Pharm Term 2b

Question 1

What are prostanoids

Answer 1

Prostaglandin+prostacyclin (which is a type of prostaglandin, PGI2) + thromboxanes d

Question 2

desirable effects of PGE2 (these are also the SIDE effects of NSAIDS because NSAIDS block these desirable effects)

Answer 2

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)

Question 3

name a non selective NSAID

Answer 3

Ibuprofen - inhibits COX 1 and 2

Question 4

name a COX 2 selective NSAID

Answer 4

coxib family- celecoxib

Question 5

name a cox 1 selective NSAID

Answer 5

aspirin - irrevserible inhibition

Question 6

Negative effects of PGE2 (these are the positive effects of NSAIDS)

Answer 6

Increased pain perception (NSAID - analgesia)
Increased body temperature (NSAID- antipyretic)
Acute inflammatory response (NSAID antiinflammatory)
Immune responses
Tumorigenesis
Inhibition of apoptosis

Question 7

side effects of therapeutic doses of aspirin

Answer 7

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.

Question 8

how does paracetamol overdose occur

Answer 8

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)

Question 9

2 types of rate limiting CCB

Answer 9

Phenylalkylamines (e.g. Verapamil)

Benzothiazepines (e.g. Diltiazem)

Question 10

what are cardiac inotropes? name 2

Answer 10

They increase the contractility of the heart (it is used in acute heart failure in some cases)
Dobutamine (beta-1 agonist)
Milrinone (phosphodiesterase inhibitor)

Question 11

LDL is associated with atherosclerosis. What other factors can act as ‘boosters’ which further increase the risk of atherosclerosis

Answer 11

Low HDL
smoking
diabetes
hypertension

Question 12

State some different drug therapies that have been used to treat high cholesterol.

Answer 12

Bile acid sequestrants  
Nicotinic acid 
Fibrates  
Statins 
Ezetimibe

Question 13

how do bile acid sequestrants work

Answer 13

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

Question 14

How do fibrates work

Answer 14

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

Question 15

ezetimibe

Answer 15

reduces cholestrol absorption from small intestine. Starves liver of cholesterol and hence it sucks in more from the blood .

Question 16

ezetimibe is absorbed and activated to become

Answer 16

Ezetimibe is Absorbed then activated as a glucuronide

Question 17

what are CETP inhibitors

Answer 17

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.

Question 18

Another name for nicotinic acid. Is this drug good?

Answer 18

niacin. most studies have shown that its not very good

Question 19

What parts of morphine molecule are crucial

Answer 19

tertiary nitrogen (receptor anchoring)
position 3 OH
Position 6 OH

Question 20

main active metabolite of morphine

Answer 20

Morphine-6-glucuronide

Question 21

fentanyl and methadone rate of clearance

Answer 21

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).

Question 22

Describe the 2 ways of codeine metabolism

Answer 22

CYP2D6 – the metabolism process activates codeine to morphine which is the active metabolite (O-dealkylation) - SLOW
CYP3A4 – deactivates codeine to norcodeine (inactive metabolite)- FAST

Question 23

Endorphins
Enkephalins
Dynorphins/Neoendorphins
What are these

Answer 23

endogenous opioids

Question 24

dynorphins function

Answer 24

neuroendocrine functions eg Appetite (hypothalamus)

Question 25

What are endorphins and enkephalins involved in regulating?

Answer 25

Endorphins: Pain (act on PAG)/Sensorimotor enkephalins: motor/ cognitive function

Question 26

3 ways that opiates exert its depressing effect

Answer 26

Hyperpolarisation (increased K+ efflux) Reduce Ca2+ influx (affects neurotransmitter exocytosis) Reduce adenylate cyclase activity (general reduction in cellular activity)

Question 27

what are the main effects of opioids

Answer 27

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

Question 28

Describe the passage of pain information from the stimulus to the thalamus.

Answer 28

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

Question 29

What happens as the pain information reaches the thalamus?

Answer 29

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.

Question 30

What does the PAG do once it has received the input from the thalamus?

Answer 30

The PAG activates the nucleus raphe magnus (NRM)

Question 31

What is the role of NRM?

Answer 31

It sends descending inhibitory neurones down to the dorsal horn The NRM is responsible for reducing painful sensation (pain tolerance) (descending inhibitory control)

Question 32

What does the NRPG do?

Answer 32

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

Question 33

Describe the role of the hypothalamus in this system.

Answer 33

sends info to PAG about general health of the individual which would affect the descending pain control

Question 34

Describe the role of the Locus Coeruleus in this system.

Answer 34

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

Question 35

What structure within the spinal cord acts like a ‘mini brain’?

Answer 35

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

Question 36

two main neurotransmitters in the afferent pathway between airway to medulla for the cough reflex

Answer 36

ACh | neurokinin (NK)

Question 37

Describe opioid withdrawal.

Answer 37

Psychological craving | Physical withdrawal resembling flu

Question 38

What are some features of opioid overdose?

Answer 38

Coma Respiratory depression Pinpoint pupils Hypotension

Question 39

What is used for opioid overdose? think of the structure

Answer 39

Naloxone - has a long alkyl group attached to the N which makes it an antagonist