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1

A1 Receptor binding effects

-increased vascular smooth muscle contraction
- mydriasis (increased contraction of pupillary sphincter m.)
- increased intestinal and bladder spincter contraction

Gq protein class

2

a2 R binding effects

- inhibition of NT release ( - NE from nerve endings, Ach from adjacent PS neurons)
- decreased sympathetic outflow
- increased platelet aggregation
- decreased lipolysis
- decreased insulin release
- decreased aqueous humor production

Gi protein class

3

B1 R effects

- increased hr, contractility
- increased renin release --> which increases BP
- increased lipolysis

Gs protein class

4

B2 R effects

-Smooth m. Relaxation (vasodilation in skeletal m., bronchodilation, uterine smooth m., GI smooth m.)
- CNS: presynaptic Rs stimulate NT release
- increased aqueous humor production
- increased HEart contraction
- increased platelet aggregation
- increased insulin secretion, increased lipolysis, increased glycogenolysis
- increased K+ uptake

Gs protein class

5

NSAIDs
(Aspirin, ibuprofen, naproxen)

Mechanism of Action

Cox inhibition

Aspirin is irreversible, others are reversible

6

NSAIDs
(Aspirin, ibuprofen, naproxen)

Use

- Decrease PGE2 synthesis, stops pain nerve sensitization

- Early intervention
against platelet action.
Acute pain suppression.

Tension headache & Migrane Acute action

7

NSAIDs
(Aspirin, ibuprofen, naproxen)

Toxicity

Bleeding, GI irritation, erosions, and ulcers

- salicyclism, increased leukotrienes (asthma, allergies) with aspirin

--> with allergy to ASA, avoid NSAIDs

8

Acetaminophen

Mechanism of action

Weak COX inhibition

9

Acetaminophen

Use

- Decease PGE2 synthesis
- Stops pain nerve sensitization
- Less GI effects than NSAIDs

Tension headaches

10

Acetaminophen

Toxicity

Liver toxicity at high doses Or EtOH consumption


N-acetylcysteine is the antidote

11

Benzodiazepines

Examples and Mechanism

Estazolam, Flurazepam. Temazepam

Potentiate GABA
at Cl-channel (increase frequency)

12

Benzodiazepines

Use

Muscle relaxant; Anxiolytic
Status epilepticus seizures

Tension headaches

EtOH withdrawal, muscle relaxant, sedative, preop-sedation/induction of mechanically ventillation

13

Benzodiazepines

Toxicity

- Drowsiness
- Impaired judgement
- Depressed motor skills
- Anterograde amnesia
- Tolerance
- Dependence

14

Antimuscarinics

Examples and MOA

Cyclobenzaprine
Methocarbamol
Orphenadrine
Amitriptyline

M3 Block; Amitriptyline (tricyclic antidepressant) inhibits reuptake of 5HT and NE

15

Antimuscarinics

Use

Local Strain, muscle spasm

Tension headaches

16

Tizanidine

Mechanism of Action

Centrally acting α2 adrenergic agonist (reduced norepinephrine outflow)

17

Tizanidine

Use

Muscle relaxant

-Migraine prophylaxis
Multiple sclerosis, amyotrophic lateral sclerosis (ALS)

Also for tension headaches

18

Tizanidine

Toxicity

Drug interactions (fluoroquinolones) with CYP1A2
raises tizanadine levels

Results in enhanced CNS effects

19

"Ergots"

Mechanism of Action, Drugs

- Ergotamine
- Ergotamine Tartrate and Caffeine (Cafergot)
- Dihydroergotamine

Vasoconstrictor at
5-HT1B/1D receptor

20

"Ergots"

Toxicity

Vasoconstriction in
coronary arteries. Avoid coronary artery disease, atherosclerosis

21

"Ergots"

Use

Counteracts the early
vasodilating phase of Acute Migrane

22

"Triptans"

MOA, Drugs

- Sumatriptan
- Almotriptan
- Rizatriptan
- Zolmitriptan
- Naratriptan
- Eletriptan

- Partial Agonist at
5HT1D/1B receptors

- Vasoconstriction to reverse vasodilatory phase

23

"Triptans"

Use

Migraine (acute) and cluster
headaches

Oral, Nasal, SQ administration; short duration requires multi-dose, but must limit daily dosing

24

"Triptans"

Toxicity

All Drugs:
Paresthesias, dizziness, muscle weakness, coronary vasoconstriction, chest pain. Not for coronary artery disease patients.

