**MERGED First Aid Pharmacology

Amiodarone, Ibutilide, Dofetilide, Sotalol

"AIDS" Class III arrhythmics MOA: K+ channel blockers, INCREASE AP duration and ERP, ↑QT interval Clinical use: when other antiarrhythmics fail Toxicity: sotalol- torsades de pointes, excessive β block Ibutilide- torsades Amiodarone- EVERYTHING! pulmonary fibrosis, hepatotoxicity, hypo/hyperthyroidism (40% iodine by weight), corneal deposits, blue/gray skin deposits that cause photodermatitis, neurologic effects, constipation, bradycardia, heart block, CHF

Disopyramide, Quinidine, Procainamide

"Double Quarter Pounder" Class IA antiarrhythmics MOA: INCREASE AP duration, effective refractory period, and QT interval Clinical use: both atrial and ventricular arrhythmias, especially reentrant and ectopic supraventricular and ventricular tachycardia Toxicity: quinidine - headache/tinnitus procainamide- drug induced SLE disopyramide- heart failure All- thombocyotopenia, torsades de pointes due to ↑QT

Flecainide, propafenone

"Fries, Please!" Class IC antiarrhythmics MOA: NO EFFECT on AP duration Clinical use: ventricular tachycardias that progress to VFib and in intractable SVT -usually only used as a last resort in refractory tachyarrhythmias Toxicity: proarrhythmic, especially in post MI (contraindicated), significantly prolongs refractory period in AV node

Olanzapine, clozapine, quetiapine, risperidone, aripiprazole, ziprasidone

"It's atypical for old closets to quietly risper from A to Z." MOA: effects on 5-HT2, dopamine, α1, and H1 receptors Clinical use: schizophrenia (both + and - symptoms), bipolar disorder OCD, anxiety disorder, depression, mania, Tourette syndrome Toxicity: fewer EPS and anticholinergic effects than traditional antipsychotics; QT prolongation -Olanzapine/clozapine: weight gain -Clozapine: agranulocytosis (require WBC monitor) -Risperidone: hyperpolactinemia

SE of lithium?

"LMNOP" Lithium SE: 1) Movement (tremor) 2) Nephrogenic diabetes insipidus 3) HypOthyroidism 4) Pregnancy problems Others: tremor, sedation, edema, heart block, hypothyroidism, polyuria (ADH antagonist causing nephrogenic DI), teratogenesis.

Name some Monoamine oxidase inhibitors.

"MAO Takes Pride In Shanghai" Tranylcypromine Phenelzine Isocarboxazid Selegiline (selective MAO-B inhibitor)

Tranylcypromine, phenelzine, isocarboxazid, selegiline

"MOA Takes Pride In Shanghai." MOA: nonselective MAO inhibition ↑levels of amine neurotransmitters (NE, 5-HT, dopamine) Clinical use: atypical depression, anxiety Toxicity: hypertensive crisis with ingestion of tyramine (found in wine and cheese) -CNS stimulation -CI with SSRIs, TCAs, St. John's wort, meperidine, detromethorphan to prevent serotonin syndrome

Mexiletine, Lidocaine, Tocainide, Phenytoin

"Mayo, Lettuce, Tomato and Pickles" Class IB antiarrhythmics MOA: DECREASE AP duration; Clinical use: acute ventricular arrhythmias (especially post MI) and digitalis induced arrhythmias (preferentially affect ischemic or depolarized purkinje and ventricular tissue) Toxicity: local anesthetics- CNS stimulation/depression, cardiovascular depression

Name the preferred drugs for the following psychiatric condition: bipolar disorder

"Mood stabilizers" (eg. lithium, valproic acid, carbamazepine), atypical antipsychotics

Protease inhibitors

"Navir tease a protease" MOA: stops cleavage of HIV polypeptide into functional parts, thus preventing maturation of new viruses Clinical use: HIV Toxicity: hyperglycemia, GI intolerance, lipodystrophy (buffalo hump); nephropathy, hematuria (indinavir) -Ritonavir inhibits P450 enzymes

What are some of the symptoms of NMS?

"Think *FEVER*" 1) Fever 2) Encephalopathy 3) Vitals unstable 4) Enzymes elevated 5) Rigidity of muscles

Metformin

(Biguanide) MOA: mechanism unknown; decreases gluconeogenesis, increases glycolysis, increases peripheral glucose uptake (insulin sensitivity) Clinical use: 1st line therapy in type 2 DM, can be used in patients w/out islet function Toxicities: lactic acidosis (contraindicated in renal failure), GI upset

Alendronate (other -dronates)

(Bisphosphonates) MOA: pyrophosphate analogs, bind hydroxyapatite in bone, inducing apoptosis in osteoclasts Clinical use: osteoporosis, hypercalcemia, Paget's disease of bone Toxicity: corrosive esophagitis (advise pts to take with water and remain upright for 30 min), osteonecrosis of the jaw

• Citalopram

(Celexa): SSRi • Fewest drug-drug interactions • Possibly fewer sexual side effects

Fluroquinolones

(Ie ciprofloxacin) MOA: inhibits DNA gyrase (topo II) and topo IV Clinical use: bacteriCIDAL for gram (-) rods of urinary and GI tracts, Neisseria, some gram (+)s Toxicity: TENDON DAMAGE --> tendonitis, tendon rupture (ppl >60 yrs or on prednisone), leg cramps/myalgias, QT interval prolongation, CI in pregnant women due to cartilage damage MOR: chr-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps

• Escitalopram

(Lexapro): SSRi • Levo-enantiomer of citalopram; similar efficacy, possibly fewer side effects • More expensive than citalopram

• Fluvoxamine

(Luvox): SSRi • Currently approved only for use in obsessive-compulsive disorder (OCD) • Nausea and vomiting more common • Lots of drug interactions

Azithromycin, clarithromycin, erythromycin

(Macrolides) MOA: binds to the 23S rRNA of the 50s ribosomal subunit to inhibit protein synthesis by blocking translocation Clinical use: bacteriostatic against atypical pneumonias (mycoplasma, chlamydia, legionella), STDs (chlamydia) and gram (+) cocci Toxicity: MACRO- Motility issues, Arrythmia (due to prolonged QT interval), acute Cholestatic hepatitis, Rash, eOsinophilia **INHIBITOR OF P450 ENZYMES** may specifically increase serum concentration of theophyllines and oral anticoagulants MOR: methylation of 23S rRNA-binding site

Morphine, fentanyl, codeine, heroin, meperidine

(Opioid analgesics) MOA: agonists at opioid receptors (mu = morphine, delta = enkephalin, kappa = dynorphin) to modulate synaptic transmission ** open K+ channels, close Ca2+ channels → ↓ synaptic transmission; inhibit release of ACh, NE, 5-HT, glutamate, substance P Clinical use: pain, acute pulmonary edema Toxicity: addiction, respiratory depression, constipation, miosis, additive CNS depression w/ other drugs; treat toxicity with naloxone or naltrexone

• Paroxetine

(Paxil): SSRi • Highly protein bound, ~ several drug interactions • More anticholinergic effects like sedation, constipation, weight gam • Short half-life leading to withdrawal phenomena if not taken consistently

• F1uoxetine

(Prozac): SSRi • Longest half-life with active metabolites; therefore, no need to taper • Safe in pregnancy, approved for use in children • More common sleep changes and anxiety • Can elevate levels of neuroleptics, leading to I side effects

Sildenafil

(Yes it is used for erectile dysfunction) but also used for PULMONARY HTN. MOA: PDE5 Inhibitor --> Increase cGMP --> Vasodilation/sm muscle relax Side Effects: Headache, flushing, dyspepsia, cyanopsia (blue-tinted vision). Risk of life-threatening hypotension in patients taking nitrates.

• Sertraline

(Zoloft) SSRi • Highest risk for gastrointestinal (GI) disturbances • Very few drug interactions • More common sleep changes

I. HAM side effects

(antiHistamine-sedation, weight gain; antiAdrenergic- hypotension; antiMuscarinic-dry mouth, blurred vision, urinary retention). Found in tricyclic antidepressants (TCAs) and lowpotency antipsychotics.

Hypertension in pregnancy: What drugs to use

**Labetalol Hydralazine Methyldopa Nifedipine

What Drug is Used to ↑ Dopamine Availability?

*A*mantadine

Etho*sux*imide is Used for What Type of Seizures?

*Absence Seizures* first line

What are the Parkinson Drugs? (*BALSA*)

*B*romocriptine *A*mantadine *L*evodopa *S*elegilie - and COMT-Inhibiotors *A*ntimuscarinics *BALSA*

What Drugs are used to Curb Excess Cholinergic Activity?

*Benz*tropine Trihexphenidyl: *A*ntimuscarinic - improves tumor and rigidity but little effect on bradykinesia in *Park*inson Disease *Park* your Mercedes-*Benz*

What are the Side Effects of Etho*sux*imide?

*EFGHIJ* - *E*thosuximide causes: - *F*atigue - *G*I distress - *H*eadache - *I*tching & urticaria - Stevens-*J*ohnson Syndrome

Etho*sux*imide Mnemonic

*S*ucks to have *S*ilent (absence) *S*eizures

Benzodiazepines are Used for What Type of Seizure?

*Status Epilepticus* first line for acute Also used for eclampsia seizures (1st line is MgSO4)

What are the IV Anesthetics?

*Th*e *Mi*ghty *K*ing *Prop*oses to *Op*rah -*Th*iopental - *Mi*dazolam - *K*etamine - *Propo*fol - *Op*ioids

What are Nonbenzodiazepine Hypnotics

*Z*olpidem *Z*aleplon Es*Z*opiclone "All *ZZZ*s put you to sleep."

Carbamazepine (Tegretol)

*• Especially useful in treating mixed episodes and rapid-cycling bipolar* disorder, and less effective for the depressed phase. • Also used in the management of trigeminal neuralgia. *• Acts by blocking sodium channels and inhibiting action potentials. • Onset of action is 5-7 days.* • Complete blood count (CBC) and liver function tests (LFTs) must be obtained before initiating treabnent and monitored regularly.

What are the Adverse Effects of Inhaled Anesthetics?

- *H*epatotoxicity - *H*alothane - *N*ephrotoxicity - *Meth*oxyflurane - Proconvulsant - *E*nflurane & *E*pileptogenic - Expansio*n* of trapped gas in body cavity *N*2O

What Type of Seizures is Carbamazepine used for?

- *Partial (focal)* first line - Tonic-Clonic

Describe the Charges of Local Anesthetics as they are Transported Across the Membrane

- 3° amine local anesthetics penetrate membrane in uncharged form - Then bind to ion channels as charged form

What is the Mechanism for *Sum*a*trip*t*an* (Triptan)?

- 5-HT 1B/1D agonist - Inhibits trigeminal nerve activation - Prevents vasoactive peptide release - Induce vasoconstriction

Heparin, Mechanism of action

- Activator of antithrombin; - decr. thrombin and factor Xa. - Short half-life.

ADP receptor inhibitors, Clinical Use

- Acute coronary syndrome - coronary stenting. - decr. incidence or recurrence of thrombotic stroke.

How are Local Anesthetics Affected by Infected (acidic) Tissue?

- Alkaline anesthetics are charged - Cannot penetrate membrane effectively - Need more anesthetic

DNA synthesis inhibitors

- Alkylating agents, cisplatin: cross-link DNA - Bleomycin: DNA strand breakage - Dactinomycin, doxorubicin: DNA intercalators - Etoposide: inhibits topoisomerase II - Irinotecan: inhibits topoisomerase I

Warfarin, Toxicity

- Bleeding - teratogenic - skin/tissue necrosis (due to small vessel microthromboses) - drug-drug interactions. - Proteins C and S have shorter half-lives than clotting factors II, VI, IX, and X, resulting in early transient hypercoagulability with warfarin use.

Heparin, Toxicity

- Bleeding - thrombocytopenia (HIT) - osteoporosis - drug-drug interactions.

Direct factor Xa inhibitors, Toxicity

- Bleeding - no reversal agent available

Thrombolytics, Toxicity

- Bleeding. - Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension.

What are the Adverse Effects of Suvorexant?

- CNS depression - Headache - Dizziness - Abnormal dreams - Upper respiratory tract infection

Warfarin, Clinical use

- Chronic anticoagulation (e.g., venous thromboembolism prophylaxis, and prevention of stroke in atrial fibrillation). - Not used in pregnant women (because warfarin, unlike heparin, crosses placenta). - Follow PT/INR.

What are the Adverse Effects of *Sum*a*trip*t*an* ?

- Coronary vasospasm: contraindicated in patients with CAD or Prinzmetal angina - Mild paresthesia - Serotonin Syndrome: in combo with other 5-HT agonists

What are the Inhaled Anesthetics?

- Desflur*ane* - Haloth*ane* - Enflur*ane* - Isflur*ane* - Sevflur*ane* - Methoxyflur*ane* - N2O

What are the Side Effects of Carbamazepine?

- Diplopia - Ataxia - Blood dycrasias (agranulocytosis, aplastic anemia) - liver toxicity - Teratogenesis - Induction of CYP450 - SIADH - Steven-Johnson Syndrome

Describe Ramelteon Adverse Effects

- Dizziness - Nausea - Fatigue - Headache

Thrombolytics, Clinical Use

- Early MI - early ischemic stroke - direct thrombolysis of severe PE

What are the Side Effects of Levetiracetam?

- Fatigue - Drowsiness - Headache - Neuropsychiatric symptoms: personality changes

What are the Side Effects of Valproic Acid?

- GI Distress - Hepatotoxicity: rare but fatal, measure LFTs - Pancreatitis - Neural Tube defects - Tremor - Weight gain Contraindicated in pregnancy

Aspirin, Toxicity

- Gastric ulceration - tinnitus (CN VIII) - Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. - Reye syndrome in children with viral infection. - Overdose initially causes hyperventilation and respiratory alkalosis, but transitions to mixed metabolic acidosis-respiratory alkalosis.

Describe Barbiturates (*Th*iopental) Pharmacokinetics

- High potency - High lipid solubility - Rapid entry into brain

What are Complications of Reversing a Succinylcholine (Depolarizing Neuromuscular Blocking Drug) Blockade?

- Hypercalcemia - Hyperkalemia - Malignant hyperthermia

Heparin, Clinical use

- Immediate anticoagulation for pulmonary embolism (PE) - acute coronary syndrome - MI, deep venous thrombosis (DVT) - Used during pregnancy (does not cross placenta). - Follow PTT.

ADP receptor inhibitors, Mechanism

- Inhibit platelet aggregation by irreversibly blocking ADP receptors. - Prevent expression of glycoproteins IIb/IIIa on platelet surface.

Warfarin, Mechanism

- Interferes with γ-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X, and proteins C and S. - Metabolism affected by polymorphisms in the gene for vitamin K epoxide reductase complex (VKORC1). - Incr. in PT - effect on extrinsic pathway - Long half-life.

Aspirin, Mechanism

- Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation. - Platelets cannot synthesize new enzyme, so effect lasts until new platelets are produced: incr. bleeding time, decr. TXA2 and prostaglandins. - No effect on PT or PTT.

Nucleotide Synthesis inhibitors

- MTX, 5-FU: ↓ thymidine synthesis - 6-MP: ↓ de novo purine synthesis - Hydroxyurea: inhibits ribonucleotide reductase

What are the Effects of Inhaled Anesthetics?

- Myocardial Depression - Respiratory Depression - Nausea/emesis - ↑ cerebral blood flow - ↓ cerebral metabolic demand

What are the other Clinical Uses of Valproic Acid?

- Myoclonic Seizures - Bipolar disorder - Migraine prophylaxis

Phenobarbital is First Line for What?

- Neonates

ADP receptor inhibitors, Toxicity

- Neutropenia (ticlopidine) - TTP may be seen.

How is a Phase I Succinylcholine (Depolarizing Neuromuscular Blocking Drug) Blockade Reversed?

- No antidote - Block potentiated by cholinesterase inhibitors

Describe Phenytoin and Fosphenytoin Side Effects

- Nystagmus - Diplopia - Ataxia - Sedation - Peripheral neuropathy - Steven Johnson Syndrome - Gingival Hyperplasia - DRESS Syndrome - Osteopenia - SLE-like syndrome - Megaloblastic anemia -Teratogenesis: fetal hydantoin syndrom - CYP450 inducer

What Types of Seizure is Tiagabine used for?

- Partial (focal)

What Types of Seizures is Topiramate Used for?

- Partial (focal) - Tonic-Clonic

What Types of Seizures are Phenytoin and Fosphenytoin used for?

- Partial (focal) - *Tonic-Clonic* first line - *Status Epilepticus* first line prophylaxis

What Types of Seizures is Valproic Acid Used for?

- Partial (focal) - *Tonic-clonic* first line - Absence

What Types of Seizures is Levetiracetam used for?

- Partial (focal) - Tonic-Clonic

What type of Seizures is Lamotrigine used for?

- Partial (focal) - Tonic-clonic - Absence

What are other Clinical Uses of Gabapentin?

- Peripheral Neuropathy - Postherpetic neuralgia

Cilostazol, dipyridamole, Mechanism

- Phosphodiesterase III inhibitor - incr. cAMP in platelets, resulting in inhibition of platelet aggregation; - vasodilators.

What is Phase II of a Neuromuscular Blockade?

- Repolarized but blocked - ACh receptors are available, but desensitized

What are the Side Effects of Gabapentin?

- Sedation - Ataxia

What are the Side Effects of Topiramate?

- Sedation - Mental dulling - Kidney stones - Weight loss - Glaucoma

What are the Side Effects of Phenobarbital?

- Sedation - Tolerance - Dependence - Induction of CYP450 - Cardiorespiratory depression

What are the Side Effects of Benzodiazepines?

- Sedation - Tolerance - Dependence - Respiratory depression

What are the Adverse Effects of Benzodiazepines (*Mi*dazolam)?

- Severe post-op respiratory depression - ↓ BP (treat OD with flumazenil) - Anterograde amnesia

Direct factor Xa inhibitors, Clinical Use

- Treatm. and prophylaxis for DVT and PE (rivaroxaban) - stroke prophylaxis in patients with atrial fibrillation. - Oral agents do not usually require coagulation monitoring.

GP IIb/IIIa inhibitors, Clinical Use

- Unstable angina - percutaneous transluminal coronary angioplasty

Cellular division inhibitors

- Vinca alkaloids: inhibit microtubule formation - Paclitaxel: inhibits microtubule disassembly

Thrombolytics

- alteplase (tPA) - reteplase (rPA) - streptokinase - tenecteplase (TNK-tPA)

Aspirin, Clinical Use

- antipyretic - analgesic - anti-inflammatory - antiplatelet ( decr. aggregation).

Direct factor Xa inhibitors

- apixaban - rivaroxaban

Direct thrombin inhibitors

- bivalirudin - argatroban (for HIT) - dabigatran PO

GP IIb/IIIa inhibitors, Tocixity

- bleeding - thrombocytopenia.

ADP receptor inhibitors

- clopidogrel - prasugrel - ticagrelor (reversible) - ticlopidine

Cilostazol, dipyridamole, Clinical Use

- intermittent claudication - coronary vasodilation - prevention of stroke or TIAs (combined with aspirin) - angina prophylaxis.

Cilostazol, dipyridamole, Toxicity

- nausea - headache - facial flushing - hypotension - abdominal pain.

Warfarin, Antidote

- vitamin K. - For rapid reversal, fresh frozen plasma.

Oral contraception (synethetic progestins, estrogen)

-Estrogen and progestins inhibit LH/FSH → no estrogen surge → no LH surge → no ovulation -Progestins cause thickening of cervical mucus -Progestins also inhibit endometrial proliferation → endometrium less suitable for embryo implantation -CI: smokers >35 y/o (↑risk of CV events), hx of thromboembolism and stroke, hx of estrogen-dependent tumor

Class I antiarrhythmics are ____ channel blockers that _____ conduction by ____ the slope of phase 0 depolarization and ____ the threshold for firing in abnormal pacemaker cells. ____kalemia causes ↑ toxicity for all class I drugs.

-Na+ channel blockers -↓ the slope of phase 0 depolarization -↑ the threshold for firing in abnormal pacemaker cells (selectively depress tissue that is frequently depolarized, as in tachycardia) -HYPERkalemia ↑ toxicity of class I drugs

Reversal of succinycholine

-Phase I (prolonged depolarization): no antidote available, cholinesterase inhibitors would just potentiate the depolarization block -Phase II (repolarized but blocked): ACh receptors are available, but desensitized; antidote = cholinesterase inhibitors (like neostigmine)

Hormone replacement therapy

-Used for relief or prevention of menopausal sx (e.g., hot flashes, vaginal atrophy), osteoporosis (↑estrogen, ↓osteoclast activity) -**Unopposed estrogen replacement ↑risk of endometrial cancer, so progesterone is added -Possible increased cardiovascular risk

What is the Inhaled Anesthetic Suffix?

-ane (except N2O)

Adverse Effects of 1st gen Antihistamines

-sedation -antimuscarinic (cross reactivity) -anti-alpha-adrenergic (HTN,dizziness) -anti-serotonin **easily crosses BBB

Reversal of digoxin toxicity

-slowly normalize K+ -lidocaine -cardiac pacer -anti-digoxin Fab fragments -Mg2+

Describe the evolution of EPS side effects.

1) 4h acute dystonia (muscle spasm, stiffness, oculogyric crisis) 2) 4d akathisia (restlessness) 3) 4wk bradykinesia (parkinsonism) 4) 4mo tardive dyskinesia

Name 7 TCA.

1) AMITRIPTYLINE 2) NORTRIPTYLINE 3) IMIPRAMINE 4) DESIPRAMINE 5) CLOMIPRAMINE 6) DOXEPIN 7) AMOXAPINE "Ami trips on a line while going up north"

Prevention of cisplatin/carboplatin related nephrotoxicity? (2 steps)

1) Amifostine (free radical scavenger) 2) Chloride (saline) diuresis

Clinical use of MAO inhibitors?

1) Atypical depression 2) Anxiety 3) Hypochondriasis

How do you treat NMS?

1) Dantrolene 2) D2 agonists (eg. bromocriptine)

Clinical use of SSRIs?

1) Depression! 2) Generalized anxiety disorder 3) Panic disorder 4) OCD 5) Bulimia 6) Social phobias 7) PTSD

What are some toxicities of SSRIs?

1) GI distress 2) Sexual dysfunction!!! (anorgasmia and decreased libido)

Toxicity of MAO inhibitors?

1) Hypertensive crisis (most notably with ingestion of tyramine, which is found in many foods such as wine and cheese) 2) CNS Stimulation Contraindicated with SSRIs, TCAs, ST John's wort, Meperidine (opioid analgesic), and dextromethorphan (to prevent serotonin syndrome)

SNRI toxicities?

1) Increased BP most common 2) Stimulant affects 3) Sedation 4) Nausea

Clinical use of TCAs?

1) Major depression 2) OCD (CLOMIPRAMINE) 3) Fibromyalgia

Clinical use of Lithium?

1) Mood stabilizer for bipolar disorder 2) Blocks relapse and acute manic events 3) SIADH

What are the 5 classes of antidepressants?

1) SSRIs (Serotonin specific reuptake inhibitors) 2) SNRIs (Serotonin-norepinephrine reuptake inhibitors) 3) TCA (tricyclic antidpressants) 4) MAO (Monoamine oxidase) inhibitors 5) Atypical antidepressants

Toxicities of TCAs?

1) Sedation 2) Alpha-1 blocking effects including postural hypotension 3) Atropine-like (Anticholinergic) SE: tachycardia, urinary retention, dry mouth

Toxicity of MIRTAZAPINE?

1) Sedation (which may be desirable in depressed patients with insomnia) 2) Increase in appetite 3) Weight gain (desirable in elderly and anorexic pts) 4) Dry mouth

Reversal of warfarin toxicity?

1) Vitamin K 2) Fresh frozen plasma for rapid reversal

What is the Mechanism of Baclofen?

1. Activates GABA-B receptors at spinal cord 2. Induces skeletal muscle relaxation

What is the Mechanism of Opioid Analgesics

1. Agonists at opioid receptors to modulate synaptic transmission - opens K+ channels, closes Ca2+ channels → ↓synaptic transmission μ = β-endorphin δ = enkephalin κ = dynorphin 2. Inhibit release of: - ACh - NE - 5-HT - Glutamate - Substance P

What are the Adverse Effects of α-agonists: Brimonidine (α2)?

1. Blurry vision 2. Ocular hyperemia 3. Foreign body sensation 4. Ocular allergic reactions 5. Ocular pruritus

What are the Adverse Effects of Local Anesthetics?

1. CNS Excitation 2. Severe cardiotoxicity - bupivacaine 3. Hypertension 4. Hypotension 5. Arrhythemias - cocaine 6. Methemoglobinemia - benzocaine

What are the Adverse Effects of Arylcyclohexylamines (*K*etamine)?

1. Cardiovascular stimulant 2. Disorientation 3. Hallucination 4. Unpleasant dreams

What are the 2 Clinical Indications for Benzodiazepines (*Mi*dazolam)

1. Endoscopy 2. Adjunctively with gaseous anesthetics and narcotics

What are the 2 Clinical Indications of Barbiturates (*Th*iopental)?

1. Induction of anesthesia 2. Short term surgical procedures

List the Amide Local Anesthetics

1. L*i*doca*i*ne 2. Mep*i*vaca*i*ne 3. Bup*i*vaca*i*ne Am*i*des have 2 *i*s

What is the Clinical Use of Dantrolene?

1. Malignant Hyperthermia 2. Neuroleptic Malignant Syndrome - toxicity of antipsychotic drugs

What are the Drugs Indicated for Alzheimer Disease Treatment?

1. Memantine 2. Donepezil, galantamine, rivastigmine, tacrine

What are the Clinical Uses of Local Anesthetics?

1. Minor surgical procedures 2. Spinal anesthesia

Opioid Tolerance does not Develop to what Effects?

1. Miosis 2. Constipation

What are the Adverse Effects of Direct (pilocarpine, carbachol) & Indirect (physostigmine, echothiophate) Cholinomimetics (M3)?

