Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology. > 14. Analgesia > Flashcards

14. Analgesia Flashcards

1
Q

How does clonidine work?

A

Alpha 2 adrenergic receptor agonist that causes pre-synaptic re-uptake of norad

If works peripherally.
Central causes analgesia at alpha 2 in substantial gelatinisation of cord

Less resp depression and N&V than opiates but more sedation and hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What kind of drug is paracetamol?

How does it work?

A

Atypical nsaid

Inhibits cox 1 and 2 and therefore prostaglandin synthesis
Increased cannabinoid receptor activation
Inhibits descending serotenergic pathways

Analgesic and antipyretic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What can paracetamol be useful for pre-op?

A

Given 1h prior to op, can stop central sensitisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the onset time, peak and duration of paracetamol IV and oral?

A

IV = 5min, peak in 40-60 and lasts 6h

Oral = onset 40m, peak 1-2h

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is paracetamol excreted?

A

Renal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the toxic doses of paracetamol OD?

What is the treatment?
S/E?

A

Potential hepatic injury at over 10g in over 50kg and over 150mg/kg in under 24h in under 50kg
Over 800mg/l can cause coma or lactic acidosis

Gastric decontamination within 1h
100% survival if NAC within 8h - hydrolysed to cysteine intracellularly to replenish glutathione stores
S/E: rash, N&V, angioedema, flushing, tachy, bronchospasm and hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the mechanism of aspirin?

A

Irreversible non-selective cox inhibitor.

Inhibits prostaglandin production, prostacyclins and thromboxane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the pathway of prostaglandin synthesis?

What drugs interact with the different steps?

What are the final products?

A

Essential fatty acids —> membrane phospholipids

Phospholipase A2 converts this to arachidonic acid (blocked by steroids)

Arachidonic acid can either be converted to leukotrines by lipoxygenase or to prostaglandin H2 by cox (inhibited by NSAIDs.

H2 makes:
Prostacyclin (vascular endothelium): increases platelet camp, but reduces activation and causes vasodilation
Prostaglandins (everywhere): smooth muscle control, inhibit gastric acid, hyperalgesia and renin release
Thromboxane A2 (platelets): increased platelets, aggregation and vasoconstriction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What do NSAIDs cause bronchospasm?

How many people does this effect?

A

Preventing formation of prostaglandin H2 causes arachidonic acid to go down other pathway to make leukotrienes

Effects 10-20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the selective and non selective NSAIDs?

A

Non = aspirin, diclofenac, ketorolac and ibuprofen

Selective = parecoxib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the good and bad effects of aspirin?

A

Analgesia
N&V (stimulates CTZ)
Respiratory alkalosis
Metabolic acidosis
Blood sugar reduced at low doses and increased at high doses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the metabolism and excretion of aspirin?

A

Rapidly metabolised by hepatic and intestinal esterases to form salicylate. Then various pathways in the liver. Two become saturated at low doses, changing from first to 0 order kinetics.

Renally excreted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the toxic levels of aspirin?

The effects?

The treatment?

A

Poisoning signs at 40-50mg/dl (2.9-3.6mmol)

Death at over 10g and 3 in kids
Mild = under 500mg/L
Moderate 500-750
Severe = over 750

See respiratory alkalosis or mixed. Alkalosis traps salicylate anions in the blood (avoid intubation or give high MV). Glucose, Coag abnormalities and AKI

Needs repeated level measurements
Charcoal in under 1h
Correct electrolytes
Vit K if prolonged PT
Glucose normalisation
Bicarbonate (2h K levels if giving this) for acidosis and urinary alkalinization
Haemodialysis if severe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the cox’s and where is each found/do?

A

Isoenzymes of each other.

Cox 1: Stomach = gastroprotection, renal = Na and water balance, platelets = aggregation

Cox 2: normally in brain, kidney, ovary and uterus (contributes to embryo implantation and labour)
Can be induced to be involved in: inflammation, pain and fever.

Cox 3: splice variant, thought to be involved in central pain.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Do we usually use selective cox 2 inhibitors?

A

No most have been withdrawn due to higher risk of VTE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the different routes for NSAIDs and what drugs use each?

A

IV = ketorolac and parecoxib
Diclofenac: oral, IV or PR
Rest oral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the general kinetic features of NSAIDs and interactions?

A

A: weak acid so rapid upper GI absorption
D: highly protein bound, can displace other protein bound e.g. morphine and phenytoin
M: high oral BA due to lower first pass
E: renal

Interact with methotrexate and lithium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When are NSAIDs used with caution?

A

Pre-eclampsia
Pregnancy
Surgeries with high bleeding or bleeding risk
Co-morbidities
No aspirin in kids (Reyes)

No increased risk with regional

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is opium?

A

Mix of alkaloids from papaver sominferum opium poppy juice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the difference between opiates and opioids?

A

Opiates are naturally occurring
Opioids are natural or synthetic with morphine like properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is a narcotic?