Serotonin syndrome: SSRIs, MAOIs, tricyclic antidepressants, St John’s Wort, linezolid

25

Propranolol

MOA

Nonselective Beta
Blocker

26

Propanolol

Use

Prevents trigeminal
nerve excitement

Migrane Prophylaxis

27

Propanolol

Toxicity

- Hypoglycemia
- Bronchoconstriction via beta2 blockade
- Vasoconstriction

28

Amitriptyline

MOA

Tricyclic blocks
reuptake of 5-HT

29

Amitriptyline

Use

Maintains serotonin
against vasodilating phase

Migrane prophylaxis

30

Amitriptyline

Toxicity

- Anticholinergic (M3) effects
- Alpha1 block (orthostasis)
- H1 block (sedation)

31

Calcium channel Blockers

Examples and MOA

E.g. Verapamil
Diltiazem

Block vascular calcium channels; Vasodilation

32

Calcium channel Blockers

Use

Prevent onset of vasoconstrictive
ischemic phase

Migrane prophylaxis

33

Ca2+ Channel blockers

Toxicity

Hypotension
Constipation
Gingival hyperplasia

34

Valproic Acid and Valproate

MOA

- Mixed action:
1. Sodium and calcium channel blocker
2. Increase GABA synthesis
3. Reduce GABA degradation
4. Decreases glutamate at NMDA receptor

35

Valproic Acid and Valproate

Use

Migrane Prophylaxis

Absence Seizures, Myoclonic Seizures, Specific Myoclonic Seizures, Generalized Tonic- Clonic Seizures.

Manic phase of bipolar disorder

36

Valproic Acid and Valproate

Toxicity

Birth defects (blocks
folate absorption), severe hepatitis, weight gain, GI upset

Inhibitor of CYP

37

Topiramate

MOA

Potentiate GABA

Blocks sodium channels and Glutamate

38

Topiramate

Use

Migrane prophylaxis

Partial Seizures,
Generalized Tonic- Clonic Seizures
Adjunct therapy for headache

39

Topiramate

Toxicity

- CNS effect
- Teratogen
- Reduced oral contraceptive effect

40

Phenothiazines
Prochlorperazine

MOA

Dopamine receptor antagonists. Also M3 and histamine H1 blockade.

41

Phenothiazines
Prochlorperazine

Use

Antiemetic

Used in migrane prophylaxis

42

Phenothiazines
Prochlorperazine

Toxicity

EPS symptoms and Parkinson’s like effects, increase in prolactin, muscarinic (M3) and histamine (H1) blockade.

Elevated QT interval.

43

Botulinum toxin

MOA

Cleavage of Snap-25 protein, which prevents vesicle fusion, release of Ach vesicles

44

Botulinum toxin

Use

Migraine prophylaxis

Blepharospasm
Focal hand dystonia
Cervical dystonia

45

Botulinum toxin

Toxicity

Absence of muscarinic actions, loss of muscle tone, fatigue, paralysis, respiratory arrest

46

Carbamazepine
Oxcarbazepine (prodrug)

MOA

Sodium channel blockade

47

Carbamazepine
Oxcarbazepine (prodrug)

Use

Trigeminal neuralgia

Partial Seizures,
Generalized Tonic-Clonic Seizures, Manic episodes

48

Carbamazepine
Oxcarbazepine (prodrug)

Toxicity

Drowsiness, Ataxia, Agranulocytosis, SIADH (hyponatremia), Teratogen, Nausea, diplopia, headache