1. Miosis - contraction of pupillary sphincter muscles 2. Cyclospasm - contraction of ciliary muscle

List the Opioid Analgesics

1. Morphine 2. Oxycodone 3. Fentanyl 4. Codeine 5. Loperamide 6. Methadone 7. Meperidine 8. Dextromethorphan 9. Diphenoxylate 10. Pentazocine

What 2 *Op*ioids are used as IV Anesthetics, What are they used in Combo with, and When?

1. Morphine 2. Fentanyl CNS Depressants during general anesthesia

What is the Clinical Use of Baclofen?

1. Muscle spasm - actor low back pain 2. Multiple sclerosis

What are the Side Effects of Opioid Analgesics?

1. Nausea vomiting 2. Pruritus 3. Addiction 4. Respiratory depression 5. Constipation 6. Miosis - except meperidine → mydriasis 7. Additive CNS depression w/ other drugs

What are the Clinical Uses of Opioid Analgesics?

1. Pain 2. Cough suppression - dextromethorphan 3. Diarrhea - loperamide, diphenoxylate 4. Acute pulmonary edema 5. Maintenance programs for heroin addicts - methadone, buprenorphine + naloxone

What is the Order of Loss?

1. Pain 2. Temp 3. Touch 4. Pressure

List the Ester Local Anesthetics

1. Proca*i*ne 2. Coca*i*ne 3. Tetraca*i*ne 4. Benzoca*i*ne all have one *i*

What are the 2 Mechanism by which Succinylcholine (Depolarizing Neuromuscular Blocking Drug) Works?

1. Produces sustained depolarization 2. Prevents muscle contraction.

What is the Clinical Indication for *Propo*fol?

1. Sedation in ICU 2. Rapid anesthesia induction 3. Short procedures

What are the Adverse Effects of Tramadol?

1. Similar to opioids 2. ↓ seizure threshold 3. Serotonin syndrome

List the Non-depolarizing Neuromuscular Blocking Drugs

1. Tubo*cur*arine 2. Atra*cur*ium 3. Miva*cur*ium 4. Pan*cur*onium 5. Ve*cur*onium 6. Ro*cur*onium

What is the Mechanism of Tramadol?

1. Very weak opioid agonist 2. Inhibits 5-HT & NE reuptake Works on multiple neurotransmitters - "*tram it all*" in with *tramadol*

Tumor lysis syndrome, Cause of acute kidney injury

1. inc nucleic acid breakdown 2. hyperuricemia

What is HTN? What 2 components determine blood pressure?

140/90 Cardiac Output Peripheral Vascular Resistance

Tolbutamide, Chlorpropamide

1st generation sulfonylureas MOA: close K+ channels in β cell membrane, cell depolarizes → Ca2+ influx → insulin release Clinical use: stimulate release of endogenous insulin in type 2 DM (useless in type 1) Toxicities: disulfiram like effects

Drugs for acute gout

1st line NSAIDS - naproxen, indomethacin Glucocorticoids Colchicine

fluticasone, budesonide: use

1st line therapy for chronic asthma (esp w/those having symptoms several time through week) VERY IMPORTANT THERAPY FOR CHRONIC TREATMENT

What is the Mechanism of Gabapentin?

1° inhibits high-voltage activated Ca2+ channels Designed as GABA analog

Glyburide, Glimepiride, Glipizide

2nd generation sulfonylureas MOA: close K+ channels in β cell membrane, cell depolarizes → Ca2+ influx → insulin release Clinical use: stimulate release of endogenous insulin in type 2 DM (useless in type 1) Toxicities: hypoglycemia

EPS side effects

4 hr acute dystonia (muscle spasms, stiffness, oculogyric crisis) 4 day akathisia (restlessness) 4 wk bradykinesia (parkinsonism) 4 mo tardive dyskinesia (stereotypic oral-facial movements)

How long does it take for antidepressants to have an effect?

4-8wks

MOA of SSRIs?

5-HT specific reuptake inhibitors

Ondansetron: MOA

5-HT3 antagonist Decrease vagal stimulation Central acting antiemetic

Zileuton

5-Lipoxygenase Inhibitor MOA: Blocks arachidonic acid conversion to leukotrienes Toxicity: Hepatotoxicity

Zileuton MOA

5-lipoxygenase pathway inhibitor. Block conversion of arachidonic acid to leukotrienes. blocks C4, D4, E4

Antiandrogens-- Finasteride: MOA

5a reductase inhibitor (decrease conversion of testosterone to DHT)

MOA: Decrease de novo purine synthesis Drugs?

6-MP

Dextromethorphan:Use

=antitussive (cough suppressant)

*Sum*a*trip*t*an* Mnemonic

A *SUM*o wrestler *TRIP*s *AN*d falls on your *head* Cluster *head*ache attacks

Anti HTN with DM

ACE inhibitors/ARBs Calcium channel blockers, diuretics β-blockers α-blockers. ACEI/ARBs protect against nephropathy

Appropriate agents for treating HTN w/ DM

ACE inhibitors/ARBs, calcium channel blockers, thiazide diuretics, β blockers **ACE inhibitors are protective against diabetic nephropathy

What are the Mechanism and Adverse Effects of Donepezil, Galantamine, Rivastigmine, & Tacrine?

AChE Inhibitor AE: Nausea, dizziness, insomnia

Who is Susceptible to Malignant Hyperthermia?

AD inherited variable penetrance

Clinical use of CNS stimulants?

ADHD, narcolepsy, appetite control

Abciximab, Structure

Abciximab is made from monoclonal antibody Fab fragments.

GP IIb/IIIa inhibitors

Abciximab, eptifibatide, tirofiban.

Antacid: General toxicity

Absorption, bioavailability, or urinary excretion of other drugs-- altering gastric and urinary pH or delaying gastric emptying. All can cause hypokalemia.

alpha-glucosidase inhibitors examples

Acarbose Miglitol

Diuretics: Electrolyte changes-- Blood pH, Acidemia

Acetazolamide (decrease HCO3- reabsorption) Potassium Sparing (aldosterone blockage-- prevents H+ secretion) also hyperkalemia--> H+/K+ exchanger all cells--> Acidemia

Clinical use of somatostatin (octreotide)

Acromegaly carcinoid syndrome gastrinoma glucagonoma esophageal varices

What is the Mechanism for Nonbenzodiazepine Hypnotics?

Act via the BZ1 subtype of the GABA receptor Effects reversed by flumazenil Sleep cycle less affected as compared with benzodiazepine hypnotics.

What is the Clinical Use of *Sum*a*trip*t*an* ?

Acute Migraine Cluster *head*ache attacks

Prednisone: use

Acute asthma attack where B agonist doesnt work

Octreotide: Use

Acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors.

Antiarrhythmics Class IB: Use

Acute ventricular arrhythmias (especially post- MI), digitalis-induced arrhythmias.

What is the Clinical Use of Selegiline, Rasagiline?

Adjunctive agent to L-Dopa in treatment of Parkinson Disease

Clinical use of glucocorticoids

Adrenal insufficiency, inflammation, immunosuppression, asthma

What is the Mechanism Agents use to Prevent Dopamine Breakdown

Agents act *centrally* (post-BBB) to inhibit breakdown of Dopamine - *S*elegiline - Tolcapone

What is the Mechanism of Agents Used to ↑ L-Dopa Availability?

Agents prevent peripheral (pre-BB) L-Dopa degradation → ↑ L- Dopa entering CNS → ↑central L-Dopa for conversion to dopamine - *L*-Dopa/Carbidopa - Entacapone, Tolcapone

Testosterone, Methyltestosterone-- MOA

Agonist at androgen receptor

Loperamide

Agonist at mu opioid receptors, slows gut motility poor CNS penetration (low addictive) Clinical use: diarrhea Toxicity: Constipation, nausea

Selective Estrogen Receptor Modulators-- SERMs: Raloxifene-- MOA

Agonist on bone-- decrease resorption Antagonist at uterus

MOA: Cross-link DNA Drugs?

Alkylating agents Cisplatin

Drugs for chronic gout

Allopurinol, febuxostat Pegloticase Probenecid

Pseudophedrine, Phenylephrine

Alpha-Adrenergic Agonists -- Used as nasal decongestant. Tox: HTN. Can also cause CNS Stim/Anxiety Note: Do not take more than 3 days, will cause rebound rhinorrhea (desensitization of receptors)

MOA of MIRTAZAPINE?

Alpha2-antagonist (increase release of NE and 5-HT) and potent 5-HT2 and 5-HT3 receptor antagonist.

Lidocaine, mepivacaine, bupivacaine

Amide local anesthetics (amide's have two I's) MOA: block Na+ channels by binding to a specific receptor on INNER portion of the channel (most effective in rapidly firing neurons bc have to get inside a channel that has already been activated) Clinical use: minor surgical procedures, spinal anesthesia Toxicity: CNS excitation (depression of inhibitory centers), HTN or hypotension, severe cardiotoxicity w/ bupivacaine

If you are Allergic to Esters give?

Amides

Thrombolytics, Antidote

Aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

Antibiotics that block protein synthesis at the 30S ribosomal subunit

Aminoglycosides (gentamicin, neomycin, amikacin, tobramycin, streptomycin) and tetracyclins

Antiarrhythmics: Class III: Names and Class

Amiodarone, Ibutilide, Dofetilide, Sotalol

Pramlintide

Amylin analog MOA: ↓gastric emptying, ↓ glucagon Clinical use: type 1 AND 2 DM Toxicities: hypoglycemia, nausea, diarrhea

What does Butorphanol Produce?

Analgesia

What is the Clinical Use of Pentazocine?

Analgesia for moderate to severe pain

Nitroglycerine, Isosorbide dinitrate: Use

Angina acute coronary syndrome pulmonary edema

Ranolazine: Use

Angina refactory to other medicines

Selective Estrogen Receptor Modulators-- SERMs: Clomiphene-- MOA

Antagonist at estrogen receptors in hypothalamus Prevent feedback inhibition-- increase release of LH and FSH--> ovulation

Selective Estrogen Receptor Modulators-- SERMs: Tamoxifen-- MOA

Antagonist on breast tissue Agonist-- bone, uterus

Leuprolide-- Toxicity

Antiandrogen, nausea, vomiting

Adenosine: Use

Antiarrhythmic

Demeclocyline

Antibiotic of the tetracycline family, but rarely used as an antibiotic. Has ADH antagonist properties, so used as a diuretic in SIADH.

Clinical use of BUPROPION?

Antidepressant, smoking cessation

Name the preferred drugs for the following psychiatric condition: Schizophrenia

Antipsychotics

Name the preferred drugs for the following psychiatric condition: tourette syndrome

Antipsychotics (eg. haloperidol, risperidone)

Dextromethorphan

Antitussive. Antagonizes NMDA Glutamate receptors. Synthetic analog to codeine. Opioid effect when used in excess; antidote naloxone. Can cause serotonin syndrome

What are the Clinical Uses of Benzodiazepines?

Anxiety Spasticity Status epilepticus - lorazepam, diazepam Eclampsia Detoxification - especially alcohol withdrawal -DTs Night Terrors Sleepwalking General Anesthetic - amnesia muscle relaxation Hypnotic - insomnia

Anastrozole/Exemestane-- MOA, Use

Aromatase inhibitor-- postmenopausal women with breast cancer

Milrinone: Adverse Effect

Arrhythmia hypotension

What are the Adverse Effects of L-Dopa/Carbidopa?

Arrhythmia - ↑ peripheral formation of catecholamines Long term use →: - dyskinesia following administration ("on-off" phenomenon) - Akinesia between doses

Insulin, rapid acting

Aspart, glulisine, lispro

• Thioridazine (Mellaril):

Associated with retinitis pigments

What are the Adverse Effects of Nonbenzodiazepine Hypnotics?

Ataxia Headache Confusion Short duration b/c of rapid metabolism by liver enzymes Cause modest day-after psychomotor depression - unlike older sedative hypnotics Few amnestic effects ↓ dependence risk than benzodiazepines

Antiarrhythmics Class IA: Use

Atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT.

Antiarrhythmics: Class III: Use

Atrial fibrillation, atrial flutter Ventricular tachycardia (amiodarone, sotalol).

What must Neostigmine be Given with and why?

Atropine To prevent muscarinic effects - i.e. bradycardia

Trazodone

Atypical antidepressant MOA: blocks 5-HT2 and α1 receptors Clinical use: insomnia Toxicity: priapism (trazo*bone*), postural hypotension, nausea

Bupropion

Atypical antidepressant MOA: ↑ norepinephrine and dopamine via unknown mechanisms Toxicity: stimulant effects (tachycardia, insomnia), headache -Seizures in anorexic/bulimic patients

Antimetabolites

Azathioprine Cladribine Cytarabine 5-fluorouracil Hydroxyurea Methotrexate 6-mercaptopurine 6-thioguanine

Increase toxicity with allopurinol or febuxostat Drug?

Azathioprine, 6-MP, 6-TG

*Antimetabolites*

Azathioprine, 6-mercaptuptopurine (6-MP), 6-thioguanine (6-TG) Cladribine (2-CDA) Cytarabine (arabinofuranosyl cytidine) 5-fluorouracil (5-FU) Methotrexate (MTX)

Antiarrhythmics Class II: Names, Class

B-blockers Metoprolol, propranolol, esmolol, atenolol, timolol, cavedilol

Dobutamine:MOA

B1 agonist

Albuterol: MOA

B2 agonist relaxes bronchial smooth muscle (short acting b2 agonist)

Terbutaline-- MOA and Use

B2 agonist, relaxes uterus Decrease contraction frequency during labor

What is the treatment for the extrapyramidal system (EPS) side effects of antipsychotics?

BENZTROPINE (Muscarinic antagonist) or DIPHENHYDRAMINE (H1 blocker)

Tamsulosin-- Use

BPH

Antiandrogens-- Finasteride: Use

BPH Hair growth -- male pattern baldness

Name 3 atypical antidepressants

BUPROPION, MIRAZAPINE, TRAZODONE

Clinical use of long acting insulin

Basal glucose control: Type 1 DM Type 2 DM GDM

Name the preferred drugs for the following psychiatric condition: alcohol withdrawal

Benzodiazepines

Cholestryamine, colestipol, colesevelam

Bile acid resins MOA: prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more Clinical use: ↓↓ LDL - slight ↑ HDL - slight ↑ TG Toxicity: patients hate it!! tastes bad, causes GI upset; ↓ absorption of fat soluble vitamins; cholesterol gallstones

Estrogens-- MOA

Bind estrogen receptors

Action of rapid acting insulin

Bind insulin receptor (tyrosine kinase activity) rapidly

Progestins-- MOA

Bind progesterone receptors-- decrease growth and increase vascularization of endometrium

Direct factor Xa inhibitors, Mechanism

Bind to and directly inhibit factor Xa.

GP IIb/IIIa inhibitors, Mechanism

Bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation.

Bismuth, sucralfate: MOA

Bind to ulcer base, providing physical protection and allowing HCO3- secretion to reestablish pH gradient in the mucous layer.

Argatroban, bivalirudin, dabigatran

Bivalirudin is related to hirudin, the anticoagulant used by leeches; inhibit thrombin directly. Alternatives to heparin for anticoagulating patients with HIT.

MOA: DNA strand breakage Drugs?

Bleomycin

*Antitumor antibiotics*

Bleomycin Dactinomycin (actinomycin D) Anthracyclines: doxorubicin, daunorubicin

Antitumor antibiotics

Bleomycin Dactinomycin (actinomycin D) Doxorubicin, Daunorubicin

What is the MOA of antipsychotics?

Block D2 receptors --> increase cAMP

What is the MOA of Local Anesthetics?

Block Na+ channels by binding to specific receptors on *inner* portion of channel

MOA of SGLT-2 inhibitors

Block reabsorption of glucose in PCT

MOA of TCAs?

Block reuptake of NE and 5HT

MOA of thionamides

Block thyroid peroxidase, inhibiting oxidation of iodide and organification (coupling) of iodine-->inhibition of thyroid hormone synthesis propylthiouracil also blocks 5' deiodinase--> decrease peripheral conversion of T4 to T3

Calcium channel blockers: MOA

Block voltage-dependent L-type calcium channels of cardiac and smooth muscle result: reduce muscle contractility.

What is the MOA of Arylcyclohexylamines (*K*etamine)?

Blocks NMDA receptors

What is Carbamazepine Mechanism?

Blocks Na+ Channel

What is the Mechanism for Phenytoin and Fosphenytoin?

Blocks Na+ channels Zero Order Kinetics

What is the Mechanism of Topiramate?

Blocks Na+ channels ↑GABA action

What is the MOA of Tolcapone?

Blocks conversion of Dopamine → 3-methoxytyramine (3-MT) by inhibiting central COMT

What is the MOA of *S*elegiline?

Blocks conversion of Dopamine → DOPAC by selectively inhibiting MAO-B

What is the Mechanism of Etho*sux*imide?

Blocks thalamic T-Type Ca2+ Channels E*TH*osuximide targets the *TH*alamus

What is the Mechanism of Lamotrigine?

Blocks voltage-gated Na+ channels Inhibits the release of glutamate

Pulmonary hypertension Drugs

Bosentan sildenafil epoprostenol iloprost

Nitrosoureas, Clinical Use

Brain tumors (including glioblastoma multiforme)

Tamoxifen, raloxifene, Clinical Use

Breast cancer treatment (tamoxifen only) and prevention. Raloxifene also useful to prevent osteoporosis.

Psyllium, methylcellulose

Bulk forming laxatives Soluble fibers; draw water into gut lumen, forming a viscous liquid that promotes peristalsis Adverse effects: bloating

*Alkylating agents*

Busulfan Cyclophosphamide, ifosfamide Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

Alkylating agents, Nitrosoureas

Busulfan Cyclophosphamide, ifosfamide Nitroureas: Carmustine, Cisplatin. Lomustine, Semustine, Streptozocin

How is lithium excreted?

By the kidneys. Most is reabsorbed at the proximal convoluted tubules following Na reabsorption.

Cardiac Glycosides (digoxin): Use

CHF (increased contractility) Atrial fibrillation (decrease conduction at AV node and depression of SA node).

___ is an antipsychotic that can cause corneal deposits

CHLORPROMAZINE

Imatinib, Clinical Use

CML GI stromal tumors

Busulfan, Clinical Use

CML. Also used to ablate patient's bone marrow before bone marrow transplantation.

Clonidine: Adverse effects

CNS depressioin bradycardia hypotension respiratory depression miosis rebound HTN w/abrupt cessation

Methylphenidate, dextroamphetamine, methamphetamine

CNS stimulants MOA: ↑ catecholamines in synaptic cleft, especially norepinephrine and dopamine Clinical use: ADHD, narcolepsy, appetite control

Antiarrhythmics Class IB: Toxicity

CNS stimulation/depression, cardiovascular depression.

Nitrosoureas, Toxicity

CNS toxicity (convulsions, dizziness, ataxia)

N-acetylcysteine: Use

COPD chronic bronchitis cystic fibrosis **antidote for acetaminophen overdose

use of theophylline

COPD and asthma but usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity)

Tx for serotonin syndrome?

CYPROHEPTADINE (5HT2 receptor antagonist)

• Thiothixene (Navane):

Can cause ocular pigment changes

What are the Adverse Effects of Pentazocine?

Can cause opioid withdrawal symptoms if patient is also taking full opioid antagonist - competition for opioid receptors

• Trifluoperazine (Stelazine):

Can reduce anxiety

sodium-glucose co-transporter 2 (SGLT-2) inhibitors

Canagliflozin Dapagliflozin Empagliflozin

Methotrexate (MTX), Clinical Use

Cancers: - Leukemias (ALL) - Lymphomas - Choriocarcinoma - Sarcomas Non-neoplastic: - Ectopic pregnancy - Medical abortion (with misoprostol) - Rheumatoid arthritis - Psoriasis - IBD - Vasculitis

ACE inhibitors-- Names

Captopril, Enalapril, Lisinopril

ACE inhibitors

Captopril, enalapril, lisinopril, ramipril MOA: Inhibit ACE -> Decreased ATII -> Decreased GFR by inhibiting constriction of efferent arterioles. Levels of renin increases as a result of loss of feedback inhibition. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator. Clinical Use: HTN, HF, proteinuria, diabetic nephropathy. Prevent unfavorable heart remodeling as a result of chronic HTN. Toxicity: Cough, Angioedema (contraindicated in C1 esterase inhibitor deficiency), Teratogen (fetal renal malformation), increased Creatinine (decreased GFR), Hyperkalemia, and Hypotension. Avoid in bilateral renal artery stenosis because ACE inhibitors will further decrease GFR -> renal failure. Captopril's CATCHH

Describe the MOA of *L*-Dopa/Carbidopa?

Carbidopa blocks peripheral conversion of L-Dopa → dopamine - inhibits DOPA decarboxylase ↓ Peripheral side effects of L-Dopa → dopamine - Nausea / vomiting

Calcium channel blockers: Non-Dihydropyridine Adverse Effect

Cardiac depression AV block hyperprolactinemia constipation hyperprolactinemia explanation: verapamil, inhibit release of dopamine constipation explanation: affects intersitial cells of Cajal, gut peristalsis

Doxorubicin, daunorubicin, Toxicity

Cardiotoxicity (dilated cardiomyopathy) Myelosuppression Alopecia Toxic to tissues following extravasation. Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity.

Trastuzumab (Herceptin), Toxicity

Cardiotoxicity. "Heartceptin" damages the heart.

3. Hypertensive crisis:

Caused by a buildup of stored catecholamines. MAOis plus foods with tyramine (red wine, cheese, chicken liver, cured meats) or plus sympathomimetics.

Describe Butorphanol Effect on Respiratory Depression

Causes less respiratory depression than full opioid agonists

Clinical use of desmopressin acetate

Central (not nephrogenic) DI

What is the Mechanism of Cyclobenzaprine?

Centrally acting skeletal muscle relaxant

Antibiotics that block protein synthesis at the 50S ribosomal subunit

Chloramphenicol, clindamycin, erythromycin (and other macrolides), linezolid, streptogramins (quinupristin, dalfopristin)

Thiazide diuretics

Chlorthalidone, hydrochlorothiazide MOA: Inhibit NaCl reabsorption in early DCT -> increased diluting capacity of nephron. Decrease Ca2+ excretion. Clinical Use: HTN, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis. Toxicity: Hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, HyperLipidemia, hyperUricemia, hyperCalcemia. Sulfa allergy. HyperGLUC

Cardiac Glycosides (digoxin): Toxicity

Cholinergic—nausea, vomiting, diarrhea, blurry yellow vision (Van Gogh). ECG— increase PR, decrease QT, ST scooping, T-wave inversion, arrhythmia, AV block. Can lead to hyperkalemia, indicates poor prognosis.

How is a Phase II Succinylcholine (Depolarizing Neuromuscular Blocking Drug) Blockade Reversed?

Cholinesterase Inhibitors

Methacholine

Cholinomimetic - direct agonist Clinical use: challenge test for asthma Action: stimulates muscarinic recpetors in airway

Carbachol

Cholinomimetic - direct agonist Clinical use: glaucoma; constricts pupil and relieves intraocular pressure Action: carbon copy of acetylcholine

Pilocarpine

Cholinomimetic - direct agonist Clinical use: open- and close-angle glaucoma; potent stimulator of sweat, tears, and saliva Action: contracts ciliary muscle of eye (open-angle glaucoma, pupillary sphincter (close-angle glaucoma); resistant to AChE. "You cry, drool, and sweat on your 'pilow.'"

Bethanechol

Cholinomimetic - direct agonist Clinical use: postop ileus, neurogenic ileus, urinary retention Action: Activates bowel and bladder smooth muscle; resistant to AChE. "Bethany, call (bethanecol) me to activate your bowels and bladder."

Donepezil, galantamine, rivastigmine

Cholinomimetic - indirect agonist (anticholinesterase) Clinical use: Alzheimer Action: ↑ACh

Physostigmine

Cholinomimetic - indirect agonist (anticholinesterase) Clinical use: anticholinergic toxicity -Crosses blood-brain barrier → CNS Action: ↑ACh "Physostigmine 'phyxes' atropine overdose."

Edrophonium

Cholinomimetic - indirect agonist (anticholinesterase) Clinical use: diagnosis of myasthenia gravis -Myasthenia gravis now diagnosed by anti-AChR Ab test Action: ↑ACh

Pyridostigmine

Cholinomimetic - indirect agonist (anticholinesterase) Clinical use: myasthenia gravis (long acting) -Does not penetrate CNS Action: ↑ACh; ↑muscle strength "Pyridostigmine gets rid of myasthenia gravis."

Neostigmine

Cholinomimetic - indirect agonist (anticholinesterase) Clinical use: postop and neurogenic ileum and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postop) Action: ↑ACh -Neo CNS = no CNS penetration

What is the Clinical Use of Tramadol?

Chronic Pain

H2 blockers: Names

Cimetidine, ranitidine, famotidine, nizatidine Table for 2 dine

H2 blockers: Toxicity

Cimetidine-- 1. Cytochrome P-450 inhibitor 2. Antiandrogenic (prolactin release, gynecomastia, impotence, decrease libido in males) 3. Cross blood-brain barrier (confusion, dizziness, headaches) and placenta. Cimetidine and ranitidine decrease renal excretion of creatinine.

Antiarrhythmics Class IA: Toxicity

Cinchonism (headache, tinnitus with quinidine) Reversible SLE-like syndrome (procainamide) Heart failure (disopyramide) Thrombocytopenia, torsades de pointes due to QT interval.

