Acetaminophen

Mechanism of Action

- Weak nonselective COX inhibitor in presence of  peroxides

- Inhibits COX3 (COX1b) in the brain

Acetominophen

Effects

- Analgesic (non-opioid)

- Analgesia, antipyretic equal to aspirin

- No anti-inflammatory or anti-thrombotic function

Acetominophen

Pharmacokinetics

- Rapidly absorbed from GI

- Peak plasma concentration in 30-60 minutes

- Metabolized in liver

- Distributes to peripheral tissue and CNS

- Renal excretion

- Plasma 1/2 life = 2-3 hours

Acetominophen

Uses

- Treatment of mild pain and fever

- Fever from virus

- Mild arthritis - analgesic

Acetominophen

Side Effects

- Well tolerated by GI

- Overdose: liver toxicity with liver failure that is enhanced by chronic EtOH use

- High chronic use associated with chronic renal failure

Tramadol

Mechanism of Action

- Inhibits uptake of NE and 5HT

- Weak Mu agonist

Tramadol

Effects

- Analgesic (non-opioid)

- Synthetic codein analog

Tramadol

Uses

Tramadol

Side Effects

- Nausea

- Vomiting

- Dizziness

- Dry mouth

- Sedation

- Headache

- Seizures

Corticosteroids

(prednisone, methylprednisolone)

Mechanism of Action

Corticosteroids

(prednisone, methylprenisolone)

Effects

- Anti-inflammatory

- Immunosuppressive

Corticosteroids

(prednisone, methylprednisolone)

Uses

Corticosteroids

(prednisone, methylprenisolone)

Side Effects

- Hypercholesterolemia

- Cataracts

- Osteoporosis

- Hypertension with prolonged use

Ibuprofen

Mechanism of Action

- Non-selective NSAID

- Propionic acid derivative

- Reversible COX inhibition (COX1 and 2)

Ibuprofen

Effects

- Analgesia

- Antipyretic

- Anti-inflammatory

Ibuprofen

Uses

- Pain and inflammation - trauma, infection, autoimmune disorder, neoplasms, joint degeneration

- RA

- OA

- AS

Ibuprofen

Pharmacokinetics

- Taken orally

- Wide distribution

- Liver metabolism

- Renal excretion

Ibuprofen

Side Effects

- Gastric irritation

- Nausea

- Dyspepsia

- Bleeding

- Peptic ulcer disease

- Acute renal failure in patients at special risk: volume depletion, preexisting renal dysfunction, CHF, hypotensive

- Aspirin alternative for children

Naproxen

Mechanism of Action

- Non-selective NSAID

- Propionic acid derivative

- Reversible CO inhibition (COX1 and 2)

Naproxen

Effects

- Analgesia

- Antipyretic

- Anti-inflammatory

Naproxen

Uses

- Pain and inflammation - trauma, infection, autoimmune disorder, neoplasms, joint degeneration

- RA

- OA

- AS

Naproxen

Pharmacokinetics

- Taken orally

- Wide distribution

- Liver metabolism

- Renal excretion

Naproxen

Side Effects

- Gastric irritation

- Nausea

- Dyspepsia

- Bleeding

- Peptic ulcer disease

- Acute renal failure in patients at special risk: volume depletion, preexisting renal dysfunction, CHF, hypotensive