Potent inducers of CYP isoenzymes (e.g. CYP3A4); induces own metabolism

49

Lorazepam
Diazepam
Midazolam
Clorazepate
Clobazam

Use

Status epilepticus initial treatment, anxiolytic, EtOH withdrawal, muscle relaxant, sedative, preop-sedation/induction of mechanically ventillation, tension headaches

50

Lorazepam
Diazepam
Midazolam
Clorazepate
Clobazam

MOA

Enhance GABA-mediated Cl- influx, increased membrane polarization

51

Lorazepam
Diazepam
Midazolam
Clorazepate
Clobazam

Adverse effects

Sedation

Tolerance can occur with chronic use

Interactions minimal

52

Ethosuximide
Use

Absence seizures

53

Ethosuximide
MOA

Blocks T-type (low-threshold) Ca2+ channels thus reducing pacemaker current underlying thalamic rhythm in spikes and waves seen in generalized seizures.

54

Ethosuximide
Adverse effects

Nausea, headache, dizziness, hyperactivity

55

Felbamate
Use

Refractory to other seizure treatments; typically used for partial and Lennox-Gastault syndrome

56

Felbamate
MOA

- Blocks glycine activation of NMDA-type glutamate receptors
- GABAa receptor potentiation

57

Felbamate
Adverse effects

Aplastic anemia and hepatotoxicity limit its use (must obtain informed consent)

Also: Nausea, vomiting, headache, dizziness, somnolence, insomnia

58

Gabapentin,
Pregabalin
MOA

Blocks presynaptic voltage-gated Ca2+ channels possessing α2δ subunit

May may modulate the release of excitatory neurotransmitters that participate in epileptogenensis and nociception

59

Gabapentin,
Pregabalin
Use

Adjunct therapy for partial seizures, also for neuropathic pain & bipolar disorder

60

Gabapentin,
Pregabalin
ADEs

Somnolence, dizziness, ataxia;
Favorable pharmacokinetic profile; dosage adjustment necessary in renal impairment

- Interactions are minimal

61

Lamotrigine
MOA

Prolong inactivation of voltage-gated Na+ channels, decreases ability of neurons to fire at high frequency

Acts on voltage-gated presynaptic Ca2+ channels-- decreases glutamate release

62

Lamotrigine
Use

Partial seizures, primary general epilepsy, Lennox-Gestault Syndrome (can be adjunct or monotherapy)

Also for bipolar disorder maintenance

63

Lamotrigine
ADEs

Dizziness, headache, diplopia, rash including potentially life-threatening Stevens-Johnson syndrome

Slow dose titration required to reduce risk of rash (over 6-8 weeks)

64

Levetiracetam
MOA

Assumed to act on synaptic protein SV2A, a/w antiseizure activity in mice

65

Levetiracetam
Use

Broad spectrum drug, focal seizures, primary general tonic/clonic seizures; off label for status epilepticus

66

Levetiracetam
ADEs

Nervousness, dizziness, depression, seizures
Pregnancy: animal studies show teratogenic effects

**No CYP or UGT metabolism

67

Phenobarbital
(Barbituates)
MOA

Enhances GABA-mediated Cl- influx

68

Phenobarbital
(Barbituates)
Use

Partial seizures, primary general tonic/clonic seizures; Status epilepticus alternative

69

Phenobarbital
(Barbituates)
ADEs

Sedation, decreased cognition, ataxia, hyperactivity

**Potent inducer of CYP isoenzymes

t½ 75-110h

70

Phenytoin, Fosphenytoin
MOA

Prolong inactivation of voltage-gated Na+ channels , decreased glutamate release

71

Phenytoin, Fosphenytoin
Use

Complex partial seizures, general tonic/clonic seizures, status epilepticus, prevention or treatment of seizures during neurosurgery

Nonseizure: ventricular arrythmias, sometimes from digitalis intodication

72

Phenytoin, Fosphenytoin
ADEs

Diplopia, ataxia, hypotension, bradycardia, gingival hyperplasia, hirsutism, neuropathy, nystagmus, jaundice, osteomalacia, skin coarsening, purple glove syndrome (IV), SJS/TEN/DRESS
- Teratogenic (interference with folic acid absorption)