Beta lactamase inhibitors: CAST

Clavulanic Acid, Sulbactam, Tazobactam Add to aminopenicillins and antipseudomonals

Drugs used in hypertensive emergency

Clevidipine, fenoldopam, labetalol, nicardipine, nitroprusside

Epoetin alfa (erythropoietin)

Clinical use: anemias (esp renal failure)

Aluminum hydroxide

Clinical use: antacid Toxicity: hypokalemia (all antacids), constipation ("aluminimum" amount of feces), hypophosphatemia, proximal muscle weakness, osteodystrophy, seizures

Magnesium hydroxide

Clinical use: antacid Toxicity: hypokalemia (all antacids), diarrhea -hyporeflexia, hypotension, cardiac arrest (hypermagnesemia toxicities)

Calcium carbonate

Clinical use: antacid Toxicity: hypokalemia (all antacids), hypercalcemia, rebound acid increase Can chelate and decrease effectiveness of other drugs (tetracycline)

Itraconazole

Clinical use: blastomycoses, coccidioides, histoplasma (the systemic mycoses)

Fluconazole

Clinical use: chronic suppression of cryptococcal meningitis in AIDS patients, candida infxns of all types

Sodium stibogluconate

Clinical use: leishmaniasis

Quinidine, artesunate

Clinical use: life threatening malaria

Protamine sulfate

Clinical use: rapid reversal of heparin toxicity (positively charged molecule binds negatively charged heparin)

Aldesleukin (IL-2)

Clinical use: renal cell carcinoma, metastatic melanoma

Oxytocin

Clinical use: stimulates labor, uterine contractions, milk let down; controls uterine hemorrhage

Trastazumab

Clinical use: targets HER2 receptor in HER2nu positive breast cancer

Oprelvekin (IL-11)

Clinical use: thrombocytopenia

Clotrimazole/Miconazole

Clinical use: topical fungal infections

Mg2+

Clinical use: torsades de pointes digoxin toxicity

Pyrimethamine

Clinical use: toxoplamosis (often with sulfadiazine)

Suramin/melarsoprol

Clinical use: trypanosoma brucei (African sleeping sickness); suramin for blood-borne disease or melarsoprol for CNS penetration

Nifurtimox

Clinical use: trypanosoma cruzi (Chagas)

action of sulfonylureas

Close K+ channel in beta cell membrane-->cell depolarizes-->insulin release via increase Ca2+ influx

___ is an antipsychotic that may cause agranulocytosis and thus require weekly WBC monitoring. It can even cause seizures!

Clozapine. "Must watch CLOZapine CLOZely!"

5-fluorouracil (5-FU), Clinical Use

Colon cancer Pancreatic cancer Basal cell carcinoma (topical)

Irinotecan, topotecan, Clinical Use

Colon cancer (irinotecan) Ovarian and small cell lung cancers (topotecan).

Sulfasalazine: MOA

Combo of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria.

• Olanzapine (Zyprexa):

Common side effect is weight gain.

• Quetiapine (Seroquel):

Common side effects include sedation and orthostatic hypotension.

Hydralazine: Adverse Effects

Compensatory tachycardia (***contraindicated in angina/CAD) fluid retention/swelling nausea headache angina Lupus-like syndrome

What is the MOA of Non-depolarizing Neuromuscular Blocking Drugs?

Competitive ACh Antagonists

Mifepristone (RU-486)-- MOA

Competitive inhibitor of progestins at progesterone receptors

2. Serotonin syndrome:

Confusion, flushing, diaphoresis, tremor, myoclonic jerks, hyperthermia, hypertonicity, rhabdomyolysis, renal failure, and death. • Occurs when there is too much serotonin, classically when selective serotonin reuptake inhibitors (SSRis) and monoamine oxidase inhibitors (MAOis) are combined • Treatment: Stop drugs

Ranolazine: Adverse Effects

Constipation dizzy headache nausea QT prolongation

Osmotic laxatives: Use

Constipation Hepatic encephalopathy-- Lactulose (only)--> gut flora degrade it to lactic acid and acetic acid--> promote nitrogen excretion as NH4+.

Aluminum hydroxide: Toxicity

Constipation and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures

Antiarrhythmics: Class IV: Toxicity

Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression).

When are Barbiturates Contraindicated?

Contraindicated in porphyria

Ondansetron: Use

Control vomiting post-operatively and chemo patients

What are the toxic Cs caused by TCA?

Convulsion, Coma, Cardiotoxicity

Which drugs have the strongest and most predictable effects on the INFLAMMATION response in asthma?

Corticosteroids ie flucatisone

ACE inhibitors-- Toxicity

Cough, Angioedema (contraindicated in C1 esterase inhibitor deficiency), teratogen, increase creatinine (decrease GFR), hyperkalemia, hypotension Avoid in bilateral renal artery stenosis--> ACE inhibitor will decrease GFR more--> Renal Failure

Infliximab: Use

Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis.

Cyclophosphamide, ifosfamide, Mechanism

Cross-link DNA at guanine N-7. Require bioactivation by liver.

Cisplatin, carboplatin, Mechanism

Cross-link DNA.

Busulfan, Mechanism

Cross-links DNA.

Prednisone, prednisolone, Toxicity

Cushing-like symptoms; - weight gain - central obesity - muscle breakdown - cataracts - acne - osteoporosis - hypertension - peptic ulcers - hyperglycemia - psychosis

What is the MOA of Haloperidol (HD treatment)?

D2 receptor agonist (typical antipsychotic)

Metoclopramide: MOA

D2 receptor antagonist. Increase resting tone, contractility, LES tone, motility No influence on colon transit time

Whats important about statins regards Coronary Artery Disease.

DECREASE Mortality!

Linagliptin, saxagliptin, sitagliptin

DPP-4 inhibitors (DPP-4 inhibits GLP-1) MOA: ↑ insulin, ↓ glucagon release Clinical use: type 2 DM Toxicities: mild UTI/URI

MOA: DNA intercalators Drugs?

Dactinomycin Doxorubicin/daunorubicin

How is Malignant Hypothermia Treated?

Dantrolene - Ryanodine Receptor antagonist

What are the Adverse Effects of Prostaglandin: Bimatoprost, Iatanoprost (PGF2α)?

Darkens color of iris (browning), eyelash growth

Antiarrhythmics Class IB: MOA

Decrease AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. Phenytoin can also fall into the IB category.

Antiarrhythmics Class II: MOA

Decrease SA and AV nodal activity by decreasing cAMP, decreasing Ca2+ currents. Suppress abnormal pacemakers by decreasing slope of phase 4. AV node particularly sensitive— increase PR interval. Esmolol very short acting.

Antiarrhythmics: Class IV: MOA

Decrease conduction velocity, increase effective refractory period, increase PR interval.

Fibrates: Effect on LDL, HDL, Triglycerides

Decrease in LDL, **triglycerides Increase in HDL

Nitrates + Beta blockers

Decrease: BP, Heart Rate, MVO2 No effect or decrease: End diastolic volume, contractility, ejection time

Beta-blockers, Verapamil (Affect Afterload)

Decrease: BP, contractility, heart rate, MVO2 Increase: End diastolic volume, Ejection time note: Verapamil works like beta blocker

Nitrates, Nifedipine (Affect preload)

Decrease: End diastolic volume, BP, Ejection time, MVO2 Increase (reflex): contractility, heart rate

Bile Acid Resins: Effect on LDL, HDL, Triglycerides

Decrease: LDL Increase: HDL ** Increase Triglycerides

Cholesterol Absorption Blocker: Effect on LDL, HDL, Triglycerides

Decrease: LDL No change to Triglycerides nor HDL

Niacin (B3): Effect on LDL, HDL, Triglycerides

Decrease: LDL, Triglycerides Increase: HDL**

Blood pH changes with diuretics

Decreases (academia): Carbonic anhydrase inhibitors: decreased HCO3- absorption. K+ sparing: aldosterone blockade prevents K+ secretion and H+ secretion. Additionally, hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells. Increases (alkalemia): loop diuretics and thiazdides cause alkalemia through: 1) Volume contraction -> Increased ATII -> Increased Na+/H+ exchange in PCT -> Increased HCO3- reabsorption ("contraction alkalosis") 2) K+ loss leads to K+ exiting all cells (via H+/K+ exchange) in exchange for H+ entering cells 3) In low K+ state, H+ (rather than K+) is exchanged for Na+ in cortical collecting tubule -> alkalosis and "paradoxical aciduria"

HMG-CoA reductase Inhibitors: Effect on LDL, HDL, Triglycerides

Decreases: LDL, Triglycerides Increases: HDL

What are the Adverse Effects of Benzodiazepines?

Dependence Additive CNS depression effects w/ alcohol Less risk of respiratory depression and coma than with barbiturates

Clinical use of SNRIs?

Depression! VENLAFAXINE: generalized anxiety, panic d/o DULOXETINE: also indicated for diabetic peripheral neuropathy

Example of long acting insulin

Detemir Glargine

Insulin, long acting

Detemir, glargine

Heparin-induced thrombocytopenia (HIT)

Development of IgG antibodies against heparin-bound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets -> thrombosis and thrombocytopenia.

Give ____ to prevent cardiotoxicity of doxorubicin/daunorubicin.

Dexrazoxane

Metoclopramide: Use

Diabetic/postsurgery gastroparesis Antiemetic

Osmotic laxatives: Toxicity

Diarrhea, dehydration Bulimics may abuse it

Magnesium hydroxide: Toxicity

Diarrhea, hyporeflexia, hypotension, cardiac arrest

Misoprostol: Toxicity

Diarrhea. Contraindicated in women of childbearing potential (abortifacient).

What are the Benzodiazepines?

Diazepam Lorazepam Triazolam Temazepam Oxazepam Midazolam Chlordiazepoxide Alprazolam

Cardiac Glycosides: Name and PK

Digoxin—75% bioavailability, 20-40% protein bound, t1/2 = 40 hours, urinary excretion.

Calcium channel blockers: Use

Dihydropyridine (except nimodipine): hypertension angina (including Prinzmetal), Raynaud phenomenon Non-dihydropyridine: hypertension angina **atrial fibrillation/flutter (via slow down conduction through AV node)

Amlodipine, clevidipine, nicardipine, nifedipine, nimodipine

Dihydropyridine Ca2+ channel blockers, act on smooth muscle MOA: block voltage-independent L-type Ca2+ channels of smooth muscle → ↓ contractility Vascular smooth muscle--amlodipine = nefidipine > diltiazem > verapamil Clinical use: HTN, angina (including Prinzmetal), Raynaud phenomenon -Nimodipine: subarachnoid hemorrhage (prevent cerebral vasopasm) -Clevidipine: hypertensive urgency or emergency Toxicity: cardiac depression, peripheral edema, flushing, dizziness, constipation, gingival hyperplasia

Calcium channel blockers: Names

Dihydropyridine: Amlodipine, nimodipine, nifedipine; Non-dihydropyridine: diltiazem, verapamil.

Dihydropyridines vs non-dihydropyridines

Dihydropyridines act on Blood vessels non-dihydropyridines act on Heart

What are the first generation antihistamines?

Diphenhydramine Dimenhydrinate Chlorpheniramine names contain -en/-ine or -en/-ate

Cardiac Glycosides (digoxin): MOA

Direct inhibition of Na+/K+ ATPase leads to indirect inhibition of Na+/Ca2+ exchanger/antiport. Increase [Ca2+]intracellular--> positive inotropy. Stimulates vagus nerve--> decrease HR.

Dopamine

Direct sympathomimetic D1=D2>β>α = DBA Low Dose = D = Vasodilates kidneys Medium Dose = B = Inc contractility & ionotropy High Dose = A = Vasoconstrict Clinical use: unstable bradycardia, HF, shock -Inotropic and chronotropic α effects predominate at high doses

Phenylephrine

Direct sympathomimetic α1>α2 VASOCONSTRICTS Clinical use: hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant)

Norepinephrine

Direct sympathomimetic α1>α2>β1 VASOCONSTRICTS Clinical use: hypotension (but ↓renal perfusion) -*Significantly weaker β2 effects than epinephrine*

Isoproterenol

Direct sympathomimetic β1=β2 Clinical use: electrophysiologic evaluation of tachyarrhythmias -Can worsen ischemia

Dobutamine

Direct sympathomimetic β1>β2, α Clinical use: HF (isotropy > chronotropic), cardiac stress testing

Albuterol, salmeterol

Direct sympathomimetic β2>β1 Clinical use: -Albuterol for acute asthma -Salmeterol for long-term asthma or COPD

Epinephrine

Direct sympathomimetic β>α Clinical use: anaphylaxis, asthma, open-angle glaucoma -α effects predominate at high doses -*Significantly stronger β2 effects than NE* Vasoconstricts, increases HR/ionotropy, & bronchodilates in Anaphylaxis

Thrombolytics, Mechanism

Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Incr. in PT and PTT, no change in platelet count.

N-acetylcysteine: MOA

Disrupts disulfide bonds >>>liquifies mucus

Arylcyclohexylamines (*K*etamine) Acts as what type of Anesthetic?

Dissociative Anesthetic

Loop diuretics: Ethacrynic acid-- Use

Diuresis in patients allergic to sulfa drugs

Anti HTN with CHF

Diuretics ACE inhibitors/ARBs β-blockers (compensated CHF), aldosterone antagonists

Appropriate agents for treating HTN w/ CHF

Diuretics, ACE inhibitors/ARBs, β blockers (generally only in compensated CHF), K+ sparing diuretics

Sildenafil: Caution

Do not use with nitrates

Hypertensive Emergency: Fenoldopam

Dopamine D1 receptor agonist—coronary, peripheral, renal, and splanchnic vasodilation. Major Decrease BP and increase natriuresis memory: fenolDOPAM

Name an example of an endocrine side effect on an antipsychotic.

Dopamine receptor antagonism -> Hyperprolactinemia -> Galactorrhea

Mannitol-- Use

Drug overdose, high intraocular or intracranial pressure

Erlotinib, Mechanism

EGFR tyrosine kinase inhibitor.

Loop diuretics: Furosemide-- Use

Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema), HTN, hypercalcemia

How are the Effects Barbiturates (*Th*iopental) Terminated?

Effect is terminated by rapid distribution into tissue and fat

Effect of inhaled corticosteroids

Effect: -inhibit formation of cytokines, prostaglandins, leukotrienes, aka all inflammatory mediators -reduce leukocyte extravasation -induce apoptosis of inflammatory cells -decrease mucus produced by goblet cells

Magnesium: MOA

Effective in torsades de pointes and digoxin toxicity.

Docusate

Emollient, osmotic draw into lumen to increase water absorption by stool Adverse effect: diarrhea

Estrogens-- Toxicity

Endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina (DES in utero), thrombi Contraindications-- ER + breast cancer, DVT history

Selective Estrogen Receptor Modulators-- SERMs: Tamoxifen-- Toxicity

Endometrial cancer, thromboembolism

Danazol-- Use

Endometriosis and hereditary angioedema

Class of drugs to treat pulmonary hypertension drugs

Endothelin receptor antagonists

Sildenafil, Vardenafil-- Use

Erectile dysfunction

What are the Erogt (1) and Non-Ergot (2) Dopamine Agonists?

Ergot: *B*romocriptine Non-Ergot: (preferred) 1. Pramipexole 2. Ropinirole

Procaine, cocaine, tetracaine

Ester local anesthetics MOA: block Na+ channels by binding to a specific receptor on INNER portion of the channel (most effective in rapidly firing neurons bc have to get inside a channel that has already been activated) Clinical use: minor surgical procedures, spinal anesthesia Toxicity: CNS excitation (depression of inhibitory centers), HTN or hypotension, arrhythmias (cocaine), hypersensitivity (if allergic to esters, give amides)

Oral Contraception-- MOA

Estrogen and progestin inhibit FSH/LH-- prevent estrogen surge --> no LH surge--> no ovulation Progestins-- thickening of cervical mucus (block sperm), inhibit endometrial proliferation (implantation)

Estrogens-- Names

Ethinyl estradiol, DES, Mestranol

Etoposide, teniposide, Mechanism

Etoposide inhibits topoisomerase II -> incr. DNA degradation.

MOA: Inhibit topoisomerase II Drugs?

Etoposide, teniposide

Metformin moa

Exact mechanism unknown. decrease gluconeogensis increase glycolysis increase peripheral glucose uptake increase insulin sensitivity

GLP-1 analogs examples

Exenatide, liraglutide (SC injection)

Guaifenesin

Expectorant that thins respiratory secretions does not suppress cough reflex "guaiFENESin-FENEStrate hole into the mucus therefore>>makes MUCUS THIN"

Cholesterol Absorption Blocker: Name

Ezetimibe

TRUE or FALSE: 3rd generation TCAs (AMITRIPTYLINE) has less anticholinergic effects than 2nd generation TCAs (NORTRIPTYLINE)

FALSE

TRUE or FALSE: Lithium has a wide therapeutic window.

FALSE. It has a narrow therapeutic window that requires close monitoring of serum levels.

Name 4 SSRIs.

FLuoxetine, PARoxetine, SErtraline, CITalopram "FLashbacks PARalyze SEnior CITizens"

What is the Benzodiazepines Mechanism?

Facilitate GABA-A action by ↑ Frequency of Cl channel opening ↓ REM sleep Long half lives and active metabolites Exceptions ATOM: Alprazolam, Triazolam, Oxazepam, Midazolam - short acting → higher addictive potential

What is the Barbiturates Mechanism?

Facilitate GABA-A action by ↑ duration of Cl channel opening → ↓ neuron firing BarbiDURATes ↑ DURATION

AE of 2nd gen antihistamine

Far less sedating than 1st gen because of decreased entry into CNS

SE of lithium in a fetus?

Fetal cardiac defects include Ebstein anomaly and malformation of the great vessels.

What else is Carbamazepine Used for?

First line for trigeminal neuralgia

Antiarrhythmics Class IC: Names

Flecainide, Propafenone

Azoles

Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole, posaconazole MOA: inhibit fungal sterol synthesis by inhibiting the P450 that converts lanosterol to ergosterol Toxicity: testosterone synthesis inhibition (esp ketoconazole), liver dysfunction due to P450 inhibition

synthetic analog of aldosterone

Fludrocortisone (mineralocorticoid with little glucocorticoid effects)

Imatinib, Toxicity

Fluid retention

How to treat Benzodiazepine OD?

Flumazenil - competitive antagonist at GABA benzodiazepine receptor Can precipitate seizures by causing acute benzodiazepine withdrawal

Antibiotics that block DNA topoisomerases

Fluroquinolones

Methotrexate (MTX), Mechanism

Folic acid analog that competitively inhibits dihydrofolate reductase ->↓dTMP->↓DNA synthesis.

Heparin, antidote

For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin).

Maraviroc

Fusion inhibitor MOA: bindins CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120

Enfuvirtide

Fusion inhibitor MOA: binds gp41, inhibiting viral entry Toxicity: skin reaction at injection site

Clinical use of GH

GH deficiency, Turner Syndrome

Concerns for alpha-glucosdiase inhibitors

GI disturbances

Risks/concerns of metformin

GI upset Most serious is lactic acidosis (contraindicated in renal insufficiency)

Exenatide, liraglutide

GLP-1 analogs MOA: ↑ insulin, ↓ glucagon release Clinical use: type 2 DM Toxicities: N/V, pancreatitis

Exanitide, liraglutide

GLP-1 analogs MOA: ↑ insulin, ↓ glucagon release Clinical use: type 2 DM Toxicities: pancreatitis, nausea, vomiting

Jimson weed (Datura)

Gardener's pupil due to mydriasis

Clinical use of BUSPRIONE?

Generalized anxiety disorder. "I'm always anxious if the bus will be on time, so I take busprione" Does not cause sedation, addictions, or tolerance. 1-2 weeks to take effect. No interactions.

Doxorubicin, daunorubicin, Mechanism

Generate free radicals. Intercalate in DNA -> breaks in DNA -> ↓ replication.

What does PPAR-y do?

Genes activated by PPAR-y regulate fatty acid storage and glucose metabolism. Activation of PPAR-y increase insulin sensitivity and levels of adiponectin

Acetazolamide-- Use

Glaucoma, urinary alkalization, metabolic alkalosis, altitude sickness, pseudotumor cerebri

risks of SGLT-2 inhibitors

Glucosuria, UTIs, vaginal yeast infections, hyperkalemia, dehydration (orthostatic hypotension)

Leuprolide-- MOA

GnRH analog-- agonist with pulsatile fashion Antagonist with continuous use (downregulates GnRH receptor in pituitary --> decrease FSH and LH)

Filgrastim

Granulocyte colony stimulating factor Clinical use: bone marrow recovery

Sargramostim

Granulocyte/macrophage colony stimulating factor Clinical use: bone marrow recovery

Antiandrogens-- Ketoconazole: Side effects

Gynecomastia, amenorrhea

Antiandrogens-- Spironolactone: Side effects

Gynecomastia, amenorrhea

Ampicillin and amoxicillin HELPSS kill enterococci

H. influenzae, E. coli, L. monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci (extended spectrum penicillins)

Diphenhydramine, Dimenhydrinate, Chlorpheniramine

H1 Antagonists. Used for allergies, motion sickness, sleep aids. Toxicity: Sedation, Antimuscarinic, Anti-alpha-adrenergic

Loratadine, Fexofenadine, Desloratadine, Cetirizine

H2 Antagonists. Used for allergies. NO sedating effect b/c less penetration into CNS than H1 antagonists.

Heparin vs. warfarin, Mechanism of action

H: Activates antithrombin, which decr. the action of IIa (thrombin) and factor Xa W: Impairs activation of vitamin K-dependent clotting factors II, VII, IX, and X, and anti-clotting proteins C and S

Heparin vs. warfarin, Duration of action

H: Acute (hours) W: Chronic (days)

Heparin vs. warfarin, Site of action

H: Blood W: Liver

Heparin vs. warfarin, Structure

H: Large, anionic, acidic polymer W: Small, amphipathic molecule

Heparin vs. warfarin, Crosses placenta

H: No W: Yes (teratogenic)

Heparin vs. warfarin, Monitoring

H: PTT (intrinsic pathway) W: PT/INR (extrinsic pathway)

Heparin vs. warfarin, Route of administration

H: Parenteral (IV, SC) W: Oral

Heparin vs. warfarin, Agents for reversal

H: Protamine sulfate W: Vitamin K, fresh frozen plasma

Heparin vs. warfarin, Onset of action

H: Rapid (seconds) W: Slow, limited by half-lives of normal clotting factors

Heparin vs. warfarin, Inhibits coagulation in vitro

H: Yes W: No

___ is an antipsychotic that can cause NMS and tardive dyskinesia

HALOPERIDOL

Trastuzumab (Herceptin), Clinical Use

HER-2 ⊕ breast cancer Gastric cancer (tras2zumab)

Hydrochlorothiazide--Use

HTN, CHF, idiopathic hypercalciuria, nephrogenic DI, osteoporosis

ACE inhibitors-- Use

HTN, CHF, proteinuria, diabetic nephropathy Prevent unfavorable remodeling from chronic HTN

Cladribine (2-CDA), Clinical Use

Hairy cell leukemia.

Halothane Example of MAC

Halothane ↑ blood and lipid solubility → slow induction & high potency

Ondansetron: Toxicity

Headache Constipation

Sildenafil, Vardenafil-- Toxicity

Headache, flushing, dyspepsia, impaired blue-green color vision Risk of life-threatening hypotension (taking nitrates)

Mifepristone (RU-486)-- Toxicity

Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain

Bevacizumab, Toxicity

Hemorrhage Blood clots Impaired wound healing.

Hypercoagulability with warfarin use, treatment

Heparin "bridging": heparin frequently used when starting warfarin. Heparin's activation of antithrombin enables anticoagulation during initial, transient hypercoagulable state caused by warfarin. Initial heparin therapy reduces risk of recurrent venous thromboembolism and skin/tissue necrosis.

HMG-CoA reductase Inhibitors: SE

Hepatoxicity (increased LFT, esp ALT), rhabdomyolysis myopathy (w/o elevation of creatine kinase (esp with fibrates and niacin)

Haloperidol, trifluoperazine, fluphenazine

High potency antipsychotics ("Try to Fly High) MOA: block D2 receptors (↑cAMP) Clinical use: schizophrenia (primarily + symptoms), psychosis, acute mania, Tourette syndrome Toxicity: -All antipsychotics: highly lipid soluble and slow to be removed from body; hyperprolactinemia; QT prolongation -High potency antipsychotics: EPS, neuroleptic malignant syndrome

Selective Estrogen Receptor Modulators-- SERMs: Clomiphene-- Toxicity

Hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances

Which drugs cause lupus like syndrome? What antibody is associated?

Hydralazine Procainamide anti-histone antibodies, esp in people who are slow acetylators, bc other cells will break down hydralazine and cause toxic metabolites that will bind to tissues and cause body to react to it as foreign material aka forms antibodies

Appropriate agents for treating HTN in pregnancy

Hydralazine, labetalol, methyldopa, nifedipine

Potassium sparing diuretics-- Use

Hyperaldosteronism, potassium depletion, CHF

Calcium carbonate: Toxicity

Hypercalcemia, rebound acid

Acetazolamide-- Toxicity

Hyperchloremic metabolic ACIDOSIS, paresthesias, NH3 toxicity, sulfa allergy

Potassium sparing diuretics-- Toxicity

Hyperkalemia (arrhythmias), endocrine effects with spironlactone (gynecomastia, antiandrogen effects)

Paclitaxel, other taxols, Mechanism

Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur).

Risks of Cinacalcet

Hypocalcemia

Risks/Concerns for pramlintide

Hypoglycemia (in setting of mistimed prandial insulin), nausea

Estrogens-- Use

Hypogonadism, ovarian failure, menstrual abnormalities, hormone replacement therapy (post menopausal women), androgen dependent prostate cancer (men)

Testosterone, Methyltestosterone-- Use

Hypogonadism, promotes development of secondary sex characteristics, stimulate anabolism (promote recovery after bury or injury)

Hydrochlorothiazide-- Toxicity

Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia Sulfa allergy

Clinical use of levothyroxine and triiodothyronine

Hypothyroidism, myxedema used off-label as weight loss supplements

Cimetidine, ranitidine, famotidine, nizatidine

H₂ blockers (take H₂ blockers before you "dine") MOA: REVERSIBLY block histamine H₂ receptors → ↓ H+ secretion by parietal cells Clinical use: peptic ulcer, mild esophageal reflux Toxicity: Cimetidine = potent inhibitor of P450 enzymes, also has antiandrogenic effects (prolactin release, gynecomastia, impotence, ↓ libido in males), can cross BBB and placenta -Cimetidine and ranitidin ↓ renal excretion of creatinine

Infliximab, adalimumab, certolizumab, golimumab use

IBD RA ankylosing spondylitis psoriasis

Risks of glucocorticoids

Iatrogenic Cushing syndrome (HTN, weight gain, moon facies, truncal obesity, buffalo hump, thinnning of skin, striae, acne, osteoporosis, hyperglycemia, amenorrhea, immunosuppression) adrenocortical atrophy peptic ulcers steroid diabetes steroid psychosis cataracts Adrenal insufficiency when drug stopped abruptly ater chronic use

Antiarrhythmics Class II: Toxicity

Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia. Metoprolol can cause dyslipidemia. Propranolol can exacerbate vasospasm in Prinzmetal angina. Contraindicated in cocaine users (risk of unopposed α-adrenergic receptor agonist activity). Treat overdose with glucagon.

