**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