- Aspirin alternative for children

Indomethacin

Mechanism of Action

- Non-selective NSAID

- Acetic acid derivative

- Reversible COX inhibitor

Indomethacin

Effects

- Anti-inflammatory

- Analgesic

- Antipyretic

Indomethacin

Uses

- Pain

- Inflammation

Indomethacin

Side Effects

Celecoxib

Mechanism of Action

- Selective NSAID

- COX-2 inhibitors

- Sulfur groupsselectively binds COX-2, but excludes COX-1

Celecoxib

Effects

- anti-inflammatory

- analgesic

- Antipyretic

- function equivalent to aspirin and ibuprofen

- No antithrombotic function

Celecoxib

Uses

- OA

- RA

- Analgesic not effective post surgery

- Possibly protective against colon carcinogenesis

Celecoxib

Pharmacokinetics

- Taken orally, GI tract absorption

- Liver metabolism by CYT P450

- Excreted in urine and feces

Celecoxib

Side Effects

- Less GI toxicity compared to nonselective COX inhibitors

- Some renal toxicity, diarrhea, dyspepsia

- Abdominal pain

- CV toxicity

- Very expensive

Allopurinol

Mechanism of Action

- Purine analog

- Reduces productionof uric acid by competitively inhibiting Xanthine Oxidase (the last two steps of uric acid biosynthesis)

- Xanthine and hypoxianthineare more soluble, and less likely to precipitate in joints

Allopurinol

Effects

Allopurinol

Uses

- Gout

- Drug of choice if there is a history of kidney stones or if creatinine clearance < 50 mL/day

Allopurinol

Pharmacokinetics

- Oral administration (completely absorbed)

- Feces/urine excretion

- 1 dose daily

Allopurinol

Side Effects

- Hypersensitivity rash

- Acute gout attach (give with colchicine and NSAIDs to begin)

- Nausea

- Diarrhea

- Affects metabolism of 6-mercaptopurine azathioprine (needto reduce dose if given with Allopurinol)

Colchicine

Mechanism of Action

- Binds tubilin and depolymerizes it

- Disrupts granulocyte mobility

- Blocks celldivision (binds mitotic spindles)

- Inhibits syntesis and release of leukotrienes

Colchicine

Effects

- Reduces gout symptoms

- Relief of pain

Colchicines

Uses

- Prophylaxis to reduce occurrence of acute attacks

- Relieve pain

- Give  within 24-48 hours of attack onset

Colchicines

Pharmacokinetics

- Oral administration, rapid absorption by GI

- Excreted unchanged in the feces/urine

Colchicines

Adverse Effects

- Avoid if the patient has a creatinine clearance < 50mL/min

- Nausea

- Vomiting

- Abdominal pain

- Diarrhea

- Myopathy

- Neutropenia

- Aplastic anemia

- Alopecia

- Contraindicated in patients who are pregnant or have hepatic/renal/cardiovascular disease

Probenicid

Mechanism of Action

- Uricosuric

- Decreases resorption of uric acid in the proximal tubule by blocking active transport of uric acid

Probenecid

Uses

- Prevent further gouty attacks

- Prevent and treat hyperuricemia

Probenecid

Adverse Effects

- GI upset

- Inhibition of renal excretion of penicillin/NSAID

Pegloticase

Mechanism of Action

- PEGylated uricase

- Converts uric acid to allantoin, an inactive and soluble metabolite readily excreted by the kidneys

Pegloticase

Uses

Pegloticase

Adverse Effects

- Lots of drug-drug interactions (P450 unknown)

- Anaphylaxis

- Infusion reactions

- Hypersensitivity

- CHF exacerbation

- Gout exacerbation

- Nausea

- Constipation

- Vomiting

- Chest pain

- Contraindicated for patients with G6PD deficiency or CHF

Pegloticase

Pharmacokinetics

- Unknown metabolism, CYP450

- Excretion unknown

- Half-life is 14.5 days

Hydrocodone

Mechanism of Action

- Binds specific opioid receptors throught the nervous system → hyper polarization and decreased activity of neurons through interaction with calcium and potassium ion channels

- Areas include: brainstem, spinal cord, peripheral nerves, amygdala, thalamus, and hypothalamus

Hydrocodone

Use

- Pain control

- Other opioids are for: cough suppression (codeine and dextromethorphan), diarrhea (diphenoxylate), acute pulmonary edema (morphine)