Rituximab, Toxicity

Incr. risk of progressive multifocal leukoencephalopathy.

Diuretics: Electrolyte changes-- Urine NaCl

Increase (with all except acetazolamide) Serum NaCl may decrease

Antiarrhythmics Class IA: MOA

Increase AP duration, increase effective refractory period (ERP), increase QT interval.

Adenosine: MOA, SE

Increase K+ out of cells--> hyperpolarizing the cell and decrease I-Ca. Drug of choice in diagnosing/abolishing supraventricular tachycardia. Very short acting (~ 15 sec). Adverse effects include flushing, hypotension, chest pain. Effects blocked by theophylline and caffeine.

MOA of BUPROPION?

Increase NE and DA via unknown mechanism

Hydralizine: MOA

Increase cGMP--> smooth mm relaxation Vasodilates arterioles does not vasodilate veins! result: afterload reduction

GLP-1 MOA

Increase glucose-dependent insulin release, decrease glucagon release, decrease gastric emptying, increase satiety

Cholesterol Absorption Blocker: SE

Increase in LFTs (rare) diarrhea

Thiazolidinediones MOA

Increase insulin sensitivity in peripheral tissue. Binds to PPAR-y nuclear transcription regulator

effects of insulin on fat

Increase triglyceride storage

Bismuth, sucralfate: Use

Increase ulcer healing, travelers diarrhea

Urine NaCl changes with diuretics

Increase with all diuretics except acetazolamide. Serum NaCl may decrease as a result.

Diuretics: Electrolyte changes-- Urine Potassium

Increase with loop and thiazide diuretics Serum potassium may decrease

Urine K+ changes with diuretics

Increase with loop and thiazide diuretics. Serum K+ may decrease as a result.

Diuretics: Electrolyte changes-- Urine Calcium

Increase with loop diuretics-- decrease paracellular calcium reabsorption-- hypocalcemia Decrease with thiazides-- enhance paracellular calcium reabsorption in distal tubule

Urine Ca2+ changes with diuretics

Increase with loop diuretics: decreased paracellular Ca2+ reabsorption -> hypocalcemia. Decreased with thiazides: enhanced Ca2+ reabsorption in DCT.

Proton pump inhibitor: Toxicity

Increased risk of C. difficile infection, pneumonia. Hip fractures, decrease serum Mg2+ with long-term use.

MOA of CNS stimulants.

Increases catecholamines at the synaptic cleft, especially NE and DA

Ephedrine

Indirect sympathomimetic Effect: Indirect general agonist, release stored catecholamines Clinical use: nasal decongestion, urinary incontinence, hypotension

Cocaine

Indirect sympathomimetic Effect: Indirect general agonist, reuptake inhibitor Clinical use: causes vasoconstriction and anesthesia -*Never give β-blockers if suspected cocaine intoxication b/c can lead to unopposed α1 activation -> extreme hypertension*

Amphetamine

Indirect sympathomimetic Effect: Indirect general agonist, reuptake inhibitor, also releases stored catecholamines Clinical use: narcolepsy, obesity, ADHD

Bleomycin, Mechanism

Induces free radical formation -> breaks in DNA strands

Infliximab: Toxicity

Infection (reactivation of latent TB), fever, hypotension.

Leuprolide-- Use

Infertility (pulsatile) Prostate cancer (continous with flutamide) Uterine fibroids (continuous) Precocious puberty (continuous)

Fluticasone, Budesonide

Inhaled Corticosteroids used for Asthma (1st line for chronic asthma) MOA: Inhibits NF-kB (Decreases inflammatory cytokine production)

Fluticasone, budesonide, beclomethasone

Inhaled corticosteroids

MOA of SNRIs?

Inhibit 5HT and NE reputake

ACE inhibitors-- MOA

Inhibit ACE--> decrease angiotensin II--> decrease GFR (prevent constriction of efferent arteriole) Increasing levels of renin (loss of feedback) ACE inhibition--> prevents inactivation of bradykinin (vasodilator)

DPP-4 inhibitor MOA

Inhibit DPP-4 enzyme that deactivates GLP-1, thereby increasing glucose-dependent insulin release, decrease glucagon release, decrease gastric emptying, increase satiety

Sildenafil: MOA

Inhibit PDE-5 from breaking down cGMP prolongs vasodilatory effect of nitric oxide

HMG-CoA reductase Inhibitors: MOA

Inhibit conversion of HMG-CoA to mevalonate (cholesterol precursor)

Alpha-glucosidase inhibitor MOA

Inhibit intestinal brush-border alpha-glucosidases delayed carbohydrate hydrolysis and glucose absorption--> decreased postprandial hyperglycemia

Sildenafil, Vardenafil-- MOA

Inhibit phosphodiesterase 5--> increase cGMP--> smooth muscle relaxation in corpus cavernosum Increase blood flow--> penile erection

MOA of fluticasone, budesonide

Inhibit synthesis of virtually all cytokines via Inactivate NF-kB (the transcription factor that induces production of TNF-alpha and other inflammatory agents)

Irinotecan, topotecan, Mechanism

Inhibit topoisomerase I and prevent DNA unwinding and replication.

Hydrochlorothiazide-- MOA

Inhibits NaCl reabsorption in early distal tubule Decrease diluting capacity of nephron Decrease calcium excetion

Ranolazine: MOA

Inhibits late phase of sodium current>>>reduces diastolic wall tension and oxygen consumption DOES NOT affect heart rate or contractility this late phase has been found in diseased hearts bc usually calcium is the dominant ion in phase 2 but for some reason Na also comes in, which causes sodium calcium exchanger to put more calcium in cell which leads to contraction; so blocking this will reduce tension

Niacin (B3): MOA

Inhibits lipolysis in adipose tissue; reduces hepatic VLDL synthesis

Hydroxyurea, Mechanism

Inhibits ribonucleotide reductase ->↓DNA Synthesis (S-phase specific).

Antiandrogens-- Spironolactone: MOA

Inhibits steroid binding 17 a hydroxylase and 17,20 desmolase

Antiandrogens-- Ketoconazole: MOA

Inhibits steroid synthesis (inhibits 17, 20 desmolase)

What is the MOA of Tetrabenazine, Reserpine (HD treatment)?

Inhibits vesicular monamine transporter (VMAT) → ↑dopamine vesicle packaging and release

What are the Clinical Uses of Nonbenzodiazepine Hypnotics?

Insomnia

What is the Clinical Use of Ramelteon?

Insomnia

What is the Clinical Use of Suvorexant?

Insomnia

Raltegravir

Integrase inhibitor MOA: reversibly inhibits HIV integrase Toxicity: ↑ creatine kinase

Dactinomycin (actinomycin D), Mechanism

Intercalates in DNA.

MOA: Inhibit topoisomerase I Drugs?

Irinotecan, topotecan

Proton pump inhibitor: MOA

Irreversibly inhibit H+/K+ ATPase in stomach parietal cells.

SSRIs, SNRIs, MAO inhibitors, TCAs, and any drug that increases serotonin can cause Serotonin syndrome. What is it?

It causes hyperthermia, confusion, myoclonus, cardiovascular collapse, flushing, diarrhea, and seizures.

RECALL: What is the MOA of DANTROLENE?

It prevents the release of Ca from the sarcoplasmic reticulum of the skeletal M. It is used to treat malignant hyperthermia and NMS.

• Ziprasidone (Geodon):

Less likely to cause weight gain.

What is a Benefit of *Propo*fol?

Less post-op nausea than thiopental

Cytarabine (arabinofuranosyl cytidine), Clinical Use

Leukemias (AML) Lymphomas

Cytarabine (arabinofuranosyl cytidine), Toxicity

Leukopenia Thrombocytopenia Megaloblastic anemia CYTarabine causes panCYTopenia.

Montelukast, Zafirlukast

Leukotriene Receptor Inhibitors.

Antiarrhythmics Class IB: Names

Lidocaine, Mexiletine

Theophylline MOA

Likely causes bronchodilation by inhibiting phosphodiesterase-->>>increase cAMP levels metabolized by cytochrome P450

DPP-4 inhibitor examples

Linagliptin Saxagliptin Sitagliptin

Typical antipsychotics are (water/lipid) soluble

Lipid

What Characteristics must CNS Drugs Have?

Lipid soluble to cross the BBB or be actively transported

Insulin, rapid acting examples

Lispro Aspart Glulisine

Organisms not typically covered by cephalosporins are LAME

Listeria, Atypicals (chlamydia, mycoplasma), MRSA, and Enterococci

Sameterol, Formoterol

Long Acting B2 Agonists Uses: Asthma prophylaxis Side Effects: Tremor & Arrhythmia

pseudophedrine, phenylephrine: Adverse Effects

Long term use>>rebound nasal congestion (Rhinitis medicamentosa) Hypertension Tachycardia Palpitations Anxiety CNS stimulation/anxiety

Octreotide: MOA

Long-acting somatostatin analog.

Diuretics: Electrolyte changes-- Blood pH, Alkalemia

Loop diuretics and thiazides Volume contraction-- Increase AT II--> increase Na+/K+ exchange in proximal tubule--> Increase HCO3- reabsorption Potassium loss--> Potassium loss in cells--> H+ uptake by cells Low K+ state-- H+ is exchanged for Na+ in cortical collecting tubule

Second generation antihistamines

Loratadine Fexofenadine Desloratadine Cetirizine usually end in -adine

Angiotensin II receptor blockers

Losartan, candesartan, valsartan MOA: Selectively block binding of angiotensin II to AT1 receptor. Effects similar to ACE inhibitors, but ARBs do NOT increase bradykinin. Clinical Use: HTN, HF, proteinuria, or diabetic nephropathy with intolerance to ACE inhibitors (e.g., cough, angioedema) Toxicity: Hyperkalemia, decreased renal function, hypotension, teratogen.

HMG-CoA reductase Inhibitors: Names, Prefix

Lovastatin, pravastatin, simvastatin, atorvastatin, rosuvastatin (-STATIN)

Type 1 Diabetes mellitus treatment strategy

Low carb diet, insulin replacement

Thioridazine, chlorpromazine

Low potency antipscyhotics ("Cheating Thieves are low) Clinical use: schizophrenia (primarily + symptoms), psychosis, acute mania, Tourette syndrome Toxicity: -All antipsychotics: highly lipid soluble and slow to be removed from body; hyperprolactinemia; QT prolongation -Low potency antipsychotics: block muscarinic, α1, and histamine receptors

Enoxaparin, dalteparin, fondaparinux

Low-molecular-weight heparins MOA: act more on factor Xa, have better bioavailability and 2-4x longer half-life; can be admin subQ and without lab monitoring; not easily reversible

Heparin, Subtypes

Low-molecular-weight heparins (e.g., enoxaparin, dalteparin) and fondaparinux - act more on factor Xa - have better bioavailability - 2-4 times longer half-life; - can be administered subcutaneously - without laboratory monitoring - Not easily reversible.

Potency is Inversely Related to?

MAC

MAO-A preferentially deactivates _____, and MAO-B preferentially deactivates _______; both types also act on dopamine and tyramine

MAO-A preferentially deactivates serotonin, and MAO-B preferentially deactivates norepinephrine/epinephrine; both types also act on dopamine and tyramine

Ceftriaxone, cefotaxime, ceftazidime

MOA: *3rd generation* beta lactam drugs that inhibit cell wall synthesis Clinical use: bactericidal for *serious gram (-) infxns* resistant to other beta lactams; ceftriaxone good for meningitis and gonorrhea, ceftazidime good for pseudomonas Toxicity: hypersensitivity rxns, *disulfiram-like* runs, *vitamin K deficiency*, potentiate nephrotoxicity of amino glycosides MOR: *structural change in PBP*

Cisplatin, carboplatin

MOA: *Cross-link DNA* Use: Testicular, bladder, ovary, and lung carcinomas Tox: *Nephrotoxicity* - prevent with *amifostine* (free radical scavenger) and chloride (saline) diuresis. *Ototoxocicity*

Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

MOA: *Cross-link DNA* *Cross blood-brain barrier -> CNS* Require bioactivation. Use: *Brain tumors* (including glioblastoma multiform) Tox: CNS (convulsions, dizziness, ataxia)

Cyclophosphamide, ifosfamide

MOA: *Cross-link DNA* at guanine N-7. Require bioactivation by liver. Use: Solid tumors, leukemia, lymphomas Tox: Myelosuppression; *hemorrhagic cystitis*, partially prevented with *mesna* (binds toxic metabolites)

Busulfan

MOA: *Cross-links* DNA Use: CML. Also used to ablate bone marrow before bone marrow transplant. Tox: *Severe myelosuppression* (in almost all cases), *pulmonary fibrosis*, hyper pigmentation

Bleomycin

MOA: *Free radical formation -> DNA strand breaks* Use: Testicular cancer, Hodgkin lymphoma Tox: *Pulmonary fibrosis*, skin hyper pigmentation, mucositis. *Minimal myelosuppression*

Anthracyclines: doxorubicin, daunorubicin

MOA: *Free radical formation*. *Intercalate in DNA* -> breaks in DNA -> dec replication Use: Solid tumors, leukemias, lymphomas Tox: *Cardiotoxicity* (dilated cardiomyopathy). *Dexrazoxane* (iron chelating agent), used to prevent cardiotoxicity. *Extravasation* -> redness, necrosis. Do NOT give IM/SC. Myelosuppression, alopecia.

Paclitaxel, other taxols

MOA: *Hyperstabilize polymerized microtubules* in M phase -> mitotic spindle can't break down -> anaphase can't occur "It is *tax*ing to stay polymerized." Use: *Ovarian* and *breast* carcinomas Tox: Myelosuppression, alopecia, hypersensitivity

Irinotecan, topotecan

MOA: *Inhibit topoisomerase I* -> prevent DNA unwinding and replication Use: Colon cancer (irinotecan); ovarian and small cell lunger cancers (topotecan) Tox: Severe myelosuppression, diarrhea

Hydroxyurea

MOA: *Inhibits ribonucleotide reductase* -> dec DNA synthesis (S-phase specific) Use: Melanoma, CML, *sickle cell disease (inc HbF)* Tox: Severe myelosuppression, GI upset

Etoposide, teniposide

MOA: *Inhibits topoisomerase II* -> inc DNA degradation Use: Solid tumors (particularly testicular and small cell lunger cancer), leukemias, lymphomas Tox: Myelosuppression, GI upset, alopecia

Dactinomycin (actinomycin D)

MOA: *Intercalates in DNA, inhibition of RNA Pol in prokaryotes and eukaryotes* Use: *Childhood tumors* such as Wilms tumor, Ewing sarcoma, rhabdomyosarcoma ("children *act* out") Tox: Myelosuppression

Azathioprine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG)

MOA: *Purine analog -> dec de novo purine synthesis* Activated by HGPRT. Azathioprine is metabolized into 6-MP. Use: Prevent organ rejection, rheumatoid arthritis, IBD, SLE; wean pts off steroids in chronic disease and to treat steroid-refractory dz Tox: Myelosuppression, GI, liver. Azathioprine and 6-MP metabolized by xanthine oxidase -> inc toxicity with allopurinol or febuxostat (rx tumor lysis syndrome)

Cladribine (2-CDA)

MOA: *Purine analog -> multiple mech* (e.g., inhibition of DNA poly, DNA strand breaks) Clinical use: *hairy cell leukemia* Tox: Myelosuppression, nephrotoxicity, neurotoxicity

Cytarabine (arabinofuranoysl cytidine)

MOA: *Pyrimidine analog* -> inhibition of DNA polymerase Clinical use: Leukemia (AML), lymphoma Tox: Leukopenia, thrombocytopenia, megaloblastic anemia CYTarabine causes panCYTopenia

Imatinib

MOA: *Tyrosine kinase inhibitor of BCR-ABL* (Philadelphia chr fusion gene in *CML*) and *c-kit* (*GI stromal tumors*) Use: *CML, GI stromal tumors* Tox: Fluid retention

Tetrabenazine, reserpine

MOA: *inhibit VMAT* (vesicular monoamine transporter); limit DA vesicle packaging and release (since one of the problems in Huntington's is ↑ DA) *Depletes catacholamines* everywhere --> diarrhea, lower sympathetic output Clinical use: Huntington's

Cefazolin, cephalexin

MOA: 1st generation beta lactam drugs that inhibit cell wall synthesis Clinical use: bactericidal for gram (+) COCCI, PEcK: Proteus mirabilis, E. coli, Klebsiella; cefazolin used prior to surgery to prevent S. aureus wound infections Toxicity: hypersensitivity rxns, disulfiram-like runs, vitamin K deficiency, potentiate nephrotoxicity of amino glycosides MOR: structural change in PBP

Cefoxitin, cefaclor, cefuroxime

MOA: 2nd generation beta lactam drugs that inhibit cell wall synthesis Clinical use: bactericidal for gram (+) COCCI, HEN PEcKS- Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp, Proteus mirabilis, E. coli, Klebsiella, Serratia marcescens Toxicity: hypersensitivity rxns, disulfiram-like runs, vitamin K deficiency, potentiate nephrotoxicity of amino glycosides MOR: structural change in PBP

Cefepime

MOA: 4th generation beta lactam drug that inhibits cell wall synthesis Clinical use: bactericidal w/ increased activity again Pseudomonas and gram (+) organisms -Use in patients with neutropenic fever Toxicity: hypersensitivity rxns, disulfiram-like runs, vitamin K deficiency, potentiate nephrotoxicity of amino glycosides MOR: structural change in PBP

Sumatriptan

MOA: 5-HT 1B/1D agonist; inhibits trigeminal nerve activation; prevents vasoactive peptide release; induces vasoconstriction Clinical use: acute migraine, cluster headache attacks Toxicity: coronary vasospasm (CI in patients w/ CAD or prinzmetal's angina)

Ondansetron

MOA: 5-HT3 antagonist; decrease vagal stimulation; powerful central acting antiemetic (At a party but feeling queasy? Keep ON DANCing!") Clinical use: control vomiting postop and in chemotherapy patients Toxicity: headache, constipation, QT prolongation

Ceftaroline

MOA: 5th generation beta lactam drug that inhibits cell wall synthesis Clinical use: broad gram (+) and gram (-) coverage including MRSA; does NOT cover pseudomonas MOR: structural change in PBP

Finasteride

MOA: 5α-reductase inhibitor (↓conversion of testosterone to DHT) Clinical use: BPH, male-pattern baldness

Albuterol

MOA: B2 Agonist. Bronchodilates Uses: Asthma exacerbation

Vinca alkaloids: vincristine, vinblastine

MOA: Bind beta-tubulin and *inhibit polymerization* into microtubules -> prevent mitotic spindle formation (M-phase arrest) Use: Solid tumors, leukemias, Hodgkin (vinblastine) and non-Hodgkin (vincristine) lymphomas Tox: Vincristine: *neurotoxicity* (areflexia, peripheral neuritis, paralytic ileus) Vinblastine: bone marrow suppression. Vin*blast*ine *blasts* *b*one marrow.

Theophylline

MOA: Bronchodilation by blocking PDE thus increasing cAMP. Side Effects: Narrow therapeutic window. Significant risk of seizures and arrhythmia

Tacrolimus (FK-506)

MOA: Calcineurin inhibitor; binds *FK506 binding protein (FKBP*). Blocks T cell activation by preventing IL-2 transcription. Clinical use: transplant rejection prophylaxis Toxicity: similar to cyclosporine, ↑ risk of diabetes and neurotoxicity; no gingival hyperplasia or hirsutism

Acetazolamide

MOA: Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and decreased total body HCO3- stores. Clinical Use: Glaucoma, altitude sickness, metabolic alkalosis, urinary alkalization, pseudo tumor cerbri. Toxicity: Hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity (in acidosis, compensatory NH3 production by PCT cells), sulfa allergy.

Bosentan

MOA: Competitively inhibits endothilin-1 receptors thus decreasing pulmonary vascular resistance. (Endothelin vasoconstricts). Clinical Use: Pulmonary HTN Toxicity: Hepatotoxicity (Monitor LFTs)

Fenoldopam

MOA: D1 receptor agonist; causes coronary, peripheral, renal and splanchnic vasodilation; ↓ BP and ↑ natriuresis (excretion of sodium in the urine via action of the kidneys) Clinical use: hypertensive emergency

Metoclopramide

MOA: D2 receptor antagonist; increases resting tone, contractility, LES tone, motility (does NOT influence colon transport time) Clinical use: diabetic and post surgery gastroparesis, antiemetic Toxicity: increases parkinsonian effects, drug interaction with digoxin and diabetic agents; CI in patients with small bowel obstruction or parkinson's

Haloperidol

MOA: DA receptor antagonist Clinical use: antipsychotic, also used in Huntington's (since one of the problems in Huntington's is ↑ DA)

Succinylcholine

MOA: DEPOLARIZING neuromuscular blocking drug; strong ACh receptor agonist → produces sustained depolarization and prevents muscle contraction Clinical use: muscle paralysis in surgery or mechanical ventilation Toxicity: hypercalcemia, hyperkalemia, malignant hyperthermia

Digoxin

MOA: DIRECT inhibition of Na+/K+ ATPase leads to INDIRECT inhibition Na+/Ca2+ exchanger/antiport; ↑ [Ca2+] intracellularly → positive inotropy (increased force of contraction); also stimulated the vagus nerve to ↓ HR Clinical use: CHF (↑ contractility); A fib (↓ conduction at the AV node and depression of the SA node) Toxicity: cholinergic- nausea/vomiting, diarrhea, blurry yellow vision -ECG- ↑ PR, ↓ QT, ST scooping, T wave inversion, arrhythmia AV block -hyperkalemia is a poor prognostic factor (shows that digoxin is significantly out competing K+ at the ATPase) **Predisposition to overdose: renal failure (↓ digoxin excretion), hypokalemia (less competition at ATPase), quinidine (↓ digoxin clearance, displaces digoxin from tissue binding sites)

Minoxidil

MOA: Direct arteriolar vasodilator Use:Androgenetic alopecia; severe refractory hypertension

Aliskiren

MOA: Direct renin inhibitor, blocks conversion of angiotensinogen to angiotensin I. Clinical Use: HTN Toxicity: Hyperkalemia, decreased renal function, hypotension. Contraindicated in diabetics taking ACE inhibitors or ARBs.

Erlotinib

MOA: EGFR tyrosine kinase inhibitor Use: *Non-small cell lung carcinoma* Tox: Rash

Methotrexate (MTX)

MOA: Folic acid analog that competitively *inhibits dihydrofolate reductase* -> dec dTMP -> dec DNA synthesis Use: Cancers: luekemias (ALL), lymphomas, *choriocarcinoma*, sarcomas. Non-neooplastic: *ectopic pregnancy*, *medical abortion* (with misoprostol), rheumatoid arthritis, psoriasis, IBD, vasculitis Tox: Myelosuppression (reversible with *leucovorin rescue*), hepatoxicity, mucositis, *pulmonary fibrosis*

Leuprolide

MOA: GnRH analogue -Agonist properties when used in pulsatile fashion -Antagonist when used in continuous fashion (down regulates GnRH receptor in pituitary → ↓FSH/LH) Clinical use: infertility (pulsatile), prostate CA (continuous use following androgen receptor blockade with *flutamide*), uterine fibroids (continuous), precocious puberty (continuous), endometriosis (continuous), dysfunctional uterine bleeding (continuous) Toxicity: antiandrogen, nausea, vomiting

Simeprevir

MOA: HCV protease inhibitor; prevents viral replication Clinical use: chronic hep C in combination with ribavirin and peg interferon alfa -Do not use as mono therapy Toxicity: photosensitivity, rash

Aspirin

MOA: IRREVERSIBLY inhibits COX1 and COX2 by covalent acetylation; lasts until platelets are produced; increases bleeding time, decreases TXA2 and prostaglandins Clinical use: antipyretic, analgesic, anti inflammatory, antiplatelet (decreases aggregation) Toxicity: gastric ulceration, tinnitus (CNVIII); chronic use can lead to acute renal failure, interstitial nephritis, upper GI bleeding; Reye's syndrome in children with viral infxn; overdose causes mixed respiratory alkalosis (stimulation of respiratory centers → hyperventilation) and metabolic acidosis

Vigabatrin

MOA: IRREVERSIBLY inhibits GABA transaminase → ↑ GABA Clinical use: simple/complex partial seizures

Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole

MOA: IRREVERSIBLY inhibits H+/K+ ATPase in stomach parietal cells Clinical use: peptic ulcer, gastritis, esophageal reflux, Zollinger Ellison syndrome Toxicity: increased risk of C. diff infection, pneumonia; hip fractures, decreased serum Mg2+ with long term use

Beclomethasone, dexamethasone, fludrocortison (mineralocorticoid + glucocorticoid activity), hydrocortisone, methylprednisolone, prednisone, traimcinolone

MOA: Metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interactions with glucocorticoid response elements, inhibition of phospholipase A2, and inhibition of transcription factors such as NF-κB Clinical use: addison's disease, inflammation, immune suppression, asthma; prednisone used for cancer chemotherapy for CLL, non-Hodgkin's lymphoma Toxicity: Iatrogenic Cushing syndrome (buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis (treat with bisphosphonates), adrenocortical atrophy, peptic ulcers, diabetes (if chronic). -Adrenal insufficiency when drug stopped abruptly after chronic use.

