Ch 11 Pharm PPT(1).pptx

Pharmacology Review Dr. Kimberly Peacher Pharmacological effects and drug interactions Knowledge and understanding of pharmacology is essential to safe dental care. This knowledge can: Serve to prevent as well as handle emergency situations ID drug interactions and adverse effe...

Pharmacology Review Dr. Kimberly Peacher Pharmacological effects and drug interactions Knowledge and understanding of pharmacology is essential to safe dental care. This knowledge can: Serve to prevent as well as handle emergency situations ID drug interactions and adverse effects ID situations in which patient treatment requires special handling Key terms to know Drug Pharmacodynamics Pharmacology Pharmacokinetics Toxicology Trade vs generic Synergism (1+1=3) Antagonism Contraindications (absolute vs relative) Tolerance Know Adverse Drug Reactions and Terminology: Toxic reaction-excessive effect on TARGET organs; dose related Side effect-NON-target organs, predictable, undesired effect; dose-related Idiosyncratic reaction-abnormal, genetic rel. resp. Teratogenic effect (thalidomide->phocomelia) Local effects (tissue necrosis->site of LA injection) Drug interactions may result in increased (toxic) or reduced effects Allergic reactions can be mild to life threatening; hypersensitivity reaction (Types I-IV), UNpredictable, ; NOT dose related Drug Schedule Schedule Abuse Handling Example Drug Potential I Highest There is no accepted Heroin, LSD medical use for these drugs. II High Written Rx with Morphine, OxyContin, signature, no phoned-in; hydrocodone, fentanyl no refills III Moderate Rx phoned-in, no more Tylenol w/ codeine, than 5 refills in 6 months Anabolic steroids, testosterone IV Less Same as III Valium, Darvon V Least Some may be OTC Codeine-containing cough meds Log dose-effect curve A graphic representation in which the curve is replotted using the log of the dose versus the response x-axis log of dose (effective or therapeutic range is at sharp increase) Y-axis response to dose (maximum response is at Reminder: plateau) X is laying down, Y are you still standing up? Characterization of Drug Action Potency (closeness to y?) related to the amount of drug needed to produce an effect. Ex. 7 Characterization of Drug Action The efficacy and the Efficacy (height) potency of a drug are related to the maximal unrelated! effect of a drug, regardless of dose. Administering more drug will NOT increase the efficacy of the drug (but increases potential for adverse effects). Ex. One drinks 1 oz. Bourbon or 12 oz. beer. What is result? What if 12 oz. of bourbon is ingested instead of 1 oz.? What about 1 oz. of beer? 8 Drug Effects* Pharmacologic effect Therapeutic effect Toxic effects Therapeutic index (TI) Routes of Administration (ROA) The route of administration of a drug affects both the onset and duration of the drug response. Onset: Time it takes for the drug to begin to have its effect Duration: The length of time of a drug’s effect 10 ROA Two major groups Enteral (placed into GI tract) Oral Rectal Parenteral (bypasses GI tract) Injection (IV, IM, SC/SQ, ID, IT, IP) Inhalation Topical (sublingual) ROA-Enteral Oral: Safest, least expensive, and most convenient ROA First pass effect (or phase I reactions)*: Occurs when orally-admin’d drugs initially pass through the hepatic-portal circulation (liver), which then reduces the amount of drug a available or even inactivate some drugs Drugs with a high first-pass effect have a LARGER oral to parenteral dose ratio meaning: they require a LARGER oral dose Rectal: Drugs are poorly and irregularly absorbed; Poor patient acceptance; suppositories 12 ROA-Parenteral IV: most rapid response, best for ER situations, most predictable blood levels; disadvantages include phlebitis, drug irretrievability, and allergy IM: sustained effects, absorbed due to the high blood flow through skeletal muscles, usually the deltoid region or gluteal mass, massage increases absorption Subcutaneous: Common route