A

Narco is Greek for numb
Drugs with analgesic and sedative properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where are endogenous opioids mostly found?

A

Hypothalamus, pituitary, periductal aqua grey, brain stem and substantial gelatinosa

Also some peripheral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the three main categories of endogenous opiates?

Receptors?

Effects?

A

Endorphins: hypothalamus and pituitary. Predominantly Mu with some delta. Give analgesia and euphoria

Enkephalins: predominantly delta, some mu. Nociception

Dynorphins: kappa receptors. Analgesia, appetition regulation and circadian rhythm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What type of receptors are opiate receptors and what are the three main types?

A

All GCPR

Mu, delta and kappa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What’re are mu receptors found?

Main agonists?

Antagonists?

Effects?

A

CNS and GI tract

Agonists: opioids and buprenorphine

Antagonists: nalpuphine and nalorphine (these are agonist antagonists as they agonise kappa receptors - antagonise morphine, but activate kappa, so if given at same time, they put a ceiling on morphine analgesia and respiratory depression). Also naloxone

Effects: analgesia, dependence, euphoria, respiratory depression etc (think IVDU)

26
Q

What’re are delta receptors found?

Main agonists?

Antagonists?

Effects?

A

Olfactory bulb, cerebral cortex, nucleus accumbens and caudate putamen

Agonists: none available

Antagonists: naloxone

Effects: analgesia and hormone release

27
Q

What’re are kappa receptors found?

Main agonists?

Antagonists?

Effects?

A

CNS

Agonists: morphine, nalorphine and nalbuphine

Antagonists: naloxone and naltrexone

Effects: analgesia, sedation, miosis and higher dysphoria than mu

28
Q

What is the main mechanism of action of opioids?

A

Inhibit descending pathways by:
Reduced signalling in substantial gelatinosa
Reduction of neurotransmitter release from pre-synaptic
Hyperpolarisarion of post synaptic reducing AP

Also in peripheral sensory neurones. Inflammation up regulates receptors and causes localised endogenous release of opiates

29
Q

What is a broad overview of the pain pathway e.g. ascending and descending?

What do opioids do to this?

A

Peripheral afferent synapses in dorsal horn
Ascending pathway goes up through nucleus raphe to periductal aqua grey in the pons (and to other parts of brain)
GABAergic interneurones reduce activity of descending inhibitory pathways

Opioids inhibit gaba release and so causes disinhibition of these pathways and reduces activity in the afferent nociceptive pathways through norad and 5HT release.

30
Q

What are the different classification types for opiates?

A

Source
Receptor affinity
Potency
Family

31
Q

What are the different source classifications of opioids?

Drugs?

A

Natural = morphine codeine and thebaine
Semisynthetic (derived from natural sources) = diacetylmorphine (heroin) and hydromorphone from morphine. oxycodone and hydrocodone from codeine and buprenorphine from thebaine.
Synthetic = fentanyl etc.

32
Q

What are the different receptor affinity classifications of opioids?

Drugs?

A

Full agonist e.g. fentanyl and morphine and pretty much all the others except below.

Partial: buprenorphine

Antagonists: naloxone

Mixed agonist and antagonist: nalbuphine and nalorphine

33
Q

What are the respiratory effects of opioids?

A

Direct suppression of rhythm generation in the venterollateral medulla
Reduced central CO2 sensitivity
Reduced peripheral sensitivity to hypoxia
Cough supression
Chest wall rigidity

34
Q

What are the CVS effects of opioids?

A

Brady and hypotension due to decreased sympathetic tone
Anaphylaxis and peripheral vasodilation due to histamine release

35
Q

What are the neuroendocrine effects of opioids?

A

Reduced ACTH, prolactin and gnrh secretion

Increased ADH

36
Q

What are the urinary effects of opioids?

A

Retention due to increased detector tone and inhibition of voiding reflex

37
Q

What is the difference between tolerance, dependence and addiction?

A

Tolerance = decreasing effect to same dose
Dependence = withdrawal on cessation
Addiction is a poly system disease, with a power compulsion to use despite not being medically needed.

38
Q

What are the 4 different forms of u agonist and drugs?

A

Morphinans: morphine, codeine etc.
Phenylpiperdines: pethidine, fentanyl and alfentanil
Diphenolpropylamines: methadone
Esters: remi

39
Q

How did morphine get its name?

A

Morpheus the Greek god of dreams

40
Q

What is the metabolism and excretion of morphine?

A

Glucuronidation in the liver and gut = enterohepatic recirculation
70% morphine 3 glucuronide
Small amount demethylated to normorphine
Rest to M6G which is more potent than morphine (most of pharmacological activity)

All renally excreted so accumulate in CKD

41
Q

What is diamorphine?

Metabolism?

A

Semi synthetic : 3,6 diacetylmorphine which is a prodrug with no u receptor activity until metabolised by tissue and plasma esterases to 6-MAM and then morphine

42
Q

What is papervertum?

A

Semi synthetic mix of 80% morphine, codeine and papeverine

43
Q

What is the structure of oxycodone?