Rituximab

MOA: Monoclonal Ab against *CD20*, which is found on most *B cell neoplasms* Use: Non-Hodgin lymphoma, CLL, IBD, rheumatoid arthritis Tox: inc risk of *progressive multifocal leukoencephalopathy*

Trastuzumab (Herceptin)

MOA: Monoclonal Ab against *HER-2, a tyrosine kinase receptor*. Helps kills cancer cells that *overexpress HER-2* thru inhibition of HER2-initiated cellular signaling and Ab-mediated cytotoxicity. Use: *HER2+ breast cancer and gastric cancer* Tox: *Cardiotoxicity*. "*Heart*ceptin" damages the *heart*.

Bevacizumab

MOA: Monoclonal Ab against *VEGF* -> inhibit angiogenesis Use: Solid tumors (colorectal cancers, renal cell carcinoma) Tox: Hemorrhage, blood clots, and impaired wound healing

Methacholine

MOA: Muscarinic (M3) Agonist. Use: Bronchial Challenge test to screen for asthma

Ipratropium, Tiotropium

MOA: Muscarinic Antagonist. Prevents bronchoconstriction. Tiotropium = Long acting Uses: COPD & Asthma

Memantine

MOA: NMDA receptor antagonist, helps prevent excitotoxicity (mediated by Ca2+) Clinical use: Alzheimer's Toxicity: dizziness, confusion, hallucinations

Tubocurarine

MOA: NONDEPOLARIZING neuromuscular blocking drug; competes w/ ACh for receptors Reversal of blockade: neostigmine, edrophonium, other cholinesterase inhibitors

Mannitol

MOA: Osmotic diuretic. Increased tubular fluid osmolarity -> increased urine flow, decreased intracranial/intraocular pressure. Clinical Use: Drug overdose, elevated intracranial/intraocular pressure. Toxicity: Pulmonary edema, dehydration. Contraindicated in anuria, HF.

Sulfonamides

MOA: PABA antimetabolites that inhibit dihydropterate synthase Clinical use: bacterioSTATIC against gram (+), gram (-), nocardia, chlamydia; triple sulfas or just sulfamethoxazole for simple UTI -Dapsone (lepromatous leprosy) closely related Toxicity: hypersensitivity, hemolysis in G6PD deficiency, nephrotoxicity, photosensitivity, kernicterus in infants, displaces other drugs from albumin (ESP WAFARIN) MOR: altered enzyme, ↓ uptake, or ↑PABA synthesis

Ketamine

MOA: PCP analog that blocks NMDA receptors; cardiovascular stimulant; dissociative anesthetic Clinical use: IV anesthetic Toxicity: disorientation, hallucinations, bad dreams

Cilostazol, dipyridamole

MOA: PDE3 inhibitor; ↑ cAMP in PLTs, thus inhibiting PLT aggregation; vasodilators Clinical use: intermittent claudication, coronary vasodilation, prevention of stroke or TIAs, angina prophylaxis Toxicity: facial flushing, hypotension, abd pain

Loop diuretics: ethnacrynic acid

MOA: Phenoxyacetic acid derivative (not a sulfonamide). Essentially same action as furosemide. Clinical Use: Diuresis in pts allergic to sulfa drugs. Toxicity: Similar to furosemide; can cause hyperuricemia; never use to treat gout.

5-fluorouracil (5-FU)

MOA: Pyrimidine analog bioactivated to 5F-dUMP -> forms complex with folic acid -> *inhibits thymidylate synthase* -> dec dTMP -> dec DNA synthesis Use: Colon cancer, pancreatic cancer, basal cell carcinoma (topial) Tox: Myelosuppression (NOT reversible with leucovorin)

Clomiphene

MOA: SERM -Antagonist at estrogen receptors in hypothalamus → prevent normal feedback inhibition and ↑release of LH and FSH from pituitary → ovulation Clinical use: infertility due to anovulation (e.g., PCOS) Toxicity: hot flashes, ovarian enlargement, *multiple simultaneous pregnancies*, visual disturbances

Tamoxifen, raloxifene

MOA: SERM - receptor *antagonists in breast* and *agonists in bone*. Block the binding of estrogen to ER+ cells. Use: Breast cancer tx (tamoxifen only) and prevention. Raloxifene used to prevent osteoporosis. Tox: Tamoxifen - partial *agonist* in endometrium -> *inc risk endometrial cancer*; hot flashes Raloxifene - *antagonist* in endometrium -> no risk of endometrial cancer

Vemurafenib

MOA: Small molecular inhibitor of *BRAF oncogene+ melanoma* Use: Metastatic melanoma

Loop diuretics: furosemide, bumetanide, torsemide

MOA: Sulfonamide loop diuretics. Inhibit cotransport system (Na+/K+/2Cl-) of thick ascending limb of loop of Henle. Abolish hypertonicity of medulla, preventing concentration of urine. Stimulate PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDs. Increase Ca2+ excretion. Clinical Use: Edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), HTN, hypercalcemia. Toxicity: Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout OH DANG!

Infliximab, adalimumab

MOA: TNF α inhibtors Clinical use: IBD, RA, ankylosing spondylitis, psoriasis

Prednisone, predinosolone

MOA: Various; bind intracytoplasmic receptor -> alter gene transcription Use: Used in CLL, non-Hodgkin lymphoma (part of combination chemotherapy regimen). Also used as immunosuppressants (e.g., in autoimmune disease) Tox: *Cushing-like sx*; weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

Misoprostol

MOA: a PGE1 analog, increases production and secretion of gastric mucous barrier, decreases acid production Clinical use: prevention of NSAID induced peptic ulcers; maintenance of patent ductus arteriosus; induction of labor Toxicity: CI in women of childbearing potential (abortifacient)

Donepezil, galantamine, rivastigmine

MOA: acetylcholinesterase inhibtors Clinical use: Alzheimer's Toxicity: nausea, dizziness, insomnia

Pyrazinamide

MOA: acidifies environment of phagolysosomes of macrophages that have engulfed TB Clinical use: TB Toxicity: hyperuricemia, hepatotoxicty

Zolpidem, zaleplon, eszopiclone

MOA: act via the BZ1 subtype of GABA receptor Clinical use: insomnia Toxicity: ataxia, headaches, confusion; cause only modest day-after psychomotor depression and few amnestic effects; lower dependence risk than benzodiazepines

Heparin

MOA: activator of antithrombin, decreases thrombin and factor Xa Clinical use: immediate anticoagulation for pulmonary embolism, acute coronary syndrome, MI, and DVT; used during pregnancy (≠ cross placenta); follow PTT to monitor Toxicity: bleeding, HIT (IgG antibodies against heparin bound to platelet factor 4 → platelets activated → thrombosis and thrombocytopenia), osteoporosis, drug-drug interactions

Testosterone, methyltestosterone

MOA: agonists at androgen receptors Clinical use: hypogonadism; development of 2° sex characteristics; stimulation of anabolism to promote recovery after burn or injury Toxicity: -Masculinization in females -↓intratesticular testosterone in males by inhibiting release of LH (via negative feedback) → gonadal atrophy -Premature closure of epiphyseal plates -↑LDL, ↓HDL

Anastrazole/exemestane

MOA: aromatase inhibitor Clinical use: postmenopausal women with ER+ breast cancer

Estrogens (ethinyl estradiol, DES, mestranol)

MOA: bind estrogen receptors Clinical use: hypogonadism or ovarian failure, menstrual abnormalities, hormone replacement -Use in men with androgen-dependent prostate CA Toxicity: ↑risk of endometrial cancer, bleeding in postmenopausal women, ↑risk of thrombi -*Clear cell adenocarcinoma of vagina in females exposed to DES in utero* -CI in ER+ breast cancer, history of DVTs

Progestins

MOA: bind progesterone receptors, ↓growth and ↑vascularization of endometrium Clinical use: oral contraceptives, endometrial cancer tx, abnormal uterine bleeding

Abcicimab, eptifibatide, tirofiban

MOA: bind the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation Clinical use: acute coronary syndrome, percutaneous transluminal coronary angioplasty Toxicity: bleeding, thrombocytopenia

Bismuth, sucralfate

MOA: bind to ulcer base, providing physical protection and allowing HCO3- secretion to reestablish pH gradient in mucous layer Clinical use: increase ulcer healing, traveler's diarrhea

Penicillin

MOA: binds PBP to block peptidoglycan cross linking Clinical use: bactericidal for gram (+) cocci/rods, gram (-) cocci (Neisseria), and spirochetes Toxicity: *hypersensitivity reactions (type II), hemolytic anemia* MOR: β-lactamase

Colchicine

MOA: binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and degranulation Clinical use: acute and prophylactic value in gout Toxicity: GI

Amphotericin B

MOA: binds ergosterol, forming pores in membrane that allow leakage of electrolytes Clinical use: serious, SYSTEMIC mycoses- cryptococcus, blastomyces, coccidioides, histoplasma, candida, mucor Toxicity: fever/chills (shake and bake), hypotension, nephrotoxicity (lessened by hydration and supplementation of K/Mg), arrhythmias, anemia, IV phlebitis

Insulin

MOA: binds insulin receptor (tyrosine kinase activity) -Liver: increase glycogen synthesis -Muscle: increase glycogen, protein synthesis; increase K+ uptake -Fat: increase TG storage Clinical use: DM type 1 and 2, gestational diabetes, life threatening hyperkalemia, stress induced hyperglycemia Toxicities: hypoglycemia

Ticarcillin, piperacillin

MOA: binds to PBP to block peptidoglycan cross linking Clinical use: extended spectrum penicillin (so already bactericidal for gram (+) cocci/rods, gram (-) cocci, and spirochetes; also covers Pseudomonas spp and gram (-) rods Toxicity: hypersensitivity reactions (type II)

Oxacillin, nafcillin, dicloxacillin

MOA: binds to PBP to block peptidoglycan cross linking; beta lactamase resistant due to bulky R group Clinical use: bactericidal, narrow spectrum- staph aureus only (except MRSA which is still resistant) Toxicity: hypersensitivity reactions (type II), interstitial nephritis

Ampicillin, amoxicillin

MOA: binds to PBP to block peptidoglycan cross linking; wider spectrum than regular penicillin Clinical use: bactericidal for gram (+) cocci/rods, gram (-) cocci, spirochetes; extended to cover H. influenza, E. Coli, L. monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci Toxicity: Type II HSR, ampicillin rash, pseudomembranous colitis MOR: β-lactamase

Propylthiouracil, methimazole

MOA: block peroxidase, inhibiting organification of iodide and coupling of thyroid hormone synthesis; propylthiouracil also blocks 5'-deiodinase so T4 can't → T3 Clinical use: hyperthyroidism Toxicity: agranulocytosis, aplastic anemia, hepatotoxicity (propylthiouracil) -**Methimazole is a possible teratogen (aplasia cutis)

Topiramate

MOA: blocks Na+ channels, ↑ GABA action Clinical use: simple/complex partial seizures, tonic-clonic seizures -Also used for migraine prevention Side effects: kidney stones, weight loss

Chloroquine

MOA: blocks detoxification of heme into hemozoin, accumulated heme is toxic to plasmodia Clinical use: plasmodial species other than falciparum (too much resistance) Toxicity: retinopathy

Ethosuximide

MOA: blocks thalamic T-type Ca2+ channels Clinical use: 1st line drug for absence seizures Toxicity: EthosuximideFGHIJ (Fatigue, GI distress, Headache, Itchiness, stevens-Johnson syndrome)

Lamotrigine

MOA: blocks voltage gates Na+ channels Clinical use: simple/complex partial seizures, tonic-clonic seizures Toxicity: stevens-johnson syndrome

Cyclosporine

MOA: calcineurin inhibitor; binds *cyclophilin*. Blocks T cell activation by preventing IL-2 transcription. Clinical use: transplant rejection prophylaxis, psoriasis, rheumatoid arthritis. Toxicity: *nephrotoxicity*, hypertension, hyperlipidemia, hyperglycemia, tremor, hirsutism, gingival hyperplasia.

Sulfasalazine

MOA: combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid; activated by colonic bacteria Clinical use: ulcerative colitic, Crohn's disease Toxicity: sulfonamide toxicity, reversible oligospermia

Flumazenil

MOA: competitive antagonist at GABA benzodiazepine receptor Clinical use: reversal of benzodiazepine and zolpidem/zaleplon/eszopiclone (nonbenzodiazepine hypnotics)

Flutamide, cyproterone

MOA: competitive inhibitor androgen receptors Clinical use: prostate CA

Mifepristone (RU-486)

MOA: competitive inhibitor of progestins at progesterone receptors Clinical use: termination of pregnancy -Administered with *misoprostol (PGE1)* → cervical ripening and uterine contractions

Ribavirin

MOA: competitively inhibits IMP dehydrogenase to stop synthesis of guanine nucleotides (IMP → GMP) Clinical use: RSV (palivizumab preferred in children), chronic hep C Toxicity: hemolytic anemia, SEVERE TERATOGEN

Lepirudin, bivalirudin, argatroban, dabigatran

MOA: derivatives of hirudin, the anticoagulant used by leeches- inhibits thrombin Clinical use: alternative for heparin in patients w/ HIT

Apixaban, rivaroxaban

MOA: direct factor Xa inhibitors Clinical use: treatment and prophylaxis for DVT and PE (rivaroxaban); stroke prophylaxis in patients with a-fib Toxicity: bleeding (no reversal agent)

Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)

MOA: directly or indirectly aid conversion of plasminogen → plasmin, which cleaves thrombin and fibrin clots; ↑ PT and PTT, no changes in platelet count Clinical use: early MI, early ischemic stroke, direct thombolysis of severe pulmonary embolism Toxicty: bleeding (CI in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe HTN)

Bromocriptine, pramipexole, ropinirole

MOA: dopamine agonists Clinical use: Parkinson's disease (when they still have endogenous DA)

Ivermectin

MOA: enhances inhibitory neurotransmission by opening glutamate gated chloride channels Clinical use: primarily for Onchocerca volvulus (IVERmectin for rIVER blindness), also strongyloides

Phenobarbital, pentobarbital, thiopental, secobarbital

MOA: facilitate GABA(A) action by ↑ DURATION of Cl- channel opening, thus ↓ neuron firing (barbiDURATes ↑ DURATion of opening) Clinical use: sedative for anxiety, insomnia -thiopental for IV induction of anesthesia (high lipid solubility so action is rapidly terminated by redistribution into tissue) Toxicity: contraindicated in porphyria patients; respiratory/cardiovascular/CNS depression, induces P450s -overdose treatment is supportive

Metronidazole

MOA: forms free radicals in bacterial (and protozoal) cells causing DNA damage Clinical use: Giardia, Entamoeba, Trichomonas, Garderella vaginalis, Anaerobes below diaphragm ("GET GAP on the Metro with metronidazole!) Toxicity: disulfiram reaction with alcohol

Ganciclovir, valganciclovir

MOA: guanosine analog, preferentially inhibits viral DNA poly bc phosphorylation by CMV viral kinase required for activity; CHAIN TERMINATOR Clinical use: CMV, especially in immunocompromised -Valganciclovir (prodrug) has better oral availability Toxicity: leukopenia/neutropenia/thrombocytopenia, renal toxicity MOR: mutated viral thymidine kinase

Acyclovir, famciclovir, valacyclovir

MOA: guanosine analog, preferentially inhibits viral DNA poly bc phosphorylation by viral thymidine kinase required for activity; CHAIN TERMINATOR Clinical use: HSV and VZV; no activity against CMV and no effect on latent forms of HSV/VZV -Valacyclovir (prodrug) has better oral availability -Use famcicylovir for herpes zoster MOR: mutated viral thymidine kinase

Imipenem/cilastatin, meropenem, ertapenem, doripenem

MOA: imipenem = *beta lactamase resistant* carbapenem that blocks peptidoglycan cross linking, always administered with cliastatin (inhibits renal dehydropeptidase I to slow inactivation of imipenem) Clinical use: bactericidal for LIFE THREATENING INFECTIONS due to gram (+) cocci, gram (-) rods, and anerobes when other meds have failed (limits due to seizure potential) Toxicity: CNS toxicity (seizures) at high plasma levels

Pioglitazone, Rosiglitazone

MOA: increase insulin sensitivity in peripheral tissue, binds to PPAR-γ nuclear transcription regulator Clinical use: used as a monotherapy in type 2 DM or in combo w/ other diabetes drugs Toxicity: weight gain, edema, hepatotoxicity, heart failure, ↑risk of fractures

Levodopa/carbidopa

MOA: increase level of DA in the brain; L-dopa can cross the BBB (unlike regular DA) and is converted by dopa darboxylase in the CNS → DA -Carbidopa = blocks peripheral conversion of L-dopa to dopamine by inhibiting DOPA decarboxylase, given w/ L-dopa to ↑ bioavailability of L-dopa in brain/limit peripheral side effects Clinical use: Parkinson's disease Toxicity: arrhythmias from increased peripheral formation of catecholamines; long term use may → dyskinesia following administration w/ akinesia between doses ("on-off" phenomenon)

Praziquantel

MOA: increased cell permeability to calcium, thereby causing contraction/paralysis and allows destruction by immune system Clinical use: tapeworms and flukes

Adenosine

MOA: increases K+ out of cells → hyperpolarization of the cell and decreased INTRACELLULAR Ca2+ (only lasts about 15 sec) Clinical use: DOC in diagnosing/abolishing SVT Toxicity: flushing, hypotension, chest pain -effects blocked by theophylline and caffeine

Phenytoin

MOA: increases Na+ channel inactivation Clinical use: 1st line drug for generalized tonic-clonic seizures -1st line drug for prophylaxis of status epilepticus -may also be used for simple or complex partial seizures Toxicity: nystagmus, ataxia, diplopia, SLE like syndrome, induction of P450s; chronic use --> gingival hyperplasia in kids, peripheral neuropathy, megaloblastic anemia (↓ folate absorption), teratogenic

Carbamazepine

MOA: increases Na+ channel inactivation Clinical use: 1st line drug for simple/complex partial seizures and tonic-clonic seizures -also 1st line drug for trigeminal neuralgia Toxicity: diplopia, ataxia, agranulocytosis, hepatotoxicity, teratogen, induction of P450, SIADH, steven-johnson syndrome

Halothane

MOA: inhaled anesthetic Effects: myocardial/respiratory depression, nausea/emesis, ↑ cerebral blood flow (↓ cerebral metabolic demand) Toxicity: **hepatotoxicity**, malignant hyperthermia

Methoxyflurane

MOA: inhaled anesthetic Effects: myocardial/respiratory depression, nausea/emesis, ↑ cerebral blood flow (↓ cerebral metabolic demand) Toxicity: **nephrotoxicity**, malignant hyperthermia

Enflurane

MOA: inhaled anesthetic Effects: myocardial/respiratory depression, nausea/emesis, ↑ cerebral blood flow (↓ cerebral metabolic demand) Toxicity: **proconvulsant**, malignant hyperthermia

Nitrous oxide

MOA: inhaled anesthetics Effects: myocardial/respiratory depression, nausea/emesis, ↑ cerebral blood flow (↓ cerebral metabolic demand) Toxicity: expansion of trapped gas in a body cavity (no malignant hyperthermia like other inhaled anesthetics)

Isoflurane, sevoflurane

MOA: inhaled anesthetics Effects: myocardial/respiratory depression, nausea/emesis, ↑ cerebral blood flow (↓ cerebral metabolic demand) Toxicity: malignant hyperthermia

Lovastatin, pravastatin (not metabolized by CYP450), simvastatin, atorvastatin, rosuvastatin

MOA: inhibit conversion of HMG-CoA to mevalonate (HMG-CoA reductase = rate limiting step in cholesterol synthesis); ↓ mortality in CAD patients Clinical use: ↓↓↓ LDL -↑ HDL -↓ TG Toxicity: hepatotoxicity (↑LFTs), rhabdomyolysis (esp when used with fibrates or niacin) -↑ toxicity with CYP450 inhibitors

Clopidogrel, ticlopidine, prasugrel, ticagrelor

MOA: inhibit platelet aggregation by IRREVERSIBLY blocking ADP receptors → prevent expression of gp IIb/IIIa on platelet surface Clinical use: acute coronary syndrome, coronary stenting, reduction of incidence or recurrence of thombotic stroke Toxicity: ticlopidine causes neutropenia

Probenecid

MOA: inhibition of uric acid reabsorption in proximal collecting tubule, also inhibits secretion of penicillin Clinical use: chronic gout, syphilis Toxicity: uric acid calculi

Diethylcarbamazine

MOA: inhibitor of arachidonic acid metabolism in filarial microfilaria Clinical use: Loa loa, Wuchereria bancrofti (elephantiasis)

Aminocaproic acid

MOA: inhibitor of fibrinolysis Clinical use: treatment of tPA toxicity

Rifampin

MOA: inhibits DNA dependent RNA poly Clinical use: TB, in combo w/ dapsone for leprosy, prophylaxis against neisseria meningitis in kids Toxicity: "Rifamin 4 R's" -RNA polymerase inhibitor, Ramps up CYP450, Red/orange body fluids, Rapid resistance used alone MOR: mutations of RNA poly

Flucytosine

MOA: inhibits DNA/RNA biosynthesis by conversion to 5-FU by cytosine deaminase Clinical use: systemic fungal infections-- especially cryptococcal MENINGITIS in combo w/ ampho B Toxicity: bone marrow suppression (duh... it's 5-FU)

Tiagabine

MOA: inhibits GABA uptake Clinical use: simple/complex partial seizures

Abciximab

MOA: inhibits Gp IIb/IIIa Clinical use: anti platelet for prevention of ischemic complications in pts undergoing PCI

Sofosbuvir

MOA: inhibits HCV RNA-dependent RNA polymerase acting as a chain termiantor Clinical use: chronic HCV in combination with ribavirin,+/- peginteferon alfa -Do not use as mono therapy Toxicity: fatigue, headache, nausea

Trimethoprim

MOA: inhibits bacterial dihydrofolate reductase Clinical use: bacterioSTATIC use in combination w/ SMX for UTIs, Shigella, Salmonella, Pneumocystitis jirovceii pneumonia tx and prophylaxis, toxoplasmosis prophylaxis Toxicity: megaloblastic anemia/leukopenia/granulocytopenia (may be less w/ leucovorin rescue)

Ethambutol

MOA: inhibits carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase Clinical use: TB Toxicity: red-green colorblindness/optic neuritis (CI in kids <6yo) "Eyethambutol"

Vancomycin

MOA: inhibits cell wall peptidoglycan SYNTHESIS by binding D-ala D-ala portion of precursors Clinical use: bactericidal for gram (+)s only, reserve for serious/multidrug resistant orgs such as MRSA, enterococci (NOT VRE) and C diff Toxicity: diffuse flushing/"red man syndrome" when infused too quickly (can prevent with antihistamines and slow infusion rate); nephrotoxicity/ototoxicity/thrombophlebitis ("NOT trouble free")

Caspofungin, micafungin

MOA: inhibits cell wall synthesis by inhibiting synthesis of B-glucan Clinical use: invasive aspergillosis, candida Toxicity: flushing due to histamine release

Terbinafine

MOA: inhibits fungal squalene epoxidase → inhibit production of lanosterol Clinical use: dermatophytoses (esp onchomycosis) Toxicity: abnormal LFTs, visual disturbances

Orlistat

MOA: inhibits gastric and pancreatic lipase → ↓breakdown and absorption of dietary fats Clinical use: weight loss Toxicity: steatorrhea, ↓absorption of fat-soluble vitamins

Zanamivir, oseltamivir

MOA: inhibits influenza neuraminidase (decreasing release of new viruses) Clinical use: treatment and prevention of influenza A AND B

Niacin (B3)

MOA: inhibits lipolysis in adipose tissue; reduces hepatic VLDL synthesis Clinical use: ↓↓ LDL -↑↑ HDL cholesterol (most of all options) -↓ TG Toxicity: red/flushed face (↓ by aspirin or long term use since mediated by prostaglandns), hyperglycemia (→acanthosis nigricans), hyperuricemia (exacerbates gout)

Sirolimus (rapamycin)

MOA: inhibits mTOR to inhibit T cell PROLIFERATION in response to IL-2 Clinical use: kidney transplant rejection prophylaxis -Also used in drug eluting stents Toxicity: anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia; *non-nephrotoxic*

Spironolactone

MOA: inhibits steroid binding, 17α-hydroxylase, and 17, 20-desmolase Clinical use: reduce androgenic symptoms in PCOS Toxicity: gynecomastia, amenorrhea

Ketoconazole

MOA: inhibits steroid synthesis (inhibits 17,20-desmolase) Clinical use: reduce androgenic symptoms in PCOS Toxicity: gynecomastia, amenorrhea

Isoniazid

MOA: inhibits synthesis of mycolic acids (only bacterial have the catalase needed to activate it) Clinical use: TB (only one that can be used as solo prophylaxis) -Different INH half-lives in fast vs. slow acetylators Toxicity: INH Injures Neurons and Hepatocytes; also causes B6 deficiency MOR: underexpression of KatG catalase

Cidofovir

MOA: inhibits viral DNA poly, does not require viral kinase activation Clinical use: CMV retinitis in immunocompromised patients, acyclovir reistant HSV Toxicity: nephrotoxicity-- coadminister w/ probenecid and IV saline to reduce

Foscarnet

MOA: inhibits viral DNA/RNA polymerase by binding to PPi binding site of enzyme, no viral kinase activation required; CHAIN TERMINATOR Clinical use: CMV retinitis when ganciclovir fails, acyclovir resistant HSV Toxicity: nephrotoxicity, seizures due to electrolyte abnormalities MOR: mutated DNA polymerase

Griseofulvin

MOA: interferes w/ microtubule function --> disruption of mitosis Clinical use: oral treatment of superficial infections, inhibits growth of dermatophytes (deposits in keratin containing tissues) Toxicity: teratogenic, carcinogenic, confusion/HA, induces P450 and warfarin metabolism

Warfarin

MOA: interferes w/ normal synthesis and γ-carboxylation of vitamin K dependent clotting factors II, VII, IX and X and proteins C and S; monitor PT Clinical use: chronic anticoagulation (after STEMI, venous thromboembolism prophylaxis, and prevention of stroke in a fib); NOT used in pregnant women bc crosses the placenta Toxicity: bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions (metabolized by P450s)

