Pharm Test 2: CNS- Anesthesia, Analgesics and CNS Stimulants

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Local anesthetics, General Anesthetics, Pain Meds, Opiods Meds, Migraine Drugs, and CNS stimulants (Amphetamines, Caffeine, Anorexiants, and Smoking Cessation)

How do local anesthetics work?

Suppress pain by blocking impulse conduction along axons near admin. site. Blocks sodium channels. Blocks sensory and motor neuron transmissions.

Which neurons are blocked first? Pain, or deep pressure?

Pain.

What is important to remember regarding large doses of local anesthetics?

Can provoke a systemic response.

How is epinephrine used with local anesthetics?

Cause vasoconstriction, confining the anesthetic response to a small area, decreasing blood loss, and prolonging drug response.

When do we use locals?

Apply to mucous membranes, skin, inject into CNS near nerves. Used to start IVs, minor surgery, dental work, diagnostic procedures, skin irritations that cause itching.

What are some adverse effects of local anesthesia?

Systemic if large dose. Skin irritation at application site, possible infection @ injection site, aspiration (if local used to suppress gag reflex).

If using cocaine as a local, what is important to remember?

Do not use epinephrine with it! It is a very powerful vasoconstrictor on its own.

What is balanced anesthesia?

The use of 2+ drugs to achieve optimal anesthesia: unconsciousness, analgesia, muscle relaxation, amnesia, rapid reversibility. Usually an inhaled anesthetic with one+ adjunctive meds.

What are the advantages of inhaled anesthetics?

Can cross the BBB, enhance transmission @ inhibitory synapses and depress activity at excitatory synapses. Distributes to areas of high blood flow first (brain, kidney, heart, liver). Very little metabolism.

What are the adverse effects of inhaled anesthetics?

Respiratory and cardiac depression (cardiac monitory and mechanical ventilation), arrythmias, malignant hyperthermia (genetic predisposition), aspiration.

When are adjuctive meds usually administered? How?

Before, during, or after the surgery. IV.

What do benzos contribute to anesthesia? Adverse effects?

Reduce anxiety, promote muscle relaxation, amnesia. But may cause respiratory depression.

What do Alpha 2 agonists contribute to anesthesia? Adverse effects?

Reduce blood pressure, reduce sympathetic outflow, reduce pain, relieve anxiety. Promote drowsiness. May cause hypotension w/ reduced renal/hepatic blood flow.

What do anticholinergics contribute to anesthesia? Adverse effects?

Reduce secretions (oral, pulmonary). May cause tachycardia/arrythmias, urine retention.

What do opiods contribute to anesthesia? Adverse effects?

Relieve pain pre- & post-op. Can cause CNS and VS suppression.

What do neuromuscular blocking agents contribute to anesthesia? Adverse effects?

Block muscle contractions, permit intubation. May cause decreased respiratory effort.

What is the purpose of IV barbituates?

Induce anesthesia, loss of consciousness. Do not block pain or cause muscle relaxation.

What is the purpose of IV benzodiazepines?

Produce unconsciousness and skeletal relaxation.

What is the basic function of cyclooxygenase?

They are prostaglandin factories.

What are the 2 types of Cyclooxygenase? What are their 'titles'?

Cox 1 (Good Cox), and Cox 2 (Bad Cox).

Why is Good Cox good?

Promotes bicarbonate, decreases gastric acid production, and maintains gastric perfusion (to protect GI). Supports renal function, and promotes platelet aggregation. Cox 1 works all the time.

Why is Bad Cox bad?

Responds to injury to cause inflammation, pain sensitization, fever, perception of pain. Promotes vasodilation. Supports renal function. Contributes to colon cancer.

How to Cox Inhibitors work?

Prohibit the cyclooxygenase enzyme, thereby stopping synthesis of prostaglandins. This reduces pain, fever, inflammation, and reduce stroke/heart attack risk.

What happens when we inhibit Cox 1?

Protection against MI and stroke (prevents platelets from clotting).

What happens when we inhibit Cox 2?

Reduces pain, inflammation, fever, colon cancer. But also promotes renal impairment, MI, and Stroke (prohibits blood vessel dilation).

Are most drugs Cox 1 inhibitors, Cox 2 inhibitors, or both?

Both.

What do Cox1/Cox2 inhibitors do? Side effects?

Reduce mild-moderate pain, reduce fever, reduce inflammation, reduce cardiovascular risks (only aspirin). Cause gastric upset/ulceration, impair kidneys (since both Cox 1 & 2 support renal fn).

Why is acetaminophen (tylenol) different from other Cox1/Cox2 inhibitors

It only has anti-inflammatory properties limited ot the CNS. It cannot prevent/reduce inflammation. But it does not cause peripheral upsets like GI, renal, or cardiovascular effects.

What are the two types of Cox1/Cox2 inhibitors?

Those w/anti-inflammatory effects, and those w/o anti-inflammatory effects in the periphery.

What dose of Tylenol can cause hepatotoxicity? What groups are at even higher risk of Tylenol overdose?

> 4 g/day. Alcoholics, ppl with hepatitis (liver damage), the elderly, and the young.

What drug is considered a First Generation NSAID (Cox1/Cox2 inhibitor)?

Aspirin (Bayer)

What are the benefits of Aspirin? Adverse effects?

Relieves pain/fever/inflammation. Prevents clots (low dose prevention of MI, stroke). Gastric ulceration, renal impairment, water retention (hypertension), tinnitus. Reye's Syndrome in children. Preg. Cat. D. Irreversible.

