Clinical Pearls for PNS drugs 1 case study

Clinical Pearls for PNS drugs 1 Parasympathetic drugs (cholingeric response)  Think SLUDGE o Salivation o Lacrimation o Urination o Defecation o Gastric upset o Emesis Clinical pearls for PNS drugs 2 Muscarinic agonist vs muscarinic antagonist symptoms  If you remember the above acronym then its important to remember if the drug is an agonist of muscarine receptors or an antagonist and then just associate symptoms of sludge with agonist and the OPPOSITE effects of those that are antagonist o Dry eyes o Constipation o Dry skin o Urinary retention o Blurred vision Oxybutynin  This is the oldest anticholinergic available for OAB so you can expect the most side effects with this one!! o Dry mouth:  Recommend they suck on peppermint or some other hard candy after taking the medication  Use biotene or something similar to prevent this symptom o Constipation o Drowsiness Solifenacin (Vesicare) Darifenacin (Enablex) Tolterodine (Detrol) fesoterodine (Toviaz)  These are the newer agents which have been altered to decrease the constipation and dry mouth side effects  However, these are still BRAND name only!!! So much more $$$ o Would recommend trying oxybutynin XL first and if patient can’t tolerate go to these more expensive options  Tolterodine is generic so is the cheapest option of all of these medications Scope patches (Scopolamine)  Comes in patches that are to be placed behind the ear every 3 days  These are most commonly prescribed before cruises or other boating adventures for motion sickness Dicyclomine  Very commonly prescribed for IBS.  This drug has been on backorder for at least a year. o Its very hard to get in Clinical pearls for PNS 3  Beta blockers are no longer considered first line therapy for hypertension o Now calcium channel blockers, thiazide diuretics and ACEInhibitors/ARBS o But still considered first line in those with heart disease (angina or hx of MI)  When used for stage fright or migraine prophylaxis most commonly seen in my clinical experience is propranolol  Cardio selective beta blockers : should be used in patients with asthma so not to cause bronchoconstriction – “A-BEAM” o Atenolol o Bisoprolol o Esmolol o Acebutolol o Metoprolol  Nonselective beta blockers o Propranolol o Nadolol  Nonselective bb with additional alpha1 blocking activity o Carvedilol o Labetalol  Always counsel your patients to not stop taking beta blockers abruptly! Always wean them off slowly o This prevents rebound cardiac excitation!  Beta blockers with Nondihydropyridines is dangerous, can drop heart rate very rapidly! Cloninine can make patients very dizzy/drowsy  Make sure they are sitting down in a chair or bed when taking first dose  This is will decrease after a few days of taking medication Beta Blockers:cardioselective (1) Atenolol (Tenormin) 25-100 mg BID · Reduces HR and myocardial contractility (avoid if HR60) · Not recommended as 1 st line unless pt has IHD or HF · Preferred in pts with bronchospastic airway disease · Avoid abrupt cessation · Nebivolol also causes NO production · No renal dose adjustment: Atenolol, Bisoprolol, Nadolol Bisoprolol (Zebeta) 2.5-10 mg daily Metoprolol tartarate (Lopressor) 100-200 mg BID Metoprolol succinate (Toprol XL) 50-200 mg daily Nebivolol (Bystolic) 5-40 mg daily Beta Blockers:nonselective (1 and 2) Nadolol (Corgard) 40-120 mg daily · Avoid in patients with reactive airway disease · Avoid abrupt cessation (can induce angina pectoris/MI) · Class wide: may cause sedation, bradycardia, and mask symptoms of hypoglycemia induced tachycardia Propranolol IR (Inderal) 80-160 mg BID Beta Blockers:mixed / Carvedilol (Coreg) 12.5-50 mg BID · Carvedilol is preferred in pts with HFrEF · Avoid abrupt cessation Clinical pearls for CNS 1 Parkinson’s Disease  The efficacy of carbidopa/L-DOPA therapy decreases over time; patients begin having “off” and “on” motions with “cog-wheel” rigidity  A number of medications are used to treat this disease, targeted at a number of different biochemical pathways o Carbidopa/L-DOPA: given together, L-DOPA is a precursor for dopamine which can cross the BBB. By administering with Carbidopa, we can increase the amount of L-DOPA which enters the CNS and decrease the peripheral side effects o Dopamine receptor agonists: pramipexole and ropinirole stimulate D3 receptors in the CNS, though may have unintended side effects, such as increased risk taking behavior o COMT Inhibitors: “AL CAPONE KILLED COMT” – entacapone, tolcapone work to inhibit COMT in the peripheral NS to increase levels of L-DOPA which can reach the CNS; these are given as adjuncts to the carbidopa/L-DOPA therapies o Anticholinergics: benztropine can be used to decrease the cholinergic side effects of the peripheral dopamine receptor activation (SLUDGE) o MAOI: selegiline can be used to selectively inhibit MAO-B in the CNS. Care should be taken to prevent serotonin syndrome by administering concurrently with TCAs/SSRIs/etc. Clinical pearls for CNS part 2 Alzheimer’s  Drug therapy o These do not REVERSE damage, they just slow the progression!! o Definitely a risk vs benefit situation, as Dr. Jarrell eluded to in her slides, sometimes these medications don’t make much of a clinical difference and some of them are very costly to the patient and cause lots of side effects  Ask family members or caregivers if they are really seeing a difference after a couple of months. If the answer is no, then maybe reconsider even putting patient on therapy! Muscle relaxants  Most common side effect is dizziness and drowsiness o This is pretty much a class wide effect. o Make them take at night to help with this side effect. Once they are used to the dizziness and drowsiness then can take multiple times throughout the day Clinical pearls for CNS 3  Anti-epileptics are tricky o More than likely these patients will suffer some sort of side effect  But the key is being able to tolerate the side effect vs having another seizure and risking brain damage o Some people can be controlled on 1 medication, some people require 2 or 3 different medications o There is not a great algorithm for choosing one medication over the other – just very personalized treatment  Phenytoin o Gingival hyperplasia o Good dental hygiene is key!  Carbamazepine o Look out for SJS and rash o Asians with HLA –B subtype more susceptible to skin rash o This is one drug that pharmacogenomics is used!! o Major CYP 3A4 inhibitor!!  Warfarin- carbamazepine will decrease the effects of warfarin and therefore require an increase in warfarin dose to get a therapeutic INR  Grapefruit juice will increase the amount of carbamazepine in the body, increasing the toxicity of the drug o Phenobarbital  Hardly used anymore!  Only in patients who have been using this for years  Vets use this to treat dogs with seizures  Controlled substance IV  Can lead to addiction  Drowsiness very common  Absolutely no alcohol! o Lamictal  Also has problem with rash and SJS o Gabapentin  Very commonly used in a number of different disease states  Make sure the patient knows they will fill like they are in a fog for the first few days!  Extreme dizziness and drowsiness  This effect will subside after a few doses  Horizant will decrease the pill burden associated with gabapentin because it’s extended release  Gabapentin commonly dosed up to 4 or 5 times daily and sometimes with multiple pills per dose  But Horizant is still brand name and expensive so try patient on regular gabapentin first then move to expensive treatment  Lyrica  Decreases some of the dizziness and fog feeling that comes with gabapentin  But it’s controlled substance V  Very expensive because its still brand name only  Topamax  Also famous for dizziness and drowsiness  Numbness in fingers and toes is also a very common side effect that is unique to this medication Clinical pearls for psychiatric drugs 1  Antipsychotic drugs are on the Beers list o These should not be used to treat dementia in elderly!!!  The first generation antipsychotic drugs are hardly used in clinical practice due to systemic side effects associated with the drugs acting on many different types of receptors besides just dopamine o Most commonly used is haloperidol  Can be used in pill form, to be taken daily for normal regimen  Can be used in IM shot form for acute attack First generation vs second generation  First generation – more famous for EPS and anticholinergic effects (dry mouth constipation, urinary retention, drowsiness)  Second generation – more famous for all metabolic syndrome effects (weight gain diabetes, dyslipidemia) Clozapine  First 2ndgeneration antipsychotic so since it’s the oldest it has the most side effects (all the kinks in the production process hadn’t been worked out yet!)  This is last line treatment after several failed attempts  Requires extensive testing and monitoring during treatment  Pharmacy has to be registered to even dispense this medication o Both MD and PharmD is required to look at CBC and approve dispensing of medication due to increased risk of agranulocytosis! Comparing all of the SGA These medications are very similar to mood stabilizer No one treatment will work each time – must individualize treatment!! Clinical pearls for antipsychotics 2 Antidepressants  Most important counseling point!!! o Explain to patients they are not going to feel better overnight!! These take 4-6 weeks before effects are felt!! o May feel a little more energy and more restful the first few days but to have full effect, it will take up to 6 weeks SSRI  Very safe and most of the time well tolerated  Make sure to monitor sodium levels - these are famous for leading to hyponatremia  Bad/vivid/weird dreams and sexual dysfunction is more associated with the older SSRI than the newer agents (fluoxetine, sertraline citalopram and escitalopram)  Withdrawal syndrome occurs more frequently in some o Still important to taper patient off medication or when switching between classes o Personally I’ve heard more complains about Cymbalta (SRNI) than any of the SSRI Zoloft  Most commonly prescribe SSRI in pregnancy (weigh risks vs benefits) but if you have to use one, this has the most research associated with it Citalopram (Celexa) and Escitalopram (Lexapro)  These are the newest SSRI, therefore they are associated with the least side effects SRNI  Remember these are norepinephrine reuptake inhibitors, so just think about what you would expect from having more norepinephrine!! o Sides effects like anorexia/weight loss, insomnia, nervousness all attribute from having extra norepinephrine and more of a stimulatory effect  All three SNRI are generic now but they are still more expensive compared to the SSRI TCA  Most common side effect is drowsiness  But think about any kind of anticholinergic side effect!!! Again, drowsiness, dizziness, urinary retention, constipation, dry mouth!  These are on the beers list and should be avoided in the elderly! MAOIs  These can lead to tyramine toxicity  Beware of cheeses o Strong aged cheeses (cheddar, blue cheese) o Cured or smoked meats or fish (sausage or salami) o Beers on tap o Soy products like miso soup or tofu  Not commonly prescribed anymore Mirtazapine (Remeron