Pharmaceutical Sciences Notes

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Antidepressants Pharmacology and Therapeutics • Source Session/Topic 32 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 32: Pharmacodynamics of Antidepressants Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Explain pathophysiology of depression Describe mechanism of action of Antidepressants Describe drug interactions associated with Antidepressants Describe side effects of Antidepressants Describe contraindications of Antidepressants Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning tasks Introduction, Learning tasks Introduction, Learning tasks 2 2 20 minutes 20 minutes Presentation Pathophysiology of depression Pathophysiology of depression Pathophysiology of depression 3 3 45 minutes 45 minutes Presentation/ Mechanism of Action of Antidepressants Mechanism of Action of Antidepressants Mechanism of Action of Antidepressants 3 3 45 minutes 45 minutes Buzzing Mechanism of Action of Antidepressants Mechanism of Action of Antidepressants Mechanism of Action of Antidepressants Buzzing 4 4 20 minutes 20 minutes Presentation/ Drug Interactions Associated With Drug Interactions Associated With Drug Interactions Associated With 4 4 20 minutes 20 minutes brainstorming Antidepressants Antidepressants Antidepressants brainstorming Antidepressants Antidepressants Antidepressants 5 5 10 minutes 10 minutes Presentation Side Effects of Antidepressants Side Effects of Antidepressants Side Effects of Antidepressants PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics 251 251 251 NTA Level 5 Semester 1 Facilitator Guide NTA Level 5 Semester 1 Facilitator Guide 6 10 minutes Presentation/ Contraindications of Antidepressants 6 10 minutes Brainstorming Contraindications of Antidepressants Brainstorming 7 05 minutes Presentation Key Points 8 05 minutes Presentation Evaluation PST 05104 Pharmacology & Therapeutics 252 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Pathophysiology of Depression (20 minutes) Monoamine theory of depression suggest that depression is due to a cerebral deficiency of monoamines particularly noradrenaline (NA), 5-hydroxytryptamine (5HT) and methyltyrosine. The following actions of drugs support the above theory: Reserpine -depletes neuronal stores of noradrenaline (NA) and 5-hydroxytryptamine (5HT) and α-methyltyrosine, which inhibits NA synthesis causing depression, Tricyclic antidepressants (TCA) of the amitriptyline type (which raise the synaptic concentration of NA and 5HT) are antidepressant and Monoamine oxidase inhibitors (MAOIs, which increase total brain NA and 5HT) are antidepressant. Another theory of depression is the serotonin-only hypothesis. o This theory emphasizes the role of 5HT and downplays that of NA in the causation of depression, and is backed by the effectiveness of the selective serotonin reuptake inhibitors, or SSRI class of drugs, in the treatment of depression. STEP 3: Mechanism of Action of Antidepressants (45 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do antidepressants produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Tricyclic Antidepressants (TCAs) Examples include amitriptyline, desipramine, imipramine, nortriptyline, clomipramine, trimipramine, doxepin, maprotiline PST 05104 Pharmacology & Therapeutics 253 NTA Level 5 Semester 1 Facilitator Guide The monoamine hypothesis suggests that depression is caused by a deficiency of synaptic neurotransmitters such as serotonin (5-HT), NA, and dopamine. Serotonin, in particular, is associated with mood. Normally, 5-HT and NA are released from presynaptic vesicles into the synaptic cleft, where they travel to postsynaptic receptors. Once released from these postsynaptic receptors, 5-HT and NA are removed from the synaptic cleft by reuptake transporters located on the presynapse. The TCAs inhibit the reuptake of serotonin (5-HT) and NA into the presynaptic cell body, increasing the amount of 5-HT and NA available to bind to postsynaptic receptors. TCAs antagonize other receptors: muscarinic, histamine (H1), adrenergic (α1) receptors. This accounts for their extensive list of side effects. Selective Serotonin Reuptake Inhibitors (SSRIs) Examples include fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram and escitalopram. The monoamine hypothesis suggests that depression is caused by a deficiency of synaptic neurotransmitters such as serotonin (5-HT), norepinephrine, and dopamine. Serotonin, in particular, is associated with mood. Normally, 5-HT is released from presynaptic vesicles into the synaptic cleft, where it travels to postsynaptic receptors. Once released from these postsynaptic receptors, 5-HT is removed from the synaptic cleft by reuptake transporters located on the presynapse. Once it is taken up presynaptically, it is degraded. SSRIs bind to this reuptake transporter, preventing the removal of 5-HT and leading to increased 5-HT available to bind to postsynaptic receptors. Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs) Examples include venlafaxine, desvenlafaxine, duloxetine and milnacipran Once released from these postsynaptic receptors, 5-HT and NA are removed from the synaptic cleft by reuptake transporters located on the presynapse. Once they are taken up presynaptically, they are degraded. SNRIs bind to these reuptake transporters, preventing the removal of 5-HT and NA and leading to increased availability to bind to postsynaptic receptors. Venlafaxine has much higher affinity for the serotonin reuptake transporter, and at low doses acts more like an SSRI. It is not until higher doses are used that it also blocks noradrenaline reuptake. o Conversely, milnacipran blocks serotonin and noradrenaline reuptake equally, whereas the other agents in this class fall somewhere between these two. PST 05104 Pharmacology & Therapeutics 254 NTA Level 5 Semester 1 Facilitator Guide Monoamine oxidase Inhibitors (MAOIs) Examples include :Selective to MAO-B: Selegiline, rasagiline, Selective to MAO-A: Moclobemide and Nonselective inhibitors: phenelzine and tranylcypromine o MAO degrades catecholamines, serotonin, and

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Drugs for Heart Failure Pharmacology and Therapeutics • Source Session/Topic 33 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 33: Pharmacodynamics of Drugs for Heart Failure Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe mechanism of action of drugs for heart failure Describe drug interactions associated with drugs for heart failure Describe side effects of drugs for heart failure Describe contraindications of drugs for heart failure Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks 2 2 45 minutes 45 minutes Presentation/ Mechanism of Action of Drugs for Heart Mechanism of Action of Drugs for Heart 2 2 45 minutes 45 minutes Buzzing Failure Failure Buzzing Failure Failure 3 3 20 minutes 20 minutes Presentation/ Drug Interactions Associated Drugs for Heart Drug Interactions Associated Drugs for Heart 3 3 20 minutes 20 minutes brainstorming Failure Failure brainstorming Failure Failure 4 4 20 minutes 20 minutes Presentation Side Effects of Drugs for Heart Failure Side Effects of Drugs for Heart Failure 5 5 20 minutes 20 minutes Presentation/ Contraindications of Drugs for Heart Failure Contraindications of Drugs for Heart Failure 5 5 20 minutes 20 minutes Brainstorming Contraindications of Drugs for Heart Failure Contraindications of Drugs for Heart Failure Brainstorming 6 6 05 minutes 05 minutes Presentation Key Points Key Points 7 7 05 minutes 05 minutes Presentation Evaluation Evaluation PST 05104 Pharmacology & Therapeutics 261 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Mechanism of Action of Drugs for Heart Failure (45 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do Drugs for Heart Failure produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Drugs for Heart Failure Diuretics o In Chronic heart failure: a diuretic is used to control symptomatic oedema and dyspnoea in patients with heart failure. o For more information on adverse effects, interactions , contraindications and mechanism refer a session on Pharmacodynamics of drugs acting on urinal genital system o Spironolactone improves survival in patients with cardiac failure and counters diuretic-induced hypokalaemia. o Diuretic-induced hypokalaemia increases the toxicity of digoxin. Conversely, spironolactone and other K+-retaining diuretics (e.g. amiloride, triamterene) can cause severe hyperkalaemia, especially if given with ACEI or sartans to patients with renal impairment. o It is therefore important to monitor plasma K+ during treatment with all diuretic therapy. Angiotensin-Converting Enzyme Inhibitors For more information on adverse effects, interactions , contraindications and mechanism refer a session on Pharmacodynamics of drugs acting on urinal genital system (session ) and Pharmacodynamics of Antihypertensive drugs(session ) When symptoms are mild, diuretics can be temporarily discontinued a day or two before starting an ACEI, reducing the likelihood of first-dose hypotension. PST 05104 Pharmacology & Therapeutics 262 NTA