Hydrocodone

Adverse Effects

- Cardiac and respiratory depression

- Constipation

- Nausea

- Miosis

- Tolerance and dependence

- Withdrawal can result in severe GI upset, anxiety, and chills

Aspirin

Mechanism of Action

- Irreversibly inhibits COX-1 and COX-2 → decreases PG synthesis → anti-inflammatory effects

- Effects of low PGE2: analgesia, anti-pyresis (decreases setpoint at thermoregulatory center in anterior hypothalamus), decreased in protective gastric mucous causing peptic ulcers

- Effects of low PGI2: increased gastric acid causing peptic ulcers

- Effects of low TxA2: anti-platelet aggregation

Aspirin

Uses

- Anti-pyretic

- Analgesic

- Anti-inflammatory

- Anti-platelet (used in primary and secondary prevention in patients at risk for cardiovascualr or cerebrovascular diease)

Aspirin

Adverse Effects

- Bleeding (especially GI) and ulcers

- Allergy

- Reye's Syndrome if given to children with viral (influenza, varicella) infections → can be fatal

- Tinnitus

- If taken in toxic amounts: respiratory and metabolic acidosis

-Treatment for overdose: sodium bicarbonate → alkalinizes the urine → promote salicylate excretion

Diazepam

Mechanism of Action

- Long-acting benzodiazepine

- Enhances GABAa receptor activation by binding a site directly adjacent to it → increased Cl^- flow through the adjacent channel → hyperpolarization → decreased activity of neurons in CNS

- Y-aminobutyric acid target

- Areas of action: limbic system, thalamus, hypothalamus

Diazepam

Effects

Diazepam

Uses

- Skeletal muscle relaxant

- Cerebral Palsy

- Musltiple sclerosis

- Anxiety

- Seizures

- Status elipticus

- Alcohol withdrawal

- Insomnia

- Panic disorder

- Muscle spasms

Diazepam

Pharmacokinetics

- Oral administration

- Lipophilic, distributes through the entire body

- Metabolized in liver

- Excreted in urine

- Crosses placenta

Diazepam

Adverse Effects

- Sedation, drowsiness, confusion

- Altered mental status

- Ataxia

- Avoid in patients with liver disease, glaucoma or those using alcohol, barbituates, or other CNS dpressants

- Dependence

- Withdrawal symptoms: altered mental status, anxiety, tachycardia, vomiting

- Overuse is associated with cardiac and respiratory depression (can treat with flumazenil which binds competitively with GABA receptors)

Cyclobenzaprine

Mechanism of Action

- Unknown

- Potentiates NE and binds to 5-HT receptors → reducing spasticity

- Appears to effect locus ceruleus

- Appears to inhibit alpha motor neurons in the ventral horn of the spinal cord

Cyclobenzaprine

Effects

Cyclobenzaprine

Uses

- Muscle spasms

- (Centrally-acting) Skeletal muscle relaxant

Cyclobenzaprine

Pharmacokinetics

- Oral administration

- Metabolized by the liver, CYP450 1A2, 2D6 (minor), and 3A4 substrate

- Excreted in urine primarily

- Half-life is 18hrs or 32hrs

Cyclobenzaprine

Adverse Effects

- Seizures

- Cardiac conduction disturbance

- Arrythmias

- MI

- Stroke and heat stroke

- Xerostomia

- Anaphylaxis

- Dizziness, fatigue, drowsiness

- Dyspepsia, nausea

- Lots of drug-drug interactions

- Depression

- Headache

- Respiratory depression

- ↓ muscle function

- Dry mouth

- Vision problems

- High doses lead to anticholinergic effects and ataxia

- Contraindicated for use with MAOIs and potassium salts

Gabapentin

Mechanism of Action

- Unknown

- Thought to bind voltage-gated ion channels in the CNS → decreases in the release of glutamate and NE

Gabapentin

Uses

- Chronic neuropathic pain

- Fibromyalgia

- Postherpetic myalgia

- Adjunct for partial seizures

Gabapentin

Adverse Effects

- Dizziness

- Sedation

- Ataxia

- Peripheral edema

Pregabalin

Mechanism of Action

- Unknown

- GABA analog; thought to interact with calcium ion channels in the CNS → decreases release of glutamate and NE

