pain killeres

Card 1: Aspirin & Salicylates

Class: Non-Steroidal Anti-Inflammatory Drug (NSAID)

Mechanism of Action: Inhibits cyclooxygenase (COX) enzymes, leading to reduced prostaglandin synthesis.

Therapeutic Uses: Mild pain (Step 1 on WHO Pain Ladder).

High-Yield Side Effects & Toxins:

Peptic Ulcer & Bleeding: Gastrointestinal mucosal injury and prolonged bleeding time.

Reye's Syndrome: Severe brain and liver damage when given to children under 2 years old with a viral infection.

Salicylism (Toxicity): Features fever, bleeding, tinnitus/hearing loss, hallucinations, hyperventilation/increased respiratory rate, tachycardia, hypotension, convulsions, and coma.

Card 2: Morphine

Class: Natural Opioid Agonist

Mechanism of Action:

Agonist at (mu), (kappa), and (delta) G-protein coupled receptors.

Opens post-synaptic K^+ channels➡ hyperpolarization (decreases neuronal excitability).

Closes pre-synaptic voltage-gated Ca^{2+} channels➡decreases excitatory neurotransmitter release (e.g., Substance P in dorsal horn).

Pharmacological Effects:

CNS: Analgesia (spinal & supraspinal), euphoria, drowsiness, pin-point pupils (severe miosis via Edinger-Westphal nucleus stimulation), respiratory center depression, cough suppression, nausea/vomiting (via CTZ stimulation).

CVS & Smooth Muscle: Orthostatic hypotension (vasomotor center depression & histamine release), peripheral bronchospasm, sphincter contraction causing constipation, urinary retention, and biliary pressure increase.

Endocrine: Decreases LH, FSH, and ACTH levels \rightarrow loss of libido, impotence, and menstrual irregularities.

Therapeutic Uses: Severe pain (burns, trauma, post-op, terminal cancer), pre-anesthetic medication, epidural/intrathecal segmental analgesia, and relief of anxiety in acute myocardial infarction or severe internal bleeding.

Contraindications:

Obstetrics: Avoid during labor (causes fetal neonatal asphyxia due to immature blood-brain barrier).

Abdominal Pain: Contraindicated in acute undiagnosed abdomen and diagnosed biliary colic/renal colic (causes sphincter contraction).

Head Injury: Contraindicated due to increased intracranial pressure/respiratory depression.

Organ Failure: Severe hepatic or renal failure.

High-Yield Board Facts:

Non-Tolerated Side Effects: Patients develop tolerance to analgesia, euphoria, sedation, and respiratory depression, but NO tolerance develops to miosis and constipation.

Withdrawal: Autonomic hyperactivity (lacrimation, rhinorrhea, sweating, dilated pupils, diarrhea, hyperpyrexia) and muscle/joint aches.

Overdose Triad: Respiratory depression + Pin-point pupils + Coma (plus hypothermia & hypotension). Treat with Naloxone.

Card 3: Codeine

Class: Natural Opioid Agonist

Mechanism of Action: Low-potency \mu-receptor agonist. Prodrug that requires metabolic conversion (approx. 10%) into morphine for analgesic activity.

Therapeutic Uses: Mild to moderate pain, powerful selective cough suppressant (antitussive), and diarrhea treatment.

High-Yield Board Facts: Significantly lower potency, efficacy, addiction potential, and withdrawal severity compared to morphine.

Card 4: Meperidine (Pethidine)

Class: Synthetic Opioid Agonist

Mechanism of Action: Synthetic(kappa) agonist.

Therapeutic Uses:

Labor Analgesia: Preferred because it does not suppress fetal respiration like morphine.

Colic Pain: Indicated for severe renal and biliary colic because it acts as a smooth muscle relaxant.

High-Yield Board Facts:

Not used for cough or diarrhea.

Less potent than morphine but more potent than codeine.

Causes rapid dependence and short withdrawal symptoms.

