Atropine poisoning. I.e. too much anti-muscarinic activity. Hot as a hare, blind as a bat, mad as a hatter, red as a beet, the bowel and bladder lose their tone and the heart runs alone.
Atropine poisoning effect on GU
urinary retention vi detrusor relaxation and contraction of the external urethral sphincter.
Atropine overdose likely in
Elderly since half life may be prolonged from 3 hours to 10-30 hours due to reduced clearance causing increased susceptibility to toxicity.
Atropine poisoning reversal
Cholinesterase inhibitor such as physostigmine, which crosses CNS as a tertiary amine (whereas others are quaternary). NOT NEOSTIGMINE.
Lipid soluble barbiturates like thiopental have super quick recovery because
Tissue restribution of drug, not metabolism of drug.
Drugs with decreased solubility in blood and increased in tissue have
Rapid recovery and rapid induction.
Drugs with increased solubility go to adipose AND
Drugs with more lipid solubility have (potency)
MORE potency. (Potency = 1/MAC)
Drugs with high blood/gas partition coefficients are more soluble in the blood and thus
Slower onset; takes longer to equilibrate with the brain because larger amoutns must be absorbed before blood becomes saturated
NO is an example of...
Poor solubility so becomes saturated more quickly; faster onset to brain
Cocaine leads clinically to
Myocardial ischemia and or coronary artery vasospasm since it’s a potent vasoconstrictor. And also chronic intranasal use -> mucosal atrophy and nasal septal perforation.
Partial agonist activity and weak antagonist activity at mu receptors. Weak antagonist activity can lead to withdrawal symptoms in patients who are dependent or tolerant to morphine or other opioids.
When used in combo with morphine and others, pentazocine can
Competitively inhibit mu receptors and produce antagonist effects reduing opioid effects.
Mu receptors action
GPCR that act through a variety of secondary messenger systems but key to remember is activation of potassium channels to cause increased potassium efflux. This leads to hyperpolarization of postsynaptic neurons and termination of pain transmission.
Opioid tolerance mechanism
Maybe involving phosphorylation of opioid receptors by protein kinase; chronic tolerance may involve increased AC or NO levels.
Ketamine blocks NMDA receptors and so block what neurotransmitter
Glutamate**; excitatory neurotransmitter that binds and activates NMDA (and so may be involved in morphine tolerance; increased phos of opioid receptors and increased NO?). Recall Glycine is a co-agonist for glutamate and is required for binding of/ activation of NMDA receptors.
Farmers and agricultural workers are exposed to pesticides so think
ORGANOPHOSPHATES. Which are irreversible AChE. So, excess ACh -> DUMBELS. They also penetrate BBB and can cause seizures and depression.
Atropine reverses Cholinergic excess but Parlidoxime is added because
Atropine acts only on Muscarinic. So, excess ACh leading to NMJ stimulation/ fasciculations and then paralysis would not be reversed by atropine. Pralidoxime restores AChE.
Pralidoxime is only effective
When given after exposure.
Malignant hyperthermia presentation
Fever and muscle rigidty after surgery under general anesthesia. Tachycardia, HTN, hyperK and myoglobulinemia also maybe present. And Cyanotic skin mottling too.
Why wait between SSRI and MAO inhibitors administration
Possible serotonin syndrome. So, wait for MAO to regenerate.
Malignant hyperthermia treatment
Malignant hyperthermia is due to
HS of skeletal muscles to inhalation anesthetics especially halothane and also muscle relaxant succinylcholine. It is inherited AD. Usually from defect on RYR on SER of skeletal muscles. Excess Ca released from SR -> ATP dependent uptake by SR -> excessive consumption of ATP -> heat and loss of ATP -> muscle damage.
Exposure to anesthetic leads to abnormally large increase in Ca during muscle contraction is known as
Rhabdomyolysis leads to release of
K, myoglobin and CK.
Atypical depression (characterized by mood reactivity, leaden fatigue, rejection sensitivity, increased sleep and appetite) treatment
Atypical depression vs Typical
Atypical will have mood reactivity, which is improvement in mood in response to something positive.
Neuroleptic malignant syndrome occurs how many days after med
Neuroleptic malignant syndrome vs Serotonin Syndrome
NMS does NOT have myoclonus but does have rigidity**
Why methadone DOC for opioid addiction
Long half life and also good bioavailabilty and super potent so continuous suppression of withdrawal
Ethosuxamide MOA vs other antiepileptics?