Pregabalin

Uses

- Chronic neuropathic pain

- Postherpetic neuralgia

- Adjunct for partial seizures

Pregabalin

Adverse Effects

- Peripheral edema

- Sedation

- Hepatotoxicity

Amitriptyline

Mechanism of Action

- 1st generation tricyclic antidepressant

- Prevents the reuptake of serotonin and NE → potentiates their effects on postsynaptic receptors

- Tricyclic antidepressants are also shown to inhibit muscarinic, histamine, and alpha-adrenergic receptors → several undesirable adverse effects

Amitriptyline

Uses

- Major depression (general TCAs)

- Chronic pain syndroms (general TCAs)

- Panic disorder (general TCAs)

- Neuropathic pain (Amitryptiline only)

Amitriptyline

Adverse Effects

- Sedation

- Postural hypotension

- Anticholinergic effects (muscarinic blockade): urinary retention, dry mouth, constipation, blurred vision)

-Priapism

- Cardiac arrhythmias (alpha-adrenergic effect)

- Contraindication when given with MAOIs, causes seizures

- TCA overdose associated with ECG changes (widening QRS complex), cardiac arrhythmias, mental status change, and seizures

First generation

Tricyclic Antidepressants

- Amitriptyline

- Desipramine

- Notriptyline

- Imipramine

- Doxepin

Second generation

Tricyclic Antidepressants

- Burpropion

- Trazadone

- Amoxapine

Duloxetine

(Serotonin-norepinephrine reuptake inhibitor)

Mechanism of Action

Duloxetine

(Serotonin-norepinephrine reuptake inhibitor)

Uses

- Major Depression

- OCD

- Anxiety Disorders

- Eating disorders

- Premenstrual dysmorphic disorder

Duloxetine

(Serotonin-norepinephrine reuptake inhibitor)

Adverse Effects

- Sexual dysfunction (decreased libido, orgasm difficulty)

- GI upset

- Loss of appetite

- Weight loss

- Tremors

- Contraindication when given with MAOIs → causes serotonin syndrome (changes in mental status, muscle stiffness, autonomic instability, and hyperthemia)

- Fluoxetine

- Paraoxetine

- Sertraline

- Fluvoxamine

- Escitalopram

- Citalopram

Hydroxychlorquine

Mechanism of Action

- May inhibit phospholipase A2 and platelet aggregation, membrane stabilization

- Antioxidant activity

- Antiheumatic/immunosuppressive effects: inhibits rheumatoid factor, acute phase reactants, and many enzymes

Hydroxychloroquine

Uses

- SLE

- Rheumatoid arthritis: early to mild, used in combination with methotrexate and sulfasalazine

- Malaria prophylaxis treatment

Hydroxychloroquine

Effects

Hydroxychloroquine

Pharmacokinetics

- Metabolized partially by the liver

- 25% excreted unchanged in urine, and bile

- Half-life is 32-50 days

Hydroxychloroquine

Adverse Effects

- Blood effects: agranulocytosis, thrombocytopenia, aplastic anemia, angioedema)

- Seizures

- Bronchospasm

- Exfoliative dermatitis

- Exacerbation of psoriasis/porphyria

- Dizziness, ataxia, headache, nausea, vomiting, abdominal pain

- Pruritis

- Weight loss

Sulfasalazine + folic acid

supplemetation

Mechanism of Action

- PABA analog

- Occupies dihydropteroate synthetase

- Colonic bacteria metabolizes the drug into two components: sulfapyridine and 5-ASA → 5-ASA blocks COX → decreased PG and LT production → anti-inflammatory

- 5-ASA may also scavenge for oxygen radicals → prevents further mucosal damage

Sulfasalazine + folic acid

supplementation

Uses

- IBD

- Rheumatoid arthritis: early/mild RA in combination with hydroxychloroquine and methotrexate

