PED 2006 brief Flashcards
where is the function of the gastrointestinal system major
metabolic and endocrine system
what is the pharmacological importance of the gastrointestinal system
gastric secretion
vomiting
bowel motility
which hormones are secreted in the endocrine
gastrin
cholecystokinin
which hormones are secreted in the pancreas
histamine
acetylcholine
what is the function of the parietal cells in the wall of the gastric gland
keep the pH between 6-7
within their structure the canaliculus releases Hcl
the tubulovesicles release hydrogen and potassium
what is the function of the canalicular membrane
contains a H+/K+ ATPase proton pump and is a Cl- co-transporter
pull potassium back in and hydrogen out - important to keep the pH isoelectrically neutral
this process required gastrin
what is gastrin
is a peptide hormone
stimulates acid secretion, pepsinogen secretion, blood flow and increases gastric motility
increases cytosolic ca2+
what is acetylcholine
a neurotransmitter
released from vagal neurons
increases cytosolic ca2+
what is histamine
hormone released from H2 receptors
increases cAMP
which diseases are associated with acid dysregulation
dyspepsia - upper abdominal pain, bloating and nausea
peptide ulceration - prolonged excess acid causes gastric and duodenal ulceration
reflux oesophagus - damage to oesophagus by excess acid secretion
Zollinger-Ellison syndrome - gastrin producing tumour
what is the therapeutic aim to treat diseases associated with acid dysregulation
to decrease secretion of gastric acid by
- reducing proton pump function (proton pump inhibitors)
- blocking histamine receptor function (H2 receptor antagonism)
- neutralising acid secretions with antacids
what are two examples of proton pump inhibitors
omeprazole
lansprazole
what is the mechanism of action of omeprazole and lansoprazole
irreversibly inhibit H+/K+ ATPase
can be used to treat peptide ulcers, reflux oesophagi’s and Zollinger-ellison
what are the pharmacokinetics of proton pump inhibitors
inactive at neutral pH
weak bases - allows accumulation in acidic environment
degrades rapidly at low pH
single dosing - 2-3 daily
what are the adverse effects of proton pump inhibitors
headache
diarrhoea
rash
masking the symptoms of gastric cancer
care should be taken with high risk groups e.g. liver failure and pregnancy
give two examples of histamine H2 receptor antagonists
cimetidine
ranitidine
what is the mechanism of action of histamine H2 receptor antagonists
competitive inhibits of H2 histamine receptors
used in peptic ulcers and reflux oesophagi’s
what are the adverse effects of H2 antagonists
diarrhoea
dizziness
muscle pain
cimetidine has androgenic action
reduction of metabolism of anticoagulants and tricyclic antidepressants - inhibit cytochrome P450s
give 2 examples of antacids
sodium bicarbonate
Mg2+/Al3+ hydroxide
what is the mechanism of action of antacids
bases that raise gastric luminal pH by neutralising gastric acid
used in dyspepsia and oesophageal reflux
what are the pharmacokinetics of antacids
relatively slow action
effects often short lived
acid rebound
what are the adverse effects of antacids
diarrhoea
constipation
belching
acid rebound
alkalosis
care must be taken with sodium content
what are helicobacter pylori infections
caused by gram negative bacteria
cause peptide ulcer formation that can lead to gastric cancer
how can helicobacter pylori infections be treated
combination therapy including PPI, antibacterial and cytoprotective agents
what are cytoprotective agents
enhance mucosal protection mechanisms and form barriers over ulcer formations
what are some examples of cytoprotective agents
bismuth chelate
sucralfate
misoprotosol
what is bismuth chelate
toxic to bacillus
they coat ulcer base, prostaglandins and bicarbonate synthesis
what is sucralfate
stimulate mucus production and prevent degradation
increases prostaglandin and bicarbonate synthesis
what is misoprostol
is a prostaglandin analogue, has direct action on parietal cells
what are prostaglandins
synthesised by gastric muscosa
they increase mucus and bicarbonate secretion
decrease acid secretion
how do NSAIDs cause gastric ulcers
inhibit prostaglandin formation which causes gastric bleeds
erosion
ulcer formation
specific COX2 inhibitors cause less GI damage
how is the frequency of gastric contractions controlled
pacemaker cells
what are pacemaker cells
found in smooth muscle cells in upper fungus
rhythmic, autonomous, partial depolarisation
depolarisation cause slow wave potentials that sweep down th stomach
how is the force of gastric contractions controlled
by neural and hormonal activity
neural activity is increased by vagal activity and decreased by adrenergic activity
hormonal activity is increased by gastrin and reduced by secretin
what happens when food is taken in
waves of peristaltic contractions throughout stomach
forceful contractions and increased pressure in antrum
retropulsion of food against close pylorus
mixing and grinding of food
what happens to receptors when food is taken in
stretch receptors are activated
vagal inhibitory neurones
relaxation of smooth muscle
little change in pressure
what is emesis
the forceful evacuation of stomach content.