to administer protein products, Irritating solutions may cause sterile abscesses or hematoma; insulin and LA ROA Intradermal: injection into epidermis; TB test. Inhalation: rapid delivery across large surface area of resp. mucosa; asthma inhalers, nitrous- oxide sedation Topical: applied to skin or mucosa, most effective in non-keratinized areas, local effect; not used on ulcerated, burned or abraded areas ADME Absorption*: the transfer of a drug from site of administration to the blood stream Bypassed in IV ROA Rate an efficiency depend of ROA Lipid soluble drugs ready cross biological membranes (blood-brain barrier, etc.) Distribution: process by which a drug leaves the blood stream and enters the body system-goes to organ with highest blood flow (perfusion) first Oral->liver Sublingual->heart ADME Metabolism: breaking down of drug-usually in liver; AKA biotransformation; Liver disease or substance abuse may cause impairment Elimination: removal of drug from body (usually by renal excretion) unchanged or as metabolite, terminating drug effects; Other routes: liver, lungs, bile, GI, sweat, milk, saliva, exhalation, & gingival crevicular fluid Ex. Fluoride is eliminates in the urine Half-Life Drug half-life (t1/2): The time it takes for the concentration of a drug to “fall” to one-half (50%) of its original blood level; relates to duration of the drugs effects When the half-life is short, the duration of action is short When the half-life is long, the duration of action is long Autonomic nervous system (ANS) ANS: controls automatic, involuntary functions BP, heart rate, GI motility, salivation, bronchial/smooth muscle tone. It has two divisions: PANS SANS ANS Parasympathetic Sympathetic Rest and digest ->Normal Fight or flight->Reactive BP~vasodilation BP~vasoconstriction HR HR blood flow~digestion Dilates bronchioles and Constricts bronchioles and pupils (mydriasis) pupils (miosis) saliva saliva Pre-ganglionic NT: ACh Pre-ganglionic NT: ACh Post-ganglionic NT: NE Post-ganglionic NT: ACh Adrenergic drugs Cholinergic drugs (sympathomimetics) (parasympathomimetics or muscarinic agents) Cholinergics (parasympathomimetics) Stimulate body functions by Contraindications direct or indirect action Asthma Indications: Peptic ulcers Xerostomia Cardiac disease urinary retention GI/Urinary obstruction glaucoma Examples Pilocarpine Nicotine Anticholinergics Inhibit body functions by blocking cholinergic (muscarinic) receptors Examples and indications: Atropine (decrease salivary flow) Imodium (diarrhea) Scopolamine (motion sickness) Dramamine (motion sickness) Adverse reactions: A: anticholinergics B: blurred vision, bladder retention C: constipation D: dry mouth Adrenergic drugs (sympathomimetics) Stimulate α and β Adverse effects: CNS receptors (anxiety, fear, tremor, Indications: Asthma, ADD, headache), cardiac vasoconstriction, CNS arrhythmia, hypertension, stimulant, decongestion, xerostomia anaphylaxis Contraindications: Examples angina Ventolin (albuterol) uncontrolled epinephrine hypertension Dopamine uncontrolled Adderall, Ritalin hyperthyroidism Adrenergic-blockers (β blockers) Inhibit alpha and beta-1 or beta-2 receptors Indications: cardiac arrhythmias, hypertension, angina, glaucoma, MI Examples (“olol”): Inderal (propranolol): Non-selective* beta blocker Lowers BP by lowering cardiac output Adverse reactions: bronchoconstriction, arrhythmias, epi in LA Tenormin (atenolol): Selective beta blocker Eliminates bronchioconstrictive effect for hypertensive asthmatic patients Lopressor (metoprolol): Selective beta blocker Used for hypertension, prevention of MI and angina Timoptic (timolol): Used topically to treat glaucoma Analgesics Aspirin Acetaminophen Nonopioid, NSAID Nonopioid MOA: inhibit prostaglandin Effects: analgesic, antipyretic synthesis Adverse effects: Effects: 4 A’s* Hepatotoxicity and liver Adverse effects: necrosis at high doses Decreased clotting, GI Contraindications: upset, hypersensitivity, Liver issues Reye’s