Level 5 Semester 1 Facilitator Guide Angiotensin Receptor Antagonists, Sartans o For more information on adverse effects, interactions, contraindications and mechanism refer a session on Pharmacodynamics of Pharmacodynamics of Antihypertensive drugs (session). o As in hypertension, the pharmacodynamics of sartans are similar to those of ACEI apart from a lower incidence of some adverse effects, including, particularly, dry Inotropic action: Through the action of Na/K/ATP ion pump blockade, the following sequence of ionic events occurs: o ↓ Na exits the cell o ↑ Intracellular Na o ↓ Na electrochemical gradient for Na-Ca exchanger o ↓ Ca exits the cell o ↑ Intracellular Ca o The increase in intracellular calcium results in increased contractility, SV, and CO. o In heart failure, sympathetic tone is increased as a compensatory mechanism to increase CO. o Digoxin increases contractility and hence SV and CO, therefore reducing the need for sympathetic compensation cough. Thus digoxin reduces the sympathetic tone in heart failure Beta blockers o For more information on adverse effects, interactions , contraindications and mechanism refer a session on Pharmacodynamics of Antihypertensives o Beta-blockers are negative inotropes and so intuitively would be expected to worsen heart failure. o There is, however, a rationale for their use in terms of antagonizing counter regulatory sympathetic activation and several randomized controlled trials have demonstrated improved survival when a β-adrenoceptor antagonist is added to other drugs, including an ACEI. Beta1-Adrenergic Agonists: Dobutamine ,Dopamine, Amrinone and Milrinone o Improves cardiac performance by their positive inotropic effects and vasodilatation ((β-2), minimum effects on HR by dobutamine) Increase in intracellular cAMP → results in the entry of Ca2+ into the myocardial cells increases, thus enhancing contraction Diminished effects after long-time infusions and possible worsening upon withdrawal o Ibopamine which is a pro-drug and has actions at β-1, β-2, D1 and D2 is not preferred because of the non-selectivity hence increased toxicity. Glucagon o Glucagon increases cyclic AMP thus increasing myocardial contraction hence used in acute cardiac dysfunction due to overdose of β-blockers Inhibitors of Phosphodiesterase III o Inhibitors of phosphodiesterase III which is specific to the heart and responsible for degradation of cyclic AMP thus increases myocardial contractility are also used. PST 05104 Pharmacology & Therapeutics 263 NTA Level 5 Semester 1 Facilitator Guide STEP 3: Drug Interactions Associated with Drugs for Heart Failure (20 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are drug interactions associated with drugs for heart failure? ALLOW

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Antihypertensive Drugs Pharmacology and Therapeutics • Source Session/Topic 34 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 34: Pharmacodynamics of Antihypertensive Drugs Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe mechanism of action of Antihypertensive Drugs Describe drug interactions associated with Antihypertensive Drugs Describe side effects of Antihypertensive Drugs Describe contraindications of Antihypertensive Drugs Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks 2 2 45 minutes 45 minutes Presentation/ Mechanism of Action of Antihypertensive Mechanism of Action of Antihypertensive 2 2 45 minutes 45 minutes Buzzing Drugs Drugs Buzzing Drugs Drugs 3 3 20 minutes 20 minutes Presentation/ Drug Interactions Associated With Drug Interactions Associated With 3 3 20 minutes 20 minutes brainstorming Antihypertensive Drugs Antihypertensive Drugs brainstorming Antihypertensive Drugs Antihypertensive Drugs 4 4 20 minutes 20 minutes Presentation Side Effects of Antihypertensive Drugs Side Effects of Antihypertensive Drugs 5 5 20 minutes 20 minutes Presentation/ Contraindications of Antihypertensive Drugs Contraindications of Antihypertensive Drugs 5 5 20 minutes 20 minutes Brainstorming Contraindications of Antihypertensive Drugs Contraindications of Antihypertensive Drugs Brainstorming 6 6 05 minutes 05 minutes Presentation Key Points Key Points 7 7 05 minutes 05 minutes Presentation Evaluation Evaluation PST 05104 Pharmacology & Therapeutics 268 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Mechanism of Action of Antihypertensive Drugs (45 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do antihypertensive drugs produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Angiotensin-Converting Enzyme Inhibitors(ACEI) o These drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II. o ACEI lower blood pressure by reducing angiotensin II and perhaps also by increasing vasodilator peptides, such as bradykinin by diminishing their inactivation. o Angiotensin II causes aldosterone secretion from the zona glomerulosa of the adrenal cortex and inhibition of this contributes to the antihypertensive effect of ACE inhibitors because of decreased sodium and water retention. Beta blockers o Β-Adrenoceptor antagonists reduce cardiac output (via negative chronotropic and negative inotropic effects on the heart). o These drugs also inhibit renin secretion and some have additional central actions reducing sympathetic outflow from the central nervous system (CNS). Angiotensin receptor blockers o Most of the effects of angiotensin II, including vasoconstriction and aldosterone release, are mediated by the angiotensin II subtype 1 (AT1) receptor. o These drugs block the AT1 receptors thus blocking Angiotensin II actions/effects. Calcium Channel blockers o Calcium-channel blockers inhibit Ca2+ influx through voltage-dependent L-type calcium channels. o Cytoplasmic Ca2+ concentrations control the contractile state of actomyosin. PST 05104 Pharmacology & Therapeutics 269 NTA Level 5 Semester 1 Facilitator Guide Calcium-channel blockers therefore relax arteriolar smooth muscle, reduce peripheral vascular resistance and lower arterial blood pressure. Diuretics o Thiazide Diuretics: Thiazide diuretics inhibit reabsorption of sodium and chloride ions in the proximal part of the distal convoluted tubule. o Excessive salt intake or a low glomerular filtration rate interferes with their antihypertensive effect. Natriuresis is therefore probably important in determining their hypotensive action. α-Adrenoceptor antagonists There are two main types of α-adrenoceptor, α1- and α2. Noradrenaline activates α1-receptors on vascular smooth muscle, causing tonic vasoconstriction. α1-Antagonists cause vasodilatation by blocking this tonic action of noradrenaline hence α1-Adrenoceptor antagonist‘s lower blood pressure. Prazosin, doxazosin and other alpha 1 receptor blockers decrease peripheral vascular resistance and lower arterial blood pressure by causing the relaxation of both arterial and venous smooth muscle. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Centrally acting drugs Methyldopa: after uptake into central neurones and methyldopa is metabolised to a false transmitter (α-methylnoradrenaline) which is an α2-adrenoceptor agonist. Activating central α2-adrenoceptors by the false transmitter inhibits sympathetic outflow from the CNS. Moxonidine is another centrally acting drug: it acts on imidazoline receptors and is said to be better tolerated than methyldopa. Other vasodilators Minoxidil: works via a sulphate metabolite which activates potassium channels. This relaxes vascular smooth muscle, reducing peripheral vascular resistance and lowering blood pressure. Nitroprusside: It is a rapid acting inorganic nitrate which degrades to NO relaxes blood vessels hence reduced blood pressure. PST 05104 Pharmacology & Therapeutics 270 NTA Level 5 Semester 1 Facilitator Guide STEP 3: Drug Interactions Associated with Antihypertensive Drugs (20 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What drug interactions associated with antihypertensives drugs? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below Angiotensin Converting Enzyme Inhibitors o ACEI interaction with Diuretics: o Diuretic treatment increases plasma renin activity and the consequent activation of angiotensin II and aldosterone thus limiting efficacy of ACEIs. o ACE inhibition interrupts the loop and thus enhances the hypotensive efficacy of diuretics, as well as reducing thiazide-induced hypokalaemia. o Conversely, ACEI have a potentially adverse interaction with potassium-sparing diuretics and potassium supplements, leading to hyperkalaemia, especially in patients with renal impairment. o As with other antihypertensive drugs, NSAIDs increase blood pressure in patients treated with ACE inhibitors. Beta Blockers o Pharmacokinetic interactions: o β-adrenoceptor antagonists inhibit drug metabolism indirectly by decreasing hepatic blood flow secondary to decreased cardiac output. o This causes accumulation