can be stimulated by pain, repulsive sights/smells, emotional factors, endogenous toxins.drugs, stimuli from pharynx/stomach, motion
how is emesis controlled
by the vomiting centre and chemoreceptor trigger zone
it is sensitive to neurotransmitter stimulus such as acetylcholine, histamine, 5-HT and dopamine
how can we stimulate vomiting
ipecauaha are locally acting in stomach
irritant effects of alkaloids emetine and cephaeline
what are the classes of anti emetics
H1 receptor antagonists
muscarinic antagonists
D2 antagonists
5-HT3 antagonists (cannabinoids, antipsychotics and steroid/neurokinin antagonists
what are the examples of H1 receptor antagonists
cyclizine
promethazine
when are H1 receptor antagonists given
most effective for motion sickness when given before the onset of nausea and vomiting
they act on vestibular nuclei
what are the adverse effects of H1 receptor antagonists
drowsiness
sedation
example of muscarinic antagonists
hyoscine
when are muscarinic antagonists used
used for motion sickness
effective against vestibular apparatus stimuli and local gut stimuli
what are the adverse effects of muscarinic antagonists
dry mouth
blurred vision
sedation
examples of D2 receptor antagonists
metoclopramide
phenothiazines
when are D2 receptor antagonists used
used for vomiting caused by renal failure and radiotherapy
they work in the chemoreceptor trigger zone
what are the adverse effects of D2 receptor antagonists
CNS effects (twitching and restlessness)
prolactin stimulation = menstrual disorders
example of 5-HT3 antagonists
ondansetron
when are 5-HT3 antagonists used
in chemotherapy an post-surgery
primarily act on CTZ
5-HT3 are released in gut following some endogenous toxins and chemotherapy drugs
what are the adverse effects of 5-HT3 antagonists
headache
diarrhoea
what are the types of drugs used to treat bowel motility
anti-diarrhoea
purgatives/laxatives
what are the causes of diarrhoea
viral - rotavirus
bacterial - campylobacter
systemic disease - inflammatory bowel disease
drug induced - antibiotics e.g. erythromycin
how do antidiarrhoeals work
stimulate opiate receptors in the bowels
increase tone of smooth muscle
suppress propulsive peristalsis
raise sphincter tone at oleo-caecal valve and anal sphincter
reduced sensitivity to rectal distension
what is the effect of anti-diarrhoeals
delay in passage of faeces through the gut and increased water and electrolyte absorption in small intestine and colon
which opioid agonist can act as anti-diarrhoeals
codeine
morphine
how do opioid agonists work as anti-diarrhoeals
activate mow receptors on myenteric neurones
cause hyperpolarisation therefor inhibition of acetylcholine release
reduces bowel motility
why is codeine preferred to morphine
opiates are susceptible to misuse as they can cause tolerance and dependence
two examples of synthetic opioid analogues
loperamide
diphenoxylate
what is loperamide
binds to opiate receptors in gut wall and is relatively free of CNS side effects
what is diphenoxylate
marketed as a cophenotrope, atropine present to discourage abuse
what are the types of laxatives
bulk forming agents
osmotic laxatives
stimulants
faecal softeners
what are the examples of bulk forming agents
ispaghula
methylcellulose
brain
how do bulk forming agents work
contain polysaccharide and cellulose components
they are not digested and retain fluid, therefore increasing faecal bulk and stimulate peristalsis
side effects of bulk forming agents
flatulence
bloating
examples of osmotic laxatives
magnesium salts
polyethylene glycol
phosphate enemas
lactulose
