Comprehensive Guide to Common Medications: Uses, Mechanisms, and Side Effects

Posted on Jun 8, 2024 in Medicine & Health

Eye Drops

MOA: Increase outflow of aqueous humor by opening up channels/vessels. Prostaglandin and A2 agonists do this. Or they decrease the aqueous humor production/secretion. Carbonic anhydrase inhibitors, A2 agonists, and beta blockers do this.

  • Prostaglandin analogs (latanoprost, bimatoprost) darken the color of the iris, can cause eyelash growth.
  • Timolol: Systemic beta-blocker like effects: bradycardia, exercise intolerance, low BP, worse asthma/COPD.
  • Brimonidine: A2 receptor gets activated and tricks the adrenergic neuron that it has enough norepinephrine in neuron and it can stop. This turns down sympathetic outflow from brain, decrease production of fluid from eye. Many side effects: Bradycardia, hypotension, depression, mood/behavior changes, drowsiness.
  • Dorzolamide: Pain with administration.
  • Benzalkonium chloride: Common preservative in eye drops. Can cause hyperemia, irritation/inflammation, long term damage. Can discolor contacts. Take them out before using. Several drops are available preservative free, they are packaged as single use.

Schizophrenia

Drugs to treat are known as anti-schizophrenic, anti-psychotics, neuroleptics. Used for many different things.

Positive Symptoms

Positive means present when shouldn’t be.

  • Hallucinations
  • Delusions
  • Disordered thought
  • Combativeness
  • Agitation
  • Paranoia

Negative Symptoms

Negative means should be there but isn’t.

  • Social withdrawal
  • Decreased motivation
  • Emotional withdrawal
  • Poor self care
  • Blunted affect

Etiology of Schizophrenia

  • Dopamine receptor hyper/hypo function. Hyper=positive symptoms. Hypo=negative/cognitive symptoms.
  • The dopamine is a secondary or minor player. Larger player in glutamatergic dysfunction. Direct/interact with DA(dopamine) system. Glutamate deficiency=symptoms of increased DA.
  • Seratonergic influence: schizophrenic patients have increased blood 5-HT. 5-HT2 receptors colocalized with D4 receptors.

Antipsychotics

First Generation (Typical)

  • Haloperidol: MOA: Believed to be via D2 antagonist actions. Higher risk of EPS. Fewer adverse metabolic effects. Primarily effect against positive symptoms.

Second Generation (Atypical)

  • Clozapine
  • Top 200: Olanzapine, risperidone, quetiapine, aripiprazole.

D2 antagonist (weak) and 5-HT2 antagonist (strong). Lower risk of EPS but significant metabolic effects. Effective against positive and negative symptoms. Both groups also act as histamine, cholinergic and adrenergic receptor antagonists.

Side Effects

  • EPS: Extrapyramidal symptoms are unwanted muscle movements. Acute dystonia: Sustained muscle contractions that cause twisting or repetitive movement. Parkinsonism causes limb rigidity. Akathisia causes profound restlessness. Tardive dyskinesia is involuntary movement of face/tongue. Higher risk in first generation. Can use anticholinergic to help with symptoms.
  • Neuroleptic Malignant Syndrome: Causes lead pipe rigidity, high fever, sweating, autonomic instability, and altered consciousness. Supportive treatment with dantrolene and bromocriptine. Different than serotonin syndrome as it causes hyperreflexia and clonic repeating movements and is treated with benzodiazepines.
  • Anticholinergic effects
  • Orthostatic hypotension
  • Sedation/antihistamine effects
  • Increased prolactin causes gynecomastia, galactorrhea, period irregularity, sexual dysfunction
  • Seizures from reduced seizure threshold
  • Sexual dysfunction, lower libido, anorgasmia, ED
  • QT prolongation, increase in risk of Torsades de Pointes. Avoid in high cardiac risk patients or with other QT prolonging drugs.

Clozapine Considerations

  • Most effective atypical antipsychotic, still used but as a last resort.
  • Can cause agranulocytosis in 1-2% of patients. Close monitoring of WBC and ANC required. Baseline and weekly blood counts, biweekly at 6 months, monthly at 1 year.
  • Can cause weight gain (obesity, heart disease, etc). >40% of patients gained >7% of total body weight.

Other Antipsychotic Uses

Antipsychotics can also be used for psychiatric conditions like manic phase of bipolar disorder, etc. Tourette’s and to prevent/treat emesis.

Vitamins and Minerals

Potassium Salts

It is a high risk medication if given too fast or too large of a dose. Can be extremely dangerous via IV.

