PHARMACOLOGY Flashcards
Antidote for opioid overdose
Naloxone
Drug for opioid withdrawal - partial agonist
buprenorphine
Morphine oral vs IV/ IM dosing equivalents
Oral - 50% bio-availability after first pass metabolism in liver
TF need to give half the dose if giving IV/ IM
10mg oral morphine equivalent to 5mg IV, IM, s/c
How long does single dose of morphine last
2-3 hours
What id the difference between potency and efficacy of a drug
Potency = DOSE. how well does the drug bind to the receptor. strength - 'Strong or weak'. Efficacy = RESPONSE. once drug is bound, how well does it bring about an effect (eg pain relief). Is it effective?
What is the difference between tolerance and dependance
Tolerance - receptors dowregulate in response to flooding (too much activity; prolonged use) = need increased potency to get efficacy (desired effect). Shift to RIGHT on dose-response curve.
Dependence is when you are addicted to a drug. This includes tolerance, withdrawal syndrome and another feature of dependence (eg drug seeking)
How do opioids work?
Inhibit endogenous pain circuit by activating opioid receptors
=inhibit ascending pain signals from peripheries/ spinal cord
=modulate pain perception in cerebral cortex (eg insula etc)
List the opioid receptors
Mu, Kappa, Delta, Nociceptin (pain)
All painkillers work on mu opioid receptors (not kappa or delta - these are more linked to depression)
Opioid side effects
Respiratory depression (inhibitory actions at brainstem respiratory nuceli - specifically, pre-botzinger nuceli) Sedation Nausea and vomiting Constipation (slows gastric emptying) Itching Immune supression
Opioid induced respiratory depression- outline management
Call for help
ABC
Naloxone IV - start low and titrate upwards till get effect.Short half life. (30 minutes)
Adult dose - usually 1ml in 10 mls of saline.
Cautions on morphine metabolism & renal failure
Morphine is metabolised by liver into a more potent form - morphine 6 glucuronide. This is usually cleared quickly in person with normal renal function.
If pt is <30% renal function, use ocycodone, as risk build up of potent metabolite that increases risk of respiratory depression
Patients at risk of opioid induced respiratory depression
High dose in opioid naive, or large acute dose (drug user)
Tolerance develops to opioid induced resp depression, so if pt has been started low and titrated up shouldnt get this. But if they have had big dose, without titration, at risk.
Cautions of tramadol and antidepressants
Tramadol acts on opioid receptors and 5HT, NA pathways. It is 5HT and NA reuptake inhibitor. So it will interact with MAO reuptake inhibitors and SSRIs
Cautions of opioids and liver failure
Avoid use or reduce dose; may precipitate coma in patients with hepatic impairment.
Bc liver function impaired, can’t adequately metabolise drug, half life of opioid t/f increases and adverse drug reactions (eg overdose) are more likely. The pre-metabolism drug compound may also be toxic, and accumulate for longer in the liver to cause liver injury.
Basically, drugs that are of low hepatic risk in a healthy person, become higher risk in pt with liver disease bc of increased accumulation of pre-metabolism compound or slow metabolism and increased t1/2.
Patient found unconscious, presents with:
mild jaundice
spider nevi
history of heavy drinking
Was suffering headache - took codine to manage this
What has happened?
The pt has inadvertently overdosed on codine and become sedated.
They have chronic liver disease (alcohol induced) so the t1/2 of the opioid in increased, Increased accumulation of active metabolite = overdose.
Patients with liver disease are more sensitive to opioids - bc there is impaired metabolism and altered half life.
What happens when you have changes in drug metabolism (eg chronic liver failure)
- Drugs have increased half life - stay around for longer in the circulation. Relevent to opioids & sedatives, that may interact with effects of liver induced encephalopathy.
- Get increased toxic metabolite, because of slower metabolism - eg analgesics.
- Liver is more sensitive to toxicity. Eg, liver toxic drugs - antibiotics, CNS drugs & some NSAIDS eg Diclofenac.
Common drugs that are toxic to the liver
Antibiotics, CNS drugs and diclofenac
Common drugs that can cause coma in patients with liver damage
Any analgesic of sedative
Increased half life = higher dose
This can have additive effect to ammonia induced encephalopathy = sedation & coma
Prescribing in liver disease - describe the main prescribing concerns/ red flags for a patient with liver failure
- Opioids/ sedatives/ any analgesic that can have its potency increased through slower metabolism, or have additive effect to hepatic encephalopathy
(NB, most opioids & NSAIDs are not toxic to the liver, but when there is liver injury, there is potential overdosing problems and additive effects to ammonia levels) - Caution with renal drugs.
NSAIDs, diuretcs etc. Bc, if pt gets any changes in fluid load this can set off liver, so want to avoid any renal toxic drugs. Diuretics (Loop & Thiazide) can also cause hypokalemia that will set off liver. - Caution using any blood thinner - heparin, warfarin, antithrombotic etc.
Pt is at risk of bleeding, bc of varices - hemorrhage risk with antithrombotics meds.
4.Caution any steroid - bc pt will have fewer proteins to bind steroid, will get increased free steroid and have greater effect.
What enzyme synthesises estrogen
Aromatase
What are aromatase inhibitors and what are they used for
Inhibit the synthesis of estrogen
Used in breast cancer treatment
What does HER2 stand for
Human epidermal growth factors