Daptomycin

MOA: lipopetide that disrupts cell membrane of gram (+) cocci Clinical use: skin infections (esp MRSA), VRE, bacteremia, endocarditis **Not used for pneumonia b/c inactivated by surfactant Toxicity: myopathy, rhabdomylosis (↑CPK)

Ocreotide

MOA: long acting somatostatin analog Clinical use: acromegaly, carcinoid, gastrinoma, glucagonoma, acute variceal bleeds Toxicity: steatorrhea

Amantadine

MOA: may increase dopamine release Clinical use: Parkinson's disease; also used as an antiviral against influenza A and rubella Toxicity: ataxia, livedo reticularis

Aztreonam

MOA: monobactam that is resistant to beta lactamases!!!! prevents peptidoglycan cross linking by binding to PBP3 Clinical use: bactericidal for gram (-) RODS only, no activity against gram (+)s or anaerobes; good for pts w/ penicillin allergies or renal insufficiency that can't tolerate aminoglycosides Toxicity: no cross reactivity w/ penicillins

Daclizumab, basiliximab

MOA: monoclonal antibodies; block IL-2R Clinical use: kidney transplant rejection prophylaxis Toxicity: edema, HTN, tremor

Muromonab-CD3 (OKT3)

MOA: monoclonal antibody that binds to CD3 on surface of T cells, blocks T cell signal transduction Clinical use: prevents ACUTE rejection of kidney transplantation Toxicity: mouse antibody, so use is limited till when the patient develops antibodies to the antibody

Butorphanol

MOA: mu-opioid receptor PARTIAL agonist and kappa-opioid receptor agonist; produces analgesia Clinical use: severe pain (migraine, labor); causes less respiratory depression that full opioid agonists Toxicity: can cause opioid withdrawal sx if pt is also taking a full opioid agonist (competition for receptors); overdose not easily reversed w/ naloxone

Pyrantel pamoate

MOA: neuromuscular depolarizing agent, causes contraction then paralysis in helminths (loose grip on wall of intestine and pass in stool naturally) Clinical use: pinworms, ascaris, hookworms (ancylostoma and necator)

Febuoxstat

MOA: non-purine analog allosteric inhibitor of xanthine oxidase Clinical use: chronic gout, lymphoma/leukemia to prevent tumor lysis syndrome Toxicity: increases concentration of azathioprine and 6-MP (metabolized by XO)

Lithium

MOA: not established Clinical use: mood stabilizer for bipolar; SIADH Toxicity: LMNOP (Lithium, Movement, Nephrogenic DI, hypOthyroidism, Pregnancy problems) -Ebstein abnormality if taken during pregnancy -Thiazide use implicated in lithium toxicity -**Narrow therapeutic window

Dextromethorphan

MOA: opioid receptor agonist Clinical use: cough suppression

Methadone

MOA: opioid receptor agonist Clinical use: maintenance programs for opiate addicts

Diphenoxylate, loperamide

MOA: opioid receptor agonists → ↓ GI motility Clinical use: diarrhea

Propofol

MOA: potentiates GABA(A) Clinical use: sedation in the ICU, rapid anesthesia induction, short procedures; less postoperative nausea than thiopental

Azathioprine

MOA: precursor of 6-MP; inhibits lymphocyte proliferation by blocking NT synthesis Clinical use: transplant rejection prophylaxis, RA, Crohn disease, glomerulonpehritis Toxicity: BM suppression; 6-MP degraded by xanthine oxidase so toxicity ↑ by allopurinol

Ezetimibe

MOA: prevents cholesterol reabsorption at small intestine brush border Clinical use: ↓↓ LDL cholesterol -No effect on HDL or TG Toxicity: rare ↑ LFTs, diarrhea

Dantrolene

MOA: prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle Clinical use: treatment of malignant hyperthermia and neuroleptic malignant syndrome

Gabapentin

MOA: primarily inhibits VGCC Clinical use: simple/complex partial seizures -also used for peripheral neuropathy, postherpetic neuralgia Toxicity: sedation, ataxia

Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose

MOA: provide osmotic load to draw water out Clinical use: constipation; lactulose also treats hepatic encephalopathy since gut flora degrade it into lactic acid and acetic acid, which promote nitrogen excretion at NH4+ Toxicity: diarrhea/dehydration

Allopurinol

MOA: purine analog, competitively inhibits xanthine oxidase (↓ conversion of xanthine to uric acid) Clinical use: chronic gout; lymphoma/leukemia to prevent tumor lysis syndrome related nephropathy Toxicity: increases the concentration of azathioprine and 6-MP (both normally metabolized by xanthine oxidase)

Teriparatide

MOA: recombinant PTH analog given subQ, ↑ osteoblastic activity Clinical use: osteoporosis, causes ↑ bone growth compared to antiresorptive therapies (e.g., bisphosphonates) Toxicity: transient hypercalcemia

Pegloticase

MOA: recombinant uricase that catalyzes metabolism of uric acid to allantoin (more water-soluble) Clinical use: chronic gout

Ibuprofen, naproxen, indomethacin, diclofenac, ketorolac

MOA: reversibly inhibit COX1 and COX2, blocks prostaglandin synthesis Clinical use: antipyretic, analgesic, anti-inflammatory; indomethacin used to close a PDA Toxicity: interstitial nephritis, gastric ulcer (PGs protect gastric mucosa), renal ischemia (PGs vasodilate afferent arteriole)

Acetaminophen

MOA: reversibly inhibits cyclooxygenase, most in CNS (inactivated peripherally) Clinical use: antipyretic and analgesic, but NOT ANTI-INFLAMMATORY Toxicity: overdose → hepatic necrosis (NAC is the antidote, regenerates glutathione)

Nystatin

MOA: same as Ampho B, but topical only bc too toxic for systemic use Clinical use: "swish and swallow" for oral candidiasis, topical for diaper rash or vaginal candidiasis

Mebendazole, albendazole

MOA: selective inhibition of parasitic microtubules, thereby blocking the uptake of glucose and other nutrients, resulting in the gradual immobilization and eventual death of the helminths Clinical use: roundworms (pinworms, ascaris lumbricoides, strongyloides stercoralis, toxocara canis/visceral larva migrans), hookworms (ancylostoma duodenale and necator americanus), some tapeworms (neurocysticercosis from injection of taenia solium eggs, echinococcus from dog feces) Toxicity: CI in pregnancy

Selegiline

MOA: selective inhibitor ofMAO-B (which preferentially metabolizes DA over NE and 5-HT), thereby ↑ availability of DA Clinical use: adjunctive agent to L-dopa in treatment of PD Toxicity: may enhance adverse effects of l-dopa

Celecoxib

MOA: selective reversible inhibitor of COX2 (found in inflammatory cells/vascular endothelium), but spares COX1 to help maintain gastric mucosa and has no effect on platelet function (TXA2 production is via COX1) Clinical use: RA and osteoarthritis, patients w/ gastritis or ulcers Toxicity: ↑ risk of thrombosis, sulfa allergy

Cinalcet

MOA: sensitizes Ca2+ sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ → ↓ PTH Clinical use: hypercalcemia due to 1° or 2° hyperparathyroidism Toxicity: hypocalcemia

Triazolam, oxazepam, midazolam

MOA: short acting benzodiazepines, facilitate GABA(A) action by ↑ FREQUENCY of Cl- channel opening, ↓ REM sleep Clinical use: anxiety, spasticity, detoxification (esp from alcohol withdrawal/DT), night terrors, sleepwalking, general anesthetic, insomnia (hypnotic effect) -** midazolam most common IV anesthetic used for endoscopy** Toxicity: higher additive dependence due to short half life, additive CNS depression w/ alcohol, less risk of respiratory depression and coma than w/ barbiturates

Nitroprusside

MOA: short acting ↑cGMP via direct release of NO Clinical use: hypertensive emergency Toxicity: can cause cyanide toxicity (releases cyanide) -Tx: sodium thiosulfate

Buspirone

MOA: stimulates 5-HT1A receptors Clinical use: generalized anxiety -1-2 weeks to see effect Toxicity: does not cause sedation, addiction, or tolerance -Does not interact with alcohol (vs. barbiturates, benzos)

Danazol

MOA: synthetic androgen that acts as a partial agonist at androgen receptors Clinical use: endometriosis, hereditary angioedema Toxicity: weight gain, edema, acne, hirsutism, masculinization, ↓HDL, hepatoxicity

Rituximab

MOA: targets CD20 Clinical use: B cell non-Hodgkin's lymphoma, CLL, RA, ITP

Aleumtuzumab

MOA: targets CD52 Clinical use: CLL ("Alymtuzumab")

Cetuximab

MOA: targets EGFR Clinical use: stage IV colorectal cancer, head and neck cancer

Omalizumab

MOA: targets IgE Clinical use: additional treatment for severe asthma

Denosumab

MOA: targets RANKL Clinical use: osteoporosis (inhibits osteoclast maturation)

Palivizumab

MOA: targets RSV F protein Clinical use: RSV prophylaxis for high-risk infants

Bevacizumab

MOA: targets VEGF Clinical use: colorectal cancer, renal cell carcinoma

Ranibizumab, bevacizumab

MOA: targets VEGF Clinical use: neovascular age-related macular degeneration

Eculizumab

MOA: targets complement protein C5 Clinical use: paroxysmal nocturnal hemoglinuria

Digoxin immune Fab

MOA: targets digoxin Clinical use: antidote for digoxin toxicity

Natalizumab

MOA: targets α4-integrin Clinical use: MS, Crohn disease

Levothyroxine, triiodothyronine

MOA: thyroxine replacement Clinical use: hypothyroidism, myxedema Toxicity: tachycardia, heat intolerance, tremors, arrythmias

Gemfibrozil, clofibrate, bezafibrate, fenofibrate

MOA: upregulate LPL to ↑ TG clearance; activates PPAR-α to induce HDL synthesis Clinical use: ↓ LDL cholesterol -↑ HDL -↓↓↓ TG (most of all the options) Toxicity: myopathy (↑ risk with statins), hepatotoxicity (↑ LFTs), cholesterol gallstones

Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate (almost 100% oral availability)

MOA: vasodilate by releasing NO in smooth muscle, causing increase in cGMP and smooth muscle relaxation; dilates veins >> arteries (so ↓ preload) Clinical use: angina, acute coronary syndrome, pulmonary edema Toxicity: reflex tachycardia, hypotension, flushing, headache, "Monday disease" -**Use with PDE inhibitors (e.g., sildenafil) CI due to risk of SEVERE HYPOTENSION

Tramadol

MOA: very weak opioid agonist, also inhibits 5-HT and NE reuptake (works on multiple NT-- "tram it all" with tramadol) Clinical use: chronic pain Toxicity: decreases seizure threshold, serotonin syndrome

Gentamicin, neomycin, amikacin, tobramycin, streptomycin, spectinomycin

MOA: work at the 30S ribosomal subunit to inhibit formation of the initiation complex and cause misreading of the mRNA Clinical use: bactericidal for serious gram (-) RODS; neomycin for bowel surgery Toxicity: nephrotoxicity, neuromuscular blockade, ototoxocity, teratogenic

Tetracycline, minocycline, doxycycline

MOA: work at the 30S ribosomal subunit to prevent attachment of charged tRNA to the A site Clinical use: bacterioSTATIC against Borrelia burgdorferi, Mycoplasma pneumoniae, Rickettsia/Chlamydia (since drug accumulates intracellularly); **Do not take with milk, antiacids, or iron bc divalent cations inhibit absorption** Toxicity: discoloration of teeth and inhibition of bone growth in kids, photosensitivity, CI in pregnancy *doxycycline is fecally eliminated and can be given to ppl w/ renal impairment* MOR: bacterial transferase enzymes

Chloramphenicol

MOA: works at 50S ribosomal subunit to block the action of peptidyltransferase Clinical use: bacterioSTATIC against meningitis (H. influenzae, N. meningitidis, S. pneumo) and Rocky Mountain spotted fever (Rickettsia rickettsii) Toxicity: anemia, aplastic anemia (dose independent), gray baby syndrome (in premies bc they lack liver UDP-glucuronyl transferase) MOR: plasmid-encoded acetyltransferase

Clindamycin

MOA: works at 50S ribosomal subunit to block translocation Clinical use: bacterioSTATIC against anaerobic infections above the diaphragm -Aspiration pneumonia, lung abscess, oral infxns Toxicity: C. diff colitis

Terbutaline, ritodrine (tocolytics)

MOA: β2 agonists that relax the uterus Clinical use: ↓contraction frequency in women during labor; prevent preterm labor

Diazepam/Lorazepam

MOA: ↑ GABA action by increasing the FREQUENCY of Cl- channel opening Clinical use: 1st line for acute status epilepticus, also used for seizures of eclampsia (1st line is MgSO4) Toxicity: dependence

Phenobarbital

MOA: ↑ GABA(A) action Clinical use: simple/complex partial seizures, tonic-clonic seizures **1st line in children** Toxicity: induction of p450

Valproic acid

MOA: ↑ Na+ channel inactivation, ↑ GABA concentration Clinical use: *absence seizueres!* -1st line drug for tonic-clonic seizures -also used for simple/complex partial seizures, myoclonic seizures Toxicity: rare but fatal hepatotoxicity, neural tube defects in fetus (CI in pregnancy), tremor, weight gain

Hydralazine

MOA: ↑cGMP → smooth muscle relaxation; vasodilates aterioles > veins (∴ afterload reduction) Clinical use: severe HTN, CHF. 1st line therapy for HTN in pregnancy (w/ methyldopa) Toxicity: compensatory tachycardia (often coadministered w/ a β blocker to prevent this; thus CI in patients w/ angina or CAD), fluid retention, angina, lupus-like syndrome

Myelosuppression reversible with leucovorin Drug?

MTX

MOA: Decrease thymidine synthesis Drugs?

MTX 5-FU

Osmotic laxatives: Names

Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose.

Sulfasalazine: Toxicity

Malaise, nausea, sulfonamide toxicity, reversible oligospermia.

Testosterone, Methyltestosterone-- Toxicity

Masculinization in females Decrease intratesticular testosterone by inhibiting release of LH (feedback)--> gonadal atrophy Premature closure of epiphyseal plates Increases LDL, lowers HDL

What are the Adverse Effects of Selegiline, Rasagiline?

May enhance adverse effects of L-Dopa

Hydroxyurea, Clinical Use

Melanoma CML Sickle cell disease (incr. HbF).

What is the Mechanism for Ramelteon?

Melatonin receptor agonist Binds to MT1 and MT2 in suprachiasmatic nucleus

Give _____ to avoid hemorrhage cystitis with cyclophosphamide.

Mesna (binds toxic metabolites)

MOA of glucocorticoids

Metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interactions with glucocorticoid response elements, inhibition of phospholipase A2, and inhibition of transcription factors such as NF-kB

Vemurafenib, Clinical Use

Metastatic melanoma

Name the preferred drugs for the following psychiatric condition: ADHD

Methylphenidate

Name 4 drugs that are CNS stimulants.

Methylphenidate, dextroamphetamine, methamphetamine, phentermine

Antibiotics that damage DNA

Metronidazole

What is Topiramate also used for?

Migraine Prevention

Risk/Concern for DPP-4 inhibitors

Mild urinary or respiratory infections; weight neutral

Clinical use of fludrocortisone

Mineralocorticoid replacement in primary adrenal insufficiency

What is Minimal Alveolar Concentration (MAC) of Inhaled Anesthetics?

Minimal Alveolar Concentration (of inhaled anesthetic) required to prevent 50% of subjects from moving in response to noxious stimulus (i.e. skin incision)

What are the Benefits of Riluzole?

Modestly ↑ survival by ↓ glutamate excitotoxicity via an unclear mechanism For *Lou* Gehrig Disease give ri*lou*zole

Omalizumab

Monoclonal Anti-IgE Antibody MOA: Binds unbound serum IgE and blocks binding to FcεRI. Used in allergic asthma resistant to inhaled steroids and B2-agonists

Rituximab, Mechanism

Monoclonal antibody against CD20, which is found on most B-cell neoplasms.

Trastuzumab (Herceptin), Mechanism

Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. Helps kill cancer cells that overexpress HER-2, through inhibition of HER2-initiated cellular signaling and antibody- dependent cytotoxicity.

Bevacizumab, Mechanism

Monoclonal antibody against VEGF. Inhibits angiogenesis.

Infliximab: MOA

Monoclonal antibody to TNF-alpha

Prednisone, prednisolone, Clinical Use

Most commonly used glucocorticoids in cancer chemotherapy. CLL Non-Hodgkin lymphoma (part of combination chemotherapy regimen). Immunosuppressants (e.g., in autoimmune diseases)

N-Acetylcysteine

Mucolytic - Loosen mucous plugs in CF by disrupting disulfide bonds. Also used as antidote for acetominophen overdose

Bortezomib, carfilzomib, Clinical Use

Multiple myeloma Mantle cell lymphoma

Besides blocking dopamine D2 receptors, antipsychotics block ___ receptors resulting in dry mouth and constipation, ___ receptors resulting in hypotension, and ___ receptors resulting in sedation.

Muscarinic Alpha1 Histamine

Atropine

Muscarinic antagonist. Used to treat bradycardia and for ophthalmic applications. Organ system effects: -Blocks DUMBBeLSS (skeletal muscle and CNS excitation mediated by nicotinic receptors) -Eye (↑pupil dilation, cycloplegia), airway (↓secretions), stomach (↓acid secretion), gut (↓motility), bladder (↓urgency in cystitis) Toxicity: ↑body temp; rapid pulse; dry mouth; dry, flushed skin; cycloplegia; constipation; disorientation; urinary retention -*Can cause acute angle-closure glaucoma in elderly (due to mydriasis)*

Scopolamine

Muscarinic antagonists Organ system: CNS Clinical use: motion sickness

Hyoscyamine, dicyclomine

Muscarinic antagonists Organ system: GI Clinical use: antispasmodics for irritable bowel syndrome

Glycopyrrolate

Muscarinic antagonists Organ system: GI, respiratory Clinical use: -Parenteral: prep use to reduce airway secretions -Oral: drooling, peptic ulcer

Oxybutynin, solifenacin, tolterodine

Muscarinic antagonists Organ system: GU Clinical use: overactive bladder... "O" for overactive bladder

Benzotropine

Muscarinic antagonists Organ systems: CNS Clinical use: Parkinson, acute dystonia "park my Benz"

Atropine, homatropine, tropicamide

Muscarinic antagonists Organ systems: eye Clinical use: mydriasis (dilation) and cycloplegia (lack of accomodation - cannot do NEAR vision)

What is the Clinical Indication of Neuromuscular Blocking Drugs?

Muscle paralysis in surgery or mechanical ventilation

What is the Clinical Use of Cyclobenzaprine?

Muscle spasms

What is the Adverse Effect of α-agonists: Epinephrine (α1)?

Mydriasis (α1)

Dactinomycin (actinomycin D), Toxicity

Myelosuppression

Paclitaxel, other taxols, Toxicity

Myelosuppression Alopecia Hypersensitivity

Azathioprine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), Toxicity

Myelosuppression GI liver Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have incr. toxicity with allopurinol or febuxostat.

Etoposide, teniposide, Toxicity

Myelosuppression GI upset Alopecia

Cyclophosphamide, ifosfamide, Toxicity

Myelosuppression Hemorrhagic cystitis, partially prevented with mesna (thiol group of mesna binds toxic metabolites).

Cladribine (2-CDA), Toxicity

Myelosuppression Nephrotoxicity Neurotoxicity

5-fluorouracil (5-FU), Toxicity

Myelosuppression, which is not reversible with leucovorin (folinic acid).

Methotrexate (MTX), Toxicity

Myelosuppression, which is reversible with leucovorin "rescue." Hepatotoxicity Mucositis (e.g., mouth ulcers) Pulmonary fibrosis.

Fibrates: SE

Myositis (risk with concurrent statins) hepatotoxicity (increased LFTs), **cholesterol gallstones (esp. with concurrent bile acid resins)

What are the Mechanism and Adverse Effects of Memantine?

NMDA receptor antagonist - helps prevent excitotoxicity mediated by Ca2+ AE: dizziness, confusion, hallucinations

What is important caution for treating acute decompensated CHF?

NO BETA BLOCKERS FOR ACUTE DECOMPENSATED CHF-- Lower BP

NO Example of MAC

NO ↓ blood and lipid solubility → Fast induction & low potency

Confusion and hallucination in elderly are due to the anticholinergic SE of TCAs. What drug would you use instead?

NORTRIPTYLINE (because it has less anticholinergic effect)

Insulin, intermediate acting

NPH

example of intermediate acting insulin

NPH

Aspirin mech

NSAID that irreversibly inhibits cyclooxygenase (both COX1 and COX2) by covalent acetylation decreased synthesis of TXA2 and prostaglandins increased bleeding time No effect on PT, PTT effect lasts until new platelets are prodouced

acute gout drugs

NSAIDs glucocorticoids colchicine tnf alpha inhibitors

Antiarrhythmics-- Class I (Inhibits...)

Na++ channel blocker. Slow or block conduction (especially in depolarized cells). Decrease slope of phase 0 depolarization and increase threshold for firing in abnormal pacemaker cells. State dependent (selectively depress tissue that is frequently depolarized [e.g., tachycardia]). Hyperkalemia causes toxicity for all class I drugs.

How do you treat the cardiovascular toxicity caused by TCAs?

NaHCO3

What do you give for dextromethorphan overdose?

Naloxone

How is Opioid Analgesic Toxicity Treated?

Naloxone (opioid receptor antagonist), acute Relapse prevention w/ naltrexone once detoxified, chronic = *t*ime = nal*t*rexone

Octreotide: Toxicity

Nausea, cramps, steatorrhea.

Risks/concerns for GLP-1 analog

Nausea, vomiting, pancreatitis, modest weight loss

How is a Non-depolarizing Neuromuscular Blocking Drug Blockade Reversed?

Neostigmine Edrophonium Other AChE inhibitors

Cisplatin, carboplatin, Toxicity

Nephrotoxicity Ototoxicity Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis.

___ is a side effect of antipsychotics with signs of rigidity, myoglobinuria, autonomic instability, and hyperpyrexia

Neuroleptic malignant syndrome (NMS)

NNRTIs

Nevirapine, efavirenz, delavirdine MOA: allosterically inhibit HIV reverse transcriptase; do not require phosphyrlation Toxicity: rash, hepatotoxicity -Efavirenz: vivid dreams and CNS symptoms -Delavirdine and efavirenz CI in pregnancy

Calcium channel blocker: Hypertensive emergency

Nicardipin Clevidipine (fast onset, short duration)

Calcium channel blocker: Which one to use for subarachnoid hemorrhage?

Nimodipine (prevents cerebral vasospasm).

Nitrates plus β blockers, effects on: EDV, BP, Contractility, HR, ejection time, MVO2

Nitrates affect preload (dilate veins >> arteries) -EDV: no effect or ↓ -BP: ↓ -Contractility: little/no effect -HR: no effect or ↓ -ejection time: little/no effect -MV02: ↓↓

Nitrates, effects on: EDV, BP, Contractility, HR, ejection time, MVO2

Nitrates affect preload (dilate veins >> arteries) -EDV: ↓ -BP: ↓ -Contractility: no effect -HR: ↑ (reflex response) -ejection time: ↓ -MV02: ↓

Hypertensive Emergency: Drugs used

Nitroprusside nicardipine clevidipine labetalol fenoldopam.

Does Ramelteon cause Dependence?

No dependence - not a controlled substance

What type of Dependency does Suvorexant have?

No or low physical dependence

What are the Adverse Effects of Diuretics: Acetazolamide?

No pupillary or vision changes

What is the Adverse Reaction to β-blockers: Timolol, Betaxolol, Carteolol

No pupillary or vision changes

• Bupropion {Wellbutrin):

NoREPINEPHRINE-DoPAMINE REuPTAKE INHIBITORS • Relative lack of sexual side effects as compared to the SSRis. • Some efficacy in treatment of adult ADHD. • Side effects include i risk of seizures and psychosis at high doses and i anxiety in some. • Contraindicated in patients with seizure or active eating disorders and in those currently on an MAOI.

Antiandrogens-- Flutamide: MOA

Non steroidal competitive inhibitor of androgens at testosterone receptor

• Hydroxyzine (Atarax):

Non-Benzodiazepine Anxiolytics • An antihistamine. • Side effects include sedation, dry mouth, constipation, urinary retention, and blurry vision. • Useful for patients who want quick-acting, short-term medication, but who cannot take benzodiazepines for various reasons.

Buspirone (BuSpar):

Non-Benzodiazepine Anxiolytics • The anxiolytic action is at 5HT-1A receptor (partial agonist). *• It has a slower onset of action than BDZ (takes 1-2 weeks for effect).* • Not considered as effective as other options, and so it is often used in combination with another agent ( eg, an SSRI), for treatment of anxiety. • *It does not potentiate the CNS depression of alcohol (useful in alcoholics), and has a low potential for abuse/addiction.*

Rituximab, Clinical Use

Non-Hodgkin lymphoma CLL IBD Rheumatoid arthritis

Diltiazem, verapamil

Non-dihydropyridine Ca2+ channel blockers, act on heart MOA: block voltage-independent L-type Ca2+ channels of smooth muscle → ↓ contractility Heart--verapamil > diltiazem > amlodipine = nifedipine Clinical use: hypertension, angina, a-fib/flutter Toxicity: cardiac depression, AV block, peripheral edema, flushing, dizziness, constipation, gingival hyperplasia -Hyperprolactinemia with verapamil

Erlotinib, Clinical Use

Non-small cell lung carcinoma

Name some atypical antipsychotics

OLAnzapine CLOZapine QUESTIapine RISPERidone Aripiprazole Ziprasidone "It's ATYPICAL for OLd CLOSets to QUIETly RISPER from A to Z"

Which antipsychotic may cause significant weight gain?