Side Effects: Fatigue, muscle weakness, weak pulse, nausea/vomiting, abdominal pain. Vesicant/blister causing at high concentration, will blister skin at contact.

Administration: For injectable potassium you must dilute. You can use higher concentration in central line. NEVER PUSH K+ (used for lethal injection).

Calcium Salts

Amount per product varies, mg strength is not reflective of how much is in the product. Body has limited absorption of ~600 mg, which declines at doses >600 mg.

Primary risk: Hypercalcemia

Toxicities:

  • GI: Nausea/vomiting, constipation
  • CNS: Lethargy, depression
  • Nephrotoxicity

Drug Interactions: May bind to other drugs and limit their absorption.

Vitamin D

Ergocalciferol, cholecalciferol.

Use Considerations:

  • Makes body absorb/keep more calcium.
  • Sun exposure 15-20 min/day.
  • Cholecalciferol (D3) is more effective than ergocalciferol (D2) at equal doses. Ergo cleared more rapidly.
  • Moderate doses (1-2k IU) are likely not adequate for patients with low serum levels.
  • Doses of 50k-300k IU have been used.

Iron Supplements

Best absorbed in ferrous Fe2+ form. Oral iron best absorbed when stomach is acidic. Ascorbic acid (vitamin C) improved Fe absorption. Heme iron (animals) several fold more absorbable. Some dietary components can form insoluble complexes with iron leading to decreased absorption (phytates, polyphenols, tannins like tea/coffee, and calcium).

Oral Therapy: Target is ~200 mg/day elemental iron. Given in 2-3 divided doses for tolerability. Slow release products have worse absorption, less acid exposure. Tolerated better because essentially lower dose.

Administration: Ideally administer iron on empty stomach, at least 1 hour before meal. If it’s not tolerated can give with food but may decrease absorption by 50%. Start at lower dose and slowly increase.

Side Effects: Mostly GI: dark feces, constipation or diarrhea, nausea/vomiting. Can be highly toxic in overdose situations. Concerning in young children, fatal overdose is leading cause of death in kids

Folic Acid

Is a B vitamin. Relatively safe. Water soluble. Body will remove excess in urine. Inadequate intake less common in US and countries that fortify cereal grains/foods. Important for people pregnant or trying to get pregnant, and patients with renal failure.

Supplementation: Oral supplementation is very effective and almost always sufficient. Well absorbed. Dose to restore supplies 1 mg/day. Maintenance 0.4 mg/day. In renal failure 1 mg/day dose may be needed indefinitely.

Cyanocobalamin (B12)

B12 deficiency can lead to CNS effects (decreased muscle tone, syncope, dizziness, paresthesia) can be irreversible with a prolonged deficiency. Content of OTC products varies widely. Generally higher in B-complex or B-12 only products than in multivitamins.

Administration: Oral, nasal, IM, deep SQ. Bioavailability limited for nasal and oral, intrinsic factor needed for absorption. People very deficient in B12 need injections.

Exam Essay

Folic acid has the ability to mask a vitamin B12 deficiency. If someone is B12 deficient, the first thing they are going to tell you is fatigue because B12 deficiency results in anemia and that causes fatigue. If they don’t present with anemia, they’ll present with neurologic problems. If someone has a B12 deficiency and happens to take folic acid, the folic acid will make the anemia better but not the neurologic problems. It doesn’t help/fix the B12 deficiency, but masks the anemia symptoms of a B12 deficiency so providers don’t screen for B12. Often won’t be noticed until patients come in for neurologic issues.

Anti-Platelet Agents

Aspirin, NSAIDS, ADP-blockers (clopidogrel, prasugrel, ticagrelor). Cilostazol & dipyridamole are not used often.

Aspirin

Blocks cyclooxygenase, that produces prostaglandins. Irreversibly binds to and inhibits the COX-1 enzymes. It forms a chemical bond and never lets go. The other NSAIDS are reversible inhibitors, not aspirin. The effects last for the life of the platelet that it binds to (T1/2=8-10 days). They are 170x more potent against COX-1 than COX-2. Aspirin leaves the blood quickly (T1/2=15-20 min), but the effects remain. Patients may need to stop aspirin before surgery, provider may want 70% of platelets back, could take 7 days. We get about 10% new platelets each day. Clear benefit in secondary prevention, uncertain role in primary. Low dose aspirin means less effect of ulcers/GI bleed. Only cardiac patients should really take aspirin (patients at moderate/severe risk of cardiovascular disease) because of toxicity/risk. 10-15% of patients may be resistant like smokers or patients with platelet reactivity. People who take aspirin when they don’t need it are more likely to cause harm via brain bleed than they are to get any benefit.