What receptor does it work on?

What is the oral BA?

How is it metabolised?

A

Semi synthetic: codeine molecule with 6-hydroxyl group replaced with a ketone group

Full u agonist

Higher oral bioavailability than morphine at 60%

Predominantly N-demethylation to noroxycodone (weak effect) and small amount to oxymorphone (strong activity)

44
Q

What is thebaine?

Formulation?

Uses?

A

Opioids with stimulant effect that can produce convulsants at thigh doses

Natural entantiomer is inactive, but synthetic work on opioid receptors

Not used clinical but is part of oxycodone and naloxone production

45
Q

What is pethidine and what receptors does it work on?

What is its lipid solubility?

Metabolism and excretion?

What are the bad effects/interactions?

A

Opioid with u and cholinergic receptor activity

Higher lipid solubility than morphine so faster onset and shorter duration

Phase 1 metabolism to 3 metabolites including norphethidine. Renally eliminated

Interacts with MAOi’s and can cause seizures of accumulates

46
Q

What happens with one and repeated/high blouses of fentanyl?

A

One = raid redistribution and 13m half life, but rapid fall to subtherapeutic

Repeated/high = remaining high plasma volume after redistribution so offset dependent on elimination which is slow 3-4h.

47
Q

How is fentanyl metabolised?

A

Dealkylated to norfentanyl - inactive

48
Q

What doses of fentanyl are required to abolish surgical stress response?

What are the side effects of this?

A

Over 50mcg/kg

Can cause: Brady, hypotension and chest wall rigidity

49
Q

What ways can we give fentanyl?

A

Iv
Patch (2 days to steady state)
Lollipop (avoids first pass metabolism)

50
Q

What is remi derived from and how does its speed and potency compare to fentanyl?

A

Fentanyl derivative
Similar speed and potency

51
Q

What is the metabolism and CSHT of remi?

Excretion?

What can boluses causes?

A

Has two ester links
Metabolised via hydrolysis by tissue and red cell esterases (unaffected by anticholinesterases as not plasma cholinesterases). These aren’t subject to polymorphisms. Broken down to carboxylic acid derivative with 1% potency

Half time post infusion stopping is 5m irrespective of infusion time

Renally excreted

Boluses can cause Brady and hypo and arrest. Need to flush cannula at the end to avoid this.

52
Q

What is the formulation of tramadol?

What receptors does it work on? What does this mean for naloxone?

A

Codeine analogue

Racemic mixture of two stereoisomer’s
One is a weak opioid agonist with some u selectivity, but also inhibits neuronal re-uptake of 5-HT
Other inhibits neuronal uptake of norad effecting descending pathways. Partially reversed by naloxone

53
Q

What are the OD effects of tramadol?

A

Some Opiate signs e.g. small pupils

Mostly serotonergic and can cause serotonin syndrome

54
Q

What is the metabolism and excretion of tramadol?

A

Four different pathways and one having a greater u affinity than parent

Can accumulate in AKI

55
Q

What is codeine and where does it come from?

What receptors does it cover?

A

Weak opiate in opium poppy at lower levels than morphine

Works at u but a little bit of delta and kappa

56
Q

What is the metabolism of codeine and what individual differences are seen?

A

Pro drug with 10 undergoing o methylation to active metabolite (morphine) and the demethylayed to inactive.

2D6 - rapid metabolisers = OD
9% of white people have a complete absence so no response.

57
Q

What is DHC?

BA?

Metabolism?

A

Synthetic codeine derivative

20% oral BA (poor absorption and high first pass)

Metabolised to dihydromorphine and norhydrocone

58
Q

What is buprenorphine and what receptors does it work on?

What causations must we take when giving it?

A

Partial u receptor agonist (also KOR and DOR)

Need to make sure other opiates have work off as partial u agonist can have a stronger affinity than other drugs, displacing them and causing withdrawal. Stop 24h before surgery and replace with other drugs.

59
Q

What is the BA of buprenorphine and routes?

Metabolism and excretion?

Is it reversible by naloxone?

A

Poor oral BA (30-60%) so given by SL, nasal, transdermal or buccal.

Metabolised to norbuprenorphine (full agonist) and excreted in bile.

Duration of action = 10h so hard to reverse with naloxone

60
Q

What is naloxone?

What is the receptor affinity?

How is it given and why?

Timings?

What are the side effects?

A

Competitive opioid receptor antagonist
Predominantly MOR but also DOR and KOR
Low oral BA so IV, IM or nasal
Works in 2m and last 30-45m (elimination HL = 2.5h)
Can cause HTN, arrhythmias and pulmonary oedema

61
Q

What is naltrexone? What receptors?

How is it given?

Metabolism and excretion?

Uses?

Timings?

A

Competitive MOR and KOR agonist
High oral but can also give IM or implant
Liver metabolism and renal excretion
Long term management of opioids or alcohol
Works in 30m and HL of 4h active metabolite has a duration of 24h

Pharmacology. (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions