GET BACK TO THE BOOK
AND TO THE WORD FILE
Drugs for neuropathic pain
CHECK THE TABLE IN THE WORD FILE
Pain due to diabetic neuropathy may be difficult to control and require multiple medications. To reduce the risk of adverse effects and improve pain control, medications should work through different mechanisms. One such combination may include a tricyclic antidepressant (eg, nortriptyline) and an anticonvulsant (eg, gabapentin).
LOCAL ANSTHESIA
Epinephrine is often added to lidocaine to produce vasoconstriction, which prolongs the duration of action of lidocaine, decreases bleeding during a procedure, and reduces systemic lidocaine absorption.
MOA: Lidocaine is a local anesthetic that interrupts nerve fiber transmission by blocking sodium channels in the neuronal cell membrane, preventing depolarization of the nerve
uncharged form – diffuse through the cell membrane
charged form –unable to penetrate the cell membrane LIKE:
Increased acidity in the surrounding tissue (INFLAMATION)
Absence seizures
a type of generalized epilepsy
Absence seizures are characteristically provoked by hyperventilation, and electroencephalogram will show generalized 3-Hz spike-wave complexes.
TX :ethosuximide
(blocking thalamic T-type Ca2+ channels.)
IF OLDER CHILDREN WITH BOTH absence seizures AND generalized onset tonic-clonic or myoclonic seizures. Treatment with a broad-spectrum antiepileptic such as valproic acid is required in these patients because it is effective for both absence and tonic-clonic seizures.
Cholinergic toxicity فكرة مهمة
1.Muscarinic effects (DUMBELS)
Diarrhea/diaphoresis
Urination
Miosis
Bronchospasm, bronchorrhea & bradycardia
Emesis
Lacrimation
Salivation
2.Nicotinic effects
Muscle weakness, paralysis & fasciculations
VERY IMPORTANT :
Organophosphates inhibit cholinesterase in both muscarinic and nicotinic cholinergic synapses, leading to decreased acetylcholine degradation and overstimulation of the corresponding receptors.
Atropine reverses muscarinic effects but does not prevent the development of nicotinic effects such as muscle paralysis.
Pralidoxime is a cholinesterase-reactivating agent that allows for degradation of excess acetylcholine and treats both the muscarinic and nicotinic effects of organophosphates.
antiepileptic
1.Phenytoin and other antiepileptic medications are inducers of cytochrome P-450 (CYP) enzymes, including CYP24, which converts 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D (inactive form). As a result, there is less 25-hydroxyvitamin D available for conversion to 1,25-dihydroxyvitamin D (active form), leading to deficiency.
2.Gingival hyperplasia is a common side effect of phenytoin and is sometimes reversible when phenytoin is withdrawn. Phenytoin causes increased expression of platelet-derived growth factor (PDGF)
3.Phenytoin metabolism depends on the function of hepatic P450 oxidases and is dose-dependent. Drugs that induce hepatic microsomal enzymes (phenobarbital, carbamazepine, and rifampin) enhance phenytoin metabolism and decrease its serum concentration.
4.Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome typically occurs 2-8 weeks after exposure to high-risk drugs such as anticonvulsants (eg, phenytoin, carbamazepine)
5.NOTE THAT MYCLONUS IS A GENERALIZED SEIZURES SO TX carbamazepine
Status epilepticus
TX:
1.BENZO
2.PHENYTOIN
Status epilepticus is a single seizure lasting >5 minutes or the occurrence of multiple discrete seizures with incomplete recovery of consciousness between episodes. The initial treatment includes intravenous lorazepam and phenytoin given concurrently. Phenytoin is a long-acting anticonvulsant that inhibits neuronal high-frequency firing by reducing the ability of sodium channels to recover from inactivation.
Opiate
MOA:
1.Activation of presynaptic mu receptors on the primary afferent neuron leads to closure of voltage-gated calcium channels and reduced excitatory neurotransmitter release.
2.Binding to mu receptors on the postsynaptic membrane causes opening of potassium channels and membrane hyperpolarization.
Propofol
Propofol and other highly lipophilic drugs readily diffuse across membranes, quickly accumulating in tissues receiving high blood flow; this accounts for their rapid onset of action.
IMPORTANT :
These compounds are subsequently redistributed to organs receiving less blood flow, which explains their short duration of action.
Alzheimer disease
TX:
1.Cholinesterase inhibitors (eg, donepezil, galantamine)
Improved cognitive function with no change in disease course IMPORTANT
2.NMDA receptor antagonists (eg, memantine)
inhibit glutamate NMDA signaling to prevent excitotoxicity (calcium overload) and subsequent neuronal apoptosis. These agents likely serve a neuroprotective role, slowing disease progression.
Essential tremor
TX: First-line treatment is the nonspecific β-adrenergic antagonist propranolol.
Essential tremor is the most common movement disorder. Patients experience a slowly progressive, symmetric postural and/or kinetic tremor that most commonly affects the upper extremities. Essential tremor is often inherited in an autosomal dominant fashion (referred to as familial tremor).