ADP (P2Y12) Inhibitors

When a platelet gets activated it releases ADP, and the ADP acts on itself by activating the P2Y12 receptor. This activates the platelet. These drugs block receptors and prevent platelet from being activated.

Side Effects: Bleeding risks. Ticlopidine risk for neutropenia and thrombotic thrombocytopenic purpura.

Uses: Often used after a stent to prevent platelet activation/clots. May be used for a full year after stent insertion so the stent can get covered in scar tissue and not be attacked. Used for people at high risk of stroke. Very effective but has high variability. Some patients may respond well, some poorly. Clopidogrel (Plavix) has onset within 2 hours, max 6. Considerable variability based on genetics/interactions. When used with aspirin or other platelet blockers, bleeding risk further increases.

Anti-Coagulants

They work on the coagulation cascade.

Warfarin

Decreased activity of factors II, VII, IX, X and protein C/S. Essentially block recycling of vitamin K by inhibiting vitamin K epoxide reductase. Many of our clotting factors need to be activated by reduced vitamin K to be fully functional. So the liver still makes these clotting factors but they are non-functional versions. This MOA is indirect, it works on the liver not the clotting factors themselves. Complicated because these factors all have different half lives. Takes 5 half lives for factors to be totally gone. You may see some effect quickly but could take 1-2 weeks to see full effect, and same for stopping, 1-2 weeks for factors to come back. Makes dosing complicated. We get fully reduced vitamin K from our food, so the vitamin K we get from food warfarin doesn’t work on. Food rich in vitamin K negates warfarin. Don’t tell patients to avoid food with vitamin K, but maintain a consistent intake weekly and account for that in dosing. Able to have customizable dose due to INR test. Typically want patients between 2-3. If stable test every 4 weeks, unstable every 2 weeks. Starting dose is guessing game. Start 5 mg, wait 2-3 days test INR and redose.

Side Effects: Bleeding/bruising, skin necrosis, osteoporosis (osteoblasts/clasts need reduced vitamin K to work, warfarin reduces vitamin K in body), purple toe syndrome.

Protein Considerations: Proteins S/C are almost opposite of clotting factors. Encourage breakdown of clots. They are vitamin K dependent too so warfarin affects them. Protein C/ factor 7 have short half lives and leave the body first. When those 2 leave, but before 2, 9, and 10 are gone there is a period where clots may actually be more likely. This is why we overlap with heparin. Skin necrosis is also thought to be due to this effect.

INR Management:

  • High INR: The higher the number the thinner the blood is. You would lower dose or stop for a day or 2. If someone has consistently high INR, you cut dose for foreseeable future.
  • Very High INR (8-9), but not actively bleeding: You can give vitamin K but this can be dangerous because could overshoot and decrease INR too far and cause clot/stroke/PE, etc.
  • Actively Bleeding on Warfarin: Give plasma or whole blood.

Specific Xa Inhibitors

Rivaroxaban, apixaban. Most are oral. Drugs get into blood, find factor 10 and inhibit it, which disrupts the cascade system. These are direct and work on clotting factor, unlike warfarin. Very straightforward, don’t often need monitoring.

Reversal Agent: Andexxa, it reverses the effects of factor 10 inhibitors. Given through IV injection, bolus, then drip. Can give if someone is bleeding uncontrollably. Plasma/blood don’t work to reverse effects of Xa inhibitors because the drug works directly on the clotting factor, so it would attack the clotting factor in the new plasma/blood too.

Direct Thrombin Inhibitor

Dabigatran, works directly on thrombin. Oral 150 mcg twice a day.

Reversal Agent: Idarucizumab.

Administration: Use/discard 120 days after opening container. Do not break/chew/crush/open capsules. Has to be discarded 120 days after because it is very sensitive to humidity. Should never be in an amber script bottle, only in manufacturer’s bottle.

Heparin

  • UFH: Unfractionated heparin, contains different size pieces of heparin.
  • LMWH: Low molecular weight heparin. LMWH is more consistent and predictable. Only need to monitor UFH using an aPTT test.

Side Effects: Can cause bleeding, reversal is protamine sulfate. Can cause heparin induced thrombocytopenia. They enhance the actions of anti-thrombin. UFH has = anti-Xa and anti-11a. LMWH has 2-4x more anti-Xa. UFH causes more variable pharmacokinetics, has variable dose dependent absorption. Onset 1-2 hours, peak 3 hours.