syndrome, Tinnitus Drug of choice for children, Contraindications: patients on blood thinners, and Blood thinners, gastric for POST-OP PAIN following ulcers, children PERIODONTAL DEBRIDMENT because of fewest side effects Analgesics Ibuprofen Narcotics/Opioids Nonopioid, NSAID Block pain receptors in brain MOA: inhibit prostaglandin w/o loss of consciousness synthesis Effects: analgesic, antitussive, Effects: Analgesic, antipyretic, sedation, euphoria antiinflammatory Adverse effects: respiratory Adverse effect: depression/sedation, Decreases clotting, GI nausea/vomiting, constipation, issues, drug interactions addiction (ACE inhibitors, aspirin, beta Sign of overdose: pinpoint blockers, steroids, loop pupils diuretics) Examples: morphine, codeine, Contraindications: Demerol, Dilaudid, Vicodin Gastric ulcers Antagonists/Addiction Narcan (naloxone) Methadone Opioid antagonist Treats narcotic Treat opioid overdose withdrawal and dependence Suppresses need for 24 -36 hours Only effective in cases of addiction to heroin, morphine, and other opioids NOT effective with methanphetamines Antibiotics/Antiinfectives Terms to know: Bacteriocidal Bacteriostatic Minimum Inhibitory Concentration (MIC) Resistance Spectrum (Broad and Narrow) Synergism Antagonism Antibiotics/Antiinfectives Penicillin Most common in dentistry (PenVK) Bacteriocidal-destroys cell wall integrity Effective against rapid growing Most likely antibiotic to produce anaphylactic reaction Most common side effect: rash Safe in pregnancy Not effective against penicillinase (beta lactamase) w/o the addition of clavulanic acid (Augmentin) Antibiotics/Antiinfectives Macrolides Bacteriostatic drugs: Interfere with protein synthesis Examples: erythromycin azithromycin (Zithromax) clarithromycin (Biaxin) Antibiotics/Antiinfectives Tetracycline Broad spectrum Bacteriostatic-protein synthesis Treats NUG/NUP and Type III (Aggressive Perio) Inhibits collagenase production Concentrates in GCF Not for pregnancy or early childhood Avoid dairy, antacids, iron Mixing with other antibiotics results in antagonism Antibiotics/Antiinfectives Cephalosporin's Bactericidal: Inhibits cell wall synthesis Related to penicillin (10% of those allergic to penicillin are also allergic to cephalosporins) Examples cephalexin (Keflex) cefaclor (Ceclor) Cefuroxime (Ceftin) Antibiotics/Antiinfectives Nitromidazoles Bactericidal action: Inhibits nucleic acid synthesis Effective against obligate anaerobes ONLY Antabuse-like reaction: avoid alcohol Think mouthwashes! Example: metronidazole (Flagyl) Antituberculosis Agents R: rifampin I: isoniazid P: pyraazinamide E: ethambutol All 4 (RIPE) required to treat TB If just I or R, intent is prevention Mantoux Skin Test (PPD) + = exposed not infected TB spread by droplet aerosol Antifungal Agents Fungal infections common with antibiotic use or steroid use; also in immunocompromised individuals Examples; Nystatin: most frequent; used for topical candidiasis Fluconazole (diflucan): systemic candidiasis Mycelex (clotrimazole) Nizoral (ketoconazole) Antiviral Agents Herpes Examples*: acyclovir (Zovirax), pevalacyclovir (Denavir), valacyclovir (Valtrex) HIV/AIDS Examples: Zidovudine (Retrovir, AZT), didanosine (Videz, ddI), zalcitabine (ddC), stavudine (d4T), laminivudine (3TC), and protease inhibitors Antianxiety: 2 major classes Barbiturates (“tal”) Benzodiazepines Principle effect: CNS (“azepam” or “azolam”) depression Useful for short-term treatment NO analgesic effect! of anxiety, insomnia, alcohol Ex. withdrawal; muscle relaxant phenobarbital-most (TMJ disorder), reverse status common barbiturate used epilepticus to treat epilepsy ALL have sedative properties Most common side effect is NO analgesic or antipsycholotic sedation effects! butabarbital Ex. secobarbital diazepam (Valium) lorazepam (Ativan) alprazolam (Xanax) Anticonvulsants Dilantin (phenytoin) Tegretol Depresses CNS to (carbamazepine) decrease seizures in Used to treat partial patients with epilepsy 50% of patients