- Juvenile arthritis

Sulfasalazine + folic acid

supplementation

Pharmacokinetics

- Not absorbed orally or as a suppository

- Onset takes 1 - 3 months

Sulfasalazine + folic acid

supplementation

Adverse Effects

- GI upset

- Skin rash

- Headache

- Bone marrow suppression

- Infertility

- Should be given with folic acid supplementation because its metabolized to sulfapyridine

Methotrexate + Leucovorin

(folinic acid)

Mechanism of Action

- Inhibits dihydrofolate reductase which whichtransforms folic acid to the active FH4 → thymidylate is diminished → decreased DNA synthesis

- FH4 is a necessary precurssor for the formation of thymidylate

Methotrexate+ Leucovorin

(folic acid)

Uses

- Immunosuppressant

- Rheumatoid arthritis

- Crohn's disease

- Scleroderma

- Psoriasis

- Chemotheray: ALL, lyphomas, breast cancer, head and neck cancer, osteosarcoma, choriocarcinoma

- Abortifacient (with prostaglandin): missed abortionsor small ectopic pregnancies

Methotrexate + Leucovorin

(folinic acid)

Effects

- Slows the appearnce of new joint erosions on radiographs

- Used alone or in combination

Methotrexate + Leucovorin

(folinic acid)

Pharmacokinetics

- Given once per week

- Folinic acid is given with methotrexates to avoid bone marrow suppression which occurs because of lack of folate enzymes

Methotrexate + Leucovorin

(folinic acid)

Adverse Effects

- Dose needed for RA is much lower than cancer use, so side effects are minimal

- Bone marrow suppression

- Pulmonary toxicity

- Nephrotoxicity

- Hepatotoxicity

- Mucositis

- Seizures

- GI upset

- Alopecia

- Nausea

- Cytopenias

Leflunomide

Mechanism of Action

Leflunomide

Uses

Leflunomide

Pharmacokinetics

- Metabolized in the liver an GI tract extensively

- CYP450 1A2 inducer, 2C8 inhibitor

- Metabolized into BCRP substrate and active metabolite teriflunomide

- Excretes in feces and urine

- Half-life is 14 days

Leflunomide

Adverse Effects

- Hepatotoxicity

- Blood effects (leukopenia, neutropenia, pancytopenia, agranulocytosis, thrombocytopenia)

- Sepsis

- Opportunistic infections

- Anaphylaxis

- Diarrhea, nausea, vomiting, abdominal pain

- Alopecia

- Rash

- Hypertension

Azathiprine

Mechanism of Action

- A structureal analog of 6-mercaptopurine, and is coverted to 6-MC within the cell

- 6-MC is converted to thio-IMP by HGPRT (enzyme involved in the salvage pathway) → thio-IMP is a purine analog whihc inhibits purine synthesis through feedback inhibition → thio-IMP is also converted to thi-GTP which is incorporated into DNA and RNA → causes strand instability

Azathioprine

Uses

- Immunosuppressant

- Systemic lupus erythematosus

- Irritable bowel disease

- Rheumatoid arthritis

- Idiopathic thrombocytopenia purpura

- Multiple Sclerosis

- Psoriasis

- Chemotherapy: leukemias (especially acute lymphoblastic leukemia), Non-Hodgkins Lymphoma

Azathioprine

Pharmacokinetics

- 6-MC is metabolized by xanthine oxidase, allopurinol inhibits this enzyme

- When allopurinal and Azathioprine are given together, serum levels of 6-MC rise

Azathioprine

Adverse Effects

- Bonemarrow suppression

- GI upset

- Increased susceptibility to infection

Cyclosporine A

Mechanism of Action

- Binds to cyclophilin in the T cell → this complex inhibits calcineurin, whichnormally activates the transcription of IL-2 → without IL-2, T cell activation is decreased → decreased cytokines