how do osmotic laxatives work
act by osmosis to retain water in the bowel to produce a softer, bulkier stool
pharmacokinetics of osmotic laxatives
act in 30 mins
2-5hrs for magnesium salts
48hrs for lactulose
side effects of osmotic laxatives
abdominal cramps
flatulence
electrolyte disturbance
examples of stimulant laxatives
Senna
bisacodyl
dantron
how do stimulant laxatives work
directly stimulate colonic nerves
movement of faecl mass and reduce transit time
side effects of stimulant laxatives
abdominal cramps
colonic atony
example of faecal softeners
docusate sodium
how do faecal softeners work
they are non-ionic surfactant with stool softening properties
reduces surface tension
allows penetration of fluid into the faecal mass
examples of inflammatory bowel disease
crohns disease
ulcerative colitis
characteristics of inflammatory bowel disease
cyclical bouts of diarrhoea
constipation
abdominal pain
treatments for inflammatory bowel disease
glucocorticoids
aminosalicylates
sulfasalazine
immunosuppression
what is asthma
obstructive airway disease
reversibly obstructs airflow due to airway stimulation and airway hyperresponsiveness
obstruction can be cause by smooth muscle contractions, inflammation, oedema, muscus and airway structural changes
major symptoms of asthma
wheezing
chest tightness
dyspnea
cough
hypoxemia
what can be used to relax smooth muscle
beta blockers - SABA and LABA
PDE blockers - theophylline
LTRAs
what can be used to block inflammatory cascades
corticosteroids - ICS
LTRAs
PDE blockers
targeted biologics
how do beta2 adrenoceptor agonists work
relaxation of smooth muscle by increasing cAMP through G proteins
adrenaline has non-selective alpha, beta1 and beta2 effects
isoprenaline is a selective beta agonist, causing bronchodilation and cardiac stimulation
how can beta 2 agonists be administered
aerosol inhalation
inhalation of nebulised solution
inhalation of powder
oral administration
two examples of short acting beta 2 agonists
salbutamol
terbutaline
when are short acting beta 2 agonists used
for acute episodes of asthma, inhalation relief within 5-10 mins
Max effect within 30mins
they last 3-5hours
examples of longer acting beta 2 agonists
salmeterol
formoterol
mechanism of action of longer acting beta 2 agonists
give daily and last around 12 hours due to their lipophilic structures
corticosteroids are used along side
side effects of beta2 adrenoceptor agonists
muscle tremor
tachycardia
cardiac dysrhythmias
risk of paradoxical bronchospasm
how are leukotrienes linked with asthma
leukotrienes are synthesised and released during the acute response by mast cells, they are also produced by inflammatory cells
mechanism of action of cysteine leukotrienes LTC4 and LTD4
they increase vascular leakage and mucus production
they can act as chemoattractants for eosinophils and basophils
produced via cys-LT1 receptors coupled to Gq-Ca2+
what are LTB4
potent chemoattractants for neutrophils
two examples of leukotrienes receptor antagonists
zafirlukast and montelukast
how do leukotrienes receptor antagonists work
selective and are a high affinity competitive antagonist for cys-LT1 receptors
they block the LTC4 and LTD4 effects on smooth muscle
what is zileuton
5-lipoxygenase inhibitors, so inhibits the formation of all 5-LOX products from LTA4 synthesis
when is montelukast used
acute prevent on exercise-induced bronchoconstriction
used in cases of allergic and perennial rhinitis
most commonly used leukotriene modulator
examples of anti-muscarinics used in asthma
ipratropium and tiotropium