TB TX Isoniazid SE
1.Isoniazid is structurally similar to pyridoxine (vitamin B6) and competes for binding sites on pyridoxine-dependent enzymes. This leads to decreased synthesis of certain neurotransmitters, which may result in peripheral neuropathy. Management involves pyridoxine supplementation.
2.rifampin induce hepatic P450 oxidases . enhance phenytoin metabolism and decrease its serum concentration.
Restless legs syndrome
TX: Alpha-2-delta calcium channel ligands (eg, gabapentin, pregabalin) and dopamine agonists (eg, pramipexole) can be used to treat persistent symptoms.
Restless legs syndrome is characterized by an uncomfortable sensation in the legs accompanied by an urge to move them; symptoms worsen with inactivity and at night and are temporarily relieved with movement.
Certain medications, including dopamine antagonists (eg, antipsychotics, certain antiemetics [metoclopramide]), first-generation antihistamines (eg, diphenhydramine), and antidepressants (eg, selective serotonin reuptake inhibitors [eg, sertraline], mirtazapine), are associated with worsening symptoms
narcolepsy
Treatment for narcolepsy includes psychostimulants (eg, modafinil) for daytime sleepiness.
NEUROMUSCULAR BLOCKING DRUGS
1.Succinylcholine can cause significant potassium release and life-threatening arrhythmias in patients at high risk for hyperkalemia, including those with burns, myopathies, crush injuries, and denervating injuries or disease.
2.Myasthenia gravis (MG) is caused by autoantibodies against postsynaptic nicotinic acetylcholine receptors, leading to fewer functional receptors and fatigable muscle weakness. Nondepolarizing neuromuscular blocking agents (eg, vecuronium) are competitive antagonists of nicotinic receptors; because of the depletion of receptors, patients with MG are extremely sensitive to these agents.
3.SLOW TO WAKE UP PEOPLE :
Succinylcholine, a depolarizing neuromuscular blocking agent, is rapidly hydrolyzed by plasma pseudocholinesterase. Patients with pseudocholinesterase deficiency have prolonged neuromuscular paralysis after drug administration.
4.Organophosphates are cholinesterase inhibitors that are widely used as pesticides in agriculture. They inhibit the breakdown of acetylcholine, leading to a state of cholinergic excess. Symptoms of organophosphate poisoning include salivation, lacrimation, diaphoresis, bradycardia, and bronchospasm.
MUSCLE RELAXANT
1.BACLOFEN GABA agonist in spinal cord
2.cyclobenzaprine centrally acting
3.DANTROLENE : (RYR) a ryanodine receptor blocker that inhibits calcium release from the sarcoplasmic reticulum, is an effective antidote.
Tx for Malignant hyperthermia and Neuroleptic malignant syndrome IMPORTANTT
4.Tizandine alpha 2 agonist centrally
Neuroleptic malignant syndrome
Caused by an overdose of haloperidol. NMS is a life-threatening adverse reaction most commonly resulting from the use of antipsychotics (neuroleptic) medications, which block dopamine receptors in the brain
Signs/symptoms
Fever (>40 C common)
Confusion
Muscle rigidity (generalized)
Autonomic instability (abnormal vital signs, sweating)
Treatment
Stop antipsychotics or restart dopamine agents
Supportive care (hydration, cooling), intensive care unit
Dantrolene or bromocriptine if refractory
ANTIHISTAMINE
First-generation H1-histamine receptor antagonists, including diphenhydramine and chlorpheniramine, can cause significant sedation, especially when used with other medications that cause CNS depression (such as benzodiazepines).
Loratadine is a second-generation antihistamine that blocks peripheral H1 histamine receptors. It does not enter the CNS and does not cause drowsiness.
MIGRANE TX: TRIPTANS
5HT AGONIST
ACUTLY : TRIPTANS ,DIHYDROERGOTAMINE
ANTIEMITICS (Prochlorperazine ,Metoclopramide
,Chlorpromazine)
FOR PROPHYLAXIS : LIFESTYLE, B BLOCKERS TOPIRAMATE,VALPORATE (anticonvulsants), AMITRIPTYLINE VERY IMPORTANT
The pathogenesis of migraines is complex and multifactorial but includes neurogenic inflammation, vasodilation, and sensitization of trigeminal afferents in the meninges. Triptans are serotonin 5-hydroxytryptamine 1B/1D agonists that stimulate the trigeminovascular serotonin receptors, resulting in inhibition of vasoactive peptide release, intracranial vasoconstriction, and decreased pain. They are used as abortive therapy for acute migraine.
haloperidol
Acute extrapyramidal symptoms (eg, dystonia, akathisia, parkinsonism) are due to D2 blockade in the nigrostriatal pathway. First-generation, high-potency antipsychotics (eg, haloperidol, fluphenazine) strongly block D2 receptors and are most likely to cause extrapyramidal symptoms.