Olanzapine and Clozapine "OLd CLOSets may get fat"

Proton pump inhibitor: Names

Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole. (-praz0le)

Tumor lysis syndrome, Definition

Oncologic emergency triggered by massive tumor cell lysis (lymphomas, leukemias)

Progestin-- Use

Oral contraceptives, treatment of endometrial cancer, abnormal uterine bleeding

Clinical use of metformin

Oral. First line therapy in type 2 DM, causes modest weight loss. Can be used in patients without islet function

What is the Mechanism of Suvorexant?

Orexin (hypocretin) receptor antagonist

Cholinesterase inhibitor poisoning

Organophosphates (ex: parathion) -> irreversible inhibition of AChE INCREASED PARASYMPATHETIC *DUMBBELSS* - diarrhea, urination, miosis, bradycardia, bronchospasm, excitation of skeletal muscle and CNS, lacrimation, sweating, salivation Reversed by atropine (competitive muscarinic inhibitor) + pralidoxime (regenerates AChE if given early -- Fixes Muscarinic & Nicotinic issues)

Selective Estrogen Receptor Modulators-- SERMs: Raloxifene-- Use

Osteoporosis

Loop diuretics: Furosemide-- Toxicity

Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout OH DANG mnemonic

Loop diuretics: Ethacrynic acid-- Toxicity

Ototoxicity, hypokalemia, Dehydration, Nephritis (interstitial), Gout, hyperuricmia

Paclitaxel, other taxols, Clinical Use

Ovarian and breast carcinomas

Antiandrogens-- Ketoconazole: Use

PCOS-- prevent hirsutism

Antiandrogens-- Spironolactone: Use

PCOS-- prevent hirsutism

Arylcyclohexylamines (*K*etamine) is an Analog of What Drug?

PCP

Misoprostol: MOA

PGE1 analog. Increase production and secretion of gastric mucus barrier. Decrease acid production.

Microtubule inhibitors

Paclitaxel

MOA: Inhibit microtubule breakdown Drugs?

Paclitaxel, other taxols

*Microtubule inhibitors*

Paclitaxel, other taxols Vinca alkaloids: vincristine, vinblastine

What it the Clinical Use of L-Dopa/Carbidopa?

Parkinson Disease

Metoclopramide: Toxicity

Parkinsonian effects Restlessness, drowsiness, fatigue, depression, nausea, diarrhea Drug interaction-- digoxin, diabetic agents Contraindicated in small bowel obstruction and Parkinson Disease

What Causes Parkinsonism?

Parkinsonism is due to a: 1. Loss of dopaminergic neurons 2. Excess cholinergic activity

4. Extrapyramidal side effects (EPS):

Parkinsonism-masklike face, cogwheel rigidity, pill-rolling tremor; akathisia-restlessness and agitation; dystonia-sustained contraction of muscles of neck, tongue, eyes, diaphragm. • Occurs with high-potency traditional antipsychotics • Reversible • Occurs within days of starting med • Can be life threatening { eg, dystonia of the diaphragm causing asphyxiation)

What Types of Seizures is Phenobarbital Used for?

Partial (Focal) Tonic-Clonic

What type of Seizure is Gabapentin Used for?

Partial (focal)

What type of Seizure is Vigabatrin Used for?

Partial (focal)

Who Suvorexant is Not Recommended for?

Patients with Liver Disease Contraindicated in patients with narcolepsy

What are the Contraindications of Suvorexant?

Patients with narcolepsy With strong CYP3A4 inhibitors

Penicillin G is the ____ form; Pencillin V is the ___ form

Pen G = IV/IM Pen V = oral

Proton pump inhibitor: Use

Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome.

H2 blockers: Use

Peptic ulcer, gastritis, mild esophageal reflux.

Bortezomib, carfilzomib, Toxicity

Peripheral neuropathy Herpes zoster reactivation

What is the Side Effect of Vigabatrin?

Permanent visual loss - black box warning

What are the Barbiturates?

Phenobarbital Pentobarbital Thiopental Secobarbital

Loop diuretics: Ethacrynic acid-- MOA

Phenoxyacetic acid derivative (not sulfonamide) Inhibits cotransport of Na+/K+/2Cl- of thick ascending limb Abolish hypertonicity of medulla-- prevent concentration of urine Increases PGE release-- vasodilate afferent arteriole Inhibited by NSAIDs Increase calcium excretion

Which B-blockers contraindicated in angina?

Pindolol and acebutolol Partial B-agonists that can cause potential cause increase in myocardial oxygen demand

Methacholine: Results

Positive: FEV1 drops by >20% with less than 4mg/L of methacholine>>so include asthma on differential Negative: asthma ruled out

Clinical use of rapid acting insulin

Postprandial glucose control: Type 1 DM type 2 DM GDM

What is the MOA of *Propo*fol?

Potentiates GABA-A

Amylin analog example

Pramlintide (SC injection)

Misoprostol: Use

Prevent NSAID peptic ulcers (NSAIDs block PGE1 production) Maintain patent ductus arteriosus. Ripen cervix for labor induction

Cholesterol Absorption Blocker: MOA

Prevent cholesterol absorption by small intestine brush boarder

Bile Acid Resins: MOA

Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more

Azathioprine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), Clinical Use

Preventing organ rejection Rheumatoid arthritis IBD SLE Used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease.

Antiarrhythmics: Class IV: Use

Prevention of nodal arrhythmias (e.g., SVT), rate control in atrial fibrillation.

Hormone Replacement Therapy-- Use

Prevention or relief of menopausal symptoms-- hot flashes, vaginal atrophy Osteoporosis-- increase estrogen, decrease osteoclast activity

Describe the MOA of Entacapone, Tolcapone

Prevents peripheral L-Dopa degradation to 3-O-methyldopa (3-OMD) Inhibits COMT

What is the Mechanism of Dantrolene?

Prevents release of Ca2+ from SR of skeletal muscle by binding to ryanodine receptors

MOA of TRAZADONE?

Primarily blocks 5-HT2 and alpha1-adrenergic receptors.

Local anesthetics principles

Principles: can be given with vasoconstrictors (usually epinephrine) to enhance local action - ↓ bleeding, ↑ anesthesia by ↓ systemic concentration -Infected tissue is more acidic, but alkaline anesthetics are charged and cannot penetrate membrane effectively → need more anesthetic -Size factor predominates over myelination, so order of nerve blockade = small myelinated > small unmyelinated > large myelinated > large unmyelinated -Order of loss: (1) pain, (2) temperature, (3) touch, (4) pressure

Antiarrhythmics Class IC: Toxicity

Proarrhythmic, especially post-MI (contraindicated). Contraindicated in structural and ischemic heart disease.

Antiarrhythmics: Class III: MOA

Prolong repolarization (via block potassium channels) Increase AP duration increase effective refractory period Used when other antiarrhythmics fail Increase QT interval. PROLONGED REPOLARIZATION**** Amiodarone has class I, II, III, IV effects, and alters lipid membrane

What is Phase I of a Neuromuscular Blockade?

Prolonged Depolarization

examples of thionamides

Propylthiouracil (PTU) Methimazole

Epoprostenol, Iloprost

Prostacyclin Analogs. Vasodilate pulmonary and systemic arterial vascular beds. Use: PULMONARY HTN Side Effects: Flushing, Jaw pain

Antiandrogens-- Flutamide: Use

Prostate carinoma

Bortezomib, carfilzomib, Mechanism

Proteasome inhibitors Induce arrest at G2-M phase and apoptosis

Osmotic laxatives: MOA

Provide osmotic load to draw water out.

Mannitol-- MOA

Proximal Convoluted Tubule Osmotic diuretic Increase tubular fluid osmolarity-- increase urine flow Decrease Intracranial and intraocular pressure

Mannitol-- Toxicity

Pulmonary edema, dehydration Contraindicated in anuria, CHF

Bleomycin, Toxicity

Pulmonary fibrosis Skin hyperpigmentation Mucositis Minimal myelosuppression

Azathioprine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), Mechanism

Purine (thiol) analogs -> ↓ de novo purine synthesis. Activated by HGPRT. Azathioprine is metabolized into 6-MP.

Cladribine (2-CDA), Mechanism

Purine analog ->multiple mechanisms (e.g., inhibition of DNA polymerase, DNA strand breaks).

Cytarabine (arabinofuranosyl cytidine), Mechanism

Pyrimidine analog ->inhibition of DNA polymerase.

5-fluorouracil (5-FU), Mechanism

Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase ->↓dTMP ->↓DNA synthesis.

Antiarrhythmics Class IA: Names

Quinidine, Procainamide, Disopyramide

celecoxib use

RA OA

Etanercept use

RA psoriasis ankylosing spondylitis

leflunomide use

RA psoriatic arthritis

How is Digoxin excreted

RENAL excretion

___ is an antipsychotic that may cause lactation, gynecomastia, and irregular menstruation due to increase in prolactin levels, and a decrease in GnRH, LH, and FSH levels

RISPERIDONE. "RISPER - the pad for all your feminine issues"

Drugs with ↓ Blood Solubility have What type of Induction and Recovery Time

Rapid Induction & recovery time

Where are Local Anesthetics Most Effective?

Rapidly firing neurons

What is Malignant Hyperthermia?

Rare, life-threatening condition in which inhaled anesthetics or succinylcholine induce fever and severe muscle contractions

Erlotinib, Toxicity

Rash

G1 restriction point modulation

Rb p53

Clonidine: Caution

Rebound HTN if stopped abruptly bc sudden increase in sympathetic outflow

Niacin (B3): SE

Red, flushed face (due to inc synth of prostaglandins, which can decreased by aspirin or long- term use) Hyperglycemia (acanthosis nigricans) (bc can cause insulin resistance) Hyperuricemia (exacerbates gout)(bc competes for excretion with uric acid)

Pseudophedrine, phenylephrine: use

Reduce hyperemia edema nasal congestion open obstructed eustachian tubes pseudoephedrine can be used illegally to make methamphetamine

Goal of Anti-angina therapy

Reduction of myocardial O2 consumption, via DECREASE determinants of MVO2--> contractility preload (end diastolic volume) afterload (blood pressure) heart rate

Clonidine:Use

Refactory HTN Last resort option administered via transdermal aka path

Nitroglycerine, Isosorbide dinitrate: Toxicity

Reflex tachycardia (treat with β-blockers), hypotension, flushing, headache. "Monday disease" in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend results in tachycardia, dizziness, and headache upon reexposure.

Insulin, short acting

Regular

Nitrosoureas, Mechanism

Require bioactivation. Cross blood-brain barrier -> CNS. Cross-link DNA.

What are the Adverse Effects of Barbiturates?

Respiratory and CV depression - can be fatal CNS depression - exacerbated by alcohol use Dependence Drug Interaction - induces Cytochrome P-450

H2 blockers: MOA

Reversible block of histamine H2 receptors--> decrease H+ secretion by parietal cells

What are antihistamines?

Reversible inhibitors of H1 histamine receptors

Antibiotics that block mRNA synthesis

Rifampin

Nitrates: Contraindicated

Right ventricular infarction Viagra (bc both would lead to increase in cGMP)

What Drug is Indicated for Treatment of ALS?

Riluzole

What Mutation is Involved with Malignant Hyperthermia?

RyR1 (voltage sensitive) → ↑ Ca2+ release from SR

• Venlafaxine (Effexor):

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRls) • *Low drug interaction potential.* = • *Can incr. blood pressure (BP); do not use in patients with untreated or labile BP.*

• Duloxetine (Cyrnbalta):

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRls) • Often used for people with depression and neuropathic pain or in fibromyalgia. • Side effects are similar to SSRis, but *more dry mouth and constipation relating to its norepinephrine effects.* • *There may be more liver side effects in patients with liver disease or heavy alcohol use.* • Expensive.

Canagliflozin

SGLT-2 inhibitors MOA: block reabsorption of glucose in PCT Clinical use: type 2 DM Toxicities: glucosuria, UTIs, vaginal yeast infections, hypotension

Clinical use of ADH antagonists

SIADH block action of ADH at V2 receptor

Venlafaxine, duloxetine

SNRIs MOA: inhibit 5-HT and norepinephrine uptake Clinical use: depression -Venlafaxine for generalized anxiety disorder, panic disorder, PTSD -Duloxetine for peripheral neuropathy Tx: ↑BP

Name the preferred drugs for the following psychiatric condition: PTSD

SSRIs

Name the preferred drugs for the following psychiatric condition: bulimia

SSRIs

Fluoxetine, paroxetine, sertraline, citalopram

SSRIs MOA: 5-HT-specific reuptake inhibitors Clinical use: depression, generalized anxiety disorder, panic disorder, OCD, bulimia, social phobias, PTSD -Takes 4-8 weeks to see effect Toxicity: fewer than TCAs -SIADH, sexual dysfunction -Serotonin syndrome

Which class of antidepressants commonly causes sexual dysfunction?

SSRIs (sertraline!)

Name the preferred drugs for the following psychiatric condition: depression

SSRIs, SNRIs, TCAs, bupropion, mirtazapine (especially with insomnia)

Name the preferred drugs for the following psychiatric condition: anxiety

SSRIs, SNRIs, busprione

Name the preferred drugs for the following psychiatric condition: Social phobia

SSRIs, beta-blockers

Name the preferred drugs for the following psychiatric condition: obsessive-compulsive disorder

SSRIs, clomipramine

Name the preferred drugs for the following psychiatric condition: panic disorder

SSRIs, venlafaxine, benzodiazepines

Antiarrhythmics Class II: Use

SVT, slowing ventricular rate during atrial fibrillation and atrial flutter.

Antiarrhythmics Class IC: Use

SVTs, including atrial fibrillation. Only as a last resort in refractory VT.

What is the clinical use of typical antipsychotics?

Schizophrenia (positive sx), psychosis, acute mania, Tourette syndrome

What is the clinical use of atypical antipsychotics?

Schizophrenia - both positive and negative symptoms. Bipolar disorder, OCD, anxiety disorder, depression, mania, Tourette syndrome.

Toxicity of TRAZADONE?

Sedation, nausea, priapism, postural hypotension "Called trazoBONE due to priapism"

What is the Clinical Use of Barbiturates?

Sedative for anxiety Seizures Insomnia Induction of anesthesia (thiopental)

Milrinone: MOA

Selective PDE-3 inhbitor

Tamoxifen, raloxifene, Mechanism

Selective estrogen receptor modulators (SERMs)—receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER ⊕ cells.

What Receptor are Neuromuscular Blocking Drugs Selective for?

Selective for Nm nicotinic receptors at neuromuscular junction but not autonomic Nn receptors

What is the Mechanism of Selegiline, Rasagiline?

Selectively Inhibits MAO-B (metabolize dopamine) → ↑dopamine availability

Methacholine: Is it a sensitive or specific test?

Sensitive so Rules Out False positive scenarios: allergic rhinitis smoking GERD Upper Respiratory Infection

MOA of Cinacalcet

Sensitizes Ca2+ sensing receptor (CaSR) in parathyroid gland to circulating Ca2+---> decrease PTH

Hydralazine: Use

Severe hypertension CHF (+nitrate, for venodilation) First-line therapy for hypertension in pregnancy, with methyldopa. Frequently coadministered with a β-blocker to prevent reflex tachycardia.

Irinotecan, topotecan, Toxicity

Severe myelosuppression Diarrhea

Hydroxyurea, Toxicity

Severe myelosuppression GI upset

Busulfan, Toxicity

Severe myelosuppression (in almost all cases) Pulmonary fibrosis Hyperpigmentation

What is the Clinical Use of Butorphanol?

Severe pain - migraine, labor

Hypertensive Emergency: Nitroprusside

Short acting; increases cGMP via direct release of NO. Acts on veins and arteries Can cause cyanide toxicity (releases cyanide which can inhibit complex IV on respiratory chain>>decreasing aerobic respiration).

Antiarrhythmics Class IC: MOA

Significantly prolongs refractory period in AV node. Minimal effect on AP duration.

ACE inhibitors vs Angiotensin II receptor blockers (-sartans)

Similar effect Do not increase bradykinin--> less risk of cough or angioedema

Risks of fludrocortisone

Similar to glucocorticoids, also edema, exacerbation of HF, hyperpigmentation

What Factor Predominates in Nerve Blockade?

Size factor over myelination small myelinated > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers

Cardiac Glycosides (digoxin): Antidote to toxicity

Slowly normalize K+ cardiac pacer anti-digoxin Fab fragments Mg2+

Vemurafenib, Mechanism

Small molecule inhibitor of BRAF oncogene ⊕ melanoma

What is the Order of Nerve Blockade?

Small-diameter fibers > large diameter Myelinated fibers > unmyelinated fibers

Oral Contraception-- Contraindications

Smokers > 35 (CV events), history of thromboembolism and stroke, or history of estrogen dependent tumor

Cyclophosphamide, ifosfamide, Clinical Use

Solid tumors Leukemia Lymphomas

Vincristine, vinblastine, Clinical Use

Solid tumors Leukemias Hodgkin (vinblastine) lymphomas Non-Hodgkin (vincristine) lymphomas

Doxorubicin, daunorubicin, Clinical Use

Solid tumors Leukemias Lymphomas

Bevacizumab, Clinical Use

Solid tumors (colorectal cancer, renal cell carcinoma)

Etoposide, teniposide, Clinical Use

Solid tumors (particularly testicular and small cell lung cancer) Leukemias Lymphomas

Antiarrhythmics: Class III: Toxicity

Sotalol—torsades de pointes, excessive β blockade. Ibutilide—torsades de pointes. Amiodarone—pulmonary fibrosis, hepatotoxicity, hypothyroidism/ hyperthyroidism (amiodarone is 40% iodine by weight), corneal deposits, skin deposits (blue/gray) resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, CHF). PFT, LFT, TFT needed

K+-sparing diuretics

Spironolactone and eplerenone; triameterene and amiloride Mechanism: Spironolactone and epleronone are competitive aldosterone receptor antagonists in cortical collecting tubule. Triamterene and amiloride act at same part of the tubule by blocking Na+ channels in the cortical collecting tubule. Clinical Use: Hyperaldosteronism, K+ depletion, HF. Toxicity: Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (e.g., gynecomastia, anti androgen effects)

Potassium sparing diuretics-- Names

Spironolactone, Eplerenone, Triamterene, Amiloride

Potassium sparing diuretics-- MOA

Spironolactone/Eplerenone-- competitive aldosterone receptor antagonists in cortical collecting tubule Triamterene and amiloride block Na+ channels in cortical collecting tubule

What is the Side Effect of Lamotrigine?

Steven-Johnson Syndrome - must be titrated slowly

Toxicity of BUPROPION?

Stimulant effects (tachycardia, insomnia), headache seizure in bulimic patients. No sexual SE.

Senna

Stimulant, enteric nerve stimulation causing colonic contraction Adverse effect: diarrhea, melanosis coli

Clinical use of oxytocin

Stimulate labor, uterine contractions, milk let-down; controls uterine hemorrhage

MOA of BUSPRIONE?

Stimulates 5-HT-1A receptors.

What is Succinylcholine (Depolarizing Neuromuscular Blocking Drug) MOA?

Strong ACh receptor agonist

Aprepitant

Substance P antagonist, blocks NK1 receptors in brain Clinical use: antiemetic for chemo induced nausea and vomiting

What is the Depolarizing Neuromuscular Blocking Drug?

Succinylcholine

Loop diuretics: Furosemide-- MOA

Sulfonamide loop diuretic Inhibits cotransport of Na+/K+/2Cl- of thick ascending limb Abolish hypertonicity of medulla-- prevent concentration of urine Increases PGE release-- vasodilate afferent arteriole Inhibited by NSAIDs INCREASE CALCIUM EXCRETION

Antibiotics to avoid in pregnancy-- SAFe Children Take Really Good Care

Sulfonamides --> kernicterus Aminoglycosides --> ototoxicity Fluoroquinolones --> cartilage Clarithromycin --> embryotoxic Tetracylines --> discolored teeth, inhibits bone growth Ribavirin --> teratogenic Griseofulvin --> teratogenic Chloramphenicol --> gray baby

What is the OD Treatment of Barbiturates?

Supportive Care - assist respiration and maintain BP

α-methyldopa

Sympatholytic (α2 agonist) Clinical use: hypertension in pregnancy Toxicity: direct Coombs + hemolysis, SLE-like syndrome

Clonidine

Sympatholytic (α2 agonist) Clinical use: hypertensive urgency (does not decrease renal blood flow), ADHD, Tourette syndrome Toxicity: CNS depression, bradycardia, hypotension, respiratory depression, miosis

Danazol-- MOA

Synthetic androgen-- partial agonist at androgen receptors

Which class of antidepressants can cause urinary retention?

TCA (due to anticholinergic effects)

Which class of antidepressants can cause cardiac arrhythmias due to overdose?

TCA - due to quinidine like effects and prolongs QT interval

What Drug is Cyclobenzaprine Structurally Related to?

TCA - similar anticholinergic side effects

Which class of antidepressants may cause seizures?

TCAs like CLOMIPRAMINE; BUPROPION

___ is an antipsychotic that can cause retinal deposits

THIORIDAZINE

TRUE or FALSE: DESIPRAMINE is less sedating but has a higher incidence of seizures.

TRUE

TRUE or FALSE: High potency drugs can cause neurologic side effects like EPS symptoms.

TRUE

TRUE or FALSE: TCAs cause respiratory depression and hyperpyrexia.

TRUE

TRUE or FALSE: Low potency drugs can cause non-neurologic SE.

TRUE - they have anticholinergic, antihistamine, and alpha1-blockade effects

Name some typical antipsychotics (neuroleptics).

TRifluperazine, FLuphenazine, Haloperidol "TRy to FLy High" CHlorpromazine, THioridazine "CHeating Thieves are low"

Tamoxifen, raloxifene, Toxicity

Tamoxifen—partial agonist in endometrium, which incr. the risk of endometrial cancer; "hot flashes." Raloxifene—no incr. in endometrial carcinoma because it is an estrogen receptor antagonist in endometrial tissue.

Name an example of EPS side effect of an antipsychotic.

Tardive dyskinesia

___ is stereotypic oral-facial movements as a result of long-term antipsychotic use, and is potentially irreversible.

Tardive dyskinesia

Bile Acid Resins: SE

Tastes bad GI discomfort (constipation) decrease absorption of fat-soluble vitamins (A,D,E,K)

NRTIs

Tenofovir (only nucleotide), emtricitabine, abacavir, lamivudine, zidovudine, didanosine, stavudine MOA: competitive inhibitor of HIV reverse transcriptase (terminate DNA chain bc lack a 3' OH) Clinical use: HIV active infection, ZDV also used for prophylaxis and during pregnancy to reduce fetal transmission Toxicity: bone marrow suppression (alleviated by GCSF and EPO, peripheral neuropathy, lactic acidosis, anemia (ZDV), pancreatitis (didanosine) *if patient has concurrent Hep B infection, use tenofovir

Mifepristone (RU-486)-- Use

Termination of pregnancy Administer with misoprostol (PGE1)

Bleomycin, Clinical Use

Testicular cancer Hodgkin lymphoma

Cisplatin, carboplatin, Clinical Use

Testicular carcinomas Bladder carcinomas Ovary carcinomas Lung carcinomas

What are the Drugs used to Treat Huntington Disease?

Tetrabenazine, reserpine Haloperidol

• Maprotiline (Ludiomil):

Tetracyclic Antidepressants Higher rates of seizure, arrhythmia, and fatality on overdose

• Amoxapine (Asendin):

Tetracyclic Antidepressants • Metabolite of antipsychotic loxapine • May cause EPS and has similar side effect profile to typical antipsychotics

Example of methylxanthines

Theophylline

Anti HTN-- Primary (essential)

Thiazide Diuretics ACE inhibitors, angiotensin II receptor blockers (ARBs) calcium channel blockers.

Appropriate agents for treating ESSENTIAL HTN

Thiazide diuretics, ACE inhibitors, ARBs, dihydropyridine calcium channel blokers

What oral hypoglycemic drugs are safe to use in renal failure?

Thiazolidinediones

Acetazolamide-- MOA

Thick ascending Tubule Carbonic anhydrase inhibitor Self limited NaHCO3 diuresis and decrease total body HCO3- stores

Neuroleptic malignant syndrome

Think FEVER (Fever, Encephalopathy, Vitals, Enzymes ↑, Rigidity of muscles) Rigidity, myoglobinuria, autonomic instability, hyperpyrexia Tx: dantrolene, D2 agonists (e.g., bromocriptine)

Selective Estrogen Receptor Modulators-- SERMs: Raloxifene-- Toxicity

Thromboembolism

Romiplostim, eltrombopag

Thrombopoietin Clinical use: thrombocytopenia

Magnesium: Use

Torsades de pointes Digioxin toxicity

Selective Estrogen Receptor Modulators-- SERMs: Tamoxifen-- Use

Treat and prevent recurrence of ER + breast cancer

Selective Estrogen Receptor Modulators-- SERMs: Clomiphene-- Use

Treats anovulation in PCOS

Amitriptyline, nortriptyline, imipramine, despramine, clomipramine, doxepin, amoxapine

Tricylic antidepressants MOA: block reuptake of 5-HT and norepinphrine Clinical use: major depression, OCD (clomipramine), peripheral neuropathy, chronic pain, migraine prophylaxis Toxicity: sedation; α-1 blocking effects; anticholinergic effects; QT prolongation -Tri-C's: Convulsions, Coma, Cardiotoxicity (tx: NaHCO3 to prevent arrhythmia) -Respiratory depression and hyperpyexia

Clinical use of short acting insulin

Type 1 DM Type 2 DM GDM DKA (IV) hyperkalemia (+glucose) stress hyperglycemia

Clinical use

Type 1 DM, Type 2 DM

Clinical use of intermediate acting insulin

Type 1 DM, Type 2 DM, GDM

Clinial use of alpha-glucosidase inhibitors

Type 2 DM

Clinical use SGLT-2 inhibitors

Type 2 DM

Clinical use of DPP-4 inhibitors

Type 2 DM

Imatinib, Mechanism

Tyrosine kinase inhibitor of BCR-ABL (Philadelphia chromosome fusion gene in CML) and c-kit (common in GI stromal tumors).