why are antimuscarinics used in asthma
cause bronchodilation and reduce mucus secretion
commonly used with beta2 agonists and steroids
increase mucociliary clearance through action on cilia of epithelial cells
how do muscarinic antagonists act as bronchodilators
they innervate all conducting airways from the trachea to the bronchioles
the parasympathetic nerves synthesise and release acetylcholine and are the primarily source of acetylcholine in the lung
pharmacokinetics of ipratropium bromide
examples of a SAMA
onset is low but can last 6-8hrs
given 3-4 times a day
what are the examples of LAMAs
tiotropium bromide
glycopyronium bromide
umeclidinium bromide
aclidinium bromide
side effects of non-selective muscarinic receptors blockage
systemic anticholinergic side effects e.g. dry mouth, gastrointestinal motility disorder, tachycardia and nausea
types of treatments for immunosuppression
ICS
biologics
why can glucocorticoids be used as anti-inflammatories
inhibit inflammatory response to injury and allergic disease
inhibit the synthesis of inflammatory mediators, cytokines, cell chemoattractants, vasoactive agents
decrease inflammatory cell infiltration and proliferation, vascular permeability and mucus secretion
mechanism of action glucocorticoids
inhibit NFkB which is a major transcription factors for all inflammatory cytokines.
this works as tranrepression of NFkB and major anti-immune effects of GCs
SGR complex inhibits HAT and recruits HDAC2
HDAC2 deacetylates and represses the genes
examples of inhaled corticosteroids
beclomethasone
budesonide
how do inhaled corticosteroids work
inhaled as a dry powder
reducing transcription and decreased formation of Th2 cytokines, reduce action of eosinophils, reduce production of IgE, reduce production of leukotriene and PAD
inhibit induction of cyclooxyrgenase
side effects of corticosteroids
adrenal suppression
reduced bone mineral density
oropharyngeal candidiasis may occur
examples of oral corticosteroids
prednisolone
hydrocortisone
when are oral corticosteroids used
short term relief of severe episodes of acute asthma
what are the long term effects of corticoid steroids
suppression of immune response to infection
Cushing syndrome
oesteoporosis
hyperglycaemia
muscle wastage
inhibition of growth
how are eosinophils involved in allergic asthma
main inflammatory cells in later/chronic allergic asthma
activated by IL5 from Th2 cells
what do eosinophils secretes
Th2 cytokines
ROS
LTC4/LTD4
what can be used to decrease production of eosinophils
mepolizumab
resilzumab
they do this by binding to IL5a
mechanism of action of benralizumab
stops IL5 binding by binding to the IL5 receptor on eosinophils
increase binding affinity for Fc RIII on natural killer cells causing apoptosis of eosinophils through ADCC
what is the innate immune system
non specific
immediate
first line of defence
no memory
what is the adaptive immune system
specific
slow
second line of defence
immunological memory
what is inflammation
protective reaction of vascularised living tissue of local injury
brings cells and molecules of host defence from the circulation to the site where they are needed
it serves to destroy, dilute or isolate the injurious agents, eliminating the necrotic cells and tissues
what are the steps of the inflammatory response (5 Rs)
recognition of the offending agent/injury
recruitment of leukocytes
removal of the offending substance
regulation of the response
what is acute inflammation
rapid onset
short duration
involved neutrophils
what is chronic inflammation
slow onset
long duration