Muscle Relaxants

Widely used for back pain, tension, headaches, fibromyalgia. Mostly short term use (2 weeks). Limited evidence of benefit. Short duration, given 3-4x a day. All are CNS depressants.

Side Effects: Drowsiness, dizziness. They don’t work on muscles, they work on the brain/spinal column.

Drugs:

  • Cyclobenzaprine: Widely used and one of the most sedating. Has anti-cholinergic effects (drying).
  • Methocarbamol: One of the least sedating, causes brown/black/green discoloration of urine.
  • Tizanidine: Activated adrenergic neuron and tricks it into thinking it released norepinephrine when it hasn’t, so it shuts down or slows sympathetic output throughout the body. Using it to effect muscles and slow everything down. Causes hypotension. Needs to taper off with prolonged use, could cause massive rebound effect because the neurons are now hypersensitive due to lack of use.

Baclofen

Anti-spasticity agent. Used for multiple sclerosis and cerebral palsy. Much more of a long term thing than muscle spasms.

Side Effects: Drowsiness, dizziness, weakness, fatigue, nausea/vomiting, constipation, urinary retention.

Administration: Can be taken orally or intrathecally. Must taper off over 2-4 weeks. Severe consequences if you don’t taper: altered mental status, rebound spasticity and rigidity, rhabdomyolysis, multi-organ failure, death.

Stimulants

Treatment of ADHD, narcolepsy, depression, fatigue. Generally increase the norepinephrine and dopamine available. Typically work pretty fast/immediately for awareness/alertness. Can take a week to see clinical benefits (like ADHD).

Side Effects: Decreased appetite, insomnia, headaches, abdominal pain. Psychosis, tics, mania and seizures can be seen with higher doses and frequent use. Can have cardiovascular concerns because increased norepinephrine can stimulate alpha and beta receptors.

Drugs: Dextroamphetamine, methylphenidate, lisdexamfetamine, dexmethylphenidate. Formulations vary considerably. Short acting 2-6 hour duration, long acting 8-12 hour duration, patch up to 9 hour duration.

Exam Essay: Asynchronous Dosing

Asynchronous dosing, concept that if a drug is twice a day, synchronous dosing would mean every 12 hours. Generally dosing approach to stimulants is twice a day, 8 hours apart such as 8 am and 4 pm. Generally take last dose no later than early evening so patients can have drug free time at night to be able to sleep. We want drug out of system by bedtime so insomnia does not occur.

Exam Essay: Drug Holiday

Not universally accepted or recommended but relatively common. There is a thought that ADHD medications are to help kids focus during the school year. So the concept is that kids don’t take this drug during the summer when it’s not needed as much.

Pros: Appetite and weight. During summer appetite will return and they can gain weight. Other pros: letting child fully be themselves without changing their behavior with drugs.

Cons: Some believe that concentrated focus is not just for the school year but is needed year round. Could have negative implications of constantly starting and stopping a drug. Pros/cons should be discussed between parent/provider.

Non-Stimulant ADHD Treatment

Clonidine: MOA is uncertain, all involve norepinephrine. Stimulants are more effective. May be used if stimulant doesn’t work. It is an alpha 2 agonist used to treat hypertension.

Side Effects: Drowsiness/fatigue, hypotension, orthostatic hypotension, bradycardia, depression. Must titrate off if stopping 0.1 mg every 3-7 days. Takes a few weeks.

Antibiotics

Mechanisms of Action

  1. Disrupt bacterial cell wall/membrane. This kills the infection without hurting the host. These are typically bactericidal and include the beta-lactams, penicillins, vancomycin, telavancin, daptomycin.
  2. Interfere with bacteria protein/DNA/RNA synthesis via ribosomes, and bacteria can’t grow. Typically bacteriostatic.
  3. Disrupt DNA transcription/translation. Typically bactericidal. Fluoroquinolones, metronidazole.

Bactericidal means it kills bacteria, at least 99.9%. Bacteriostatic drugs inhibit or slow growth, they work because the body will clear the bacteria too. You need to use a bactericidal drug if someone is immunosuppressed. Also use one if it is too dangerous to wait for the immune system to kick in as in sepsis or meningitis.

Amoxicillin, Amoxicillin/Clavulanic Acid

In the class penicillins. Broad class, many on the market. 4 classes: natural, extended spectrum, antistaphylococcal, antipseudomonal. Also there are beta-lactamase inhibitor combinations. They are renally excreted so they are sensitive to renal function and probenecid.

Resistance Issues: Bacteria produce penicillinase that destroys beta lactam rings that makes the drug work. So the beta-lactamase/penicillinase enzyme cut/break the ring and make it ineffective.