- Blocks T-cell differentiation

Cyclosporine A

Uses

- Immunosuppressant in transplant patients

- Graft versus host disease

- Rheumatoid arthritis

- Irritabole bowel disease

- Psoriasis

Cyclosporine A

Pharmacokinetics

Cyclosporine A

Adverse Effects

- Nephrotoxicity

- Hepatottoxicity

- Increased susceptibility to infection

- Increased incidence of lymphomas

- Hyperglycemia

- Hyperkalemia

- Hypertension

- Most side effects are dose-dependent

Mycophenolate

Mechanism of Action

Mycophenolate

Uses

- Immunosuppressant

- Used with transplant patients

- Psoriasis

- Systemic lupus erythematosus

Mycophenolate

Pharmacokinetics

Mycophenolate

Adverse Effects

- Allergy

- Increase Susceptibility to infection

- Pancytopenia

- GI upset an GI bleed

- Increase risk of lymphomas

Entanercept, Enfliximab

Adalimumab, Certolizumab petol

Golimumab

Mechanism of Action

- Inhibitsbinding of TNFa and TNFb to receptors → decreases effects of TNFa → anti-inflammatory effects

- TNF a is a cytokine produced by macrophages and T cells that stimulates the release of other inflammatory cytokines (IL-1, IL-6, and IL-8)

Entanercept, Infliximab

Adalimumab, Certolizumab pegol

Golimumab

Uses

- Rheumatoid arthritis

- Psoriatic arthritis

- Ankylosing Spondylitis

Etanercept, Infliximab

Adalimumab, Certolizumab pegol

Golimumab

Adverse effects

- Etanercept: injection site reactions, URT infections, possible carcinogenic

- Infliximab/Adalimumab: increased susceptibility to infection, infusion reaction, abnormal LFTs

- Also used to treat rheumatoid arthritis

- Mechanism of action unknown but believed to exert anti-inflammatory effects by inhibiting macrophage activity and decreasing lysosomal enzyme activity

Anakira

Mechanism of Action

- IL-1 blocker

- Inhibits IL-1 type 1 receptors

- Modulates various inflammatory and immunological responses

- Anti-cytokine

Anakinra

Uses

- Rheumatoid arthritis, moderate to severe

- Neonatal-onset multisystem inflammatory disease

Anakinra

Pharmacokinetics

- Metabolism unknown

- Excreted in the urine

- Half-life is 4-6 hours

Anakinra

Adverse Effects

- Hypersensitivity (fever, rash)

- Serious infection

- Neutropenia

- Malignancy

- Injection site reaction

- Nausea, vomiting diarrhea

- Headache

- URI

- Contraindicated for patients with BCG live vaccine, influenza live nasal vaccine, smallpox vaccine, other live vaccines

Rituximab

Mechanism of Action

Rituximab

Uses

- Non-Hodgkins lymphoma and chronic lymphocytic leukopenia

- Rheumatoid arthritis

- Wegener granulomatosis

- Microscopic polyangitis

Rituximab

Adverse effects

- Infusion reactions: hypotension, respiratory failure, cardiac arrest)

- Acute renal failure cause by tumor lysis syndrome

- Increased susceptibility to infections

- To avoid infusion reactions, avoid pre-medicating patients with anti-histamine and acetaminophen prior to infusion

Abatacept

Mechanism of Action

- Anti-LFA3

- Selectively modulates T-cell activation, altering the immune response

- Costimulatory blocker

Abatercept

Uses

- Rheumatoid Arthritis, moderate to severe

- Juvenile idiopathic arthritis

Abatacept

Pharmacokinetics

- Metabolism is unknown

- Excretion is unknown

- Half-life is 13-14 days

Abatacept

Adverse Effects

- Malignancy

- Severe infection

- Sepsis

- Pneumonia

- Cellulitis

- Pyelonephritis

- Headache

- URI

- cought

- Nausea, diarrhea, dyspepsia, abdominal pain

- Hypertension

- Dizziness

Tocilizumab

Mechanism of Action

- Anti-IL-6

- Binds to and inhibits IL-6 receptors, reducing inflammation and altering the immune response

