Pharmacology Flashcards

Flashcards for Pharmacology review, focusing on Skeletal Muscle Relaxants, Eicosanoids, NSAIDs, Gout, Rheumatoid Arthritis, and Antifungal Drugs.

Neuromuscular Blockers (NMBs)

Drugs mainly used as adjuvant to anesthetics for muscle relaxation during procedures.

Spasmolytic Drugs

Drugs mainly used in spastic disorders of skeletal muscles to reduce muscle tone.

Non-Depolarizing NMBs

A type of NMB, prototype: d-tubocurarine, that competitively blocks postsynaptic Nm receptors.

Depolarizing NMBs

A type of NMB, prototype: Succinylcholine, that causes initial fasciculations and induces persistent depolarization.

Succinylcholine Mechanism of Action (Small Dose)

Competitive blockade of postsynaptic Nm receptors at the neuromuscular junction (NMJ).

Succinylcholine Mechanism of Action (Large Dose)

Blocks presynaptic Nn receptor, decreasing Ach release; blocks Na+ channels of Nm receptors.

Phase I Block (Depolarization Block)

More block by Neostigmine. Succinylcholine induces persistent depolarization of the Motor End Plate (MEP) since it is slowly hydrolyzed by pseudo Choline esterase

Phase II Block (Desensitization Block)

Antagonized by neostigmine. On prolonged use of succinylcholine, the membrane repolarizes but receptors are desensitized to ACh.

Succinylcholine Indications

Adjuvant to general anesthesia, assists mechanical ventilation, facilitates endotracheal intubation, and controls convulsions in electroconvulsive therapy.

Succinyle choline apnea

Adverse effect of Succinylcholine, fresh blood transfusion for Phase I, Neostigmine preceded by atropine for Phase II, due to ↓pseudo ChE

Malignant hyperthermia

A severe adverse effect of Succinylcholine and halothane, treated by Dantrolene (spasmolytic drug), HCO3 (Bicarbonate) and fluids and cooling blankets

Adverse Effects of Curare

Histamine release (bronchoconstriction, allergy, hypotension), ganglion blockade (hypotension), and prolonged action in renal disease.

Effect of Curare

Antagonized by Neostigmine (preceded by atropine) and potentiated by anesthetic drugs and aminoglycoside antibiotics

Newer Competitive NMBs Advantages

More potent than curare (except Rocuronium), no ganglion blocking effect (less hypotension), less or no histamine release, and available by other routes of elimination.

Sugammadex

Reversal agent encapsulated rocuronium & vecuronium in its lipophilic core, allowing concentration gradient.

Hoffman elimination

Spontaneous breakdown of Atracurium and Cisatracurium.

Treatment of NMB Toxicity

Artificial respiration, Neostigmine (preceded by atropine), or Sugammadex as alternative.

Spasmolytics

Drugs that reduce muscle tone with minimal effect on active contractions.

Diazepam Mechanism

Centrally acting GABAA agonist.

Baclofen Mechanism

GABAB agonist acting in the spinal cord.

Dantrolene Mechanism

Peripherally acting by inhibiting Ca++ release from sarcoplasmic reticulum.

Botulinum toxins Mechanism

Inhibits Ach release by local injection into skeletal muscles.

Eicosanoids

Includes Prostaglandins (PGs), Leukotrienes (LTs), and Thromboxane A2 (TXA2).

PLA2

Phospholipase A2; releases arachidonic acid from phospholipids.

COX

Cyclooxygenase; converts arachidonic acid to prostaglandins.

LOX

Lipoxygenase; converts arachidonic acid to leukotrienes.

Physiological Roles of Prostaglandins (PGs)

Include platelet function, kidney function, inflammation, thermoregulation, and gastro-protection.

Effects of PG Inhibitors

Include analgesic nephropathy, Na+ & water retention, hyperkalemia, and ulcerogenic effects.

Misoprostol

Ulcer risk down, GIT motility up, analogue of PGE, used with NSAIDs prevent ulcers.

Epoprostenol

A PGI2 analogue used as an antiplatelet in dialysis and for peripheral vascular diseases.

Alprostadil

PGE1 analogue: used in erectile dysfunction.

