MT3 Flashcards
Phytocannabinoids
derived from the Cannabis plant
Synthetocannabinoids
man made
Endocannabinoids
present naturally in the body (eg Anandamide)
toxic effects of soaps/detergents on cells
sodium and alkali kill many bacterias and viruses along with mechanical scrubbing
acids and alkalis toxic effect on microbes
prevent growth;
benzoic acid in food;
heavy metals - toxic effect on microbes
prevent growth
halogens - toxic effects on microbes
hypochlorous acid used in pools with chlorine
Alcohols - toxic effect on microbes
70% alcohol used in labs
Phenols - toxic effects on microbes
disrupts membranes;
Denature proteins;
inactivates enzymes;
oxidizing agents - toxic effect on microbes
disrupt disulphide bonds thus structure of membrane
alkylating agents - toxic effects on microbes
disrupts structure of proteins and nucleic acids
dyes - toxic effects on cells
some interfere with cell replication
Peptidoglycan
the fibrous scaffold in the wall of bacteria
Penicillin-binding protein (PBP)
the enzyme that helps to make the peptidoglycan scaffold
beta lactamase
an enzyme that causes resistance to antibiotics
porins
protein pores that pierce the membrane
pain
an unpleasant sensory and emotional experience associated with actual or potential tissue damage
nociception
the physiological processes in responses to a noxious stimulus
Allodynia
pain in response to a normally innocuous stimulus
hyperalgesia
enhanced pain to a normally painful stimulus
morphine
10% of opium
high analgesia
addictive
most prominent in plant
codeine
0.3-2% of opium
less powerful analgesia than morphine
less addictive than morphine
Heroine
Highly potent analgesia but extremely addictive.
Passes through BBB faster than morphine.
opiate
drugs derived from opium
opioid
agents with opiate-like actions
narcotic
Sleep inducing drugs producing dependence
naloxone
a non-specific opioid receptor antagonist.
therapeutic indication for opioids
- option for cancer pain
- primary option for acute pain
- unclear use for chronic pain (less efficacious, SEs)
- requires continuous assessment
negative side effects of opioids
Severe constipation Somnolescence (sleepy) Cardioresp. depression Tolerance Dependence
tolerance
increased doses required to achieve therapeutic level
203 weeks after frequent opioid use
treating tolerance
Rotation to another opioid
RE-couple to a non-opioid adjunct.
You should start low and go slow.
Physical dependence
Mild: lacrimation, sweating, yawning
Severe: anorexia, cramps, nausea, vomiting, restlessness, irritability, tremor, HR/BP changes, chills, spasms, PAIN
psychological dependence
Compulsive drug-seeking behaviour.
Happens when drugs have mood-enhancing properties
treating dependence
stop drug intake
naltrexone - miu antagonist
methadone - miu agonist
methadone
miu-agonist for treating dependence.
Good oral bioavailability
Selective, long-lasting/slow withdrawal
addiction
state of physical and psychological dependence; preoccupation with acquiring and using drugs despite knowledge of adverse health effects. occurs to detriment of other activities.
paradoxical opioid-induced hyperalgesia
prolonged opioid use leads to increased pain.
- sensitize peripheral nociceptors
- sensitize dorsal horn neurons
- altered descending control mechanisms
Use glutamate antagonist because glutamate receptor involvement.
peripherally restricted opioids
- future of opioid analgesia
- Target pain at source
- Less nociceptor sensitization
- Don’t pass BBB –> less addictoin, CNS effects
how to improve opioid receptor levels
- inhibit B-arrestin activity
- inhibit receptor degradation (protease inhibitors)
- promote receptor recycling
people with arthritis experience
- reduction in quality of life
- disability
- loss of sleep/fatigue
- depression
- PAIN
eicosanoids
Include prostaglandins.
Discovered via knowledge that semen’s vasomotor activity.
Uterine smooth muscle contracts/relaxes in its presence.
prostaglandins
what is it?
how is it made?
involved in causing inflammation and pain.
