Analgesics

Question 1

Anti-nociceptive action

Answer 1

Periaqueductive efferent tract,in the spinal cord release ofserotonin (5-HT),norepinephrine (NE) andencephalins (Enk) is stimulated and thus primary afferent painimpulse (SP, Glu) transmission is blocked

Question 2

MOA analgeisa

Answer 2

1. NSAIDs response to peripheral stimuli (inflammation) - modulation of signal transduction by reducing hyperalgesia andsensitization of nociceptive neurons.
2. Na + channel blockers reduce action potential transmission in nociceptive fibers.
3. Opioid and non-opioid analgesics, antidepressants, antiepileptics andα2-adrenoceptor agonistsaffect signal transduction in the ascending and / or descending pathways (peripheral to CNS or vice versa)

Question 3

OPIODS

Answer 3

three subtypes of opioid receptors mu (OP3 or MOP), delta (OP1 or DOP),kappa (OP2 or KOP)

Opioid receptor agonists stimulatepresynaptic Ca2 + channel blockade,thus inhibiting the excitablerelease of neurotransmitters (e.g. glutamate, substance P, CGRP) and the opening of postsynaptic K + channels, leading to hyperpolarization and non-excitability of the postsynaptic poleSpinal analgesia reduces signal transduction in afferent fibers Supraspinal analgesia -reduces neuronal activity in Thalamus

Question 4

Effects of opioid receptors

Answer 4

spinal analgesia
supraspinal analgesia
respiratory depression
sedation
dysphoria, hallucinations
euphoria
muscle rigidity
vasodilation
bradycardia
puritis
nausea, vomiting
decreased cell immunity
myosis
decreased gastro-int motility
cough suppression

Question 5

MorphineOxycodone

Answer 5

µ, δ, k receptor agonists
Analgesic and sedative effects

Traumatic pain relief
Postoperative pain (multimodal analgesia)
Tumor-induced pain (basic pain)CHF with pulmonary edema (morphine only)

Question 6

Fentanyl

Answer 6

µ, δ receptor agonist, partial receptor agonist for the k receptorAnalgesic activitystronger than morphine,sedative effect(lipophilic, short acting) (lipofils, īslaicīgs)
Tumor pain (breakout pain)

Question 7

Tramadol

Answer 7

Weak receptor affinity for µAnalgesic effect enhanced by * SNRI (especially SSRI)Analgesic and sedative effects
Pretsāpju un sedatīva iedarbība

Moderate intensity pain

Question 8

Buprenorphine

Answer 8

Partial agonist of µ receptors, antagonist of k Very strong µ receptor affinity, low intrinsic activity and very slow dissociation. Mild k receptor antagonist.The effect on δ receptors is unclearAnalgesic and sedative effectsApplicable to addiction reduction programs in the detox phase
Abstinence of potent opioid receptor agonists or opiates
Severe to moderate pain

Question 9

Opioid antagonists

Answer 9

NaloxoneSignificant µ, δ, k opioid receptor antagonismShort-term action
Opioid overdose
Limiting abuse of buprenorphine
Reducing the risk of opioid-induced constipation

Question 10

Side effects of opioid

Answer 10

Respiratory depression (possible at therapeutic doses)(children and the elderly are very sensitive to morphine!)
Nausea, vomiting (~ 40% of cases cause temporary irritation of the vomiting center)
Suppression of cough reflex (interferes with evacuation of bronchial secretion)
Pupil constriction (miosis)(differential diagnosis, barbiturates dilate pupil)
Increase in GI tone (constipation)
Bradycardia, hypotension
Itching (histamine induced)
Increasing the tone of the Oddi Sphincter
Increasing urinary tone (urinary retention)
Muscle rigidity
Euphoria (if the disease is painful - reduces anxiety)
Tolerance (increase the dose gradually to produce an effect)
Addiction (propensity to use)
Abstinence (pain, epileptic seizures after discontinuation)O

Question 11

Opioid overdose

Answer 11

Triad of symptoms: miosis, coma, respiratory depression

Question 12

Non-opioid analgesics

Answer 12

Paracetamol

Prostaglandin H2 synthetase inhibitorInhibition of COX2 / COX3 in the CNSInhibition of PG synthesis centrallyHas a central effect on the proinflammatory cytokine release

Analgesic and antipyreticwith a slight anti-inflammatory effect(unable to block COX in locally where acidic environment is determined by peroxides)

Short-term treatment of moderate intensity postoperative pain i / v
Symptomatic treatment of mild to moderate pain p / o
Fever

Question 13

Paracetamol overdose

Answer 13

Lethal dose for adults 7-10 gSymptoms progress within 4-6 days -liver failure (hepatic cytolysis), encephalopathy and coma

In case 2 the active intermediate metabolite is formedNAPQI (N-acetyl-p-benzoquinone imine),which is rapidly neutralized by glutathione at therapeutic doses.Increasing the dose of paracetamol depletes glutathione reserves,NAPQI levels increase and liver failure develops

Antidote that restores glutathione reserve - acetylcysteine i / vin the first 10 h
IA: Ethanol enhances paracetamol toxicity

Question 14

Serotonin (5HT1) receptor agonists

Answer 14

ZolmitriptanSumatriptan5HT1d agonists, 5HT1b partial agonists, vasoconstriction of blood vessels of brain sheath, analgesic effect

Migraine attack therapy

Question 15

CGRP antagonist

Answer 15

Galkanezumab
Erenumab

Migraine attack prophylaxis

Question 16

CO-analgesics

Answer 16

ClonidineAdjuvant opioid therapyCarbamazepineN. trigeminus neuralgiaValproic acidPrevention of migraine attacksGabapentinPostherpetic neuralgiaAmitriptylineFibromyalgia