Methicillin was originally anti-staph. Not available anymore. MRSA is a strain resistant to methicillin/penicillins because there is a genetic change of binding site so the penicillin can’t bind anymore.

Anti-staph penicillins are only good against staph infections (MSSA, MSSE).

Antipseudomonal penicillins are effective against pseudomonas. All the aerobic gram-negative bacteria that are hard to treat and develop resistance quickly.

Hypersensitivity Concerns: 5-8% report allergy, the minority probably has a true allergic reaction. 0.05% with anaphylactic reactions. All antibiotics will cause diarrhea because they are non-specific and kill a wide range of normal bacteria as well.

Cephalosporins

Cephalexin (first generation) and cefdinir (third generation). Have beta-lactam ring structure. 10% cross-reactivity with penicillins. They are divided into generations.

  • First Generation: Similar to extended-spectrum penicillins. Good for typical things like strep throat, UTI, some skin infections.
  • Second Generation: Similar to first generation but have better activity against things found in the gut. May be given as a sort of prophylactic or prevention.
  • Third Generation: Similar to anti-pseudomonas penicillins, broad spectrum against gram negative organisms, they are strong.
  • Fourth Generation: Most broad spectrum. Gram positive, gram negative, anaerobic, all of it. Something you give when you’re not sure what you’re treating yet.
  • Fifth Generation: Useful against MRSA, other highly resistant gram-positive organisms.

Tetracyclines

Doxycycline and minocycline. Broad spectrum agents including atypicals, H. pylori, acnes and MRSA. Atypical: mycoplasma, chlamydia, legionella. These don’t have a cell wall, you can’t use anything bactericidal because they target cell walls. These can hide in cells.

Unique Considerations: Avoid later in pregnancy or in children under 8 years old because the drug permanently binds to and stains teeth/bones. Victim to chelation.

Side Effects: Nausea/vomiting/diarrhea, GI upset, cramps, photosensitivity (more prone to burning). Caution with expired medications as they can break down into something toxic and cause Fanconi syndrome with anemia and renal damage.

Macrolides

Erythromycin, azithromycin. Very effective, work against atypicals. Several members have serious drug interactions (not azithromycin). Azithromycin has short doses, only a few days. It is unique, it leaves blood quickly but effects last a long time. It concentrates in cells of immune system. So you don’t have a lot in your body/blood to cause drug interactions. These cause increased GI motility, effects burn out quickly so not good long term, but can be good for gastroparesis in a hospital.

Side Effects: Abdominal pain, nausea/vomiting/diarrhea, QT prolongation. Association with sudden cardiac death syndrome. Don’t take with anti-arrhythmics.

Fluoroquinolones

Ciprofloxacin, levofloxacin, ofloxacin. They are bactericidal. Effective against gram positive and gram negative, some of the more serious ones. Resistance is a major concern due to widespread use. They are divided into generations or as “respiratory quinolones”. They are all available orally, well-absorbed, and predictable.

Side Effects: Neuropsychiatric effects from CNS stimulation, tendon rupture and hypo/hyperglycemia. Hypo/hyperglycemia may be from the drug binding to pancreatic cells and causing a small release of insulin. Then, after a few days the quinolone in the pancreas may inhibit the release of insulin. Drug is useful for children with cystic fibrosis to avoid constant hospitalization since it is strong and can be taken orally. Most tendon damage is a spontaneous rupture of the Achilles.

Sulfamethoxazole/Trimethoprim

Sulfa antibiotics. They block bacteria’s ability to make folic acid. Bacteria have to make folic acid, without it they can’t make proteins and can’t make RNA/DNA. They are broad spectrum including MRSA. Have a drug interaction with warfarin.

Considerations: Allergy, cross-sensitive to other sulfas. Can precipitate in acidic urine so you should be drinking water. Can cause hemolytic anemia (G6PD), sulfas cause oxidative stress in people with G6PD deficiencies, and this can cause hemolytic anemia. Can cause severe skin reactions.

Clindamycin

Not a macrolide. It is bacteriostatic. It works against anaerobic bacteria, including MRSA. Does not work against C. difficile. Anaerobic bacteria are widely seen in the gut and in abscesses. Best for infections above the diaphragm. Most at risk for causing C. difficile overgrowth because it kills other bacteria which allows C. diff to take over. It widely distributes except for in the CNS. It is largely metabolized and has mixed elimination.

Side Effects: Diarrhea, pseudomembranous colitis. Can cause hepatotoxicity, rashes, and blood dyscrasias.