Ethosuxamide – blocks T-type Ca channels vs other antiepileptics, P, C and V, slow Na+ channels/ decrease conduction of AP by prolonging Na inactivation.
Drug of choice for complex partial seizures
What drug can be used for absence and simple/complex/tonic clonic
TCA **/ Amitryptiline
Milk before bedtime can do what
Hyponotic action perhaps via its tryptophan which then can lead to serotonin synthesis.
Blocks choline upake by presynaptic neuron preventing ACh synthesis through depletion of intracellular choline.
Non competitively blocks transport VAT (vesicular ACh transporter) preventing ACh from entering secretory vesicles
inhibits acetyltransfersase, blocking synthesis of ACh from acetate and choline
Phenelzine is a
Beta receptor activity on uterus
Uterine relaxation; which is called tocolysis (used in obstetrics to defer premature labor).
Adrenergic B2 agonists are used to defer preterm labor to
Relax uterus. Ritrodine and terbutaline are two examples.
RiLUzole for LOU Gehrig’s works how
Decreases Glutamate release.
Serotonin syndrome symptoms
NMJ excitation (hyperreflexia, clonus, myoclonus and rigidity); autonomic stimulation (hyperthermia, tachycardia, diaphoresis, tremor) and altered mental status (agitation and confusion).
Serotonin syndrome, what antidepressants implicated
SSRI, SNRI, MAO-I, TCA
Serotonin syndrome, what non antidepressants are implicated
Tramadol, Ondanseron, Linezolid, Triptans. TOO LIT -> TO LiT.
Serotonin syndrome antidote
Supportive care (airway, hydration, temperature) AND if severe serotonin receptor antagonists such as CRPROHEPTADINE, a first generation histamine antagonist with nonspecific serotonin receptor antagonistic properties. Can also give short acting antihypertensives but avoid long acting ones like propranolol.
What is precursor of serotonin
Lithium can lead to hypothyroidism so need to check TSH levels; if hypothyroid may present with
Weight gain, dry skin, hair loss, constipation and bradycardia.
Management of status epilepticus
IV lorazepam (most rapid onset) and load with phenytoin as prophylaxis -> phenobarbital -> intubate and general anesthesia
Valproic acid moa
Blocks NMDA receptors and affects K+ current as well as blocking Na+ channels and GABA receptors.
First symptom of alcohol withdrawal
Tremulousness/ the shakes -> then GI, anxiety, agitation, autonomic disturbances. DT starts 48-72 hours after last drink. Subside by 4-5 days after last drink.
Why does tolerance and withdrawal happen from alcohol
Alcohol -> downregulation of GABA (binds GABAa inhibitory receptors and potentiates GABA) inhibits NMDA receptors leading to upregulation and there is also an increase in the synthesis of mediators such as NE, 5HT and dopamine.
Fluctuant arousal level (starting 48-72 hours after), severe sympathetic hyperactivity, hallucinations and formication. And generalized tonic-clonic seizures too.
Treatment of DT
Long acting benzos like Diazepam unless there is liver disease in which case best to give short acting benzo
Alcohol affects which GABA reeptors
Gaba A; enhances their inhibitory effect
Diphenhydramine and Chlorpheniramine, 1st gen antihistamines, also have
Anti-muscarinic effects, anti-serotoniergic effects and anti alpha adrenergic.
Short acting benzos like Triazolam may be used for insomnia since its has few undesirable day time effects; also may be used at beginning of SSRI treatment if there is significant increase in anxiety related symptoms
First line for essential tremor (high frequency with sustained posture like outstretched arms; worsened with movement or when anxious; autosomal dominant maybe)
Beta blockers specifically propranolol and primidone. Though patients say alcohol works too.
Focal (simple and complex; one hemisphere) seizures, what drugs?
Generalized (two hemispheres) seizures, what drugs?
Valproate, Topiramate, Lamotrigine, Ethosuxamide.
Brief involuntary jerking movements of both extremities in adolescence with preservation of consciousness
Juvenile myoclonic epilepsy, idiopathic familial GENERALIZED (since both limbs -> both hemispheres) and so broad spectrums are needed.
Myoclonic seizure vs Tourette syndrome
Tourette will have urge to make movement precede the movement and the tics are usually suppressible. Treatment is fluphenazine, a dopamine antagonist.
Drug of choice for trigeminal neuralgia
Carbamazepine key a/e
Stabbing pain on face/ electrical shock like, generally unilateral and may be triggered by chewing, teeth brushing, shaving or washing an affected area of the face or exposure to warm or cold temperatures
Trigeminal neuralgia. May last for several months.