*Nonlinear elimination kinetics at therapeutic doses;
*Potent inducer of CYP isoenzymes

73

Topiramate
MOA

Likely:
Prolonged inactivation of voltage-gated Na+ channels

Increased GABA synthesis and decreased GABA degradation

Blocks kainite and AMPA glutamate receptors

Weakly inhibits carbonic anhydrase

74

Topiramate
Use

Partial seizures, Primary General Tonic/Clonic seizures, Lennox-Gestalt syndrome (adjunctive)

Nonseizure: Migrane prophylaxis, cluster headaches, neuropathy, weight loss with phenteramine

75

Topiramate
ADEs

- Somnolence
- cognitive slowing
- confusion
- paresthesias
- Hyperthermia most commonly in children; metabolic acidosis; renal calculus

Use with caution in patients with renal impairment and those with hepatic impairment

-Inhibits CYP2C19 and a weak inducer of CYP3A4

76

Valproate
MOA

increased GABA synthesis, increased GABA transport from synapse, and decreased GABA degradation, or may mimic GABA actions at postsynaptic receptor sites

Possibly blocks voltage-gated Na+ channels

Possibly blocks T-type Ca2+ channels thus reducing pacemaker current underlying thalamic rhythm in spike and waves seen in generalized seizures

Possible histone deacetylation

Possible block of NMDA receptors

77

Valproate
Use

Generalized tonic/clonic seizures,
Focal seizures,
Absence seizures,
Status Epilepticus (off-label)

Nonseizure: Acute mania with bipolar disorder, migrane prophylaxis, diabetic neuropathy

78

Valproate
ADEs

Nausea, tremor, weight gain, hair loss, teratogenic, thrombocytopenia, hyperammonia, hepatotoxic, rare acute pancreatitis (Boxed warning)

Inhibits CYP isoenzymes

79

Aspirin
MOA

Irreversible acetylation of serine on COX-1and 2. Blocks Thromboxane (TXA2)

80

ASA
Use

Analgesic, Antipyretic, Anti-inflammatory, Low dose antiplatelet

81

ASA
Toxicity

-Bleeding, GI irritation, erosion, ulceration, allergic reactions (leukotriene mediated)

-Compensated resp. alkalosis. (Manage by ion trapping)

-salicylism (ringing ears), Reye’s syndrome

82

Dipyridamole
MOA

- Phosphodiesterase inhibitor -blogs PGI2 binding (increases cAMP, cGMP, and NO
--->Vasodilator (PGI2).
- Inhibits TXA2 synthesis and receptors; Antiplatelet

83

Dipyridamole
Use

Combine with aspirin for stroke and TIA prevention

84

Dipyridamole
Toxicity

Bleeding, hypotension, vasodilation

85

Cilostasol
MOA

Phosphodiesterase inhibitor (increases cAMP). Acts to stabilize platelets; Antiplatelet

86

Cilostasol
Use

Intermittent claudication.
Thrombosis in peripheral vascular disease.
Prevents stroke.

87

Cilostasol
Toxicity

Vascular headache, tachycardia (secondary to vasodilation)

88

Clopidogrel
MOA

Irreversible ADP receptor blocker. Stops expression of surface GPIIb/IIIa.
Prodrug; Antiplatelet

89

Clopidogrel
Use

Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.

90

Clopidogrel
Toxicity

Bleeding.
Alternative if patient has aspirin contraindication.
Safer than Ticlopidine.

May lose effect due to inactive CYP2C19.
14% of population is variant and cannot convert clopidogrel to active form. These patients are at risk for MI stroke and death.

91

Ticlopidine
MOA

Irreversible ADP receptor blocker. Stops expression of surface GPIIb/IIIa.
Prodrug; Antiplatelet

92

Ticlopidine
Use

Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.

93

Ticlopidine
Toxicity

Bleeding.
**Neutropenia,
agranulocytosis, thrombotic thrombocytopenic purpura (TTP) and aplastic anemia

94

Prasugrel
MOA

Irreversible ADP receptor blocker. Stops expression of surface GPIIb/IIIa.
Prodrug; Antiplatelet

95

Prasugrel
Use

Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.

