Pharmacology Flashcards

Question

Selective Factor Xa Inhibitors

Answer 1

* Fondaparinux * Apixaban (Eliquis) * Rivaroxaban (Xarelto)

Answer 2

* Synthetic pentasaccharide * **Indirect Factor Xa inhibitor** * Binds ATIII to inactivate Xa * **Given SC** * Indications * **DVT** * **Acute PE**

Answer 3

* **Direct inhibitor of Factor Xa** * **Given PO** * Approved for **non-valvular A. fib**

Answer 4

* **Direct inhibitor of Factor Xa** * **Given PO** * Indications * **Prophylaxis for venous thromboembolism s/p knee and hip replacements** * **Prophylaxis for stroke in pts w/ nonvalvular A. Fib**

Answer 5

* Desirudin * Bivalirudin * Argatroban * Dabigatran etexiliate (Pradaxa)

Answer 6

* Derivative of hirudin * **Direct thrombin inhibitor** * Indications * **Prevent post-op venous thromboembolism** * **Given SC** * Demonstrated superiority to LMW heparin

Answer 7

* Synthetic peptide analog of hirudin * Direct thrombin inhibitor * **Given IV** * **Used during PCI**

Answer 8

* **Direct thrombin inhibitor** * **Given IV** * Indications * **Thrombosis in pts w/ HIT** (heparin-induced thrombocytopenia) * **During PCI in pts w/ HIT**

Answer 9

* **Direct thrombin inhibitor** * **Given PO** * Prodrug ⇒ activated by a CYP450 * **Does not require monitoring**

Answer 10

* Approved for **stroke prevention in A. Fib** * Efficacy equal to warfarin * May haved reduced risk of bleeding vs warfarin * **Pregnancy category C drug** * Weigh risks vs benefits

Answer 11

↑ plasmin activation ⇒ fibrin degradation ⇒ thrombolysis * Streptokinase * Anistreplase * tPA

Answer 12

* Protein from Strep * **Activates plasminogen ⇒ plasmin** * **Given IV** over 30-60 mins * **Less effective than tPA for CVA**

Answer 13

* **Plasminogen + streptokinase** * Protein acetylated to protect active site * **Given IV over 30-60 mins** * Protecting group comes off in plasma * **Less effective than tPA for CVA**

Answer 14

* Protease that **preferentially activates plasminogen bound to fibrin** * **Given IV bolus** ⇒ immediate action

Answer 15

* **Ischemic strokes** * **Multiple PEs** * **Central DVTs** * **Acute MI** * Given within 1st hour ⇒ ↓ mortality * Given within 6 hours ⇒ ↓ mortality vs streptokinase * NOT used for unstable angina or NSTEMI

Answer 16

* **Attack plasmodium in erythrocyte stage** * Provides cure for plasmodium w/o exoerythrocytic stage * _P. vivax and P. ovale_ ⇒ only suppresses attack but relapses can occur * Includes: 1. **Chloroquine/hydroxychloroquine** 2. **Quinine** 3. **Mefloquine** 4. **Pyrimethamine + sulfadoxine** 5. **Aretemether+lumefantrine** 6. **Atovaquone+proguanil (Malarone)**

Answer 17

Exact mechanism unknown * Weak base ⇒ **accumulates in lysosomes of parasites** * **May prevent metabolism of Hb by inhibiting heme polymerase** * Heme accumulates causing oxidative stress

Answer 18

* **Usually given PO** * Rapidly and completely absorbed in GI tract * **Antacids interfere w/ absorption** * **Can be given IM or IV** but PO safer

Answer 19

* **Used in an acute attack or for prevention** * P. falciparum resistant in many areas * Use where plasmodium sensitive to tx * **Drug of choice for pregnant women w/ uncomplicated cases of chloroquine-sensitive malaria**

Answer 20

* Low dose PO ⇒ prophylaxis * Few side effects * **_High dose PO ⇒ treatment for attacks_** * **Retinopathies** * Taken up by tissue w/ high [melanin] * **Corneal opacity** * **Porphyrias** * **Headache and confusion** * **Extraocular muscle palsies** * Pruritus and skin eruptions * Depigmentation of hair * Partial alopecia * Exacerbation of psoriasis * **_High dose IV_** * **Affects Na⁺ channels ⇒ hypotension or arrhythmias**

Answer 21

Mechanism unclear. May act similar to hydroxychloroquine ⇒ affects heme metabolism.

Answer 22

* **PO** * T_1/2 is 10 hours, longer w/ severe cases of malaria * **Antacids inhibit absorption** * **IV** * Used for severe cases of malaria * **Requires cardiac monitoring**

Answer 23

**Effective against _all erythrocyte forms_ of malaria.** No effect on exoerythrocytic forms. * **_PO_** * **Treat chloroqine-resistant falciparum and vivax** * Not as effective as chloroquine * Uusally use in combo w/ other drugs like Doxycycline * **Quinine + clindamycin** for chloroquine-resistant P. falciparum in _pregnant patients_ * **_IV_** * **Severe cases of falciparum whether resistent to chloroquine or not** * Not used for prophylaxis

Answer 24

* _Cardiac muscle sensitivity_ * **Arrhythmias** * **Hypotension** * **CNS disturbances** * Causes release of insulin ⇒ **hypoglycemia** * Gastric irritant ⇒ nausea/vomiting * High doses needed for falciparum ⇒ **cinchonism** * **Nausea, dizziness, tinnitus, HA, blurred vision** * Prolonged use ⇒ **Blackwater fever** * **Acute hemolytic anemia associated with renal failure**

Answer 25

Exact mechanism unknown. Drug intercalates into DNA. May disrupt polymerization of hemozoin.

Answer 26

* **Only given PO** * T_1/2 of 13-33 days ⇒ **given once a week** * **Should not be combined with other drugs that effect cardiac conduction** * Ex. Quinidine or β-blockers

Answer 27

* 1° for **prophylaxis for chloroquine-resistant P. falciparum** * **Pregnancy category B** ⇒ may be used during pregnancy for prophylaxis * Can be used to **treat acute cases of resistant P. falciparum** * Not as quick as quinine * _Does not replace quinine for severe cases_

Answer 28

* _Low dose ⇒ prophylactic_ * **Vivid dreams** * _High dose ⇒ treatment_ * **Neuropsychiatric sx** * **Vertigo and lightheadedness** * **Visual disturbances** * **GI disturbances** * Nausea * HA * Insomnia

Answer 29

Pts with hx of **epilepsy or psychiatric disorders**.

Answer 30

* _Coverage_ * **Primarily active against erythrocytic forms** * **Some activity against primary plasmodium infection in the liver** * _Mechanism_ * Pyrimethamine ⇒ ⊗ dihydrofolate reductase * More specific for enzyme in protozoa * Sulfadoxine ⇒ ⊗ dihydropteroate synthase * **Together ⊗ sequential steps of folic acid pathway**

Answer 31

* Only given PO * Generally used in combo w/ quinine * Use w/ caution in pregnancy

Answer 32

Usually used in combo with quinine for acute cases

Answer 33

* **Blood dyscrasias** * Granuloytopenia * Thrombocytopenia * Neutropenia * Aplastic anemia * **Folic acid deficiency** * Supplement if during pregnancy * **Steven Johnson syndrome**

Answer 34

Combo more effective than monotherapy. * **Aretemether** ⇒ free radical mechanism * **Lumefantrine** ⇒ may work similar to chloroquine * Maybe affects heme metabolism

Answer 35

Given oral only

Answer 36

* For chloroquine-resistant P. falciparum * Not effective for prophylaxis

Answer 37

* Well-tolerated * May cause * GI symptoms * **Palpitations** * **MSK sx** * **Neurological sx**

Answer 38

* **Atovaquone** ⇒ ⊗ cytochrome bc1 complex (III) of ETC in plasmodia * **Proguanil** ⇒ lowers effective concentration at which atovaquone collapses the mitochondrial membrane potential

Answer 39

* **Recommended for prophylaxis** * Does not have neuro side effects of mefloquine * **Treatment of uncomplicated chloroquine-resistant or multidrug-resistant malaria**

Answer 40

* Abd pain * Nausea * Diarrhea * Headache

Answer 41

* Use with caution in severe renal impairment * Contraindicated in pregnancy

Answer 42

**Only drug effective against exoerythrocytic stage.** * _Primaquine + drug for erythrocytic stage_ * **Radical cure of plasmodium vivax and ovale** * Can be used in **terminal prophylaxis for known exposure** to P. vivax and P. ovale * **Somewhat effective against the primary form**

Answer 43

**Only given PO.** T_1/2 of 3-6 days ⇒ **requires daily dosing**

Answer 44

Generally well-tolerated. **Contraindicated in G6PD deficiency and pregnancy.**

Answer 45

* Long pregnanglionic neurons ⇒ **ACh** **⇒** **neuronal type nicotinic receptors** * Short postganglionic neurons ⇒ **ACh ⇒ muscarinic receptors**