What are the benefits of Second generation NSAIDs (Cox1/Cox2 inhibitor) over First generation NSAIDs?

They are reversible, with less serious side effects. Pain relief, antipyretic, and anti-inflammatory. But can increase risk of cardiovascular events. Gastric ulcers, bleeding, renal impairment.

What are the benefits of Third Generation Cox-2 inhibitors?

Reduced pain, fever, and inflammation w/o the bad effects of Cox1 inhibition (GI ulcers).

Are there many third generation drugs out there?

No. Most were pulled due to high incidence of stroke, MI, and heart failure. Only Celebrex is available, and even then under careful supervision.

How do opioids work?

They resemble the body's natural analgesics, binding to receptors in the brain/spinal cord to relieve acute/chronic pain, somatic pain, visceral pain, superficial pain, referred pain, and neuropathic pain.

What are the three opioid receptors? Which is the most important?

Mu, Kappa, Delta. Mu is the most important as opioid analgesics act primarily on these receptors.

What are Mu receptors associated with?

Analgesia, respiratory depression, euphoria, sedation, physical dependence

What are Kappa receptors associated with?

Analgesia and sedation

What are Deltoid receptors associated with?

Nothing; they don't interact with opioids.

What other organs can opioids affect?

GI, GU to cause decreases peristalsis & urine retention

What is important to know regarding opioids and dose?

There is no ceiling dose. It is possible to tolerate very high doses of opioid analgesics.

What opioid analgesic is the gold standard?

Morphine.

Why are opioid analgesics combined with other analgesics?

Allow for optimum pain control with a smaller dose of the opioid.

What are some general uses for opioid meds?

Pain relief, relieve labor pains (Demerol), suppress cough, slow GI motility, reduce O2 demand on the hrt, induce sedation, provide balance anesthesia.

What are contraindications for opioid use?

Allergy, RR <12, Elevated intracranial pressure ( depressed respiration causes CO2 buildup, which can lead to cerebral edema), Pregnancy (fetal dependence), liver impairment.

What are some adverse effects of opioid use?

Respiratory depression, sedation, tolerance, physical/psychological depedence, constipation/urine retention, hives, flushing, hypotension (histamine release). Most effects will disappear w/ time, except constipation.

What can be used to treat respiratory depression, constipation, urinary retention induced by opioids?

Opioid antagonists. But also reverse pain relief.

Why are Nonopioid Centrally Acting Analgesics better than opioids?

Since they do not work at opioid receptors, they do not cause respiratory depression, dependence, or abuse.

What causes migraine headaches? What are some triggers?

A neurovascular disorder involving dilation/inflammation of intracranial blood vessels. Stress, foods, sleep loss, loud noises, premenstrual drop in hormone levels. Drops in 5HT and rises CGRP may cause it.

What do migraine drugs seek to correct?

Correct low 5HT and rise CGRP by increasing 5HT, lowering CGRP.

What drugs can be used to treat migraines?

Nonspecific analgesics (to treat/stop migraine, not the cause). Serotonin Agonists.

How do Serotonin Agonists help treat migraines?

Increase serotonin levels, to cause constriction of intracranial blood vessels, suppress CGRP release.

What other types of drugs can be used to treat migraine prophylaxis?

Antidepressants, antiepileptics, beta antagonists, and estrogen patches.

How to CNS stimulants cause increased CNS activity?

Enhance neuronal excitation, suppress neural inhibition.

What conditions can CNS stimulants be used to treat?

Narcolepsy, ADHD, weight loss.

What are amphetamines? Where do they primarily work?

Powerful CNS stimulants. Work in the periphery (cardiac and vasoconstriction). Promote NE and DA release and inhibit reuptake in the CNS and peripheral nerves.

What are amphetamines used for?

Improve mood, arousal, wakefullness, and alertness. Reduces fatigue, augment self-confidence and initiative. Stimulate respirations. Supress appetite and perception of pain. Can increase heart rate, A/V conduction, force of contraction

What are some side effects of amphetamine use?

Can increase heart rate, A/V conduction, force of contraction to cause dysrhythmias and hypertension. Tolerance leads to loss of 'good mood', loss of appetite suppression, and heart/blood vessel stimulation. Physical dependence causes withdrawal symptoms and depression, excessive sleep, excessive eating/craving for drug. Abuse r/t euphoria. Suicide risk in children/adol.

What are some therapeutic applications of amphetamines?

ADHD, narcolapsy, obesity (not any more though).

What effects can caffeine cause?

Decreased drowsiness/fatigue, increased attention. Dilates peripheral blood vessels and constricts CNS vessels to relieve headaches. Promote bronchodilation (relief mild asthma symptoms). Diuretic effect on kidney.

What are some adverse effects of caffeine?

High doses cause nervousness, tremors. Increased heart rate could cause arrythmias.

What are anorexiants used for?

an appetite suppressant.

How does the anorexiant Sibutramine/Meridia work?

Inhibits the reuptake of NE, 5HT, and DA to decrease appetite.

How do CNS stimulants (varenicline/Chantix) work to stop smoking?

They partially block nicotine receptors, allowing for mild activation by dopamine. They thereby get some of the pleasureable effects from the dopamine release, but it also provides a lower dose to help reduce craving and the intensity of withdrawal symptoms. By blocking the receptors, they block the reward nicotine gives.

What are adverse effects of smoking cessation drugs (varenicline/Chantix)?

N/V, stomach pain, constipation, fatigue/weakness, headache, sleep problems/vivid dreams, suicidal thoughts/attempts.

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