involved monocytes, macrophages and lymphocytes
what are the cardinal signs of inflammation
redness
heat
swelling
pain
loss of function
what causes acute vascular inflammation
dilation of small vessels, leading to slowed blood flow
increased vascular permeability to the microvasculature, enabling plasma proteins and leukocytes to leave the circulation
what causes acute cellular inflammation
emigration of the leukocytes from the microcirculation, accumulating at the site of the injury before activating to eliminate the pathogen
what are the key inflammatory mediators
histamine
plasma proteins
prostaglanding
leukotrienes
cytokines
chemokine
what are histamines
produced by mast cells/basophils
cause vasodilation and increased permeability
lead to leukocyte recruitment
what are plasma proteins
produced by the liver
cause vasodilation and increased permeability
leading to leukocyte recruitment
what are prostaglandins
produced by mast cells, basophils and neutrophils
cause vasodilation and increase permeability
what are leukotrienes
produced by mast cells, basophils and neutrophils
cause increase permeability and allow leukocyte recruitment
what are cytokines
produced by mast cells and macrophages
cause vasodilation and increased permeability
allow leukocyte recruitment
what are chemokine
produced by mast cells and macrophages
allow leukocyte rectuiment
what are the two main cellular mediators for chronic inflammation
macrophages
lymphocytes
what are macrophages
cause phagocytosis
initiate tissue repair and secrete cytokines
what are lymphocytes
cause T cells to secrete chemokine and B cells to secrete antibodies
activation is caused by antigen presentation
types of drugs that reduce inflammatory and immune response
non-steroidal anti inflammatory drugs
steroidal anti-inflammatory drugs
anti histamines
immunosuppressant drugs
immune check point inhibitors
what are the signalling pattern recognition receptors
PAMP binds to toll like receptors
this activates transcription of NFkB and IRF3/7 leading to secretion of cytokines and inflammation
what is COX1
works as a housekeeper
many unwanted responses are thought to be exerted mainly through COX-1 isoform inhibition
what is COX2
induced upon inflammatory cell activation
anti-inflammatory, analgesic and antipyretic activity, antipyretic activation of NSAIDs thought to be exerted when COX2 isoforms are inhibits
what is the mechanism of NSAIDs
reversible competitive inhibition (ibuprofen), reversible non-competitive inhibition (paracetamol) and irreversible inhibition (aspirin
what causes the symptoms of inflammation
COX2
what causes the symptoms of non-selective NSAIDs
COX1
what causes fever from inflammation
caused by pyrogens
caused by the secretion of cytokines into bloodstream, which migrate to the brain, bind to receptors on brain endothelial cells, activated prostaglandin E2 synthesis
what causes the side effects from NSAIDs
gastrointestinal problems - inhibitions of synthesis of stomach pge
skin rashes
renal effects - inhibition of synthesis of PGI2 and PGE
brocnhospasms
side effects of COX2 inhibitors
increase the risk of thrombotic events such as heart attacks and stroke
side effects of NSAIDs
adverse cardiovascular effects as COX2 decrease platelet aggregation and vasodilation
COX1 cause releases of platelet of thromboxane causing thrombotic vasoconstriction
what are lipocortins
is a GR agonists and is an examples of a steroid anti-inflammatory drugs
blocks phospholipase A2
what causes the effects of cortisol anti-inflammatory
by the induction of lipocortin which inhibits phospholipase A2.