- Monoclonal antibody

Tocilizumab

Uses

- Rheumatoid arthritis, moderate to severe

- Juvenile idiopathic arthritis, polyarticular or systemic

Tocilizumab

Pharamacokinetics

- Metabolism unknown

- Excretion unknown

- Half-life is 11-13 days

Tocilizumab

Adverse Effects

- Severe infections

- Opportunistic infections

- Sepsis

- Tuberculosis

- Malignancy

- GI perforation

- Neutropenia

- Thrombocytopenia

- Infusion reaction

- Headache

- Hypertension

- Contraindicated for patients with live vaccines (BCG, influenza nasal, smallpox)

Cyclophosphamide

Mechanism of Action

- Metabolized to a hydroxylated compound → is an alkylating agent which cross-links DNA → decreases DNA and RNA synthesis

- Implicated in teh supression of B and T-cell function

Cyclophosphamide

Uses

- Chemotherapy: solid and hematologic malinancies (breast, ovarian, non-Hodgkin lyymphoma)

- Immunosuppressive

- Rheumatoid arthritis

- Systemic lupus erythematosus

- Wegener granulomatosis

- Nephrotic syndrome

Cyclophosphamide

Adverse Effects

- GI upset

- Alopecia

- Infertility

Dapsone

Mechanism of action

- PABA antagonist

- Inhibits folic acid synthesis

- Similar to sulfonamides

Dapsone

Uses

- Used with rifampin and clofazimine to treat leprosy

- Prophylaxis against P carinii infection in HIV patients

Dapsone

Adverse Effects

- G6PD-deficient hemolytic anemia

- GI intolerance

- Rash

Thalidomide

Mechanism of Action

- Unknown

- Believed to exert anti-inflammatory effects by decreasing TNFa production

Thalidomide

Adverse Effects

- Sedation

- Increased risk of DVT

- Contraindicated with pregnacy because it is a teratogenic; causes phocomelia, which is shortening or absence of the limbs

Calcitonin

Mechanism of Action

- Inhibits osteoclasts and may increase osteoblast activity

- Helps regulate calcium via, bone, renal, and GI effects

- Less effective than bisphosphonates

Calcitonin

Effects

Calcitonin

Uses

- Paget's disease

- Hypercalcemia

Osteoporosis (postmenopausal)

Calcitonin

Pharmacokinetics

- Intranasal administration

- Parenteral administration form rarely used for osteoporsis

- Metabolism by kidneys primarily, blood, peripheral tissues

- Excretion via urine, minerally unchanged

- Half-life is 70-90 minutes

Calcitonin

Adverse effects

- Osteogenic sarcoma if used for Paget's

- Anaphylaxis

- Hypersensitivity

- Bronchospasm

- Angioedema

- Hypercalcemic tetany

- Nausea, vomitin

- Injection site reaction

- Flushing, rash pruritis

Bisphosphonates

Mechanism of Action

Bisphosphonates

Uses

- Osteoporsis prevention and treatment

- Hypercalcemia-associated bone metastasis

- Paget's disease

- Multiple myeloma

- Preffered agento for postmenopausal osteoporosis

Bisphosphonates

Pharmacokinetics

- Oral administration without food

- IV administration available

- Bind hydroxyapatite in bone

- Renal excretion

Bisphosphonates

Adverse Effects

- Osteonecrosis of the jaw

- GI upset, especially with esophageal erosions

- Esophageal ulcers

- Atrial fibrillation

- Musculoskeletal pain

Estrogen

Mechanism of Action

Estrogen

Uses

- Osteoporosis prevention (postmenopausal)

- Hypoestrogenism

- Metastatic breast cancer

- Advanced prostate cancer

- Dysfunctional uterine bleeding

- Uremic bleeding

- Vulvovaginal atropy (menopausal)

