for abuse and dependency
cognitive impairment
what are the side effects of glucocorticoid receptor antagonists
hyperglycaemia
increased risk of infection
insomnia
mood swings
weight gain
oesteoporosis
what is the mode of action of metformin
metformin primarily lowers blood glucose levels by decreasing hepatic glucose production. it also improves insulin sensitivity, enhancing peripheral glucose uptake and utilisation. it has minor effect on slowing intestinal glucose absorption
what is the pharmacology of metformin
class - biguanide
absorption - oral with bioavailability of 50-60%
distribution - widely distributed in the body tissue
metabolism - not metabolised, excreted unchanged in urine
half life - 4-8hrs
side effects of metformin
gastrointestinal issues - nausea, vomiting, diarrhoea, abdominal discomfort
lactic acidosis
vitamine b12 deficiency - long term use can reduce b12 absorption
what is the mode of action of mealtime insulin therapy
involves administering rapid-acting or short acting insulin before meals to manage postprandial blood glucose spikes. these insulins mimic the body’s natural insulin response to food intake
what is the pharmacology of rapid acting mealtime insulin therapy
types - insulin lisper, aspart, glulisine
onset - 10-30mins
peak - 30-90mins
duration 3-5hrs
what is the pharmacology of short acting mealtime insulin therapy
types - regular insulin
onset - 30-60mins
peak - 2 hours
duration - 5-8hrs
what are the side effects of mealtime insulin therapy
hypoglycaemia
weight gain
injection site reactions
allergic reactions
mode of action of medications that increase insulin secretion
stimulate the pancreas to secrete more insulin. they act on the beta cells in the islets of langerhans
classes of medications that increase insulin secretion
sulphonylureas - glipizine, glyburide, glimepiride
meglitinides - repaglinide, nateglinide
pharmacology of sulphonylureas
mechanism - bind to the sulphonylurea receptors on pancreatic beta cells, causing depolarisation and calcium influx, which triggers insulin release
half life - 10-24hours
pharmacology of meglitinides
mechanism - short action than sulphonylureas; stimulate insulin release by binding to a different site on the sulphonylurea receptors
side effects of medications that increase insulin secretion
hypoglycaemia - high with sulphonylureas
weight gain
gastrointestinal issues
allergic reactions
mechanism of action of anticholinergics as bronchodilators
block muscarinic receptors
preventing of acetylcholine - inhibit the parasympathetic nervous systems action
reduced bronchoconstriction - decreased intracellular cyclic GMP levels, leading to relaxation to bronchial smooth muscle and bronchodilation
examples of anticholinergics that work as bronchodilators
ipratropium
tiotropium
when are anticholinergics used as bronchodilators
chronic obstructive pulmonary disease
asthma
adverse effects of anticholinergics as bronchodilators
dry moth
cough
headache
urinary retention
blurred vision
mechanism of action of beta 2 agonists as bronchodilators
activation of beta2 adrenergic receptors
increased cAMP levels
smooth muscle relaxation - elevated cAMP levels lead to the activation of protein kinase A, which phosphorylates target proteins resulting in the relaxation of bronchial smooth muscle
examples of beta2 agonists
short acting - albuterol, levealbuterol
long acting - salmeterol, formoterol
when are beta2 agonists used
asthma
COPD
exercise induced bronchospasm
adverse effects of beta 2 agonists
tremor
tachycardia
palpitations
hypokalaemia
hyperglycaemia
mechanism of action of theophylline as bronchodilator
phosphodiesterase inhibition - the enzymes responsible for breakdown of cAMP
increase cAMP levels
bronchodilation - elevated cAMP results in the relaxation of bronchial smooth msucle
anti-inflammatory effects
when is theophylline used as bronchodilator
asthma
COPD
side effects of theophylline
narrow therapeutic window index, requiring monitoring of blood levels
gastrointestinal disturbance
central nervous system effects
cardiac arrhythmias
tremors
what are the psychological symptoms of anxiety
excessive worry
restlessness
irritability
difficulty concentrating
fear
panic attack
sense of impending doom
physical symptoms of anxiety
increased heart rate
sweating
trembling or shaking
muscle tension
headaches
fatigue
gastrointestinal issues
dizziness
insomnia
behavioural symptoms of anxiety
avoidance
procrastination
compulsive behaviours
social withdrawal
cognitive symptoms of anxiety
negative thought
overthinking
indecisiveness
examples of short acting benzodiazepines
alprazolam
lorazepam
triazolam
midazolam
therapeutic uses of short acting benzodiazepines
anxiety disorders
insomnia
preoperative sedation - midazolam
panic attacks - alprazolam
seizure control - lorazepam
examples of long acting benzodiazepines
diazepam
clonazepam
chlordiazepoxide
therapeutic uses of long acting benzodiazepines
anxiety disorders
seizure disorders - clonazepam and diazepam
muscle spasms - diazepam
alcohol withdrawal - chlordiazepoxide and diazepam
panic disorder - clonazepam
what are the factors determining benzodiazepine half life
lipid solubility
metabolism
age and liver function
route of administration
how does lipid solubility effect benzodiazepine half life
higher lipid solubility have a faster onset of action and are rapidly distributed into the central nervous system but may also redistribute into peripheral tissues, prolonging their half life
how does metabolism effect half life of benzodiazepine
hepatic metabolism
active metabolite - long half life
phase 1 metabolism - long half life
phase 2 - short half lives
how does age and liver function effect benzodiazepine half life
elderly - metabolism slower so longer half life. can risk to accumulation
liver impairment - longer metabolism = longer half life