causes decreased inflammatory mediators such as prostaglandin, leukotrienes and platelet activating factors
decreased capillary permeability, decreased phagocytic action of leucocytes, decreased histamine release, decreased activity of mononuclear cells and proliferation of tissue
how can glucocorticoids cause Cushing syndrome
increase hyperglycaemia so they can lead to dysregulation of insulin
what are the 4 types of allergic reaction
reaction mediated by IgE antibodies
cytotoxic reaction mediated by IgG or IgM antibodies
reaction mediated by immune complexes
delayed reaction mediated by cellular response
what causes type 1 hypersensitivity
caused by exposure to allergen
APC processes antigen and presents it to Th2 cells released IL4 and IL12 which activates B cells
B cells proliferate and differentiate into plasma cells that synthesise and secrete IgE antibody
IgE binds to mast cells by Fc region, sensitising the mast cells
what can be cause by exposure to antigen
the release of histamine and other mediators
increased smooth muscle contraction, peripheral vasodilation, increased vascular permeability causing bronchospasm, abdominal cramps and rhinitis
extravasation of capillary blood causing erythema
histamine release causes pruritic
fluid shift into interstitial space causing oedema, swollen eyes
examples of localised type 1 hypersensitivity reaction
hay fever
asthma
hives
angioedema
examples of systemic type 1 hypersensitivity
anaphylaxis
signs of allergic rhinitis
red, itchy, watery eyes
sneezing
congestion and runny nose
sore throat
fatigue
what causes allergic rhinitis
mediated by histamine binding to H1 receptors
how do anti-histamines work
by binding to the H1 receptor and reduce its activity
they are inverse agonists
examples of 1st generation antihistamines
chlorophenamies
diphenhydramine
side effects of 1st generation antihistamines
caused by anticholinergic activity
drowsiness
difficulty to urinate
examples of second generation antihistamines
certizine
loratadine
less likely to have side effects as they don’t pass the blood brain barrier
what is anaphylaxis
sudden and rapid onset of allergic symptoms
can be life threatening due to breathing and circulation problems
can lead to skin and/or mucosal changes
what is used to treat anaphylaxis
adrenaline as it prevents and relieves airway obstruction
this promotes cardiac output and increases total peripheral resistance to increased blood pressure
when is hydrocortisone used
to prevent biphasic late responses
what is immunosuppression
block T cell mediated immune response
primarily by blocking the expression and activity of the T cell growth factors activating cytokine interleukin 2
what can be used to treat immunosuppression
prednisolone (glucocorticoid)
tacrolimus or cyclosporin (calcineurine inhibitors)
sirolimus (dual calcineurin/mTOR inhibitors)
daclizumab/basiliximab (IL2 receptor antagonists)
mycophenolate (nucleic acid synthesis antagonists)
how does antibody opsonisation benefit the immune system
enhances phagocytosis (agglutination and chemoattraction)
neutralisation
natural killer cell activation and increasing components of the classical component cascade
how to prevent NFkB activation of inflammatory genes
T cells and B cells are activated when GR complexes directly bind to the p65 subunit of NFkB and this prevent NFkB activation of inflammatory genes including il2
GR promotes IkBa synthesis, which prevents p50/p65 nuclear translocation
how do daclizumab and basiliximab cause immunosuppression
they prevent IL2 binding to the receptor and thus IL2 mediated T cell activation
daclizumab is a humanised monoclonal antibody to the alpha subunit of the IL2 receptors of T cells
basiliximab is a chimeric mouse - human monoclonal to the IL2-Ra of T cells
what is OKT3
TCR receptor antagonist
is a murine monoclonal antibody against the chain of CD3 complex.
OKT3 acts in 2 phases, firstly causes increased T cell depletion from the circulation by the liver
secondary it promotes the removal of an important activator domain of the T cell receptor from cytotoxic T cells and helper T cells
what is immunotherapy
involves the stimulation of immune cells by a range of immune cell checkpoint protein interaction
this can also be inhibited by PDL/PD1
when is immunotherapy used
in cancer treatment by activating the bodies own immune system to recognise and kill cancer cels
PD1 receptor antagonists are a novel group of checkpoint inhibits for the treatment of multiple solid cancer
how can immune cells cause cancer
when PD1 receptor on T cells binds to PD-L1 antigen on tumour cells, the T cell is deactivated, allowing the cancer cell to evade immune attack
PD1 immune checkpoint inhibitors MOA can prevent tumour cells from binding to the inactivating antigen PDL1, enabling the T cells to remain active
what are antibiotics
inhibit the growth or destroys bacteria.