Answer 46

* Short preganglionic neurons ⇒ ACh ⇒ neuronal-type nicotinic receptors * Long postganglionic neurons ⇒ NE ⇒ alpha or beta adrenergic receptors * Except sweat glands ⇒ use M₃ receptors

Answer 47

hexamethonium

Answer 48

* Synthesis * Choline + acetate CoA by **choline acetyltransferase** * Stored in vesicles * Degraded by **acetylcholinesterase**

Answer 49

* Synthesis * Tyrosine → DOPA by ***tyrosine hydroxylase*** * Rate-limiting * L-DOPA → dopamine by ***decarboxylase*** * Within vesicles * Dopamine → NE by ***dopamine β-hydroxylase*** * In the adrenal medulla * NE → Epi by ***PNMT*** * Termination of action * Reuptake * Degradation by MAO and COMT

Answer 50

SNS ⇒ β₂ ⇒ bronchodilation PNS ⇒ M₃ ⇒ bronchoconstriction

Answer 51

* **SNS ⇒ β₁** * SA node ⇒ inc. HR (+ chronotropic) * AV node ⇒ inc. conductance (+ dromotropic) * Myocytes ⇒ inc. FOC (+ ionotropic) * **PNS ⇒ M₂** * SA node ⇒ dec. HR (- chronotropic) * AV node ⇒ dec. conductance (- dromotropic) * No innervation of ventricles * Exogenous ACh ⇒ dec. FOC (- ionotropic)

Answer 52

* **SNS** * Skin and viscera ⇒ **α₁** by Epi/NE ⇒ vasoconstriction * Skeletal muscle ⇒ **β₂** by Epi ⇒ vasodilation * **PNS** * No innervation * Exogenous muscarinic agonists ⇒ NO ⇒ vasodilation

Answer 53

* **SNS ⇒ α₁** ⇒ dilator radial muscle contraction ⇒ pupil size inc. * **PNS ⇒ M₃** ⇒ constrictor circular muscle contraction ⇒ pupil size dec.

Answer 54

* **SNS ⇒ β₂** ⇒ relax ciliary muscle ⇒ tension on suspensory ligaments ⇒ flat lens ⇒ far vision * **PNS ⇒ M₃** ⇒ contract ciliary muscle ⇒ relax suspensory ligaments ⇒ convex lens ⇒ near vision

Answer 55

**SNS ⇒ β₂** ⇒ glycogenolysis ⇒ inc. BGL

Answer 56

* Activated by sensory afferents * Can occur along multiple levels * Ganglion or spinal cord

Answer 57

Controlled by hypothalamic and brain stem centers.

Answer 58

**Direct** ⇒ receptor agonists **Indirect** ⇒ acetylcholinesterase inhibitors

Answer 59

ACh ⇒ **M₃ receptors** ⇒ NO by endothelial cells ⇒ vasodilation * Low dose ACh IV ⇒ ↓ BP ⇒ reflex ↑ HR * High dose ACh IV ⇒ profound bradycardia * Due to direct effect on the heart

Answer 60

* ACh * First excite nicotinic receptors * Continued stimulation ⇒ desensitization * Normally prevented by action of AChE * **In the presence of AChE inhibitors** * **Endogenous ACh causes fasciculations then paralysis**

Answer 61

Due to muscarinic \> nicotinic stimulation. DUMBELS

Answer 62

Rapidly hydrolyzed ⇒ limited applications 1. **Intraocularly** ⇒ produce miosis s/p lens extraction 2. **Intracoronary** * Cause vasodilation during dx coronary angiography * Dx vasospastic angina via direct effect on smooth muscle causing contraction

Answer 63

* Action: * **Agonist @ mAChRs** * Indications: * **Test for bronchial hyperreactivity & asthmatic conditions** * Carefully ⇒ dangerous drug

Answer 64

* Action: * **Agonist at all AChRs** * Indication: * **Wide-angle glaucoma** * Not the preferred agent

Answer 65

* Action: * **Agonist at GI mAChRs** * Indications: 1. **Post-op for abdominal surgery** 2. **Post-partum to reduce bladder distention** 3. **Promote salivation** * Alternative to Pilocarpine

Answer 66

Methacholine and Betanechol ⇒ mAChR activities Carbachol ⇒ mixed AChR activities * **Decreased night vision** * **Difficulty focusing on distant objects** * DUMBELS

Answer 67

1. **Asthma** * May precipitate an asthma attack d/t M₃ mediated bronchoconstriction 2. **Urinary obstruction** 3. **Acid-peptic disease** * May induce gastric acid secretion

Answer 68

* ACh and related esters charged quaternary amines * Do not enter CNS * Most muscarinic agonists may cause arousal response @ high doses * At "normal" therapeutic doses ⇒ actions confined to peripheral tissues

Answer 69

* Action: * Agonist @ mAChRs * 3° amine ⇒ enters CNS * May cause hallucinations and convulsions * Indications: * **_Eye drops_** ⇒ miotic agent (lasts about 1 day) * **Wide-angle glaucoma** * Not the preferred agent * **Acute closed-angle glaucoma** * If pressure too high * **_PO_** * Xerostomia ⇒ **stimulation salivation**

Answer 70

* _Chronic use_ * **Decreased night vision** * **Difficulty focusing on distant objects** * DUMBELS without muscle effects

Answer 71

* Found in some species of mushrooms * **Ingestion ⇒ muscarine poisoning** * DUMBELS * **Reversed with atropine**

Answer 72

* Action: * **Activates ganglionic nACh receptors** * **Receptor blockade w/ persistent stimulation** * Nicotine patches for smoking cessation * **Potential for ganglionic blockade @ high doses** ⇒ **Nicotine poisoning** * May be used as a pesticide * Complex effects * Depends on dose and timing * Tachy or brady * HTN or hypotension

Answer 73

* Mechanism 1. ACh binds ⇒ choline released 2. Hydrolysis of acyl intermediate * Blood has 'true' AChE inside RBCs * Plasma has butyrylcholinesterase * Hydrolyzes butyrylcholine faster than ACh

Answer 74

Block AChE ⇒ ↑ [ACh] * Found in agricultural pesticides * Some used as chemical warfare agents * 3° vs 4° amines * Reversible * Edrophonium * Carbamates * Physotigmine * Neostigmine * Pyridostigmine * Irreversible * Organophosphates * Echotiophate * Malathion * Parathion * Sarin/Soman

Answer 75

* **Reversible competitive cholinesterase inhibitor** * Blocks ACh access to active site * 4° amine * **Does not enter CNS** * Short duration of action ⇒ 1-5 mins * **Used to test for myastenia gravis**

Answer 76

* Reversible AChE inhibitor * Block active site while undergoing slow hydrolysis * Includes: * Physotigmine * Neostigmine * Pyridostigmine

Answer 77

* **Reversible competitive substrate for AChE** * Indications: * **Wide-angle glucoma** ⇒ faciliate efflux of aqueous humor * Not the preferred agent * 3° amine ⇒ **enters CNS** * **Reverses effect of atropine & other antimuscarinic drugs** * Adverse effects ⇒ **cataracts**

Answer 78

* **Reversible competitive substrate of AChE** * Indications: * **Paralytic bladder or GI tract** * **Myastenia gravis** * 4° amine ⇒ does not enter CNS * Short duration of action ⇒ **2-4 hours**

Answer 79

* Reversible competitive substrate of AChE * Indications: * Choice for myastenia gravis * Longer acting ⇒ 3-6 hrs * Nerve gas prophylactic

Answer 80

* Some muscarinic side effects * Tolerance usually develops w/ extended use * May exacerbate * COPD * Asthma * Gastric ulcer

Answer 81

Inactivate AChE by covalent attachment * Organophosphate hydrolyzed by AChE * Acyl intermediate replaced by phosphoryl group * Cleaved extremely slowly * Bond can be strengthened over time ⇒ **aging** * AChE can be r**eactivated w/ strong nucleophile during early stages** of inhibition before aging

Answer 82

* Only clinically useful organophosphate * Used in glaucoma

Answer 83

* Pro-drug insecticide organophosphate * Once activated undergoes detoxification in mammals via plasma esterases * Involved in farm poisonings

Answer 84

* Potent insecticide 'pro-drug' organophosphate * Metabolized by mixed-function oxygenases * Responsible for most cases of poisoning and death

Answer 85

* "Nerve gas" * Extremely toxic organophosphate * Used in chemical warfare

Answer 86

Acute intoxication ⇒ **mix of muscarinic, nicotinic, and CNS effects** SLUDGE-BAM