Faster onset, more consistent action than clopidogrel.

96

Prasugrel
Toxicity

Multi-enzyme conversion to active metabolite, therefore less problems with enzyme inactivity.
Conversion by CYP3A4 and CYP2B6; not CYP2C19.
Bleeding.

97

Ticagrelor
MOA

Reversible ADP receptor blocker

Direct acting; Antiplatelet

98

Ticagrelor
Use

Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.

Faster action than clopidogrel
Prevents thrombotic events

99

Ticagrelor
Toxicity

Drug inhibits CYP3A4 (so will increase concentrations of drugs such as statins).

Bleeding

100

Abciximab
MOA

High affinity for GPIIb/IIIa receptors

Blocks the glycoprotein IIb/IIIa pathway involved in cross-linking platelets

Long-acting (7-10 days)

101

Abciximab
Use

Angioplasty, stent, CAD, Stroke

102

Abciximab
Toxicity

Bleeding

103

Eptifibatide
Tirofiban
MOA

Short-acting,
reversible, binds GPIIb/IIIa receptors

Antiplatelet

104

Eptifibatide
Tirofiban
Use

Angioplasty, stent, CAD, Stroke

105

Eptifibatide
Tirofiban
Toxicity

Bleeding

106

Heparin
Unfractionated
MOA

Binds Antithrombin III to reduce active clotting factors (II and Xa)

107

Heparin
Unfractionated
Use

IV anticoagulant.
Rapid acting, t1/2 1.5 hrs.
Does not cross placenta (safe in pregnancy)

108

Heparin
Unfractionated
Toxicity

Bleeding
- Use protamine to bind heparin (antidote).
Thrombocytopenia
Osteoporosis
Hyperkalemia
Hypersensitivity

109

Low Molecular Weight Heparins
MOA

Enoxaparin, Dalteparin, Tinzaparin

Binds Antithrombin III to reduce active clotting factors

110

Low Molecular Weight Heparins
Use

SQ anticoagulant. Rapid acting t1/2 4-6 hrs

111

Low Molecular Weight Heparins
Toxicity

Bleeding, less thrombocytopenia

112

Fondaparinux
Idraparinux
MOA

Synthetic pentasaccharide of heparin which binds to antithrombin III.
Selective for factor Xa vs II

113

Fondaparinux
Idraparinux
Use

Anticoagulant

Fondaparinux: s.c., t1/2 17-21 hrs (dosed once daily)

Idraparinux: s.c., t1/2 80 hrs (dosed once per week)

114

Fondaparinux
Idraparinux
Toxicity

Bleeding, but minimal thrombocytopenia

115

Warfarin
MOA

Blocks vitamin K epoxide reductase. Stops clotting factor synthesis.

116

Warfarin
Use

Delay of 4-5 days for anticoagulant benefit. - Check INRs

Hypercoagulopathy, vascular necrosis, and protein C deficiency can be controlled by heparin.

Crosses placenta (teratogen)

117

Warfarin
Toxicity

Bleeding.

Add vitamin K or replace clotting factors (severe bleed).

Drug interactions (protein
binding and CYP mediated)

118

Bivalirudin
Argatroban
Dabigatran
MOA

Hirudin-like Direct Thrombin Inhibitors (DTI)

119

Bivalirudin
Argatroban
Dabigatran
Use

Alternative to heparin in HIT. Rapid injectable, short-acting. Angioplasty, stent.

Dabigatran to prevent stroke in nonvalvular atrial fibrillation--Oral formulation

120

Bivalirudin
Argatroban
Dabigatran
Toxicity

Bleeding, but no thrombocytopenia.

Idarucizumab is the antidote.

All require dose adjustment in renal impairment.

121

Rivaroxaban
Apixaban
Edoxaban
MOA

Direct factor Xa inhibitor
(oral drugs)
Rapid onset

122

Rivaroxaban
Apixaban
Edoxaban
Use

DVT, prevent strokes in patients with atrial fibrillation
VTE prophylaxis and treatment

Little monitoring, unlike warfarin

123

Rivaroxaban
Apixaban
Edoxaban
Toxicity

Bleeding risk especially with drugs that inhibit CYP3A4.