bacteriostatic inhibit multiplication
bactericidal kill bacteria
how do antibiotics work
target cell wall synthesis, membrane synthesis, protein synthesis, metabolic pathways and nucleic acid synthesis
what is flucloxacillin
beta-lactase resistant penicillin that targets gram positive and beta-lactamase resistant bacteria
what is benzylpenicillin
natural penicillin that targets gram positive bacteria
what is amoxicillin
broad-spectrum penicillin that targets gram positive and negative bacteria
what is mecillinam
reverse spectrum penicillin that targets gram negative bacteria
what is mezlocillin
extended spectrum penicillin that targets gram positive, gram negative and pseudomonas aerginose bacteria
what is cephalosporins
used to treat septicaemia, pneumonia and meningitis
effects is exerted through penicillin binding protein
given parentally, IM or IV
excreted in the kidney
examples of cephalosporin
cefaclor
cephalexin
cefotaxime
how do cells become resistant to penicillin
producing beta-lactamases and modifying penicillin binding proteins
what can inhibit protein synthesis
chloramphenicol
erythromycin
tetracycline
streptomycin
how do chloramphenicol work
binds to 50S portion and inhibits formation of peptide bonds
how does erythromycin work
binds to 50S portion, prevents translocation - movement of ribosomes along mRNA
how do tetracyclines work
interfere with attachment of tRNA to mRNA-ribosome complex. they are bacteriostatic and bind competitively to the A site. resistance to this antibiotic is growing
used to treat borrelia, chlamydia and rickettsia
how do streptomycin work
changes shape of 30S portion and causes code on mRNA to be read incorrectly
how do amunoglycosides work
inhibit protein synthesis by interfering with mRNA translation, this is enhanced by penicillin. they can cause ototoxicity and nephrotoxicity
mechanism of action of macrolides
inhibit protein synthesis by binding to 50S subunit and preventing translocation
they are metabolised by demethylation in liver CYP3A4
when are macrolides used
to treat legionella, chlamydia and mycoplasma and effective against gram positive bacteria
side effects of macrolides
heart arrhythmias a
GI disturbance
action of sulphonamides
inhibit dihydropteroate
well distributed and cross BBB
action of trimethoprim
inhibits dihydrofolate reductase
given oral and used to treat UTI and respiratory tract infection
action of fluoroquinolone
inhibits DNA gyrase
taken orally and well absorbed but don’t cross BBB
inhibits CYP1A2
use of fluoroquinolone
kill gram positive and negative bacteria and enterobacter
side effects of fluoroquinolone
GI problems
prolongation of QT interval
what is mycobacteria
causes tuberculosis and leprosy
non-motile, slow growing bacteria with very thick, waxy, lipid-rich hydrophobic cell wall
this cell wall contains mycotic acid so can survive in macrophages
what is rifampicin
semisynthetic derivative of rifamycin
used against gram positive, negative and mycobacteria
induces CYP3A4 so increased degradation of glucocorticoids and warfarin
inhibits prokaryotic DNA-dependent RNA polymerase
given orally and crosses BBB
what is daptomycin
a lipopeptides and inserts into the membrane leading to cell death
attacks gram positive bacteria including MRSA and VRSA
poorly absorbed so given orally
it is eliminated from the body by renal excretion
can cause damage to musculoskeletal system, eosinophilic pneumonia and peripheral neuropathy
types of DNA viruses
adenovirus
herpesvirus
papillomavirus
types of RNA viruses
paramyxovirus
rhabdovirus
togavirus
influenza virus
retrovirus
stages in the viral replication cycle
attachment to host cells
uncoating of virus
control of DNA, RNA and protein porduction
this leads to the production of viral subunits causing the assembly and release of visions
action of antiviral drugs
penetrate infected cells by targeting unique enzymes and metabolic pathways
interfere with viral nucleic acid synthesis and/or regulation
some specific targets include viral cell binding, interrupting virus un-coatin or stimulating the host cell immune system
what is viral latency
the recurrence of an infection due to non-replicating cells, joint replication process and limited immune detection
no antiviral agents eliminate viral latency
which types of acute infections are associated with viral latency
rhinovirus
rotavirus
influenza virus