Produced by oxygenation of arachidonic acid in cell membranes via COX1 or COX2
Aspirin
- Classic NSAID
- Derived from bark of willow trees
- Inhibits COX1 and COX2
- Anti-platelet (clotting)
- 500mg-4g/day
Other NSAIDs
Ibuprofen, naproxen, diclofenac
- COX1/2 inhibitors
- similar pharm to aspirin (analgesic, anti-inflam, but no anti-clotting)
- Longer half-life; more potent
recommendations for CX2 NSAID use
- select patient at low risk for thrombotic events
- prescribe lowest dose required to control symptoms
- add 81mg aspirin + proton pump inhibitor with increased risk of thrombotic events
NSAID/opioid combos
- can’t keep escalating NSAID doese
- FDA requires synergy + better than placebo
- Less likely opioid abuse
- Ease of prescribing combo
- effective analgesia and minimized SEs of each component
topical NSAIDs
- mostly used for arthritis pain
- Minimized central SEs
- Can produce irritation due to vehicle
advantages of smoked cannabis (3)
- pain relief
- improve sleep
- reduced anxiety
disadvantages of smoked cannabis (3)
- not appropriate for all patients
- Psychotropic SEs
- Smoking not safest mode of admin
TRPs
Transient receptors potential channels.
- more than 30 different TRPs and 6 families
- molecular sensors of taste, temp and pain
- many have dual functions
Antibiotics
chemical agents produced by one organism that have some toxic or inhibitory effect on another organism or cell.
selective toxicity
Idea that you can use toxic drugs, which as long as they are more toxic to your target than to normal tissues, can be useful.
- antimicrobial drugs
- anticancer drugs
Bacterosidal
ex.
needed when?
druggs that kill bacteria when they are introduced.
ex. penicillin
required if the patient is immunosuppressed
bacteriostatic drugs
ex.
inhibit growth of bacteria. Growth resumes when the drug was removed.
ex. sulfonamides.
Success depends on there being an effective immune response
what to do about beta lactamases?
1) use a beta-lactamase-resistant antibiotics (eg. Nafcillin)
2) Combine with a beta lactamase inhibitor (Eg. clavulanate)
benefits of newer generations of cephalosporins
1 - better activity against gram -ve
2 - better able to move into tissue spaces
3 - more resistant to B-lactamases
Advantages and disadvantages of using antimicrobial drugs in combinations
ADVANTAGES:
- wider spectrum for mixed infections.
- Reduced dose for individual agents.
- Synergism between antibiotics.
DISADVANTAGES
- Increased possibility of adverse reactions.
- Antagonism between antibiotics.
- Greater risk of antibiotic resistance.
Example of an antagonistic antibiotic combination
Chloramphenicol + aminoglycoside
4 methods of antibiotic resistance
1) Decreased entry
2) Bypass pathway
3) Enzymatic degradation
4) Altered target gate
Sulfonamide resistance (3)
May be due to
- Decreased permeability of cell membrane
- Bacteria make a diff form of DHPS that binds sulphonamide poorly.
- Increased production of PABA made by the bacteria.
Trimethoprim resistance (3)
May be due to:
1) Decrease perm of cell mem
2) Bacteria prod a form of DHFR that binds trimethoprim poorly
3) Bacteria prod more DHFR
Cancer definition
Loss in the normal control mechanisms that govern cell survival, proliferation, and differentiation
Principles of chemotherapy
- Agent must be tolerable to treatment can be completed
- Administer max tolerable dose
- Cyclic therapy with dose and regimen chose for max effectiveness
- Combinations to increase efficacy
- Surgery followed by chemo
Modes of interfering with TK signalling
- MOA against TK ligand
- MOA against TKR
- Small molecule inhibitors
primary resistance to drug
- drug is ineffective on first attempt
- most commonly related to impaired response to cell death signals in tumour cells
acquired resistance
- drug worked at first, then became ineffective
- related to adpatation and mutation of tumour cells