No antidote, use antifibrinolytics for severe bleed

Impaired renal or hepatic function result in increased drug effect.

124

Streptokinase
Urokinase
MOA

Natural tissue plasminogen activator (tPA); a protease which targets plasminogen to plasmin

125

Streptokinase
Urokinase
Use

Infused in thrombosed vessel to lyse clot. (Fibrinolytic)

Streptokinase is a bacterial protein, can induce allergic reactions.
Replaced with newer drugs (alteplase)

126

Streptokinase
Urokinase
Toxicity

All drugs increase bleeding.

Contraindications: Prior intracranial hemorrhage and malignant intracranial neoplasms

Reversed by aminocaproic acid tranexamic acid.

Block plasmin interaction with fibrin

127

Anistreplase
MOA

(Streptokinase
plus plasminogen)
Activates plasminogen to plasmin

128

Anistreplase
Use

Infused in thrombosed vessel to lyse clot.

129

Anistreplase
Toxicity

All drugs increase bleeding.

Contraindications: Prior intracranial hemorrhage and malignant intracranial neoplasms

Reversed by aminocaproic acid tranexamic acid.

Block plasmin interaction with fibrin

130

Alteplase
Reteplase
Tenecteplase
MOA

Human Recombinant tissue plasminogen activators tPA

Faster onset of action than alteplase

Longer t1/2 than alteplase or reteplase

131

Alteplase
Reteplase
Tenecteplase
Use

Infused in thrombosed vessel to lyse clot.

Use IV asap, within 3 hrs for optimal benefit

Use: MI, acute ischemic stroke, pulmonary embolism, central venous catheterization.

132

Alteplase
Reteplase
Tenecteplase
Toxicity

All drugs increase bleeding.
Contraindications: Prior intracranial hemorrhage and malignant intracranial neoplasms

Reversed by aminocaproic acid tranexamic acid.

Block plasmin interaction with fibrin

133

Nifedipine
MOA

Calcium channel blocker

134

Nifedipine
Use

Common to all CCBs; antianginal, antihypertensive

Arterioles relax, TPR and afterload decrease.
BP falls, heart works less for systole.

Stroke prevention

135

Nifedipine
Toxicity

Arteriole action only
Decreases TPR, BP.
May elicit the SANS reflex and tachycardia.
Common to all “dipines”

136

Labetalol
MOA

Alpha and Beta 1,2 antagonist, antioxidant potential

137

Labetalol
Use

Hypertensive crisis, congestive heart failure, cocaine withdrawal

138

Labetalol
Toxicity

Bronchoconstriction, masking hypoglycemia (beta-2), orthostasis (alpha-1)

139

“Statin” drugs MOA
Lovastatin
Atorvastatin
Pravastatin
Simvastatin
Rosuvastatin

Competitively inhibit HMG CoA reductase.

140

“Statin” drugs use
Lovastatin
Atorvastatin
Pravastatin
Simvastatin
Rosuvastatin

There is an increase in the number of LDL receptors
LDL decreases 25-45%.

Stroke prevention

141

“Statin” drugs Toxicity
Lovastatin
Atorvastatin
Pravastatin
Simvastatin
Rosuvastatin

Hepatic toxicity, Myopathy, rhabdomyolysis

Drug interactions: enzyme inhibitors

142

Cytochrome P450 Enzyme inhibitors

- grapefruit juice
- protease inhibitors,
- amiodarone
- cimetidine
- azole antifungals (e.g. ketoconazole)
- erythromycin
- sulfonamides
- isoniazid
- valproic acid
- quinidine
- acute alcohol abuse

143

Cytochrome P450 Enzyme inducers

- St John’s wort
- phenytoin, phenobarbital, carbamazepine
- griseofulvin
- rifampin
- chronic alcohol abuse
- nevirapine

144

B3 R effects

Gs

Increased lipolysis, increased thermogenesis, increased bladder relaxation