- Vasomotor symptoms (menopausal)

Estrogen

Pharmacokinetics

- Metabolized by the liver

- CYP450 3A4 partial substrate

-Enterohepatically recirculated

 - Converted to active estrogen

- Metabolites include estradiol and estrone

- Excreted via urine

Estrogen

Adverse Effects

- Endometrial cancer

- Myocardial infarction

- Stroke

- Thromboembolism

- Rentinal thrombosis

- Hypertension

- Breast/ovarian cancer

- Vaginal bleeding

- Breast changes/pain

- Weight and mood changes

- Depression

Selective Estrogen Receptor Modulators

Mechanism of Action

- Mixed estrogen agonist/antagonist

- Competitive for estrogen-receptor → minimizes some natural growth processes promoted by the E-ER complex and promotes others

Selective Estrogen Receptor Modulators

Uses

- Chemotherapy; ER-positive breast cancer

- Osteoporosis

Selective Estrogen Receptro Modulator

Adverse Effects

- Increased risk of thromboembolism

- Hot flashes

- GI upset

- Fluid retention

- Vaginal bleeding

- Raloxifene does not increase risk of endometrial cancer like Tamoxifen

Denosumab

Mechanism of Action

- Monoclonal antibody against RANKL

- Binds to receptor activator of nuclear factor kappa-B ligand (RANKL), inhibiting osteoclast formation, maintenance, and survival and reducing bone resorption and turnover

Denosumab

Uses

- Postmenopausal osteoporosis

Osteoporosis in males

- Cancer-induced bone loss

Denosumab

Pharmacokinetics

- Metabolism unknown

- Excretion unknonw

- Half-life is 25 days

Denosumab

Adverse Effects

- Hypocalcemia

- Malignancy

- Osteonecrosis of the jaw

- Pancreatitis

- Back/extremity pain

- Hypercholesterolemia

- Athralgia

- URI

- Many side effects!

Teriparatide

Mechanism of Action

- Parathyroid Hormone

- Regulates bone metabolism, intestinal calcium absorption, and renal tubular calcium and phosphate reabsorption

- Recombinant N-terminal human PTH

- Stimulate bone formation

Teriparatide

Uses

- Postmenopausal osteoporosis

- Osteoporosis in males

- Steroid-induced bone loss

Teriparatide

Effects

- Increases spinal bone density

- Decreases risk of vertebral fracture

- Should be reserved for patients with high fracture risk who can't tolerate other treatment

Teriparatide

Pharmacokinetics

- Subcutaneous administration

- Metabolized by the liver

- Excretion via urine

- Half-life is 1 hr

Teriparatide

Adverse Effects

- Osteosarcoma

- Orthostatic hypertension

- Depression

- Pneumonia

- Athralgia

- Nausea, diarrhea, dyspepsia

- Muscle spasms

- Rash

- Insomnia

- Dizziness

- Many others!

Calcium

Mechanism of Action

Calcium

Uses

- Postmenopausal osteoporosis

- Dyspepsia

- Dietarysupplement

Calcium

Pharmacokinetics

Calcium

Adverse Effects

-Hypercalcemia

- Nephrolithiasis

- Milk-alkali syndrome

- Hypomagnesemia

- Nausea

- Constipation

Vitamin D

Mechanism of Action

- Stimulates intestinal calcium and phosphorus absorption

- Stimulate bone mineralization

VItamin D

Uses

- Postmenopausal Osteoporosis

- Vitamin D deficiency

- Dietary supplement

Vitamin D

Pharmacokinetics

- Metabolized by the liver and kidney

- Excreted via bile primarily, urine

- Half-life is 10-21 days

- Stored in fat deposits for prolonged periods

Vitamin D

Adverse Effects

- Hypervitaminosis D

- Hypercalcemia

- Hypercalciuria

- Nephrotoxicity

- Hyperphosphatemia

- Nausea, vomiting, anorexia

- Creatine elevation

- Weakness