Answer 87

* **Organophosphate** ⇒ much longer lasting AChE inhibition * See signs of nicotinic excess * **Carbamates** * Mostly muscarinic parasympathetic symptoms

Answer 88

Respiratory failure * Bronchoconstriction * Bronchorrhea * Central respiratory depression * Weakness/paralysis of respiratory muscles

Answer 89

1. **Atropine** * Reverse muscarinic effects 2. **Pralidoxime (PAM)** * Reactivate phosphoryl enzyme * Only effective early before "aging" 3. **Diazepam** * Prevent/alleviate convulsions 4. **Supportive measures for respiratory distress**

Answer 90

* Actions d/t ⊗ of PNS influence in tissues * Predominantly PNS tone in most tissues except vasculature and sweat glands * mAChR blockade lets SNS influence predominant

Answer 91

**Non-specific muscarinic antagonist.** 3° amine ⇒ enters CNS * _Ocular_ * **Mydriasis** * **Blocks accommodation** * **Inhibits lacrimation** * _Cardiac_ * Standard doses ⇒ blocks vagal input * **↑ HR and AV conduction** * Very low doses ⇒ block presynaptic receptors * May initially ↓ HR * _Respiratory_ * **Bronchodilation** * **Inhibit secretion** * _GI_ * **↓ lower esophageal tone** * ↓ GI tone ⇒ **↑ transit time** * **↓ gastric acid secretion** * _GU_ * Relaxes detrusor ⇒ **urinary retention** * _CNS_ * **Stimulation then sedation** * **Dizziness and imbalance** * High doses ⇒ confusion and/or hallucinations * _Others_ * Inhibits sweating ⇒ hyperthermia ⇒ **cutaneous vasodilation** * **Dry mouth**

Answer 92

1. **Reverse muscarinic or AChE inhibitor poisoning** 2. **Long-lasting pupil dilation** for eye exams * Not preferred 3. Combo w/ diphenoxylate (Lomotil) ⇒ **anti-diarrheal** 4. "Pharmacological patch" for amblyopia 5. Sinus bradycardia and AV block 6. **Prevent muscarinic side effects** in AChE inhibitor treatment in Myastenia gravis

Answer 93

* **Muscarinic antagonist** * Used for **motion sickness** * Administered as a patch * Side effects ⇒ **drowsiness** * **3° amine ⇒ enters CNS** * More sedating than Atropine

Answer 94

**Muscarinic antagonist.** **Fast but short acting mydriatic agents.** May be used in combo w/ alpha-adrenergic agonist.

Answer 95

* Muscarinic antagonist * 4° amine given by inhalation * **Bronchodilator** for asthma and COPD

Answer 96

* Similar to ipratropium * Inhaled muscarinic antagonist * Longer acting

Answer 97

* **Antagonist at bladder mAChRs** * **Management of overactive bladder** * Fewer adverse effects like dry mouth and blurred vision * **Contraindicated in pts w/ narrow-angle glaucoma**

Answer 98

* **Muscarinic antagonist @ GI mAChRs** * Relaxes intestinal smooth muscle * **Used for irritable bowel symptoms**

Answer 99

* Muscarinic antagonist * **Low doses preferentially inhibit secretion** * Used pre-op to inhibit secretions * Prevent excessive sweating * **Prevent muscarinic side effects of Neostigmine to reverse NMJ block**

Answer 100

* **Lipid soluble mAChR antagonist** * **Used to relieve extrapyramidal sx** * Parkinson's * Pts taking antipsychotics

Answer 101

* **Antihistamines** * Diphenhydramine * **Antidepressants** * Tricyclics (e.g. amitriptyline) * **Phenothiazine antipsychotics** * Chlorpromazine

Answer 102

* Act by ⊗ neuronal nAChR of all autonomic ganglia * Apparent effects still mostly sympathetic-like * Blocks all autonomic influence * Removes the predominant PNS tone of most tissues * Apparent opposing effect

Answer 103

* **Ganglionic blocker** * Prevents baroceptor reflex * First effective anti-hypertensive * No longer used * Poorly absorbed * Autonomic side effects

Answer 104

* **Ganglionic blocker** * Uses: * Improve GI absorption * Tourette's syndrome

Answer 105

Acts via Gq.

Answer 106

Acts via G_i.

Answer 107

Acts via G_s.

Answer 108

Acts via G_s.

Answer 109

Acts via G_s.

Answer 110

* **Long-term** ⇒ via transcription or translation changes * **Short-term** ⇒ via phosphorylation * **Homologous** ⇒ receptor unresponsive to its own agonist * **Heterologous** ⇒ activation of one receptor leads to desensitization of another receptor

Answer 111

* Mechanism * α₁ ⇒ G_q ⇒ ↑ Ca²⁺ ⇒ ⊕ MLCK ⇒ myosin-℗ ⇒ * **Contraction of arterial resistance vessels** * **↓ venous capacitance** * Predominate in skin and splanchnic vessels * **Pure α₁ agonist** * **↑ BP ⇒ reflex bradycardia** * Blocked by ganglionic blockers or anti-muscarinics * Useful in hypotension * Overstimulation ⇒ hemorrhage d/t ↑ BP

Answer 112

* Stimulated when NE released into synapse * Results in dec. NE release * α₂ agonist PO ⇒ ⊕ α₂ receptors in CNS ⇒ ↓ SNS output ⇒ ↓ BP

Answer 113

* Mechanism * β₁ ⇒ G_s ⇒ cAMP ⇒ ℗ of Ca²⁺ channels ⇒ Ca²⁺influx * **+ chronotropic, inotropic, and dromotropic** * May also ⇒ ℗ of troponin C ⇒ **inc. sensitivity of contractile apparatus** * Useful in cardiogenic shock * Overstimulation ⇒ arrhythmias

Answer 114

* Mechanism * β₂ ⇒ Gs ⇒ cAMP ⇒ PKA ⇒ phosphorylation and inhibition of MLCK ⇒ vasculature relaxation and vasodilation

Answer 115

PP = SBP - DBP * Some agents ↑ PP * ↑ SBP * No effect or ↓ DBP

Answer 116

(Mean arterial pressure - Mean venous pressure) / CO

Answer 117

**Pure α agonist** ⊕ α1 ⇒ vasoconstriction ⇒ ↑ BP ⇒ reflex bradycardia No effect on β1 ⇒ no effect on PP

Answer 118

* No effect on β2 ⇒ acts like α-agonist w/ β1 activity * Injected NE ⇒ ↑ BP and ↑ PP * Reflex bradycardia masks the direct stimulatory effects of β1 activation on the heart

Answer 119

**Activates β receptors.** ↑ HR and ↑ PP ↓ BP

Answer 120

**β activation \> α activation** Combined effect of β2 \> α1 ⇒ modest ↑ BP

Answer 121

**_α1 predominates_** Significant ↑ BP ⇒ reflex bradycardia Looks more like a response to NE

Answer 122

**_Non-selective β activation_** * β1 ⇒ heart ⇒ ↑ SBP, ↑ HR * β2 ⇒ vasodilation of vascular beds ⇒ ↓ DBP * Results in ↑ PP

Answer 123

High doses ⇒ ⊕ dopamine, ⊕ beta, and ⊕ alpha receptors * β1 ⇒ ↑ HR , ↑ SV * β2 ⇒ vasodilation ⇒ ↓ TPR ⇒ ↓ BP * α1 ⇒ ↑ SBP * D1 ⇒ ↓ DBP * Via renal, skin, and splanchnic vasodilation * D2 ⇒ ⊗ NE release

Answer 124

Stimulate beta-2 receptors ⇒ bronchodilation & relax SM in other areas Used for asthma or to prolong labor.