which types of persistent infections are associated with viral latency
lymphocytic choriomeningitis virus
which types of latent, reactivating infections are associated with viral latency
herpes simplex
which types of slow viral infections are associated with viral latency
measles
HIV
how does antiviral resistance occur
by rapid replication rates and high mutation rates
mutations prevent binding of drug to active sites of key enzymes such as protease and reverse transcriptase
what does herpes virus cause
cold sores - simplex
chicken pox - varicella zoster
glandular fever - epstein barr
what are the symptoms of herpes virus
flu-like symptoms
blister/ulcer stage
where does herpesvirus resides
herpes virus infects sensory ganglia where it becomes latent
this latency can become stimulated again from external infection
action of acyclovir
antiviral action
utilises virus specific thymidine kinase and then undergoes conversion to di and triphosphate forms via host cells kinases, when it triphosphate form it has antiviral action
inhibits viral DNA polymerase by being a DNA chain terminators
characteristics of HIV infections
by destruction of host immune systems
they are opportunistic infection, rare neoplasm and can cause death
how is HIV transmitted
congenitally
parentally
sexual contact
what are the 2 forms of HIV
HIV1 is responsible for human aids
HIV2 is less virulent form of immune suppression
what is primary HIV infection
asymptomatic
there is seroconversion which is negative to positive HIV antibody detection
increase viral load
stages of AIDs
asymptomatic - 25-35% develop persistent generalised lymphadenopathy
progression to severe infection - weight loss and increased opportunistic infections such as bronchitis and sinusitis
greater weight loss - oral candidiasis, hairy leukoplakia and mycobacterium tuberculosis is developed
HIV wasting syndrome, kaposis sarcoma, DNA toxoplasmosis, HIV encephalopathy
mechanism of action of HIV
viral DNA
RNA
translation into viral components
viral assembly
host cell death
the immune target cells involves cytotoxic/helper T lymphocytes.
reverse transcriptase converts DNA to viral RNA
How to inhibit HIV life cycle
fusion inhibitors
CCR5 inhibitors
NRTIs
NNRTI
protease inhibitors
examples of fusion inhibitors
enfurviritde
action of fusion inhibitors
inhibits the fusion of cellular and viral membranes
usually given by subcutaneous injections and most effective as combination therapy
examples of CCR5 inhibitor
maraviroc
action of CCR5 inhibitors
it binds to the CCR5 receptor on the membrane of human CD4 cells. this binding prevents the interaction of HIV1 GP120 and human CCR5 receptor which is necessary for entry into the cells
examples of a nucleoside reverse transcriptase inhibitor
zidovudine
action of NRTI
prevents HIV replactions
active when phosphorylated intracellularly to its triphosphate and then inhibits reverse transcriptase. this causes premature termination of viral DNA elongation
further action of zidovudine
inhibits mammalian lambda and beta DNA polymerase, so increases toxicity in man
side effects of NRTIs
headache
nausea
anemia
leucopenia
neutropenia
examples of non-nucleoside reverse transcriptase inhibitors
nevirapine
delaviridine
efavirenz
action of NNRTIs
bind to reverse transcriptase causing denaturation
induce cytochrome p450
examples of protease inhibitors
saquinavir
ritonavir
action of protease inhibitors
targeting virus specific protease enzyme which is required for post translational processing of gag and gag-pol poly proteins into functional proteins
inhibition of protease interrupts viral spread
examples of highly active anti-retroviral therapy
NRTI + NNRTI or PI
what is a combination pill for HIV treatment
Atripla
contain emtricitabine
tenofovir
efavirenz
what is raltegravir
an integrase inhibitors and inhibits integration of transcribed viral DNA into host cell chromosomes
categories of neuro drugs
sedatives - exert calming effect
hypnotics - sleep inducing
anticonvulsant - inhibit seizures
anxiolytics and antidepressatns - reduce anxiety and stress
antipsychotics - treatment for psychotic disorders
mood stabilisers - anti-manic agents
why target GABA receptors
inhibit neurotransmission
sedatives and hypnotics directly hyperpolarize
muscle relaxants such as baclofen indirectly hyperpolarize by inhibiting K+ channel
what are GABA A receptors
ligand gated
chloride permeable ion channels