Metronidazole

Can kill C. diff. Targets anaerobes and some protozoans. Treatment for C. diff works orally or IV.

Side Effects: Nausea/vomiting/diarrhea, loss of appetite, cramping, and metallic taste in mouth. Used for GI tract and abscesses. Has a disulfiram effect (maybe) which is a violent reaction when alcohol is ingested.

Other Antibiotics

  • Mupirocin: Anti-MRSA. Topical/intranasal. Inhibits protein synthesis. Used to get rid of colonization, may be used before surgery to wipe out any MRSA.
  • Nitrofurantoin: Used for UTI’s. Activated in urine and makes urine toxic to bacteria. Take with food to increase absorption.
  • Neosporin

Estrogens

Estrogen Therapy

Most common uses are estrogen replacement, contraception and acne. They act via binding to the estrogen receptor in the cell nucleus and altering gene transcription and translation. Work towards the development and maintenance of female reproductive tract and secondary sex characteristics. They inhibit bone resorption and increase bone mass. They have a favorable effect on lipids. They have a generally favorable effect on heart disease risk factors. Pre-menopausal women on estrogen therapy have a lower risk of heart disease than men of the same age. Cause both pro and anti coagulant effects. They increase factor II, VII, IX, X and XII. They decrease antithrombin, and increase fibrin breakdown. Women should not be on estrogen just to decrease heart disease because of the other side effects of estrogen. Starting hormone therapy post menopause does not necessarily reduce the risk of heart disease, it may increase it. Heavily dependent on when you start therapy. A lot of tissues in the body see estrogen as a growth factor, so it can promote the growth of certain tissues. If someone has a cancer of those tissues, and gets estrogen, the cancer can grow quicker.

Cancers: Endometrial, breast, ovarian. We know it causes endometrial. We are unsure about breast/ovarian if it causes it or just makes it grow faster.

Progestin Therapy

Similar to estrogens, act via binding to nuclear receptor and altering gene transcription. Has many uses: contraception, dysfunctional uterine bleeding, amenorrhea, infertility/pregnancy maintenance, endometrial carcinoma and hyperplasia. Progestin use with estrogen will counteract the risk of cancer from estrogen alone. You cannot use estrogen by itself with people with a uterus.

Hormone Replacement Therapy

Approved for post menopausal women with moderate/severe vasomotor symptoms, moderate/severe vulvar and vaginal atrophy, prevention of osteoporosis, premature surgical menopause, and primary hypogonadism. Various products available: oral, IM, transdermal, topical/vaginal.

Estrogen/Progestin Products: Estradiol, progesterone.

Hormonal Contraceptives

Have multiple mechanisms of action. They can inhibit ovulation, thicken the cervical mucus, and impair endometrial implantation. Progestin only mini-pills only block ovulation 60-80% of the time.

Side Effects: Thromboembolism (all hormonal contraceptives), cerebrovascular disease, CAD, endometrial, breast or other hormone-dependent cancers, impaired liver function, abnormal vaginal bleeding.

Risk of Cardiovascular Death: 35-44 years old and a smoker. Risk of cardiovascular death is related to dose. Newer medications have lower doses so there are lower deaths overall. There are MANY different types and doses, to tailor the doses to an individual based on side effects and tolerability.

Types:

  • Monophasic: Constant hormones for 21 days, placebo for 7 days.
  • Bi/Tri/4 Phasic: Varying level of dose throughout cycle. These are meant to mimic normal highs and lows of estrogen and progestin naturally.
  • Extended Cycle: Hormones for 84 days, placebo for 7.
  • Continuous: Hormones for 84 days + low dose hormones 4-7 days, or full dose 365 days.
  • Progestin Only Mini-Pill: Progestin for 28 days. Mini pill less effective, dosing habits are critical, irregular bleeding may occur. They are safer for nursing mothers. They leave the system quicker, and regular dosing must be at the same time every single day.

Specific Hormonal Contraceptives: Ethinyl estradiol (many in top 200). Norethindrone is progestin only.

Additional Considerations: New progestins may be less androgenic, have better effects on acne and oily skin. May have a diuretic effect and be better for bloating and weight gain. Hyperkalemia with drospirenone, progestins have anti-aldosterone effects. Possible risk of venous thromboembolism is common to all newer generation progestins, 50% higher risk than the old progestins.

Perfect Use: Same time, every single day, never missing a dose. Critically important for progestin only products because ovulation can still occur 20-40% of the time.

Drug Interactions of Contraceptives: They are metabolized in the liver. Risk when combined with enzyme inducers. Antibiotics can have effects on contraceptives: estrogens go through metabolic process called conjugation. In oxidative metabolism you tweak one small part of chemical molecule and it makes it a little more water soluble and creates a handle or spot where your liver can attach a pre-formed water soluble compound. Now the whole thing is water soluble and can leave the body. It becomes excreted in bile and travels to large intestine where the enzymes are that break off the water soluble piece off the estrogen so you’re left with just estrogen. It gets reabsorbed into blood through large intestine and enters blood stream. The glucuronidase that cuts off the water soluble piece is made by bacteria in the gut, an antibiotic can get rid of gut bacteria so there are less of the glucuronidase so they can’t break the water soluble piece off so there’s no second peak of estrogen and therefore less exposure.

Androgen Replacement

Main therapeutic uses are hypogonadism, replacement therapy in men and women, delayed puberty. Replacement products are testosterones and testosterone esters.

Side Effects: Virilization: which is acne, deepening of voice, increased libido, increase face and body hair, male pattern baldness, genital enlargement, menstrual abnormalities. Premature epiphyseal closure, dyslipidemia, increased growth of prostate cancer, edema, gynecomastia, and there’s an abuse potential.

Testosterone Androgen Replacement

: uses testosterone, fluctuation concentrations and effects. The implantable pellets have a more consistent concentration. There’s a topical option. Patch can have irritation as site. gel solution comes with a risk of transfer via contact. no oral route, not absorbed by gut. Topical is not well absorbed. Have to use a lot mg wise. 10% of applied product is absorbed. You can transfer the drug via contact like hugging and sex. Avoid contact without clothing covering the area, or wash before contact. where you put the topical matters. BISPHOSPHONATES: used to treat/prevent osteoporosis, and treat certain cancers. gets incorporated into the bone, decreases the number and activity of osteoclasts. They become incorporated into the bone. not well absorbed, low bioavailability. Take on empty stomach, avoid taking with calcium/antacids, it can be chelated. Can cause esophagitis: take with a full glass of water. Remain upright for at least 30 minutes after taking. Take on empty stomach because of low bioavailability to maximize how much gets absorbed. AE’s: musculoskeletal pain, osteonecrosis of jaw, usually follow dental procedures. Esophageal cancer, hyperparathyroidism, renal toxicity. Risk for atypical fractures that occur in abnormal places or with an abnormally small amount of force. If you use drug over 9 years you have 200x more likely chance of atypical fracture. However, they are still incredibly uncommon. You prevent WAY more typical fractures than you are causing atypical fractures. ESSAY: drug holiday: some may recommend a drug holdiday for these to lessen risk of esophageal cancer and atypical fractures. So patients get treated for a while, get bone mineral density scan, if in normal range, they stop the drug and get regular density scans. if low, they start again. Alendronate is the drug. Oral, daily or weekly product. Or IV 1x a year. ANTIFUNGALS: Azole antifungaks block an organisms ability to make ergosterol, which is needed for cell membrane structure/function. By blocking ergosterol you kill the organism. They block the CYP enzyme that makes ergosterol. Drugs are not specific and have high drug interaction risk because they block the CYP enzyme that breaks down drugs. So these drugs inhibit the metabolism of other drugs. Drugs: fluconazole, ketoconazole. Many of these drugs are sensitive to gastric pH. Ketoconazole requires an acidic pH. Fluconazole has no special considerations. AE’s: All: N/V/D, headache, hepatotoxicity. Ketoconazole: gynecomastia, decreased libido, menstrual cycle changes. Loading doses are required for many products depending on use. Higher, more frequent doses for initial 1-2 days. ANTIVIRALS: Nucleosides and nucleotides analogs: inhibit viral DNA polymerase or reverse transcriptase. They use renal excretion. They are generally well tolerated, some serious toxicities. Risk of resistance where virus won’t phosphorylate drug. Drugs: acyclovir, valacyclovir. Timing of these drugs is very important. Must be given early in course of infection, because they help slow the spread. Could still be helpful later in infection, but not as much. Should be given 48-72 hours after symptoms start. Neuroaminidase inhibitors: treat flu viruses. They prevent newly formed virus particles from leaving the cell and spreading. They are eliminated in urine. N/V but less when given with food. Should start within 48 hours of symptom onset. Can be used as prophylaxis: treat 1-2 weeks post-exposure. Or as a treatment with a higher dose for 5+ days. Drug is oseltamivir (tamiflu). VACCINES: act as an antigen to stimulate immune system to produce antigen specific antibodies. Types of vaccines: Live attenuated (weakened) vaccine. These are the most consistent with natural immunity. They retain the ability to replicate. Cannot give to immunocompromised pts. They are far more effective, and don’t require boosters as often if at all. You can actually get the illness from the vaccine, but shouldn’t with a hhealthy immune system. Inactivated vaccines: non-infectious, no replication. IG levels fall over time, boosters are needed. They are safer in immunocompromised pts. May cause more AE’s due to adjuvants. Adjuvants are things manufacturers add to a vaccine to hopefully cause a bigger immune response. They’re irritating and promote inflammation, etc. Cause side effects such as pain, body aches and chills. Vax can be sensitive to food allergies. Egg, gelatin, bakers yeast. Ethical concerns: some vaccines use cell lines from aborted fetuses. Vatican says they’re okay to use but do not endorse the manufacturing process. Can you get a vax when ill? if mild, yes. if mod/severe, no. Can you give ibuprofen/acitominophen prior to vax? no because it could lower immune response to a vaccine. Can treat for pain/fever etc after vaccine if needed. Can you give too many vaccines in one day? no your immune system can handle it. its preference. rare cases that vaccines cannot mix. follow CDC guidelines. CANCER THERAPIES: Strategies for improving drug response: Intermittent chemotherapy, burst of drug, then no drug, etc. 3 days on chem/ 18 off, repeat, more cycles. These drugs are very hard on the body, by giving a burst of a drug you hit cancer cells hard and then give the body cells a chance to rest. It encourages more cancer cells to be in rapid, actively dividing phase where they’re more sensitive to death the next round of chemo. Combination therapy: decreased resistance, increased clinical response, possible decrease in toxicity. Novel routes of admin, for example hepatic artery, implantable wafers, etc. Major drug related toxicities: Neutropenia when bone marrow becomes damaged by chemotherapy. Not enough neutrophils in body. Increase the incidence and the severity of the infection. Nadir at day 10-14, recovery 1 week later. Can be delayed, Nadir at 3-4 weeks, recovery at 7 weeks. Thrombocytopenia: decrease in platelets. Increased risk of bleeding/bruising. Anemia: less common b/c RBC half life is 120 days. Stomatitis: damage to oral mucosal onset in few days and may persist several weeks. can try and manage with good hygiene and mouthwashes. Diarrhea: loperamide, diphenoxylate. CINV (chemo induced nausea and vomiting): a major treatment related problem. Dehydration, electrolyte imbalances, nutrient deficiencies, esophageal tears. Common reason that patients refuse treatment. Direct stimulation of CTZ/vomiting center. May persist hours to days and be mild to severe. Cytotoxic agents rated on the ability to cause N/V. Prevention is far more effective than treatment. Other toxicities: Alopecia: onset 7-10 days, max 1-2 months. Reproductive toxicities. Hyperuricemia: caused by cells dying from chemo and releasing purines that get metabolized to uric acid. May cause damage to kidneys due to the crystals. So we can give a prophylactic to prevent uric acid crystals forming, usually allopurinol or an enzyme. There can be direct injury to skin, veins, and tissues. many chemos are vesicants and cuse blisters. If chemo leaks out of a vein it can do considerable soft tissue damage. Special considerations some may need to be given in larger veins, pts need to be checked on during infusion, etc. If extravasation occurs and needle slips, you need to use ice most of the time. For vincas use heat. some have antidotes. Targeted therapy: a more precise specific cancer therapy. Have different MOAs, some block growth factor or surface receptors, some inhibit intracellular enzymes, some mark cells for immune attack, some target delivery of toxic compunds, some inhibit angiogenesis. These drugs have far less systemic effects are are better tolerated by far and safer. Some might be more effective. Cons: not for everyone, or every time of cancer. Only small percent of people have the kinases that there is a drug for. Anti hormones: block growth factors for hormone sensitive cancers (estrogen) blocks conversion of androtenedion to estrone and testosterone to estradiol. Drug is anastrozole. can cause hot flashes, vasodilation, osteoporosis, arthralgia, mood disorders. AE’s related to the hormone. Kinase inhibitors: Kinases are enzymes in cells that add phosphate groups to proteins. Some cancers produce a mutated kinase that makes it hyperactive that allows for unregulated growth. Kinase inhibitors aim to reverse that, stopping the abnormal characteristics and growth. AE’s: N/V/D; rash. Can cause myelosuppresion, HTN, QT prolongation, skin/hair changes, lung disease, anorexia, fatigue, edema.Drugs sensitive to gastric pH. need to give either with food or on an empty stomach. Many interactions with PPIs, antacids. etc. most are oral.