Answer 125

* **Alpha-1 agonists** * Contract dilator muscles ⇒ **mydriasis** * Used w/ muscarinic antagonists for eye exams * **Alpha-2 agonists** * Work on ciliary body ⇒ **↓ aqueous humor secretion** * Used to treat glaucoma * **Beta-2 agonists** * Relax ciliary muscle ⇒ **allows aqueous humor to escape via uveoscleral pathway** * Treat glaucoma (not preferred)

Answer 126

* **Alpha-1 agonists** * Contraction of urethral sphincters * **Beta-2 and beta-3 agonists** * Relaxation of detrusor muscle * Net effect of sympathetic stimulation ⇒ **urinary retention**

Answer 127

* PNS \> SNS in causing salivation * PNS ⇒ watery secretion w/ K⁺ and amylase * **Alpha-1 agonists** * Small and transient inc. in watery secretion w/ K⁺ * **Beta-1 agonists** * Enhances effect of PNS on amylase secretion * Net effect of sympathetic stimulation ⇒ **small amount of thick saliva**

Answer 128

_Epi has complex effects on BGL_ * **Liver** ⇒ α1 and β2 ⇒ inc. glycogenolysis and gluconeogenesis ⇒ hyperglycemia * **Pancreas** * First activates alpha-2 ⇒ dec. insulin secretion ⇒ large inc. in BGL * Then activates beta-2 receptors ⇒ modest inc. in insulin ⇒ allows muscle to use glucose

Answer 129

CNS has alpha, beta, and dopamine receptors. * Epi cannot enter CNS except @ high doses * Adrenaline rush or feeling of disaster * Some agents can enter CNS * Arousal, euphoria, anorexia, etc

Answer 130

NE, Epi, and Dopamine

Answer 131

Direct Acting Adrenergic Agonist * Potent vasoconstrictor * Used for hypotension

Answer 132

Direct Acting Adrenergic Agonist * **Drug of choice for anaphylactic shock** * Cardiac arrest * Reduction of bleeding during surgery * Prolonging action of some local anesthetics

Answer 133

Direct Acting Adrenergic Agonist * Cardiogenic shock * Septic shock * Adjunct in hypovolemic shock

Answer 134

**Direct pure alpha-1 agonist** * Mydriasis w/o cycloplegia (dilate) * Nasal decongestant * Terminate paroxysmal atrial tachycardia (reflex effect) * Hypotension

Answer 135

**_Direct pure alpha-2 agonist_** Vascular and CNS * HTN esp. in renal disease * Central action ⇒ dec. SNS outflow ⇒ dec. BP * Analogues used in glaucoma * Benzo and opiate withdrawal

Answer 136

Converted to methyl-NE centrally **Direct alpha-2 agonist in CNS** Dec. SNS outflow ⇒ dec. BP

Answer 137

**_Direct β1 \> β2 agonist_** * Inotropic vasodilator * Uses: * Cardiogenic shock * Acute heart failure * Cardiac stimulation

Answer 138

**Non-specific β-agonist** * Not the drug of choice for anything * Uses * Bronchospasm and asthma * Not DOC * Refractory heart block * Refractory bradycardia

Answer 139

**_Direct β2 Agonists_** Used for asthma, COPD, and bronchitis. Salmeterol is long-lasting.

Answer 140

**Beta-3 agonist** Overactive bladder

Answer 141

**Causes release of NE.** **Weak adrenergic activity.** Significant CNS stimulation * Uses * Decongestant (main use) * Bronchospasm * Hypotension

Answer 142

Cocaine Amphetamine Tyramine

Answer 143

* Peripharal * Blocks NE reuptake ⇒ inc. NE ⇒ inc. sympathetic responses * CNS * Blocks dopamine reuptake ⇒ profound stimulatory effect

Answer 144

* Substrate for NE transporter * Enters vesicles ⇒ displaces NE ⇒ NE exits presynaptic terminal * Stimulant used in ADHD

Answer 145

* **Found in some food** * Normally metabolized by MOA in liver and GI tract * Drugs that block MAO allows tyramine into circulation * **Actions similar to amphetamine** * Releases large amount of NE * **Can cause a hypertensive crisis**

Answer 146

* Place in recumbent position & fluid resusitate * **Vasoconstrictive agents only in an emergency to preserve profusion to critical organs** * Can also cause dec. flow

Answer 147

Cardiogenic vs septic vs hypovolemic Goal to maintain tissue perfusion. * Usual treatment * Volume replacement * Treat underlying problem * Vasoconstriction ⇒ shock * Use alpha-blockers * Vasodilation ⇒ shock * Use vasoconstrictor (alpha-1 agonist) * Cardiogenic shock * Dopamine or dobutamine * Dopamine * beta-1 ⇒ stimulates heart * D1 ⇒ maintain kidney profusion

Answer 148

* **Epi short term** * Help redistribute blood flow to the heart during resuscitation * Pacemaker should be placed ASAP * NO Isoproterenol ⇒ more likely to inc. cardiac work

Answer 149

* **Epinephrine** * Control bleeding during surgery on external areas * Prolong action of local anesthetics by restricting blood flow * **Cocaine** * Used for nasopharyngeal surgery * Vasoconstriction * Anesthetic * **Agents w/ alpha-1 agonist activity** * Nasal decongestants * Dec. volume of nasal mucosa * Cause rebound hyperemia when stopped * Local application w/ nasal sprays can cause ischemic changes in mucosa

Answer 150

Beta-2 selective drugs preferred. Albuterol, metaproterenol, terbutaline, salmeterol Mainly for asthma.

Answer 151

Epinephrine drug of choice * beta-2 ⇒ bronchodilation * beta-1 ⇒ stimulates heart * alpha-1 ⇒ maintains perfusion

Answer 152

* **Phenylephrine** * Dilate eyes * Allergic hyperemia * **Apraclonidine** * Alpha-2 agonist for glaucoma * **Epinephrine** * Acting as beta-2 agonist ⇒ rarely used * Beta-blockers first line agents

Answer 153

* _Cardiovascular_ * **Orthostatic hypotension** * ⊗ alpha-1 ⇒ dec. peripheral vascular resistance ⇒ dec. BP * **± Reflex tachy** * More likely w/ nonspecific alpha blockers * ⊗ presynaptic alpha-2 ⇒ inc. NE @ heart * Abrupt withdrawal after long-term treatment can cause rebound HTN * _GU_ * Alpha-1 activation ⇒ contraction of urethral sphincters and prostate * **Blockade can facilitate flow**

Answer 154

* High dose Epi ⇒ alpha \> beta effect * **↑ BP** * If alpha-antagonist given before Epi * Only see beta effects * **β2** ⇒ **↓ BP** * **β1 and reflex tachy** ⇒ **↑** **HR**

Answer 155

* **Miosis** * **Nasal stuffiness** * **GI hypermotility** * Sexual dysfunction (centrally mediated) * Dry mouth * Dizziness * Somnolence * Headache

Answer 156

**Irreversible non-selective alpha blocker** * Indications * **HTN due to Pheochromocytoma** * Dec. BP when SNS tone high * **Raynaud's** * Adverse effects * Tachycardia * Due to block of presynaptic alpha-2 and reflex mechanisms

Answer 157

**Competitive non-selective alpha blocker** * Indications * **Hypertensive emergencies** * Short half-life * Adverse effects * Tachycardia d/t α₂ block

Answer 158

**Competitive α1 blocker** * Indications * **Mild HTN** * Adverse effects * Less likely to cause tachycardia

Answer 159

**Selective alpha-1 blocker** Longer half-life than Prazosin * Indications * **Mild HTN** * **BPH** * Adverse effects * Less likely to cause tachycardia

Answer 160

**Selective alpha 1A and 1D blocker.** Predominant in prostate. **Used in BPH.**

Answer 161

* Tumor of adrenal medulla releasing NE and Epi * HTN, HA, tachycardia, sweating * **Alpha-1 blockers used pre-operatively** * Phenoxybenzamine most often * Also used for inoperable tumors * **Beta-blockers may be given** * Only after alpha-1 blocker to avoid unopposed alpha-1 vasoconstriction

Answer 162

* Beta-blockers * Alpha-1 blockers

Answer 163

* **Prazosin or phenoxybenzamine ⇒ alpha blockers** * Treat vasospasm in peripheral circulation (Raynaud's phenomenon) * Calcium channel blockers preferred * Behavioral modifications first

Answer 164

Use alpha-1 blocker * Prazosin or doxazosin * Tamsulosin more selective for prostate * Less effect on BP * Can use for pt w/ prior orthostatic hypotension

Answer 165

erectile dysfunction

Answer 166

**Low bioavailability** d/t significant 1st pass metabolism Several drugs metabolized by **CYP450** **enzymes**

Answer 167

* **Bradycardia** * Treat w/ glucagon * Rebound HTN w/ abrupt withdrawal * Dec. contractility * Dec. excitability * **Inc. BP then dec. BP** * Early rise due to unopposed alpha-1 * Late fall due to * Dec. renin * CNS effects * Inhibit NE effects @ heart * **Can precipiate heart failure in patients with abnormal cardiac function**

Answer 168

* **Block β-2** ⇒ bronchoconstriction * Worse w/ asthmatics * Avoid non-specific beta blockers

Answer 169

Dec. production of aqueous humor. Most widely used drug for glaucoma.