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Anticoagulants Pharmacology and Therapeutics • Source Session/Topic 35 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 35: Pharmacodynamics of Anticoagulants Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe mechanism of action of Anticoagulants Describe drug interactions associated with Anticoagulants Describe side effects of Anticoagulants Describe contraindications of Anticoagulants Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning tasks Introduction, Learning tasks Introduction, Learning tasks 2 2 40 minutes 40 minutes Presentation/ Mechanism of Action of Anticoagulants Mechanism of Action of Anticoagulants Mechanism of Action of Anticoagulants 2 2 40 minutes 40 minutes Buzzing Mechanism of Action of Anticoagulants Mechanism of Action of Anticoagulants Mechanism of Action of Anticoagulants Buzzing 3 3 20 minutes 20 minutes Presentation/ Drug Interactions Associated with Drug Interactions Associated with Drug Interactions Associated with 3 3 20 minutes 20 minutes brainstorming Anticoagulants Anticoagulants Anticoagulants brainstorming Anticoagulants Anticoagulants Anticoagulants 4 4 20 minutes 20 minutes Presentation Side Effects of Anticoagulants Side Effects of Anticoagulants Side Effects of Anticoagulants PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics 277 277 277 NTA Level 5 Semester 1 Facilitator Guide NTA Level 5 Semester 1 Facilitator Guide 5 15 minutes Presentation/ Contraindications of Anticoagulants 5 15 minutes Brainstorming Contraindications of Anticoagulants Brainstorming 6 05 minutes Presentation Key Points 7 05 minutes Presentation Evaluation 8 10 minutes Presentation Assignment PST 05104 Pharmacology & Therapeutics 278 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Mechanism of Action of Anticoagulants (40 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do Anticoagulants produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Anticoagulants Heparins: o Heparin is a sulphated acidic mucopolysaccharide that is widely distributed in the body. o The unfractionated preparation is extracted from the lung or intestine of ox or pig, and is a mixture of polymers of varying molecular weights. o Since the structure is variable, the dosage is expressed in terms of units of biological activity. o Low-molecular-weight heparins (LMWH) are fragments or short synthetic sequences of heparin with much more predictable pharmacological effects, and monitoring of their anticoagulant effect is seldom needed. o They have largely replaced unfractionated heparin in therapy. Unfractionated Heparin(UFH) o Unfractionated heparin has been replaced by LMWH for most indications, but remains important for patients with impaired or rapidly changing renal function. o Treatment is monitored by measuring the activated partial thromboplastin time (APTT) four to six hours after starting treatment and then every six hours, until two consecutive readings are within the target range, and thereafter at least daily. o Dose adjustments are made to keep the APTT ratio (i.e. the ratio between the value for the patient and the value of a control) in the range 1.5–2.5. o Mechanism: PST 05104 Pharmacology & Therapeutics 279 NTA Level 5 Semester 1 Facilitator Guide The main action of heparin is on the coagulation cascade. It works by binding to antithrombin III, a naturally occurring inhibitor of thrombin and other serine proteases (factors IXa, Xa, XIa and XIIa), and enormously potentiating its inhibitory action. A lower concentration is required to inhibit factor Xa and the other factors early in the cascade than is needed to antagonize the action of thrombin, providing the rationale for low-dose heparin in prophylaxis. o As an antithrombin drug, it inhibits platelet activation by thrombin Low Molecular Weight Heparins (LMWH) Low-molecular-weight heparins (LMWH) preferentially inhibit factor Xa. They do not prolong the APTT, and monitoring (which requires sophisticated factor Xa assays) is not needed in routine clinical practice, because their pharmacokinetics are more predictable(less protein binding and first-order kinetics) than those of unfractionated. LMWH (e.g. enoxaparin and dalteparin) are at least as safe and effective as unfractionated products, except in patients with renal impairment. Thrombocytopenia and related thrombotic events and antiheparin antibodies are less common than with unfractionated preparations. Once-daily dosage makes them convenient, and patients can administer them at home, reducing hospitalization. However, LMWH are eliminated solely by renal excretion, unlike unfractionated heparin; as a consequence, unfractionated heparin should be used rather than low-molecular-weight preparations in patients with significant renal dysfunction. Mechanism: as discussed on UFH Direct Factor Xa Inhibitors: Rivaroxaban: Direct factor Xa inhibitors are agents that inhibit clotting by inhibiting a specific component of the coagulation cascade. Factor Xa converts prothrombin to thrombin (factor IIa). Thrombin is an enzyme that catalyses the final step in the coagulation cascade, the conversion of fibrinogen to fibrin. Fibrin is a fibrous protein that forms a mesh, providing structural rigidity to a clot. The mesh is created by the cross-linking of fibrin, and this cross-linking step is facilitated by factor XIII. In addition to converting fibrinogen to fibrin, thrombin also activates factor XIII; thus thrombin not only catalyses the creation of the key component of the clot, it also facilitates the provision of structural rigidity to the clot. Thrombin also activates factors V, VIII, and XI, therefore amplifying the coagulation cascade. In addition, thrombin activates platelets, leading to their aggregation. Direct factor Xa

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Antiplatelet Drugs Pharmacology and Therapeutics • Source Session/Topic 36 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 36: Pharmacodynamics of Antiplatelet Drugs Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe mechanism of action of Antiplatelet Drugs Describe drug interactions associated with Antiplatelet Drugs Describe side effects of Antiplatelet Drugs Describe contraindications of Antiplatelet Drugs Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning tasks Introduction, Learning tasks Introduction, Learning tasks 2 2 45 minutes 45 minutes Presentation/ Mechanism of Action of Antiplatelet Drugs Mechanism of Action of Antiplatelet Drugs Mechanism of Action of Antiplatelet Drugs 2 2 45 minutes 45 minutes Buzzing Mechanism of Action of Antiplatelet Drugs Mechanism of Action of Antiplatelet Drugs Mechanism of Action of Antiplatelet Drugs Buzzing 3 3 20 minutes 20 minutes Presentation/ Drug Interactions Associated with Antiplatelet Drug Interactions Associated with Antiplatelet Drug Interactions Associated with Antiplatelet 3 3 20 minutes 20 minutes brainstorming Drugs brainstorming Drugs 4 4 20 minutes 20 minutes Presentation Side Effects of Antiplatelet Drugs Side Effects of Antiplatelet Drugs Side Effects of Antiplatelet Drugs 5 5 20 minutes 20 minutes Presentation/ Contraindications of Antiplatelet Drugs Contraindications of Antiplatelet Drugs Contraindications of Antiplatelet Drugs 5 5 20 minutes 20 minutes Brainstorming Contraindications of Antiplatelet Drugs Contraindications of Antiplatelet Drugs Contraindications of Antiplatelet Drugs Brainstorming 6 6 05 minutes 05 minutes Presentation Key Points Key Points Key Points PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics 286 286 286 NTA Level 5 Semester 1 Facilitator Guide NTA Level 5 Semester 1 Facilitator Guide 7 05 minutes Presentation Evaluation PST 05104 Pharmacology & Therapeutics 287 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Mechanism of Action of Antiplatelet Drugs (45 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do Antiplatelet Drugs produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Salicylates: acetylsalicylic acid (ASA) o ASA works by irreversibly inhibiting COX-1, an enzyme that catalyses the formation of cyclic endoperoxide, which in turn is then converted to Thromboxane A2 (TXA2) in platelets. TXA2 is a potent inducer of platelet aggregation and release. o Inhibition of TXA2 leads to the antiplatelet effects of ASA. Adenosine Diphosphate (ADP) Blockers o Platelets are activated by adhering to damaged endothelium by linking of glycoprotein Ia (GPIa) receptors with collagen and GPIb receptors with von Willebrand factor (vWF). The activation of platelets leads to aggregation and clot formation. o Platelet activation leads to synthesis and release of mediators involved in platelet aggregation: TXA2, Serotonin (5-HT) and ADP. o Mediators such as ADP promote platelet aggregation by increasing GP receptor expression and promoting binding of fibrinogen to GPIIIa/IIb receptors. o Ticlopidine, prasugrel, and clopidogrel inhibit the ADP-dependent pathway of platelet activation and subsequent aggregation. Antiplatelet IIb/IIIa Inhibitors o IIb/IIIa receptors are located on the outside of platelets, in very high numbers (50,000 to 80,000 per cell); in the resting platelet they are inactive. o Fibrinogen and vWF bind to IIb/IIIa receptors; once bound, they bind to foreign surfaces and also bridge other platelets to induce platelet aggregation. PST 05104 Pharmacology & Therapeutics 288 NTA Level 5 Semester 1 Facilitator Guide These