Zero-order kinetics and also it is dose dependent, is a p450 inducer and is affected by co-administration with other p-450 inducers or inhibitors.
Trazadone, more like
TrazaBONE. Priapism. Avoid using in adolescent boys. Recall, it is a highly sedating antidepressant that can be used to treat insomnia or as an adjunct to the SSRIs when there is a depression associated insomnia.
Long term levodopa treatment can be complicated by periodic and sometimes unpredictable* fluctuations in motor function. Good mobility during on periods and increased bradykinesia and rigidity during off periods. Fluctuations are thought to be from metabolism of drug or progressive nigrostriatal neurodegeneration?
Progressive nigrostriatal neurodegeneration. Also, drug holidays have not been shown to work and abrupt stopping of drug also does not work. Also motor fluctuations are not typically self-limiting.
Donepezil, a cholinesterase inhibitor (appears to improve cognition, behavior and functioning in activities of daily living); antioxidants (for neuroprotection) and NMDA receptor antagonism (like Memantine)
Antihistamine side effects and exception
Blockage of other pathways – muscarininc (blurry vision, dry mouth, urinary retention), serotonergic (appetite stimulation), alpha adrenergic (postural dizziness) pathways. Also lipophilic – causing sedation and cognitive dysfunction. EXCEPTION – second generation antihistamines such as fexofenadine. Minimal sedative and antimuscarinic effects.
Antihistamines end in
-ramine or –zine.
Seizures, agitation and insomnia
NE transmission without significantly affecting ACh, serotonin or histamine
Depression with associated psychomotor retardation or hypersomnia and also for nicotine dependence
General anesthetics moa
Increase inhibitory action of GABA; lock potassium channels in hyperpolarization -> loss of consciousness, analgesia, amnesia, skeletal muscle relaxation, inhibition of reflexes
General anesthetics affects on brain outside of intended effects
Increases cerebral blood flow and thus ICP. Undesirable.
Anesthetics preferred in patients with asthma?
Halothane and sevofluorane since these are the only ones that lead to bronchodilation. (Recall halothane is one that can cause focal to massive hepatic necrosis)
All anesthetics are respiratory depressants except
NO. They decrease minute ventilation and cause hypercapnia. Also decrease mucociliary clearance, predisposing to post-operative atelectasis.
Fluorinated anesthetics lead to what effect on heart
Decrease in CO and hypotension
Drug-induced parkinsonism is from
D2 blockers of nigrostriatal pathway. Antipsychotics (first generation > second generation) and anti-emetics (metoclopramide)
Drug-induced parkinsonism treatment
Centrally acting anticholinergics like benztropine and amantadine (increases dopamine release and blocks reuptake) but NOT levodopa and dopamine agonists (bromocriptine, pramipexole) which can precipitate psychosis
Anticholinerigcs should be avoid in elderly especially with BPH and or angle closure glaucoma
...Not sure why. 601564
Pufferfish poisoning/ teradotoxin action
Binds to voltage-gated sodium channels in nerve and cardiac tissue preventing sodium influx and depolarization/ AP.
Teradotoxin/ puffer symptoms
Dizziness, weakness, loss of reflexes, paresthesias of face and extremities, nausea, vomiting, diarrhea and at higher doses –severe hypotension and general paralysis and death may occur
Cold feels hot and hot feels cold/ temperature related dysesthesia
Specific for ciguatoxin
Ciguatoxin/ exotic fish/ eel action
Binds to voltage gated sodium channels and keeps them open causing persistent depolarization.
Dark meat fish like mahi mahi or mackerel stored at warm temp/ scrombroid action
Bacterial histidine decarboxylase converts histidine to histamine leading to acute onset burning sensation of mouth, flushing of face, urticarial, pruritus, headache, and sometimes anaphylaxis
If someone has shock after dark meat fish what to give them
Antihistamiens and maybe anaphylactics
What is often misdiagnosed as allergy to fish
DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is a rare and potentially life threatening drug reaction typically occurring 2-8 weeks after drug exposure. Associated drugs
Anticonvulsants (phenytoin, carbamaze), allopurinol, sulfonamides (sulfasalazine), antibiotics (vanco) Thought is that it’s a drug induced herpes virus reactivation following by clonal expansion of T cells.
Labs studies of DRESS syndrome usually show
EOSINOHPILIA. Recall, the skin rash is diffuse and morbillifom and can progress to confluent erythema with follicular accentuation.
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