Answer 170

* β2 blockade * Inhibit epi mediated stimulation of glycogenolysis * Can mask sx of hypoglycemia by blocking tachycardia and tremors

Answer 171

* Non-specific beta blockers inhibit hormone sensitive lipase * Inc. VLDL and triglycerides * Dec. HDL * No change to LDL * Inc. LDL/HDL ratio due to HDL decrease * Less likely to occur when beta-blocker has intrinsic sympathomimetic activity

Answer 172

**Propranolol, pindolol, and metoprolol** * **Via blockade of sodium channels** * Has local anesthetic action * **Can affect myocyte sodium channels** * Only a problem at high doses * Prolong QRS duration * Impair cardiac function * **Contraindicated in patients with glaucoma**

Answer 173

**Pindolol and Acebutolol have beta-agonist properties.** Considered partial agonists. * Capable of β stimulation, especially when catecholamines low * Less bradycardia * Slight vasodilation * Minimal change in lipids

Answer 174

If they can enter the CNS: * Dizziness * Fatigue * Depression * Sexual dysfunction

Answer 175

**Non-specific β-blocker** 1. Many indications * HTN * Angina * Arrhythmias * Migraine * Thyroid toxicosis * Essential tremor 2. **Readily enters CNS** * Can cause excessive somnolence and impaired cognition 3. **Membrane-stabilizing activity (highest)** * High doses ⇒ prolong QRS and impair cardiac conduction * Contraindicated in glaucoma

Answer 176

**Non-specific β-blocker** * **Indications:** * **Widely used for glaucoma** * **HTN** * **MI** * No membrane stabilizing activity

Answer 177

**Non-specific β-blocker** * **Same indications as propanolol** * **HTN** * **Angina** * Arrhythmias * Migraine * Tyroid toxicosis * Essential tremor * **Very long half-life**

Answer 178

**Non-selective β-blocker with intrinsic sympathomimetic activity.** **Used for HTN in pts w/ bradycardia or PVD.** Less likely to cause bradycardia and lipid changes.

Answer 179

**β1-selective** * Preferred in pts who had bronchoconstriction after propanolol * Used in pts w/ COPD, DM, PVD with caution * **Atenolol** * Very low lipid solubility ⇒ **does not enter CNS** * **Widely used for HTN** * **Metoprolol** * High lipid solubility ⇒ enters CNS * MSA * **Still widely used for HTN**, MI, angina

Answer 180

**β1-selective** * Very short acting w/ T_1/2 10 mins * **Good for critically ill pts** * **Indications:** * **Intraop and postop HTN** * **Arrhythmias**

Answer 181

**β1-selective** * Less likely to cause bronchoconstriction * **Used for glaucoma**

Answer 182

**β1-selective blocker with intrinsic sympathomimetic activity.** **Used for HTN in patients w/ bradycardia.** Less likely to cause bradycardia and lipid changes.

Answer 183

**Nonspecific β blocker**, less than propranolol. **Some ISA at β2.** **α1 blocker,** less than phentolamine **Used for HTN and severe HTN.**

Answer 184

**Non-specific β-blocker \> α1 blocker.** **Used to treat CHF and HTN.** Contraindicated in severe heart failure. Effectiveness in CHF partially due to: * Attenuation of oxygen free radical action * Inhibition of vascular smooth muscle mitogenesis

Answer 185

**Indirect acting adrenergic antagonist** * **Blocks vesicular transport system both peripherally and centrally** * NE not take up into vesicles * Also effects dopamine and serotonin * **Depletion of amines in CNS** * Severe adverse effects * Depression

Answer 186

1. **HTN** * Usually in combo w/ diuretics or ACEi 2. **Ischemic heart disease** * _Timolol, propranolol, and metoprolol_ * Reduces freq. of angina & improves exercise tolerance * Contraindicated in bradycardia or hypotension 3. **Arrhythmias** * Slow AV nodal conduction * **Used for A. Fib and A. Flutter** * **Treat ventricular arrhythmia w/ ectopic beats d/t excess E/NE** 4. **Heart failure** * _Carvedilol_ in moderate heart failure * Not used in acute heart failure 5. **Glaucoma** * Most widely used along w/ prostaglandin analogues * Applied directly to eye but has some systemic absorption * Can effect heart or cause bronchoconstriction * May combine w/ Ca²⁺ channel blockers to slow AV nodal conduction 6. **Hyperthyroidism** * Ideal for condition * Blocks beta-activation by ANS * Blocks conversion of thyroxine to triiodothyronine 7. **Migraines** * Prophylaxis of headaches 8. **Tremors, performance anxiety** * Low doses used to reduce tremors

Answer 187

**⊗ HMG-CoA reductase** * Rate-limiting step in cholesterol biosynthesis * Moderate transient ↓ [cellular cholesterol] * Activation of SREBP2 signal cascade * **SREBP2 transcription factor** * ↑ LDL receptor expression * ↑ uptake of LDL * ↓ plasma LDL

Answer 188

* **Primary prevention** ⇒ ↓ mortality from CVD in people without CVD * **Secondary prevention** ⇒ ↓ mortality from CVD after MI * Reduction greater in secondary * **Max 60% ↓ in LDL** * Depends on dose and med used * **Max 10% ↑ in HDL**

Answer 189

* Generally well-tolerated * Adverse effects * **Myopathy and/or rhabdomyolysis** * \<0.1% of pts on high dose of potent statin * **↑ liver enzymes** * Need q6-month LFTs * **Contraindications** * **Liver disease** * **Pregnancy** * Cholesterol needed for fetal growth

Answer 190

Cholestyramine Colesevelam Colestipol

Answer 191

**Bind bile acids and promote excretion.** 1. ↑ excretion shunts more cholesterol into bile acid synthetic pathway 2. ↓ hepatic cholesterol 3. ↑ LDL receptor expression 4. ↓ plasma LDL

Answer 192

All 3 sequestrants produce similar effects. * **Max 25% ↓ in LDL** * Should be present in small intestine following a meal for max effect * Usually taken with food

Answer 193

* _Adverse effects_ * **Bloating** * **Dyspepsia** * **May lead to ↑ serum triglycerides** * Caution in pts with hypertriglyceridermia * Or use in combo with agent that ↓ TAG * _Contraindications:_ * **Dysbetalipoproteinemia** * **TAG \> 400 mg/dL** * _Interactions_ * **Binds other lipid soluble compounds** * Can bind other drugs and cause excretion * Statins * Thiazides * Warfarin * Thyroxine * Digoxin * Should not take these meds 1 hour before - 4 hours after taking sequestrant * **Interferes with Vit K** * ↑ risk of excessive bleeding on warfarin

Answer 194

Ezetimibe Plant sterols

Answer 195

Prevent absorption of cholesterol by small intestine. Dec. delivery of cholesterol to liver leads to dec. plasma LDL.

Answer 196

* As a monotherapy ⇒ **max 15-20% ↓ in LDL** * **Can be used in combo w/ statin** * Effects are additive * Minimal adverse effects

Answer 197

Gemfibrozil Fenofibrate

Answer 198

**Activate peroxisome proliferator-activated receptor α (PPARα).** * PPARα is a nuclear receptor * Dimerizes w/ retinoid X receptor (RXR) * **Activates genes associated w/ FA metabolism including** * Lipoprotein lipase * Apo AI * Net effect * **↓ TGL levels** * **↑ HLD levels**

Answer 199

* **1° for hypertriglyceridemia and/or to raise HDL levels** * Max 50% dec. TGL * Max 20% inc. HDL * As monotherapy, **moderate effect in LDL levels** * Can be used w/ statins

Answer 200

* Adverse effects * GI discomfort * **Gallstones** * **Hepatotoxicity** * _Contraindications_ * **Severe renal disease** * **Severe hepatic disease** * **Can inc. free warfarin levels** * Inc. risk of bleeding

Answer 201

"Nicotinic acid or Vit B3" * At low physiological levels (10-20 mg/day) * Need for synthesid of NAD and NADP * _At high doses (1500-3000 mg/day)_ * **Acts via GPCR to dec. adipocyte hormone sensitive lipase activity** * Less substrate for hepatic lipoprotein synthesis * Dec. plasma TGL and LDL * **Inc. plasma Apo AI levels** * Inc. HDL

Answer 202

* **Most effective agent to inc. HDL** * **Max 35%** * Dec. TGL max 50% * Dec. LDL max 25%

Answer 203

Used as monotherapy for **moderately high LDL with low HDL**. Used as an adjunct to statin therapy.