exhibit seizures, trigeminal gingival hyperplasia neuralgia Often used in conjunctoin Does NOT cause with phenobarbital gingival hyperplasia Phenobarbital (prev. slide) Antidepressants Selective serotonin Monamine oxidase reuptake inhibitors inhibitors (MAO’s or (SSRI’s) MAOI’s) Ex. Rarely used today due to fluoxetine (Prozac) fatal interactions with sertraline (Zoloft) analgesics, SSRI’s, and/or citalopram (Celexa) certain foods containing tyramine (aged cheese, escitalopram oxalare smoked meats, fish, beer, (Lexapro) wine, etc.) paroxetine (Paxil) Antihistamine Benadryl (diphenhydramine) Most common Treats mild allergic reactions Side effects Xerostomia sedation Diabetes Agents Insulin Oral hypoglycemic Used to treat type 1 drugs Subcutaneous “protein Used to treat type 2 product” metformin Hypoglycemia is most (Glucopahge) common side effect increases bodies sensitivity to insulin glyburide (Micronase, Diabeta) stimulates the release of insulin from b-cells in pancreas Respiratory Agents Diseases include: asthma, COPD, upper respiratory tract infections Asthma SABA (short-acting brochodilators) albuterol (Ventolin, Proventil), pirbuterol (Maxair) Provide immediate relief of asthma symptoms LABA (long-acting brochodilators) Salmeterol (servent) and formoterol (Foradil) Relive asthma symptoms for longer periods of time Respiratory Agents Asthma (cont’d) Corticosteroids Used long term to prevent asthma atackds Examples beclomethasome dipropioate (QVAR) fluticasone (Flovent) triamcinolone acetonide (Azmacort) flunisolide (Aerobid) Corticosteroids plus LABA Advair Respiratory Agents COPD Anticholinergics-first line of treatment Ipratropium (Atrovent) is drug of choice for long term management Upper respiratory infection Nasal decongestants (beta-blockers) Expectorants Antitussives-may be opioids or related drugs GI Agents Treat gastric ulcers or GERD Histamine blocking Sodium bicarbonate agents “tidine” Systemic antacid; may be Block H2 histamine contraindicated in receptors which cardiovacular patient due reduces acid secretions to sodium content Tagamet (cimetidine) Proton-pump inhibitors and Pepcid (famotidine) (PPI) “prazole” Should NOT be used Inhibit gastric secretion with antacids Prilosec (omeprazole) and Prevacid (lansoprazole) Bisphosphonate Drugs Used to treat osteoporosis (Fosamax, Boniva) Also used to treat cancer~IV infusion Associated with osteonecrosis of the jaw Risk remains for years after use Prednisone Glucocorticosteroid (“sone” and “lone”) Used in treating autoimmune and inflammatory disorders, Addison's disease, and allergic reactions by reducing inflammatory response and suppressing immunity Increases risk of delayed healing and risk for infection, exacerbates hypotension, may increase blood sugar, osteoporosis with long- term use May lead to adrenal suppression Putting patient at risk for adrenal crisis Cardiovascular Agents Angina Pectoris Congestive Heart Failure Nitroglycerin is drug of Cardiac glycosides most choice for acute angina common drug Works as a vasodilator Increases strength and force “smooth muscle relaxant” of heart contraction Administered sublingually Ex. Should be located in Lanoxin (digoxin) emergency kit Digitalis Dental considerations: caution with vasoconstricting LA, gag reflex, increased salivation Cardiovascular Agents Anticoagulant Therapy Hypertension (next slides) Used to prevent stroke and Usually asymptomatic; MI (intravascular clotting) MOST common of all Risk of gingival hemorrage cardio diseases-affection Ex. 60 million in US Coumadin (warfarin)* Several families of drugs Plavix (clopidogrel) used to treat: Diuretics Prevent clot after MI or Beta-adrenergic blockers stoke or other disorders Calcium channel clockers Aspirin (CCB’s) Heparin-injection at Angiotensin Converting hospital Enzyme (ACE) Inhibitors Cardiovascular Agents: Hypertension Diuretics (water pills) 1st Beta-adrenergic blockers or Promoting excretion of Na Beta blockers “olol” 2nd and H2O which decreases BP