Card 5: Tramadol

Class: Synthetic Codeine Analog / Dual-Action Analgesic

Mechanism of Action: Weak \mu-receptor agonist AND blocks reuptake of Norepinephrine (NE) and Serotonin (5-HT) in the CNS

Therapeutic Uses: Mild to moderate visceral pain (diagnostic procedures, injury, surgery).

Contraindications & High-Yield Toxicity:

SSRI Therapy: Strictly contraindicated with SSRIs due to the risk of triggering Serotonin Syndrome.

6.Fentanyl

Synthetic  μ  agonist,  with  80  times  higher  analgesic  effect  & respiratory depression than morphine reversed by naloxone, used in anesthesia⭐️⭐️⭐️

 Because  of  high  lipid  solubility,  it  enters  brain  rapidly  and produces peak analgesia in 5 min after i.v. injection.

 The duration of action is short- 30–40 min

 Transdermal  fentanyl  has  become  available  for  use  in  cancer/ terminal illness or other types of chronic pain for patients requiring opioid analgesia.

Transdermal fentanyl patches are approved in sustained pain.

Rectal administration

Oral  transmucosal  administration:  Fentanyl  in  a  dissolvable  sugar- based lollipop or rapidly dissolving buccal tablet have been approved for the treatment of cancer pain Trans-nasal administration

7.Methadone

Slow tolerance & less physical dependence with mild withdrawal symptoms

 Used for treatment of opioid abstinence (withdrawal) syndrome

 Produces long QT syndrome: potentially fatal adverse effect OPIOID ANTAGONIST Naloxone

 Pure opioid antagonist used to treat respiratory depression in opioid toxicity

 Cause withdrawal symptoms in addicts CHRONIC PAIN: ROUTES OF ADMINISTRATION OF OPIATES

Spinal delivery: Administration of opioids into the epidural or intrathecal space

STAGES OF ANESTHESIA

A.  Stage  1:  Analgesia:  sometimes  with amnesia. Consciousness may be impaired but is not lost.

B.  Stage  2:  Disinhibition:  the  patient  appears to  be  delirious  and  excited.  Amnesia  occurs, respiration is typically irregular

C.  Stage  3:  Surgical  Anesthesia:  the  patient  is unconscious,  no  pain  reflexes;  respiration  is very regular, and blood pressure is maintained.

D.  Stage  4:  Medullary  Depression:  the  patient develops  severe  respiratory  and  cardiovascular depression  that  requires  mechanical  and pharmacologic support to prevent death.

Important concepts!

Characters of an Ideal anesthetic drug:

1.Smooth and rapid induction.

2. Rapid recovery.

3. Wide safety margin.

4. Minimal side effects.

1. MAC (Minimum Aliphatic Concentration)

• Definition: The concentration of an inhaled anesthetic needed to prevent movement (immobility) in 50% of patients during a surgical incision.

• Measure of Potency: Inversely related the lower the MAC value, the more potent the drug.

• Influencing Factors:

  • Decreased by: CNS depressants and aging (elderly patients need less).

  • Increased by: CNS stimulants.

2. Stages of Anesthesia

• Induction: Time from starting the anesthetic until effective surgical anesthesia is reached.

• Maintenance: The period while the patient is actively kept under surgical anesthesia.

• Recovery: Time from stopping the drug until consciousness returns (mainly driven by redistribution from the brain back to the blood, lungs, and other tissues).

3. Factors Affecting the Speed of Induction

The speed of onset and recovery depends heavily on the blood-gas partition coefficient (how quickly the drug equilibrates with blood and reaches the brain). Three main factors control this rate:

• A. Solubility

  • Low solubility➡ Faster induction (quicker to leave blood and enter the brain).

  • High solubility ➡ Slower induction (takes longer to saturate the blood).

• B. Inspired Gas Partial Pressure

  • A higher partial pressure in the lungs leads to faster anesthetic levels in the blood.

• C. Ventilation Rate

  • Greater ventilation ➡ Faster rise in alveolar/blood partial pressure Faster onset of anesthesia.