Answer 204

* _Common_ * **Flushing** * **Itching** * Can be reduced by taking ASA or other NSAIDs * Time-release formulas (Niaspan) can reduce incidence * _Less common / more severe_ * **Hepatoxocitity** * **Hyperuricemia** * **Impaired insulin sensitivity** * **Potentiation of statin-induced myopathy** * _Contraindications:_ * **Chronic liver disease** * **Severe gout**

Answer 205

"Fish oils, EPA, DHA" * **Mech. appears to involve regulation of transcription factors PPARα, PPAR𝛾, SREBP-1c** * Dec. TGL synthesis and inc. FA oxidation * **Can dec. TGL max 50% in hypertriglyceridemia** * Used when plasma TGL \> 500 mg/dL * ***Lovaza*** ⇒ prescription strength

Answer 206

**alirocumab (Praluent)** **evolocumab (Repatha)** * PCSK9 affects LDL-R recycling * **↑ PCSK9 activity ⇒ ↓ LDL-R** * **Monotherapy ⇒ max 40-50% dec. in LDL** * **Combo w/ statins ⇒ max 70% dec. in LDL** * Use approved for pts who cannot achieve LDL goals with other treatments

Answer 207

* Mechanism * Substrate for VLC acyl-CoA synthetase-1 (ACSVL1) * CoA derivative of drug inhibits ATP citrate lyase (ACL) * **Inhibition of ACL reduces choleserol synthesis** * Skeletal muscle does not have ACSVL1 ⇒ med is liver-specific * **Shown in trials to reduce LDL w/o muscle side effects of statins**

Answer 208

Released in 2019 * **Focuses primarily on statin use** * **Requires LDL testing 3 months after starting or changing dose** * Every 6-12 months afterwards * For patients nonresponsive to statins, recommend **adding ezetimibe and/or PSCK9 inhibitors** * No others currently recommended

Answer 209

**↑ O₂ delivery to cardiac tissue by ↑ coronary blood flow** and/or **↓ O₂ demand by ↓ cardiac work** * _Stable angina_ ⇒ dec. cardiac work through systemic vasodilation * _Unstable angina_ ⇒ dec. cardiac work & thrombogenesis * _Variant angina_ ⇒ reverse coronary spasm

Answer 210

* HR * Contractility (inotropic state) * Arterial pressure (afterload) * Ventricular volume (wall stress, preload)

Answer 211

* Aortic diastolic pressure * Duration of diastole * Coronary vascular resistance

Answer 212

Arteriolar and venous tone ⇒ ∆ peripheral vascular resistance ⇒ ∆ arterial blood pressure

Answer 213

SM uses MLCK to trigger crossbridge formation. 1. **↑ cGMP** * cGMP facilitates de-Phos of MLCK * Prevents myosin interaction w/ actin * Ex. organic nitrates 2. **↓ [Ca²⁺] by preventing entry** * ↓ activity of MLCK * Ex. Ca²⁺ channel blockers (verapamil, diltiazem, dihydropyridines) 3. **Stabilize/prevent membrane depolarization by ↑ K⁺ permeability** * Prevents activation of voltage-gated Ca²⁺ channels * Ex. K⁺ channel openers (minoxidil, hydralazine) 4. **↑ cAMP** * cAMP ↑ rate of inactivation of MLCK * Not used in treatment of angina d/t effects on HR and contractility

Answer 214

* Release NO @ target tissues * **NO activates guanylyl cyclase ⇒ cGMP ⇒ de-℗ of MLCK ⇒ vasodilation** * At therapeutic doses ⇒ actions mostly confined to smooth muscles * **Venodilation** ⇒ ↓ preload and ventricular filling ⇒ ↓ myocardial O₂ demand * Main effect * **Dilation of large coronary arteries and arterioles** ⇒ redistribution of blood flow from epicardial to endocardial regions ⇒ some relief from ischemia

Answer 215

* **Isosorbide 5-mononitrate can be given PO** * Avoids extensive 1st pass metabolism seen w/ nitroglycerin and isosorbide dinitrate * Longer duration of action * **Nitroglycerin & isosorbide dinitrate given sublingual and slow-release buccal** * Bypass liver and 1st pass * Reach terapeutic levels rapidly * **Amyl nitrite given by inhalation** * Also bypass hepatic system * **IV preparations available** * Rapid metabolism ⇒ **only used for acute treatment** * Long-lasting slow release preps available but usefulness limited by tolerance

Answer 216

* **Repeated admins ⇒ loss of effectiveness** * Tolerance seen after use of long-acting or IV for severals hours * **Large degree of cross-tolerance between nitrates** * Maybe due to dec. release of NO but mech. unknown * **Systemic compensation** w/ salt and water retention can also be involved

Answer 217

↓ Ca²⁺ influx ⇒ ↓ intracellular Ca²⁺ ⇒ relaxation * Main target is **L-type Ca²⁺ channels** * Two classes ⇒ bind to different sites * **Dihydropyridines (DHPs)** * _nifedipine, amlodipine, felodipine_ * **Major effect as vasodilators only** * ↓ arterial tone and systemic vascular resistance * Arterial dilation (major) * Venodilation * ↑ coronary blood flow * **Non-DHPs** * _verapamil and diltiazem_ * **Vasodilators and negative inotropes and chronotropes** * ↓ myocardial contractile force

Answer 218

* _All CCBs_ * **Stable angina** * **HTN** * _Verapamil and diltiazem only_ * **Unstable angina** * **SVT**

Answer 219

* _All CCBs_ * **Hypotension** * **Reflex tachycardia (DHP only)** * _Verapamil and diltiazem only_ * **Bradycardia** * **Reduced cardiac contractility**

Answer 220

* _All CCBs_ * **Hypotension** * _Verapamil and Diltiazem only_ * **Sick sinus syndrome** * **AV nodal disease** * **Heart failure** * **Use with care with β-blockers**

Answer 221

* **All β-blocker equally effective** * **↓ HR and ↓ contractility ⇒ ↓ myocardial O₂ demand** * **Often used w/ DHP CCBs** * Do not use w/ verapamil or diltiazem * These already have their own neg. inotropic/chronotropic effects

Answer 222

* **Thought to inhibit late Na⁺ current** * ↓ Na⁺ entry ⇒ ↑ Ca²⁺ transport by Na⁺/Ca²⁺ exchanger ⇒ **↓ ischemia-induced Ca²⁺overload** * **Improved diastolic function** * **Dec. O₂ demand** * **For stable angina in pts who do not respond to other treatments** * **Contraindicated in pts w/ QT prolongation** * Due to actions on cardiac channels * May cause arrhythmias

Answer 223

**Primary goal to reduce myocardial oxygen consumption.** * Hospitalize/bed rest * **β-blockers** * **Antiplatelet** (ASA, clopidogrel) & **anticoagulant** (heparin, LMWH) * Long term: use **lipid lower drugs** like statins * Reduce further plaque formation * Catherizations * _Not used:_ * CCBs ⇒ do not prevent progression to MI or reduce mortality * Fibrinolytic agents ⇒ ineffective

Answer 224

* Caused by reversible coronary vasospasm * **Usually responsive to nitrates and all CCBs** * Do not use β-blockers ⇒ may exacerbate

Answer 225

All arrhythmias result from: 1. _Disturbances in impulse formation_ ⇒ **ectopic pacemakes** 2. _Disturbances in impulse conduction_ ⇒ **nodal block or re-entry circuits** 3. Both Many underlying causing including ischemia, hypoxia, autonomic influences.

Answer 226

* Normal conduction * Impulse travels down α and β paths at the same speed * Refractory period prevents impulse from travel back up * AP travels in the right direction * _Abnormal conduction_ * Unidirectional block prevents/slows travel down β path * Impulse from α path can go in both directions @ junction * Impulse can travel up β path back to atrial tissue * **Unidirectional block due to paths α and β having different refractory periods ⇒ "temporal block"**

Answer 227

1. **Sodium channel blockade** * Affects phase 0 of atrial/ventricular muscle and His/Purkinje system * Raises threshold and reduces conduction velocity 2. **Block SNS effects / Inc. PNS** * Affects SA pacing and AV conduction 3. **Prolong effective refractory period (ERP) via K⁺ channel blockade** * Blocks re-entry * Rephases heart 4. **Calcium channel blockade** * Affects SA pacing and AV conduction

Answer 228

1. **Selectively inhibit Na⁺ or Ca²⁺ channels of depolarized cells** * Drugs with high affinity for activatable channels (Phase 0) or inactivated channels (Phase 2) but low affinity for resting channels * Use or state dependent blockade 2. **Block electrical activity where there is a fast tachycardia** * Many activations and inactivations per unit time 3. **Block electrical activity where there is significant depolarization of the resting potential** * Many inactivated channels during rest

Answer 229

1. **Reduce Phase 4 slope by blocking Ca²⁺ or Na⁺ channels** * Dec. rate of phase 4 depolarization 2. **Block sympathetic effects directly** * Inc. threshold for firing

Answer 230

1. **Prolong ERP in delayed β path to stop re-entry** * Keep things in phase 2. **Impair propogation in β path to prevent retrograde travel** * Make block bi-directional 3. **Steady-state reduction in the number of available channels**

Answer 231

Vaughn Williams Classification * **Class I ⇒ Na⁺ channel blockers** * "Membrane stabilizing agents" * Further subdivided into IA, IB, IC * **Class II ⇒ β-blocking agents** * **Class III ⇒ K⁺ channel blockers** * Prolong AP by inhibiting repolarization * Increases ERP * **Class IV ⇒ Ca²⁺ channel blockers** * _Others:_ * Digoxin * Adenosine * Mg2+ * Ivabradine