by cardiac output; blood volume and pressure *Block beta receptors~SANS 2 main types (“ide”): 2 types: Thiazide diuretics: Non-selective: affects hydrochlorothiazide both beta-1 and beta-2 (HCTZ) is most common No asthma or other resp. Loop diuretics: propranolol (Inderal) furosemide (Lasix) is most Selective: affects only common beta-1 atenolol (Tenormin) metaprolol (Lopressor) Cardiovascular Agents: Hypertension CCB’s ACE Inhibitors (“pril”) BP by causing systemic Blocks conversion of vasodilation angiotensin I to angiotensin II Not effected by NSAIDs (causes vasodilation) Common oral effects: Effect decreased by NSAIDs gingival enlargement and Dysgeusia is common xerostomia Adverse reactions: Ex. hypotension, allergic rxn, dry Nifedipine (Procardia, cough Adalat) Ex. Verapamil (Calan, Isoptin) isinopril (Prinivil, Zestril) Amlodipine (Norvasc) captopril (Capoten) Diltiazem (Cardizem) enalapril (Vasotec) Drugs of Abuse Cocaine: Methamphetamine CNS stimulant CNS stimulant Causes vasoconstriction NO epi if used in last 24 and dilation of pupils hours NO epi if used in last 24 Associated with severe hours oral effects Heroin Rampant caries, Opioid drug that causes xerostomia, soda CNS and respiratory consumption, burned depression mucosa, “meth mouth” Caused sedation and Males, 19-40 most dilated “pinpoint” pupils common Emergency Drugs Emergency Drug Situation Indicated epinephrine Anaphylaxis/severe allergic rxn diphenhydramine Mild to moderate allergic rxn hydrocortisone Adrenal crisis albuterol Asthma; resp. diseases nitroglycerin Chest pain oral carbohydrate/glucose Diabetic complications/hypoglycemia diazepam (Valium) Management of seizure naloxone (Narcan) Opioid overdose oxygen Most emergency situations except hyperventilation and COPD AHA Guidelines for Conditions Requiring Antibiotic Premedication Cardiac conditions needing antibiotic premedication Prosthetic/artificial heart valve Previous infective endocarditis Specific congenital heart defects: Unrepaired cyanotic congenital heart disease Repaired heart defect with prosthetic patch or device Cardiac transplantation with cardiac valvular disease Renal dialysis shunt Ventriculoatrial hydrocephalic shunt (not stent) Trigger terms: transplant, unrepaired, partially repaired, prosthetic (fake), residual effect, IE AHA Guideline Regimen for Antibiotic Premedication Miscellaneous hints Statins: lower cholesterol Lipitor (atorvastatin) Lescol (fluvastatin) Mevacor (lovastatin) Zocor (simvastatin) Crestor (rosuvastatin) Thyroid Hypothyroidism: levoxythyroxine (Synthroid) Iodine deficiency=goiter Miscellaneous hints Pupil dilation: sign of opioid overdose, cocaine use Alcohol + nitroglycerin = hypotension Estrogen Steroid hormone most frequently used for contraception, post-menopausal therapy, menstrual disturbances Estradiol most potent estrogen produced May promote: endometrial carcinoma and breast cancer, increase gingival inflammation Ex: Estraderm, Premarin Miscellaneous hints 3 drugs that commonly cause gingival overgrowth: Phenytoin (Dilantin) CCBs such as nifedipine Cyclosporins Cardiac dose of epinephrine containing LA is 2 carpules. Rx Abbreviations ac: before meals stat: immediately d: day bid: twice per day h: hour tid: three times per po: by mouth day hs: at bedtime qid: four times per pc: after meals day qd: every day prn: as needed gt: drop sig: label ud: as directed tab: tablet General Anesthetics* Potent CNS depressants Stage 2: delirium/excitement Produce reversible loss of Begins with consciousness and insensitivity unconsciousness to pain stimulus Associated with involuntary Stages and Planes: movement and excitement Stage 1: analgesia Stage 3: surgical anesthesia reduced pain sensation Stage where major surgery Conscious and responsive in completed Respiration and reflexes are Stage 4: resp. or medullary regular paralysis Nitrous oxide Complete cessation of all End of stage marked by loss respiration of consciousness If not reversed immediately, death occurs