➡

1. Balanced Anesthesia

• Definition: Using a combination/mixture of drugs (rather than a single high-dose agent) to achieve safer and more effective anesthesia with fewer side effects.

• Components:

  1. Pre-anesthetic medications

  2. Intravenous (IV) anesthetics

  3. Inhaled anesthetics

2. Local Anesthetics (LAs)

• Definition: Blocks sensory nerve transmission from a specific body region to the Central Nervous System (CNS).

A. Routes of Administration / Uses

• Topical application

• Local infiltration

• Field block

• Nerve block

• Intravenous regional anesthesia (Bier block)

• Spinal anesthesia

• Epidural anesthesia

• Ophthalmic use (eye drops/procedures)

B. Nerve Fiber Sensitivity (Differential Block)

Nerve susceptibility depends on diameter, myelination, firing rate, and location:

• Small fibers are blocked more easily than large fibers.

• Myelinated fibers are blocked more easily than unmyelinated fibers.

C. Pharmacokinetics & pH Effect

• Local anesthetics are weak bases.

• Physiologic pH: The uncharged (lipophilic) form predominates, which is essential to cross biological membranes and enter the nerve.

• Infected / Inflamed Tissue (Low pH): The drug becomes mostly charged (ionized/cationic) \rightarrow cannot easily diffuse through membranes \rightarrow reduced anesthetic efficacy.

3. Awake Craniotomy

• Definition: A neurosurgical procedure where the patient is deliberately kept awake for all or part of the surgery.

• Purpose: Allows real-time brain mapping to resect brain tumors located in critical functional areas (e.g., motor or language cortex) without causing permanent damage.

Anesthetic Techniques for Awake Craniotomy

1. Conscious Sedation Throughout ("Awake-Awake-Awake"):

   • Patient remains under moderate sedation throughout the entire case.

   • Common Drugs: Low-dose Propofol and/or Remifentanil infusions, or Dexmedetomidine (a highly selective \alpha_2-adrenergic agonist).

2. Asleep-Awake-Asleep Technique:

   • Asleep Phase: General anesthesia using a rapid-acting agent (e.g., Sevoflurane).

   • Awake Phase: Patient is awakened intraoperatively for brain mapping and testing.

   • Asleep Phase: Patient is re-anesthetized for closure.

CLASSIFICATION OF DRUGS USED FOR GENERAL ANAESTHESIA Inhaled

⚫  Gas: Nitrous oxide

⚫  Volatile Liquids: halothane, desflurane, enflurane⭐⬇ metabolic rate,⬆ ICP (due to cerebral vasodilatation), Dose -dependent EEG changes (Enflurane)⭐️

. Hypotension - Myocardial depression (Halothane, Enflurane)

️isoflurane Intravenous:

⚫  Barbiturates: Thiopentane

⚫  Benzodiazepines: Midazolam

⚫ Opioids: Fentanyl

⚫ Ketamine: produces Dissociative anaesthesia

⚫ Propofol INHALED ANESTHETICS  Example: Gas: Nitrous oxide,

Volatile Liquids: halothane

 Mechanism of action: Facilitate GABA-mediated inhibition, block brain NMDA and AChN receptors

Pharmacokinetics:

⚫  Their partial pressure, or “tension,” in the inhaled air or in blood or other tissue is a measure of their concentration and progress of anaesthesia MINIMUM ALVEOLAR

Hypotension ,Decrease hepatic flow-Hepatotoxicity-(Halothane)⭐️

Halothane-related mild type I hepatotoxicity:  self-limiting,  and  relatively common ,  and  is  characterized by increases in serum  transaminase  and  by altered postoperative  drug metabolism.