Answer 232

* **All Na⁺ channel blockers** * **Bind to the open and/or inactivated states** * Traps channel in non-functional state * Drug must dissociate before channel can reopen * **All show use or frequency dependent block** * Inc. frequency of AP firing leads to inc. block * Useful in treating tachycardias

Answer 233

**Quinidine, procainamide, disopyramide** * **Strongly blocks activated Na⁺ channels** ⇒ inhibits fast Na⁺ current (Strong Class I effect) * Slows phase 4 in Purkinje and ventricular muscle * Slows phase 0 * ↑ threshold for AP * **Weakly blocks K⁺ channels** (Mild Class III effect) * ↑ AP duration * ↑ ERP * **Antimuscarinic (vagolytic) activity** * ↑ SA rate * ↑ AV conduction * Pro-arrhythmic * _Effects on EKG_ * **↑AP duration** * **↑ QRS** * **↑ QT**

Answer 234

* Depressed conduction & lengthened repolarization ⇒ **refractory heterogeneity** * **Torsade de pointes** * **Quinidine syncope** * Recurrent episodes of lightheadedness * **Proarrhythmic** * Not shown to reduce mortality * **Never first-line agents**

Answer 235

Class IA * _Actions:_ * **Strong Na⁺ and moderate K⁺ block** * **Anti-muscarinic activity** * **Weak α blocker activity** * _Indications:_ * **All forms of arrhythmias** * **Esp. A. Fib and A. Flutter** * Lots of drug interactions * Quinidine-digoxin * ↑ digoxin levels ⇒ **digitalis toxicity** * **Pro-arrhythmic**

Answer 236

Class IA * Actions: * **Strong Na⁺ and moderate K⁺ block** * **Less antimuscarinic effects** * Indications: * Similar to quinidine * **Sustained ventricular arrhythmias asociated with acute MI** * **IV-only** * No long term use * **Lupus-like condition in ⅓ of pts after 6 months of use** * Rash, inflammation * Disappear after withdrawal

Answer 237

Class IA * Actions: * Strong Na⁺ and moderate K⁺ block * **Strong antimuscarinic effects** * **⊖ inotrope** * Unknown mech * Indications: * **Ventricular arrhythmias**

Answer 238

**Lidocaine, mexiletine, tocainide, phenytoin** * **Weakly blocks Na⁺ channels** in _activated and inactivated states_ * Slightly ↓ rate of phase 0 * Slightly ↓ AP duration * **Preferentially acts on depolarized tissue** * Ischemia, acidosis, fast stimulation rate * @ therapeutic doses does not alter electrical activity of normal tissue * Fast dissociation rate from channels

Answer 239

**Acute suppression of ventricular arrhythmias.** Esp. after MI or cardioversion.

Answer 240

* **Many CNS-related side effects** * Tremor * Lightheadedness * Nausea of central origin * **β-blockers may dec. lidocaine clearance** * Must monitor levels

Answer 241

**Flecainide, Propafenone** * **Potent Na⁺ channel block** * Very slow dissociation rate * **Blocks I_to K⁺ current (Phase 1)** * Marked effect on His/Purkinje system * Little effect on APD/ERP * EKG effects: * **Significant QRS widening** * **May slightly prolong AP duration** * Does not distinguish between normal and depolarized tissue

Answer 242

* **Life-threatening ventricular arrhythmias** * **Widely used to prevent recurrence of A. Fib** * Flecainide only used in pts without significant LV disease or coronary heart disease * **PSVT**

Answer 243

**Can be very pro-arrhythmic.** First dose usually given in the hospital so pt can be monitored.

Answer 244

β-blockers **Propranolol, Sotalol, Acebutalol, Esmolol** * **Block sympathetic effects** * _Primarily affects SA and AV nodes_ * **↓ phase 4 depol in SA node** * ↓ HR * **↓ AV nodal conduction** * **↑ ERP of AV node** * Can interrupt re-entry circuits * **Slight prolongation of AV node AP** * SNS slightly ↑ K⁺ currents * **↓ myocardial O2 consumption** * Can ↓ risk of arrhythmia * **See ↑ PR interval**

Answer 245

**Shown to reduce arrhythmia-associated mortality.** * Supraventricular arrhythmias * Control of ventricular rate in A. fib and A. flutter * Ventricular arrhythmias associated with re-entry circuits * Tachycardia induced by exercise or stress

Answer 246

* Bronchoconstriction * Use with cause in asthmatics * Sudden withdrawal can cause "rebound hypersensitivity"

Answer 247

* **Block K⁺ channels** * Prolong AP duration & ERP * **Acts only on the repolarization phase** * Conduction velocity is unaffected * Little effect on phase 0

Answer 248

1. Amiodarone 2. Dronedarone 3. Bretylium 4. Sotalol 5. Ibutilide 6. Dofetilide

Answer 249

* **Ventricular arrhythmias** * **Prophylactic control of V. tach** * Amiodarone highly effective for **recurrent A. Fib and A. Flutter**

Answer 250

**Pure Class III** (↑APD, ↑ERP) * **Used for A. fib** * Ibutelide IV * Dofetilide PO

Answer 251

Class III * D and L isomers * Both have class III activity * **L-sotalol** * **β-blocker activity** * **Mainly used to maintain sinus rhythm after cardioversion**

Answer 252

Class III * Also **blocks release of catecholamines from nerves** after initial stimulation of release * Rarely used as an antiarrhythmic

Answer 253

* **Has actions from all 4 classes** * _Effects:_ * **↓ sinus rate** * **↓ automaticity** * **Interrupt re-entry circuit** * **⊖ inotrope** * **Vasodilator** * **Highly effective for reucrrent A. fib or A. flutter** * Elimination half-life of 30-180 days * _Many adverse effects_ ⇒ black box warning * **Cardiac effects** * **Pulmonary fibrosis** * **Thyroid issues** * **Hepatonecrosis** * **Photodermatitis** * Routine EKGs, CXR, LFTs, and thyroid panels are mandated

Answer 254

Class III * Amiodarone analog * Much shorter half-life of 1-2 days * **Does not have the pulmonary fibrosis or thyroid effects** * **Used for recurrent ventricular arrhythmias**

Answer 255

**Verapamil & Diltiazem** * **Calcium channel blockers** * Mostly affects SA and AV nodes * **↓ SA node automaticity** ⇒ ↓ HR * **↓ AV nodal conduction** * **Terminate AV re-entry** * Avoid with β-blocker use * EKG: **↑ PR**

Answer 256

1. A. Fib (rate control) 2. PSVT

Answer 257

Systemic effects ⇒ **hypotension**

Answer 258

* **Opens K⁺ channels** * Class IV-like * **Indirectly inhibits Ca²⁺ channels and I_f** * Mostly affects nodal tissues * **↓ SA firing rate** * **↓ AV conduction** * IV only w/ very short half life of 10-30 secs * **Drug of choice for PSVT** * Can be used as dx test for ventricular vs atrial cause of V tach * Will suprress atrial cause only * **Effects reduced by adenosine receptor blockers** * Caffeine and theophylline

Answer 259

* **Weakly blocks I_Ca²⁺** * **Inhibits I_Na⁺ and I_f potassium channels** * Indications * **Used for torsades des pointes** * Can be used to slow ventricular rate but not for PSVT

Answer 260

* **⊗ I_f current in SA node** * Responsible for phase 4 depolarization * **↓ HR** * **↓ O2 demand** * Indications: * **CHF patients with tachycardia** * Inappropriate sinus tachycardia

Answer 261

* **⊗ Na/K ATPase** * **Has vagomimetic actions** * ↓ HR * ↓ AV nodal conductions * **Used in A. Fib patients with heart failure** * Can be proarrhythmic

Answer 262

* Acute * IV adenosine \> verapamil or diltiazem * Carotid message * Chronic * Oral verapamil, diltiazem or β-blockers

Answer 263

* _Rate Control_ * **β-blocker or calcium channel blockers** * Ventricular rate controlled by limiting rate of impulse propagation through AV node * Safety profile of rate-control drugs are better so try this first * _Rhythm Control_ * **Class III or Class IC agents** * IC ⇒ flecainide or propafenone * III ⇒ amiodarone, dofetilide * **Cardioversion** * Suppress atrial automaticity to restore sinus rhythm

Answer 264

* Acute * IV lidocaine * Drug of choice * IV amiodarone or flecainide also used * Recurrent * Oral amiodarone/dronedarone

Answer 265

3 basic therapeutic goals 1. **Improve myocardial contractility** * Inotropic agents 2. **Reduce afterload** * ACE inhibitors * Some vasodilators 3. **Reduce preload** * Diuretics * Vasodilators

Answer 266

Can increase cardiac contractility by: * ↑ resting Ca²⁺ levels * ↑ Ca²⁺ entry during an action potential * ↑ Ca²⁺ sensitivity of contractile apparatus