drugs bind to the IIb/IIIa receptor complex on the platelet and prevent binding of endogenous ligands including fibrinogen and vWF, thus inhibiting aggregation of the platelet Dipyridamole Dipyridamole was introduced as a vasodilator, but provokes rather than prevents angina (via a steal mechanism). It is used acutely as in stress tests for ischaemic heart disease (e.g. combined with nuclear medicine myocardial perfusion scanning). It is also used chronically, combined with aspirin, for its antiplatelet effect in patients with cerebrovascular disease. Dipyridamole inhibits phosphodiesterase which leads to reduced breakdown of cAMP, and inhibits adenosine uptake with consequent enhancement of the actions of this mediator on platelets and vascular smooth muscle.. STEP 3: Drug Interactions Associated with Antiplatelet Drugs (20 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are drug interactions associated with antiplatelet drugs? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below Salicylates: acetylsalicylic acid (ASA) o Aspirin not only influences haemostasis when co-administered with warfarin by its effect on platelet function, but also increases the likelihood of peptic ulceration, displaces warfarin from plasma albumin, and in high doses decreases prothrombin synthesis. When low doses of aspirin are taken regularly with warfarin may be more than offset by clinical benefits to patients at high risk of thromboembolism following cardiac valve replacement. o For details refer session on Pharmacodynamics of Antinflammatory drugs Dipyridamole Dipyridamole increases the potency and duration of action of adenosine. This may be clinically important in patients receiving dipyridamole in whom adenosine is considered for treatment of dysrhythmia. PST 05104 Pharmacology & Therapeutics 289 NTA Level 5 Semester 1 Facilitator Guide STEP 4: Adverse Effects of Antiplatelet Drugs (20 minutes) Antiplatelet Drugs Salicylates: acetylsalicylic acid (ASA) o GI: GI effects are caused by reduced levels

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Local Anaesthetics Pharmacology and Therapeutics • Source Session/Topic 37 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 37: Pharmacodynamics of Local Anaesthetics Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe mechanism of action of Local Anaesthetics Describe drug interactions associated with Local Anaesthetics Describe side effects of Local Anaesthetics Describe contraindications of Local Anaesthetics Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks Introduction, Learning Tasks 2 2 45 minutes 45 minutes Presentation Mechanism of Action of Local Anaesthetics Mechanism of Action of Local Anaesthetics Mechanism of Action of Local Anaesthetics 3 3 20 minutes 20 minutes Presentation/ Drug Interactions Associated With Local Drug Interactions Associated With Local Drug Interactions Associated With Local PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics 293 293 NTA Level 5 Semester 1 Facilitator Guide NTA Level 5 Semester 1 Facilitator Guide brainstorming Anaesthetics 4 20 minutes Presentation Side Effects of Local Anaesthetics 5 20 minutes Presentation/ Contraindications of Local Anaesthetics 5 20 minutes Brainstorming Contraindications of Local Anaesthetics Brainstorming 6 05 minutes Presentation Key Points 7 05 minutes Presentation Evaluation PST 05104 Pharmacology & Therapeutics 294 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Mechanism of Action of Local Anaesthetics (45 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do local anaesthetics produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Local anaesthetics are drugs which upon topical application or local injection cause reversible loss of sensory perception, especially of pain in a localized area of the body. They block generation and conduction of nerve impulses at a localized site of contact without structural damage to neurons. Clinically they are used to block pain sensation from or sympathetic vasoconstrictor impulses to specific areas of the body Local Anaesthetics are classified as follows; o Injectable anaesthetic: Low potency, short duration – Procaine and Chlorprocaine Intermediate potency – Lidocaine (Lignocaine) and Prilocaine High potency and long duration – Tetracaine, Bupivacaine, Ropivacaine, Surface anaesthetic: Soluble – Cocaine, Lidocaine, Tetracaine and Benoxinate Insoluble – Benzocaine, Butylaminobenzoate and Oxethazine o Miscellaneous drugs: Clove oil, phenol, chlorpromazine and diphenhydramine etc. The mechanism of action of Local Anaesthetics is