 Halothane-related  type  II  hepatotoxicity:  massive  centrilobular  liver  cell necrosis  often  leading  to  fulminant  liver  failure.⬆TFA

Sensitize heart to catecholamines

Myocardial depression

INTRAVENOUS: KETAMINE

PRODUCES DISSOCIATIVE ANAESTHESIA Mechanism of action: Blocks excitation by glutamate at NMDA receptors

Pharmacokinetics: Moderate duration of action—hepatic metabolism

Pharmacological actions: • Analgesia, amnesia and catatonia but consciousness retained • cardiovascular (CV) stimulation Adverse side effects  Increased intracranial pressure

Local Anesthetics

Mechanism of Action

Blocks Voltage-Gated Na+ Channels: Prevents Na+influx ➡ blocks membrane depolarization ➡ halts action potential propagation along the nerve.

Specific Drug Profiles

Lidocaine: Medium-acting; also used as a Class IB antiarrhythmic.

Bupivacaine: Long-acting, but carries a high risk of cardiotoxicity.

Levobupivacaine & Ropivacaine: S-enantiomers with reduced cardiotoxicity compared to bupivacaine.

Proparacaine & Tetracaine: Commonly used for ophthalmic procedures.

Co-administration with Epinephrine

Rationale: Local anesthetics (like lidocaine) cause vasodilation. Adding epinephrine (a vasoconstrictor):

1. Decreases systemic absorption \rightarrow extends duration of action.

2. Reduces peak blood concentration \rightarrow lowers risk of systemic toxicity.

Contraindications: Avoid epinephrine in regions supplied by end-arteries (digits, nose tip, ears, penis) due to the risk of severe ischemia and tissue necrosis.

تجميعات

-A patient came into the ER with lacrimation, increased heart rate, sweating

and dilated pupils. Which drug is used to manage his condition?

A. Naloxon

B. Morphine

C. Opioid

D. Methadone

Answer: D

-.A 50 year old man is having sleep apnea and he wants to take an opioid for

his severe back pain. Which of the side effects will likely occur?

A. Respiratory depression

Answer: A

1. A pregnant woman in labour who previously had biliary colic. What analgesic should be given for her labour?

A. Meperidine

Answer: A

2. A patient came in the ER with lacrimation, increase heart rate, sweating and dilated pupils. Which drug is used to manage his condition?

A. Naloxone

B. Morphine

C. Opioid

D. Methadone

Answer: D

3. Which one of the following drugs is used during labor?

A. Methadone

B. Morphine

C. Meperidine

D. Opioid

Answer: C

4. Which one of the following is used during anesthesia?

A. Fentanyl

B. Tramadol

C. Meperidine

D. Opioid

Answer: A

5. A 20-year-old patient came to the ER with respiratory distress, pin-point pupil, hypothermia and hypotension. What’s the drug of choice to treat him?

A. Morphine

B. Meperidine

C. Codeine

D. Naloxone

Answer: D

الصيغة الاصلية:

Morphine poisoning antidote?

A. Naloxone

Answer: A

6. A 30-year-old woman is undergoing labour, Which of the following analgesic drugs is suitable for her?

A. Morphine

B. Codeine

C. Fentanyl

D. Meperidine

Answer: D

الصيغة الاصلية:

During labour an anesthetic drug is given

A. Meperidine

Answer: A

تجميعات محاضرة Drugs used for anesthesia:

-Which inhalation anaesthetic is associated with dose-dependent EEG

changes?

A. Halothane

B. Enflurane

C. Desflurane

D. Isoflurane

Answer: B

1. Which inhalation anaesthetic is associated with dose-dependent EEG changes?

A. Halothane

B. Enflurane

C. Desflurane

D. Isoflurane

Answer: B

2. What is the mechanism of action of benzodiazepines and barbiturates?

A. Block Na+ channel

B. Enhance GABA inhibition

C. Block Ca++ channel

Answer: B

3. Which one of the following is the mechanism of action of benzodiazepines?

A. Enhance Gaba binding and opening of chloride channel

B. Increase Na influx

C. Increase Ca influx

D. Enhance Gaba binding and closure of chloride channel

Answer: A

4. Which one of the following is used during Anesthesia?

A. Fentanyl

B. Tramadol

C. Meperidine

D. Opioid

Answer: A