Pharm Term 2b Flashcards
What are prostanoids
Prostaglandin+prostacyclin (which is a type of prostaglandin, PGI2) + thromboxanes d
desirable effects of PGE2 (these are also the SIDE effects of NSAIDS because NSAIDS block these desirable effects)
Bronchodilation (NSAID not given to asthmatics)
Renal salt and water homeostasis (NSAID reduces renal blood flow)
Gastroprotection (NSAIDS increased GI ulcer)
Vasoregulation (dilation and constriction depending on receptor activated, NSAIDS have CVS risks)
name a non selective NSAID
Ibuprofen - inhibits COX 1 and 2
name a COX 2 selective NSAID
coxib family- celecoxib
name a cox 1 selective NSAID
aspirin - irrevserible inhibition
Negative effects of PGE2 (these are the positive effects of NSAIDS)
Increased pain perception (NSAID - analgesia)
Increased body temperature (NSAID- antipyretic)
Acute inflammatory response (NSAID antiinflammatory)
Immune responses
Tumorigenesis
Inhibition of apoptosis
side effects of therapeutic doses of aspirin
Gastric irritation and ulceration Bronchospasm in sensitive asthmatics Prolonged bleeding times Nephrotoxicity Side effects are likely because of the fact that it inhibits COX covalently (irreversibly), not because it is selective for COX-1.
how does paracetamol overdose occur
Paracetamol is metabolised into NAPQI (toxic). Glutathione S transferase is capable of converting this to an inactive reduced form instantly. During overdose, this enzyme is overwhelmed and NAPQI accumulates and oxidises thio groups of hepatic enzymes, leading to cell death (liver failure)
2 types of rate limiting CCB
Phenylalkylamines (e.g. Verapamil)
Benzothiazepines (e.g. Diltiazem)
what are cardiac inotropes? name 2
They increase the contractility of the heart (it is used in acute heart failure in some cases)
Dobutamine (beta-1 agonist)
Milrinone (phosphodiesterase inhibitor)
LDL is associated with atherosclerosis. What other factors can act as ‘boosters’ which further increase the risk of atherosclerosis
Low HDL
smoking
diabetes
hypertension
State some different drug therapies that have been used to treat high cholesterol.
Bile acid sequestrants Nicotinic acid Fibrates Statins Ezetimibe
how do bile acid sequestrants work
They bind to bile acids and stop them from being reabsorbed as part of the enterohepatic recycling. Since bile acids are made from cholesterol, this forces the body to use cholesterol to make new bile acids and hence lowers cholesterol
How do fibrates work
They activate PPAR-alpha
PPAR activation leads to:
- lowered plasma fatty acids and lower triglycerides
- Increased plaque stability (hence) lowers risk of thrombosis from plaque and in general
- decreased inflammation, foam cell formation etc
ezetimibe
reduces cholestrol absorption from small intestine. Starves liver of cholesterol and hence it sucks in more from the blood .
ezetimibe is absorbed and activated to become
Ezetimibe is Absorbed then activated as a glucuronide
what are CETP inhibitors
CETP inhibitors inhibitcholesterylester transfer protein(CETP), which normally transfers cholesterol fromHDL cholesteroltovery low densityorlow density lipoproteins(VLDL or LDL). Inhibition of this process results in higher HDL levels and reduces LDL levels.CETP inhibitors do not reduce rates of mortality, heart attack, or stroke in patients already taking a statin.
Another name for nicotinic acid. Is this drug good?
niacin. most studies have shown that its not very good
What parts of morphine molecule are crucial
tertiary nitrogen (receptor anchoring)
position 3 OH
Position 6 OH
main active metabolite of morphine
Morphine-6-glucuronide
fentanyl and methadone rate of clearance
Fentanyl is metabolised rapidly (it can be broken down by cholinesterases in the blood). (but still the clearance is not as quick as morphine) Methadone is metabolised slowly so remains in the blood for longer (very slow clearance).
Describe the 2 ways of codeine metabolism
CYP2D6 – the metabolism process activates codeine to morphine which is the active metabolite (O-dealkylation) - SLOW
CYP3A4 – deactivates codeine to norcodeine (inactive metabolite)- FAST
Endorphins
Enkephalins
Dynorphins/Neoendorphins
What are these
endogenous opioids
dynorphins function
neuroendocrine functions eg Appetite (hypothalamus)
What are endorphins and enkephalins involved in regulating?
Endorphins: Pain (act on PAG)/Sensorimotor
enkephalins: motor/ cognitive function
3 ways that opiates exert its depressing effect
Hyperpolarisation (increased K+ efflux)
Reduce Ca2+ influx (affects neurotransmitter exocytosis)
Reduce adenylate cyclase activity (general reduction in cellular activity)
what are the main effects of opioids
Analgesia
Euphoria (legally causing euphoria in patients)
Depression of cough centre (anti-tussive)
Depression of respiration (medulla)
Stimulation of chemoreceptor trigger zone (nausea/vomiting)
Pupillary Constriction
G.I. Effects
Urticaria
Describe the passage of pain information from the stimulus to the thalamus.
The painful stimulus is detected by a sensory neurone
This then synapses with a spinothalamic neurone in the dorsal horn, which then passes the information to the thalamus
What happens as the pain information reaches the thalamus?
The thalamus immediately activates the PAG
The thalamus also sends the pain information to the cortex, which processes the pain and modulates the firing of PAG
The way in which the cortex affects PAG firing is based on previous experiences, memories etc.
What does the PAG do once it has received the input from the thalamus?
The PAG activates the nucleus raphe magnus (NRM)
What is the role of NRM?
It sends descending inhibitory neurones down to the dorsal horn
The NRM is responsible for reducing painful sensation (pain tolerance) (descending inhibitory control)
What does the NRPG do?
NRPG – nucleus reticularis paragigantocellularis
It is independent of the thalamus
As soon as you sense pain, the NRPG is activated, which then activates NRM
You’re trying to suppress pain even before the brain has had a chance to think about it
Describe the role of the hypothalamus in this system.
sends info to PAG about general health of the individual which would affect the descending pain control
Describe the role of the Locus Coeruleus in this system.
The locus coeruleus is the sympathetic outflow that has a negative effect on pain perception
A stress response will activate LC and cause pain suppression.
Reason: at a time of stress, you wouldn’t want a painful stimulus to affect your fight or flight response
What structure within the spinal cord acts like a ‘mini brain’?
Substantia gellatinosa
Some of the descending input from the NRM (not all of the input will go through NRM, some will directly inhibit the dorsal horn) will be processed by the substantia gellatinosa, which then decides the level of inhibition necessary
two main neurotransmitters in the afferent pathway between airway to medulla for the cough reflex
ACh
neurokinin (NK)
Describe opioid withdrawal.
Psychological craving
Physical withdrawal resembling flu
What are some features of opioid overdose?
Coma
Respiratory depression
Pinpoint pupils
Hypotension
What is used for opioid overdose? think of the structure
Naloxone - has a long alkyl group attached to the N which makes it an antagonist