Answer 267

1. **⊗ Na/K ATPase** * ↑ [Na⁺]_{intracellular} ⇒ ↓ activity of Na/Ca exchanger ⇒ ↑ [Ca²⁺]_{intracellular} ⇒ **stronger contraction** 2. **Vagomimetic actions** * ∆ electrical activity of the heart * ↓ HR * ↓ AV nodal conduction * **Reduces O₂ demand** * **Allows more efficient filling** * **↑ efficiency of failing heart**

Answer 268

**Low therapeutic index ⇒ high risk of toxicity** Due to blockade of Na/K ATPase: * Cardiac manifestations * **AV junctional rhythm** * **Premature ventricular depolarization** * **AV blockade** * Extracardiac manifestations * **Color vision abnormality** * **Disorientation** * **Gynecomastia** * Anorexia * Nausea * Diarrhea

Answer 269

* **Agents that ∆ renal clearance of digoxin** ⇒ ↑ plasma digoxin levels ⇒ ↑ potential for toxicity * Ex. Quinidine * Digitoxin is cleared via hepatic system * **Diuretics which cause hypokalemia** ⇒ ↑ risk of toxicity for both digoxin and digitoxin

Answer 270

β-adreneric stimulation ⇒ ↑ cAMP β1 ⇒ ⊕ inotropic & ⊕ chronotropic effects β2 ⇒ peripheral vasodilation

Answer 271

**β1 selective agonist** * **High inotropic effect** * **Low chronotropic effect** * Not orally active * Shows desensitization * **Limited to IV use for acute heart failure**

Answer 272

Used to treat acute heart failure. * _At low doses_ * **Release of NE at the heart** * **β1 adrenergic stimulation** * Acts at dopamine receptors in the periphery * **⊗ peripheral NE release** * **Vasodilation** * Enhanced renal and cerebral perfusion * _At high doses_ * **Direct α1 adrenergic activity** * **Vasoconstriction**

Answer 273

Treatment of **acute heart failure** in cases where **systolic pressure needs to be increased due to cardiogenic shock.**

Answer 274

**↑ cAMP levels** Avoids receptor desensitization. * **Amrinone (Inocor)** * **Hepatotoxic** * Induces nausea * **Limited to short-term IV treatment for acute HF** * **Milrinone (Primacor)** * PO was shown to have **higher mortality rate than digitalis long term** * **Limited to IV treatment of acute HF**

Answer 275

**Reduce salt and water retention.** * ↓ ventricular preload * ↓ edema * ↓ cardiac size * ↑ pumping efficiency

Answer 276

* **Mild to moderate CHF** * **Dietary sodium restriction** * **Thiazide diuretic** like hydrochlorotiazide * **Severe CHF** or when thiazide maxed out * **Furosemide** is diuretic of choice

Answer 277

**Aldosterone antagonist** * Aldosterone blockade can lead to **significant reduction in mortality** * **Diuresis** * Also inhibits other effects of aldosterone * **Fibrosis of myocytes** * **Increased vascular sensitivity to Ang II** * **Inhibiton of NO release** * Most common side affect ⇒ **hyperkalemia** * Also has weak progesterone receptor agonist and mixed estrogen agonist/antagonist activity * **Breast enlargement in women** * **Gynecomastia in males**

Answer 278

Aldosterone antagonist * Similar benefits to spironolactone * No progesterone/estrogen activity * Fewer side effects

Answer 279

* **Used to acutely reduce workload of failing heart** * **Arteriolar dilation** ⇒ ↓ afterload * Use in pts w/ **low ventricular output** * Ex. **hydralazine** * **Venodilation** ⇒ ↓ preload * Use in pts w/ **high filling pressures and pulmonary congestion** * Ex. **nitrates** * Generally only used when other drugs haven't worked

Answer 280

**Isosorbide dinitrate + Hydralazine** * For self-described **African Americans with CHF** * Hydralazine may potentiate effect of nitrate * Reduces tolerance * **Appears effective** * **Does reduce mortality**

Answer 281

Recombiant human B-type natriuretic peptide * **Activates guanylate cyclase** * **Causes vasodilation** * ↓ right atrial pressure * ↓ pulmonary capillary wedge prssure * May be an inc. in short-term mortality * Usefulness not proven

Answer 282

**Choice for chronic CHF.** **Provides a significant improvement in cardiac function.** * ↓ peripheral resistance ⇒ ↓ afterload * ↓ aldosterone secretion * ↓ salt and water retention ⇒ ↓ preload * ↓ circulating angiotensin levels * ↓ sympathetic activity * ↓ long term remodeling of the heart

Answer 283

* Prevents Neprilysin degradation of vasoactive peptides * Natiuretic peptides * Bradykinin * **Conteracts neurohormonal overactivation** * ↓ vasoconstriction * ↓ volume loading * ↓ cardiac remodeling * Not shown to be effective alone * Neprilysin also breaks down Ang II so inhibition inc.

Answer 284

Neprilysin inhibitor sacubitril + ARB valsartan * Improved effects on morbidity and mortality * Used to reduce risk of cardiovascular death and hospitalization in chronic HF pts

Answer 285

* Certain β-blockers improves outcome of pts w/ mild CHF * May work by counteracting effects of excess SNS activation d/t low CO * **Carvedilol** * Nonselective β-blocker + some α-antagonist * Most effective * **Metoprolol and Bisprolol** * β1 selective

Answer 286

**Block I_f in SA node ⇒ ↓ phase 4 depolarization ⇒ ↓ HR** Reduces hospitalizations associated with worsening heart failure and mortality.

Answer 287

* Renin * Protease made @ renal juxtaglomerular apparatus * Angiotensinogen * Plasma glycoprotein made by liver, kidney, brain, fat * Ang I * Formed by proteolysis of angiotensinogen by renin * Weak vasoconstrictor activity * Ang II * Formed by proteolysis of Ang I by ACE * Very potent vasoconstrictor * Ang III * Formed by aminopeptidase on Ang II * Weak vasoconstrictor activity

Answer 288

* **AT₁** * **G_q ⇒ IP₃/DAG system** * **Vasoconstriction** * **Mitogenic activity** * **Main clinical effector** * AT₂ * Highest in fetus * Post-natal role unclear

Answer 289

Vasodilator peptide Degraded by ACE

Answer 290

Renin release is rate-limiting step in Ang II formation. Controlled by local renal mechanisms and CNS. * **Renal vascular receptor** * Dec. stretch ⇒ renin release * **Macula densa** * Dec. sodium delivery ⇒ renin release * **SNS** * NE ⇒ β1 ⇒ renin release * **Ang II** * Acts on juxtaglomerular cells to reduce renin release

Answer 291

* Blood pressure * **Potent vasoconstrictor** * Adrenal cortex * Simulates zona glomerulosa to **release aldosterone** * Inc. salt and water retention * CNS * CNS mediated pressor response ⇒ **inc. SNS** * **Stimulates thirst** * **Stimulates ADH and ACTH release** * Cell growth * **Mitogen activity for vascular and cardiac muscle cells**

Answer 292

**Orally-active direct renin inhibitor** * Not non-inferior to ACEi or ARBs * **Induces reactive renin release** * Not first-line therapy * **Contraindicated in combo w/ ACEi or ARS in DM**

Answer 293

* **⊗ Ang I ⇒ Ang II** * ↓ TPR ⇒ ↓ BP * Do not induce reflex sympathetic activation * Can use safely in pts w/ ischemic heart disease * **⊗ Bradykinin breakdown** * Bradykinin has vasodilator activity * ↓ BP * Responsible for cough and rash

Answer 294

Pharmacokinetic classes: * **Class I** * Active as is * **Captopril** * **Class II** * Prodrugs * **All except Captopril and Lisinopril** * **Class III** * Water soluble, active as it, excreted unchanged by kidney * **Lisinopril**

Answer 295

* **HTN** * Esp. in DM b/c doesn't impair insulin sensitivity * **CHF** * Shown to reduce mortality * **Diabetic nephropathy** * **Post MI** * **Type 2 DM** * Lessens new microalbuminuria

Answer 296

* **Dry cough** * **Skin rash** * Hypotension * **Hyperkalemia** * **Acute renal failure** * Teratogenesis * **Angioedema**

Answer 297

* Neutropenia * Loss of taste * Oral lesions * Proteinuria

Answer 298

Share with ARBs and direct renin inhibitors. * Pregnancy * Severe renal failure * Hyperkalemia * Bilateral renal stenosis * Pre-existing hypotension * Severe aortic stenosis * Obstructive cardiomyopathy

Answer 299

**Losartan, Valsartan** * Same effect on BP as ACEi * Fewer side effects * May have lower incidence of angioedema

Pharmacology Flashcards

(341 cards)