NSAIDs Actions

Anti-inflammatory, Analgesic, Antipyretic effects. Aspirin having 4A: Add Antiplatelet effect; Paracetamol: having 2A: Analgesic + Antipyretic effects with weak or NO anti-inflammatory effects

Types of Cyclooxygenase (COX) Enzyme

COX-1: Mainly constitutive; COX-2: Inducible in inflammation, constitutive in endothelium & kidney; COX-3: Mainly in CNS

Aspirin Mechanism of Action

Irreversible (acetylation) inhibition of COX-1 & COX-2, blocking production of PGs & TXA2.

Salicylate elimination Follows dose dependet elimination

t½ varies from 2 hours in low doses up to 30 hours in toxic doses.

Main Uses of Aspirin at Low Dose

Prophylaxis for transient ischemic attacks & Angina pectoris, Acute myocardial infarction (300 mg in acute attack).

Uses of Aspirin at Intermediate Dose

Antipyretic in fever (Febrile diseases) & Mild to moderate pain, headache, dysmenorrhea. Postpartum, postoperative & cancer pain (added to opioids

Uses of Aspirin at High-Dose

Inflammatory, Rheumatic fever, Rheumatoid arthritis & other inflammatory joint diseases

Adverse Effects of Aspirin

GIT, Nephrotoxicity, CVS events, Hypersensitivity reactions, Bleeding tendency, Hepatotoxicity

Aspirin and GIT

due to ↓protective PGE & direct irritation of aspirin. How to avoid: Add Misoprostol or PPIs (proton pump inhibitors: omeprazole) to ↑PG & ↓HCL

Reversal for Bleeding tendency of Aspirin

Displacement warfarin from plasma protein, Antiplatelet effect (Low dose aspirin) & Hypoprothrombinemia (High dose aspirin) SO: Stop aspirin 1 week before surgery

Acute toxicity of Aspirin

Respiratory alkalosis & acidosis, Metabolic acidosis

Mechanism of action: Selective COX-2 inhibitor

.↑ Risk of gastric ulceration with glucocorticoids; spared COX-1, constitutive. nephrotoxicity, Stroke & infarction, ↓ Effects of ACEIs (↓PG production in response to Bradykinin

Non selective NSAIDs

Efficacy (stronger) Adverse effects; arthritis renal colic & postoperative pain

Preferred to aspirin because

Patients allergic to aspirin, Peptic ulcer (no GIT disturbances), Peptic ulcer (no GIT disturbances), Gout (aspirin may cause hyperuricemia) & Bleeding disorders (does not affect platelet function

Paracetamol Mechanism

.Analgesic,antipyretic weak anti-inflammatory action; oral: Adults: 1000 mg 3-4 times daily. Maximum: 4 g daily & Children: 10-15 mg/kg/6 h. Maximum 5 doses/day

Treatment

Analgesic nephropathy Hepatotoxicity Precursors for glutathione synthesis: Acetylcysteine (orally or IV) & Methionine (orally)

Pathophysiology of gouty arthritis

Uric acid, deposition of urate crystals in joints, migration of leucocytes phagocytose urate crystals

Food increasing uric acid

Meat, Seafood, Beans,….

URAT-1

.Urate Anion Transporter:Allopurinol, Probenecid - Sulfinpyrazone - Benzbromarone, Pegloticase & Colchicine

Mechanism of Action with NSAID and inflammation

PGs Indomethacin (NSAIDs), Leucocyte migration & LTB4 production

Action Glucocorticoids

Choice of route oral, parenteral or local joint injection number of inflamed joints severity of disease

Action to avoid

Allopurinol - Febuxostat, Uricosurics : Add colchicine or NSIADs first 6 months treatment chronic gout

Action to for Pegloticase

patients who Gout who did not respond to Allopurinol, Add antihistamines corticosteroids

Drug-Modifying Antirheumatic Drugs;DMARDs Therapy

Goal relieve pain, inflammation, swelling, stiffness joint destruction avoid joint replacement surgery,

Action start 1st with

NSAIDs pain swelling prevent progression disease joint damage,

Drug-Modifying Antirheumatic Drugs;DMARDs

diagnosisMade progression disease joint damage,delayed onset

Action Combinations of DMARDs

lose effectiveness timeMonitors hepatic, renal & bone marrow.Cortis toxic chronic use, severe exac patient intolerant DMARDs

Systemic lupus erythematosus :SLE

.Hydroxychloroquine Mild cases , Azathioprine- Methotrexate More potent than hydroxychloroquine