Sulfasalazine: Use

Ulcerative colitis, Crohn disease.

What is the Mechanism of Inhaled Anesthetics?

Unknown

What is the Mechanism of Levetiracetam?

Unknown May modulate GABA and glutamate release

Hormone Replacement Therapy-- Risk

Unopposed estrogen-- increase endometrial cancer Progesterone is added Increase CV risk

Fibrates: MOA

Upregulate LPL>>increase TG clearance Activates PPAR-α to induce HDL synthesis

Treatment for P. falciparum

Use combo of artemether/lumifantrine or atovaquone/proguanil

When should Pilocarpine be used?

Use pilocarpine in emergencies - very effective at opening meshwork in canal of Schlemm

Clinical use of meglitinides

Used as monotherapy in type 2 DM or combined with metformin

Clinical use of thiazolidinediones

Used as monotherapy in type 2 DM or combined with metformin or sulfonylureas. Safe to use in renal impairment

Clinical use of TRAZADONE?

Used primarily for insomnia, as high doses are needed for antidepressant effects.

Name 2 SNRIs.

VENLAFAXINE DULOXETINE

What is the MOA of atypical antipsychotics?

Varied effects of 5-HT2, DA, and alpha- and H1-receptors.

Prednisone, prednisolone, Mechanism

Various; - bind intracytoplasmic receptor; - alter gene transcription.

Calcium channel blockers: order of preference

Vascular smooth muscle: amlodipine = nifedipine > diltiazem > verapamil. Heart: verapamil > diltiazem > amlodipine = nifedipine.

What can Local Anesthetics be given with and what are the Benefits?

Vasoconstrictors - usually epinephrine - to enhance local action ↓ bleeding ↑ anesthesia by ↓ [systemic]

Nitroglycerine, Isosorbide dinitrate: MOA

Vasodilate by increasing NO in vascular smooth muscle>> increase in cGMP>>smooth muscle relaxation. Dilate VEINS >> arteries. DECREASE preload.

Antiarrhythmics: Class IV: Names and Class

Verapamil, Diltiazem Ca++ channel blockers

Class IV antiarrhythmics

Verapamil, diltiazem MOA: decrease conduction velocity, increase ERP and PR interval Clinical use: prevention of nodal arrhythmias (like SVT) Toxicity: constipation, flushing, edema, CHF, AV block, sinus node depression

Vinca Alkaloids

Vinblastine Vincristine

Vincristine, vinblastine, Mechanism

Vinca alkaloids that bind β-tubulin and inhibit its polymerization into microtubules -> prevent mitotic spindle formation (M-phase arrest).

MOA: Inhibit microtubule formation Drugs?

Vinca alkaloids: vinblastine, vincristine

Vincristine, vinblastine, Toxicity

Vincristine: - Neurotoxicity (areflexia, peripheral neuritis) - Paralytic ileus Vinblastine: - blasts bone marrow (suppression).

All Local Anesthetics are?

Weak bases

What are the Adverse Effects of Butorphanol?

Weak opioid withdraws symptoms if patient is also taking full opioid antagonist OD is not easily reversed with naloxone

Danazol-- Toxicity

Weight gain, edema, acne, hirsutism, masculinization, Lowers HDL levels, hepatotoxicity

Risks/concerns glitazones/thiazolidinediones

Weight gain, edema. Hepatotoxicity, HF, increased risk of fractures

Which oral hypoglycemic drugs cause weight gain? Which ones cause weight loss?

Weight gain: sulfonylureas, thiazolidinediones, meglitinides Weight loss: metformin, GLP-1 analogs DPP-4 inhibitors are weight neutral

Dactinomycin (actinomycin D), Clinical Use

Wilms tumor Ewing sarcoma Rhabdomyosarcoma. Used for childhood tumors ("children ACT out").

Serotonin syndrome

With any drug that ↑5-HT (e.g., MAO inhibitors, SNRIs, TCAs) Hyperthermia, confusion, myoclonus, CV instability, flushing diarrhea, seizures Tx: cyproheptadine (5-HT2 receptor antagonist)

Which antipsychotic can prolong the QT interval?

Ziprasidone "ZIP up that LONG QT chain"

Omalizumab

a monoclonal IgG that binds mostly unbound serum IgE and blocks binding to FceRI. so IgE cant bind to Fc receptors on mast cells and basophils>>>prevents degranulation

Tamsulosin-- MOA

a1-antagonist-- inhibiting smooth muscle contraction Selective for a1A, D receptors (on prostate) vs. vascular a1B receptors

"Mean" GNATSS caNNOT kill anaerobes

aMINoglycosides: Gentamicin, Neomycin, Amikacin, Streptomycin, Spectinomycin; Nephrotoxic, Neuromuscular blockade, Ototoxic, Teratogenic; can't kill anaerobes because require O2 for uptake into the cell

use of albuterol

acute attack

How can Salmeterol, formoterol be used for asthma-prophylaxis?

added with steroids can be used alone in diseases with less inflammation (ie COPD)

Tumor lysis syndrome, Treatment

aggressive hydration allopurinol rasburicase

bisphosphonates

alendronate ibandronate risedronate zoledronate

Hypertension in pregnancy: what precaution?

all HTN drugs cross the placenta so have to be careful of teratogen effects ie DONT USE ARBs/ACEi bc they will lead to renal issues in fetus

TNF alpha inhibitors

all tnf alpha inhibitors predispose to infection, including reactivation of latent TB, since TNF is important in granuloma formation and stabilization

When is omalizumab used?

allergic asthma with increased IgE levels resistant to inhaled steroids and long-acting beta 2 agonists

Clinical use of 2nd gen antihistamine

allergy

Clinical use of first gen antihistamines

allergy allergic rhinitis acute uriticaria motion sickness sleep aid

Gout Drugs preventive

allopurinol febuxostat pegloticase probenicd

• Mirtazapine (Remeron):

alpha-ADRENERGIC RECEPTOR ANTAGONISTS • Useful in the treatment of refractory major depression, especially in patients who need to gain weight. • Side effects include sedation, weight gain, dizziness, somnolence, tremor, dry mouth, constipation, and rare agranulocytosis. • No sexual side effects and few drug interactions.

Pseudoephedrine, phenylephrine: MOA

alpha-adrenergic agonists >>nasal vasoconstriction decreases nasal tissue swelling used as nasal decongestants

Sildenafil: Addtl Use

also used to treat erectile dysfunction

Zileuton

an antileukotriene

Dextromethorphan: MOA

antagonize NMDA glutamate receptor (a calcium channel ion)

Infliximab, adalimumab, certolizumab, golimumab mech

anti tnf alpha monoclonal antibody

NSAID use

antipyretic analgesic anti inflammatory indomethacin is used to close a PDA

acetaminophen clinical use

antipyretic analgesic but not anti-inflammatory used instead of aspirin to avoid reye syndrome in children w viral infection

NSAIDs

any full do se NSAID (naproxen, indomethacin) avoid salicylates (may decrease uric acid excretion, particularly at low doses)

Theophylline: AE

arrhythmia seizures nausea/vomiting metabolized CYP450 (interactions: phenytoin, cimitidine)

montelukast, zafirlukast: Use

aspirin-induced asthma exercised induced asthma

Conditions aggravated by all cholinomimetic agents

asthma, COPD, peptic ulcers

Antibiotics that block peptidoglycan SYNTHESIS

bacitracin, vancomycin

Example of glucocorticoids

beclomethasone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, triamcinolone

What is contraindicated in heart failure and cardiogenic shock

beta blockers ie metoprolol bc need sympathetic stimulation for that minimal CO that is happening, dnt want to take that away

colchicine

binds and stabilizes tubulin to inhibit microtubule polymerization impairing neutrophil chemotaxis and degranulation acute and prophylactic value GI side effects

Montelukast, zarfirlukast: MOA

block leukotriene receptors (cysLT1) (blocks C4,D4,E4 from binding to their receptors)

What does theophylline interfere with?

blocks action of adenosine caffeine does that too (both are non selective antagonist at adenosine receptor)

early response in asthma

bronchoconstriction--> symptoms of asthma

Trastuzumab tox

cardiotoxicity

Clonidine: MOA

central alpha 2 agonist presynaptic for sympathetic neurons effect: decrease in sympathetic outflow

Example of first gen sulfonylureas

chlorpropamide tolbutamide

Bile Acid Resins: Names

cholestyramine, colestipol, colesevelam

Ivabradine: Use

chronic stable angina if pt cant take beta blocker chronic Heart failure with reduced ejection fraction (allows for slow depolarization so that heart can properly fill)

allopurinol

competitive inhibitor of xanthine oxidase less conversion of hypoxanthin and xanthine to urate used in lymphoma and leukemia to prevent tumor lysis assoc urate nephropathy increase conc of azathioprine and 6-MP (both normally metaolized by xanthin oxidase)

Bosentan: MOA

competitively antagonize Endothelin-1 receptors >>>decrease pulmonary vascular resistance bosEN-TAN: EndotheLIN

Ipratropium: MOA, use

competitively block muscarinic receptors, preventing bronchoconstriction treats COPD and asthma

ADH antagonists

conivaptan tolvaptan demeclocycline (tetracycline family, may cause bone/teeth abnormalities)

Pramlintide MOA

decrease gastric emptying, decrease glucagon Always used with insulin

Use of methacholine

diagnosis bronchial hyper responsiveness aka ASTHMA (and COPD) bronchial challenge test to help diagnose asthma

leflunomide adverse

diarrhea, HTN, hepatotoxicity, teratogenicity

Type 2 DM treatment strategy

dietary modifcation and exercise for weight loss; oral agents, non-insulin injectables, insulin replacement

Gestational DM

dietary modifications, exercise, insulin replacement if lifestyle modification fails

Caution with digoxin

do not give in pt with RENAL FAILURE do not give to someone with hypokalemia

When should α-agonists: Epinephrine (α1) not be used?

do not use in close-angle glaucoma

bisphosphonate adverse

esophagitis (if taken orally, pt advised to take w water and remain upright for 30 min) osteonecrosis of jaw atypical stress fractures

Side effects of epoprostenol, iloprost

flushing jaw pain

Etanercept mech

fusion protein (receptor for tnf alpha + IgG1 Fc) produced by recombinant dna entanercept intercepts TNF

aspirin adverse

gastric ucleration tinnitus (CN VIII) chronic use can lead to acute renal failure, interstitial nephritis, GI bleed reye syndrome in children toxic doses cause respiratory alkalosis early but transitions to mixed metabolic acidosis-respiratory alkalosis

Fibrates: Names

gemfibrozil, clofibrate, bezafibrate, fenofibrate

example of second gen sulfonylureas

glimepiride glipizide glyburide

Cyclophosphamide tox

hemorrhagic cystitis

Clinical use of thionamides

hyperthyroidism PTU blocks Peripheral conversion and is used in Pregnancy

Risks/Concerns of meglitinide

hypoglycemia (increased risk with renal failure), weight gain

Risks/concerns of insulin

hypoglycemia, lipodystrophy, rare hypersensitivity reactions

NSAIDS

ibuprofen naproxen indomethacin ketorolac diclofenac meloxicam piroxicam

Ach effect on bronchial tone

increase bronchoconstriction

Milrinone: Effect on heart vs vascular

increase cAMP>> increase Ca influx>>>increase heart rate and contractility increase cAMP>inhibits myosin light chain kinase>>vasodilation

Effects of insulin on liver

increase glucose stored as glycogen

effects of insulin on muscle

increase glycogen, protein synthesis; increase K+ uptake

Clecoxib adverse

increased risk of thrombosis sulfa allergy

late response in asthma

inflammation-->bronchial hyperreactivity

What mediates bronchoconstriction?

inflammatory processes and parasympathetic tone

cornerstone of chronic therapy for persistent asthma

inhaled corticosteroids

N-acetylcysteine: What is it?

inhaled mucolytic- liquifies mucus in chronic bronchopulmonary diseases (ie COPD)

probenicid

inhibits reabosprtion o furic acid in proximal convoluted tubule (also inhibits secretion of penicillin) can precipitate uric acid calculi

febuxostate

inhibits xanthin oxidase

NSAID adverse

interstitial nephritis gastric ulcer (prostaglandins protect gastric mucosa) renal ischemia (prostaglandins vasodilate afferent arteriole) aplastic anemia

Salmeterol, formoterol: MOA

long acting b2 agonists

Tiotropium: MOA, use

long acting muscarinic antagonist mainly binds M3 treats COPD

Aspirin clinical use

low dose (< 300 mg per day) less platelet aggregation intermediate dose (300 - 2400/day) antipyretic and analgesic high dose (2400-4000/day) anti inflammatory

Ivabradine: Adverse Effects

luminous phenomena (aka visual brightness) hypertension (reflex response) bradycardia

Biguanide example

metformin

What to use for theophylline overdose?

metoprolol its cardioselective and will block the production of more cAMP

Bosentan: Caution

must monitor LFTs bc it can be HEPATOTOXIC

5-FU

myelosuppression

6-MP

myelosuppression

Methotrexate

myelosuppression

examples of meglitinides

nateglinide repaglinide

Zileuton: AE

need to check LFTs before starting (hepatotoxic)

Cisplatin/Carboplatin tox

nephrotoxic and acoustic nerve damage

Methacholine MOA

nonselective Muscarinic agonist an acetylcholine analog

fluticasone, budesonide: AE

oral thrush long term use: cushionoid effect

glucocorticoids

oral, intra-articular, parenteral

teriparatide use

osteoporosis causes increased bone growth compared to antiresorptive therapies (bisphosphonates)

bisphosphonates use

osteoporosis hypercalcemia paget dz of bone metastatic bone dz osteogenesis imperfecta

acetaminophen adverse

overdose produces hepatic necrosis; acetaminophen metabolite NAPQI deplates glutathione and forms toxic tissue byproducts in liver Nacetylcysteine is antidote - regenerates glutathione

Calcium channel Blocker: Dihydropyridine Adverse Effect

peripheral edema flushing (Due to vasodilation) dizziness (due to decreased TPR) Gingival Hyperplasia

Vincristine tox

peripheral neuropathy

Thiazolidinediones examples

pioglitazone rosiglitazone

What do the antileukotrienes do?

prevent the late response: inflammation, which would lead to bronchial hyperreactivity

Rasburicase, Clinical use

prevention and treatment of tumor lysis syndrome

Clinical use of Cinacalcet

primary or secondary hyperparathyroidism

Epoprostenol, iloprost

prostacyclin analogs PGI2 >>>direct vasodilatory effects on pulmonary and systemic arterial vascular beds. Inhibit platelet aggregation Decrease vascular tone

Bleomycin, Busulfan tox

pulmonary fibrosis

bisphosphonates mech

pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity

• Nefazodone carries a Black Box Warning for

rare but serious liver failure (1per250,000-300,000 people).

Teriparatide mech

recombinant PTH analog given subcutaneously daily increased osteoblastic activity

Rasburicase, Mechanism

recombinant uricase that catalyzes metabolism of uric acid to allantoin

pegloticase

recombinant uricase that catalyzes metabolism of uric acid to allantoin (a more water soluble product)

example of short acting insulin

regular insulin

Tumor lysis syndrome, Cause of hyperkalemia

release of K+

Tumor lysis syndrome, Cause of hyperphosphatemia

release of phosphate

What are the factors predisposing to Digoxin toxicity

renal failure (decreased excretion), hypokalemia (permissive for digoxin binding at K+-binding site on Na+/K+ ATPase) verapamil, amiodarone, quinidine (decrease digoxin clearance; displaces digoxin from tissue-binding sites)

celecoxib mech

reversibly and selectively inhibits COX isoform 2 which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain spares COX1 which helps maintain gastric mucosa does not have corrosive effects of other NSAIDs on GI lining spares platelet function as TXA2 production is dependent on COX1

NSAID mech

reversibly inhibit COX1 and COX2 block prostaglandin synthesis

Acetaminophen mech

reversibly inhibits cyclooxygenase, mostly in CNS inactivated peripherally

Leflunomide mech

reversibly inhibits dihydroorotate dehydrogenase, prevents pyrmidine synth suppresses t cell proliferation

Risks of sulfonlureas in general

risk of hypoglycemia especially in renal failure, weight gain First gen: disulfram-like effects

Teriparatide adverse

risk of osteosarcoma (avoid use in pt with paget dz of bone or unexplained elevation of alk phos) avoid in pt who have had prior cancers or radiation therapy transient hypercalcemia

Ivabradine: MOA

selective inhibition of funny sodium channels prolongs slow depolarization phase (phase 4) decreases SA node firing slows heart rate does NOT affect contractility reduces O2 demand

Milrinone: Clinical Use

short term for acute decompensated heart failure

Risks of thionamides

skin rash agranulocytosis (rare) aplastic anemia hepatotoxicity Methimazole is a possible teratogen (can cause aplasia cutis)

Adenosine effects on bronchial tone

stimulate bronchoconstriction

MOA of meglitinides

stimulate postprandial insulin release by binding to K+ channels on beta-cell membranes (site different from sulfonylureas)

Clinical use of sulfonylureas

stimulate release of endogenous insulin in type 2 DM Require some islet function, so useless in type 1 DM

Antibiotics that block nucleotide synthesis by inhibiting folic acid synthesis

sulfonamides, trimethoprim

Dextromethorphan: Drug class, cautions?

synthetic codeine analog that has mild opioid effect when used in excess causes dissociative hallucinations at high dose >>which can cause mild abuse potential may cause serotonin syndrome when combined with other serotonin promoting agents

Risks of levothyroxine and triiodothyronine

tachycardia heat intolerance tremors arrythmias

Levothyroxine (T4), triiodothyronine (T3) MOA

thyroid hormone replacement

AE for salmeterol and formoterol

tremor and arrythmia

Clinical use of GLP-1 analogs

type 2 DM

What are the antimuscarinic effects?

urinary retention dry mouth blurry vision***** (impairs accommodation via parasympathetic innervation of ciliary muscle) delirium increased body temperature flushing similar to atropine side effects

Dobutamine: use

used for heart failure, cardiogenic shock

Glaucoma drugs

α agonists: ↓ aqueous humor synthesis **Cause mydriasis -> do not use in closed-angle glaucoma β antagonists: ↓ aqueous humor synthesis Diuretics (acetazolamide): ↓ aqueous humor synthesis via inhibition of carbonic anhydrase Cholinomimetics: ↑ outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork Prostaglandin (latanoprost, PGF2α): ↑ outflow of aqueous humor

INFs

α- chronic hep B and C, Kaposi's sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma β- MS γ- NADPH oxidase deficiency (CGD) Toxicity: neutropenia, myopathy

Phenoxybenzamine

α-blocker - nonselective, irreversible Clinical use: pheochromocytoma (used preop to prevent hypertensive crisis) Toxicity: orthostatic hypotension, reflex tachy

Phentolamine

α-blocker - nonselective, reversible Clinical use: give to pts on MAO inhibitors who eat tyramine-containing foods → avoid hypertensive crisis Toxicity: orthostatic hypotension, reflex tachy

Acarbose, Miglitol

α-glucosidase inhibitors MOA: inhibition at intestinal brush border delays sugar hydrolysis and glucose absorption → ↓ postprandial hyperglycemia Clinical use: monotherapy in type 2 DM or w/ other diabetes drugs Toxicities: GI upset

Prazosin, terazosin, doxazosin, tamsulosin

α1 selective blocker Clinical use: urinary symptoms of BPH; PTSD (prazosin); hypertension (except tamsulosin) Toxicity: 1st-dose orthostatic hypotension, dizziness, headache ____=α1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α1A,D receptors (found on prostate) vs. vascular α1B receptors.

Mirtazapine

α2 selective blocker (also potent 5-HT2 and 5-HT3 receptor antagonist) Clinical use: depression Toxicity: sedation, ↑ serum cholesterol, ↑ appetite

Class II antiarrhythmics

β blockers (metoprolol, propranolol, esmolol, atenolol, timolol) MOA: decreases SA and AV nodal activity by ↓cAMP, ↓Ca2+ currents, suppress abnormal pacemakers by decreasing the slope of phase 4, ↑ PR interval bc AV node particularly sensitive Clinical use: ventricular tachycardia, SVT, slowing ventricular rate during a fib and a flutter Toxicity: impotence, exacerbation of asthma, bradycardia, AV block, sedation, masking of hypoglycemia -Metoprolol- dyslipidemia -Propanolol- exacerbate Prinzmetal's angina

β blockers, effects on: EDV, BP, Contractility, HR, ejection time, MVO2

β blockers affect afterload -EDV: no effect or ↓ -BP: ↓ -Contractility: ↓ -HR: ↓ -ejection time: ↑ -MV02: ↓

What is the Mechanism for Butorphanol?

κ-opioid receptor agonist and μ-opioid receptor partial agonist

What is the Mechanism of Pentazocine?

κ-opioid receptor agonist and μ-opioid receptor weak antagonist or partial agonist

• Risperidone (Risperdal):

• Can cause incr. prolactin • Some orthostatic hypotension and reflex tachycardia • Has long-acting injectable form called Consta

What are the low potency antipsychotics?

• Chlorpromazine (Thorazine): • Thioridazine (Mellaril):

• Chlorpromazine (Thorazine):

• Commonly causes orthostatic hypotension • Can cause bluish skin discoloration • Can --> photosensitivity • Can treat nausea and vomiting, as well as intractable hiccups

Important psychiatric meds that are CYP450 inhibitors:

• Fluvoxamine (1A2, 206, 3A4) • Fluoxetine (2C 19, 2C9, 206) • Paroxetine (206) • Duloxetine (206) • Sertraline (2C 19)

High-Potency, Typical Antipsychotics

• Haloperidol (Haldol): • Fluphenazine (Prolixin): • Pimozide (Orap): Associated with heart block, ventricular tachycardia, and other cardiac effects

• Loxapine (Loxitane):

• Higher risk of seizure. • Metabolite is an antidepressant.

• Clozapine (Clozaril):

• Less likely to cause tardive dyskinesia. • Only antipsychotic shown to be more efficacious. • Associated with tachycardia and hypersalivation. • More anticholinergic side effects than other atypical or highpotency typicals. • Myocarditis can develop. • There is a 1-2% incidence of agranulocytosis and 2-5% incidence of seizures. • You must stop clozapine if the absolute neutrophil count drops below 1500/μL. • Clozapine is the only antipsychotic shown to decr. the risk of suicide.

Midpotency, Typical Antipsychotics

• Loxapine (Loxitane): • Thiothixene (Navane): • Trifluoperazine (Stelazine): • Perphenazine (Trillion)

• Paliperidone (Invega):

• Metabolite of risperidone • Long-acting injectable form (Sustenna)

Carbamazepine SIDEEFFECTS

• The most common side effects are GI and CNS (drowsiness, ataxia, sedation, confusion). *• Possible skin rash (Stevens-Johnson Syndrome).* • Leukopenia, hyponatremia, aplastic anemia, thrombocytopenia, and agranulocytosis. • Elevation of liver enzymes, causing hepatitis. *• Teratogenic effects when used during pregnancy (neural tube defects).* • It also has significant drug interactions with many drugs metabolized by *the cytochrome P450 pathway, including inducing its own metabolism through auto induction, requiring increasing dosages.*

SEROTONIN RECEPTOR ANTAGONISTS AND AGONISTS

• Trazodone (Desyrel) and Nefazodone (Serzone):

• Aripiprazole (Abilify):

• Unique mechanism of partial D2 agonism • Can be more activating (akathisia) and less sedating • Less potential for weight gain

• Trazodone (Desyrel) and Nefazodone (Serzone):

• Useful in treatment of refractory major depression, major depression with anxiety, and insomnia (secondary to its sedative effects). • They do not have the sexual side effects of SSRis and do not affect rapid eye movement (REM) sleep. • Side effects include nausea, dizziness, orthostatic hypotension, cardiac arrhythmias, sedation, and priapism (especially with trazodone).

What it the Mechanism of L-Dopa/Carbidopa?

↑ Dopamine level in brain L-Dopa can cross BBB (unlike dopamine) L-Dopa is converted by dopa decarboxylase in CNS → dopamine Carbidopa - peripheral DOPA decarboxylase inhibitor Given w/ L-Dopa to ↑ bioavailability of L-Dopa in brain and limit peripheral side effects

What is the Mechanism of Tiagabine?

↑ GABA by inhibiting reuptake

What is the Mechanism of Vigabatrin?

↑ GABA by irreversibly inhibiting GABA transaminase

What is the Mechanism of Benzodiazepines?

↑ GABA-A Action

What is the Mechanism of Phenobarbital?

↑ GABA-A Action

What is the Mechanism of Valproic Acid?

↑ Na+ channel inactivation ↑ [GABA] by inhibiting GABA transaminase

Arylcyclohexylamines (*K*etamine) has what effect onCerebral Blood Flow

↑ cerebral blood flow

What is the MOA and Toxicity of *A*mantadine?

↑ dopamine release ↓ dopamine reuptake Toxicity: - Ataxia - Livedo reticularis

Drugs with ↑ Lipid Solubility have What effect on Potency?

↑ lipid solubility = ↑ potency

What is the Mechanism of Direct (pilocarpine, carbachol) & Indirect (physostigmine, echothiophate) Cholinomimetics (M3)?

↑ outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork

What is the Mechanism of Prostaglandin: Bimatoprost, Iatanoprost (PGF2α)?

↑ outflow of aqueous humor via ↓ resistance of flow through uveoscleral pathway

What is the Effect of Glaucoma Drugs?

↓ IPO via ↓ amount of aqueous humor (inhibit synthesis/secretion or ↑ drainage)

What is the Mechanism of α-agonists: Brimonidine (α2)?

↓ aqueous humor synthesis

What is the Mechanism of β-blockers: Timolol, Betaxolol, Carteolol?

↓ aqueous humor synthesis

What is the Mechanism of Diuretics: Acetazolamide?

↓ aqueous humor synthesis via inhibition of carbonic anhydrase

What is the Mechanism of α-agonists: Epinephrine (α1)?

↓ aqueous humor synthesis via vasoconstriction (epinephrine)

Barbiturates (*Th*iopental) Adverse Effect

↓ cerebral blood flow