as follows; All local anesthetics are membrane stabilizing drugs They slows down speed of Action Potential (AP) ultimately stoping AP generation PST 05104 Pharmacology & Therapeutics 295 NTA Level 5 Semester 1 Facilitator Guide They reversibly decrease the rate of depolarization and repolarization of excitable membranes They inhibiting sodium influx through sodium-specific ion channels in the neuronal cell – voltage-gated sodium channels When the influx of sodium is interrupted – action potential cannot rise and signal conduction is inhibited Local anesthetic s bind (located at inner surface) more readily to sodium channels in activated state – and slows its reversion to the resting state – refractory period is increased – ―state dependent blockade‖ – no action on resting nerve. STEP 3: Drug Interactions Associated with Local Anaesthetics (20 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are drug interactions associated with local anaesthetics drugs? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below Anti-arrhythmics: increased myocardial depression when anti-arrhythmics given with Bupivacaine, Levobupivacaine, Prilocaine or Ropivacaine Beta-Blockers: Increased risk of bupivacaine toxicity when given with Propranolol STEP 4: Side Effects of Local Anaesthetics (20 minutes) CNS Stimulation: It is dose-related spectrum of effects and All effects are due to depression of neurons First an apparent CNS stimulation (convulsions most serious) followed by CNS depression (death due to respiratory depression) Premonitory signs include: ringing in ears, metallic taste, and numbness around lips Cocaine causes euphoria (unique in its ability to stimulate CNS) Lidocaine causes sedation even at non-toxic doses. Cardiocascular system Arrhythmias: o The adverse cardiovascular effects of local anaesthetics are due mainly to myocardial depression, conduction block and vasodilatation. PST 05104 Pharmacology & Therapeutics 296 NTA Level 5 Semester 1 Facilitator Guide Reduction of myocardial contractility probably results indirectly from an inhibition of the Na+ current in cardiac muscle The resulting decrease of [Na+]i in turn reduces intracellular Ca2+ stores and this reduces the force of contraction. Interference with atrioventricular conduction can result in partial or complete heart block, as well as other types of dysrhythmia Hypotension Vasodilatation, mainly affecting arterioles, is due partly to a direct effect on vascular smooth muscle, and partly to inhibition of the sympathetic nervous system. This leads to a fall in blood pressure, which may be sudden and life-threatening. Cocaine is an exception in respect of its cardiovascular effects, because of its ability to inhibit noradrenaline reuptake STEP 5: Contraindications of Local Anaesthetics (20 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are the contraindications of Local Anaesthetics? ALLOW few students to respond? WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below Local anaesthetics should not be injected into

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of General Anaesthetics Pharmacology and Therapeutics • Source Session/Topic 38 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 38: Pharmacodynamics of General Anaesthetics Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe mechanism of action of General Anaesthetics Describe drug interactions associated with General Anaesthetics Describe side effects of General Anaesthetics Describe contraindications of General Anaesthetics Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD projector Handout 38.1. Side Effects of Inhalation Anaesthetics SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks 2 2 40 minutes 40 minutes Presentation Mechanism of Action of General Mechanism of Action of General 2 2 40 minutes 40 minutes Presentation Anaesthetics Anaesthetics Anaesthetics Anaesthetics 3 3 15 minutes 15 minutes Presentation/ Drug Interactions Associated With General Drug Interactions Associated With General 3 3 15 minutes 15 minutes brainstorming Anaesthetics Anaesthetics brainstorming Anaesthetics Anaesthetics 4 4 15minutes 15minutes Presentation Side Effects of General Anaesthetics Side Effects of General Anaesthetics 5 5 15minutes 15minutes Presentation/ Contraindications of General Anaesthetics Contraindications of General Anaesthetics 5 5 15minutes 15minutes Brainstorming Contraindications of General Anaesthetics Contraindications of General Anaesthetics Brainstorming 6 6 05 minutes 05 minutes Presentation Key Points Key Points 7 7 05 minutes 05 minutes Presentation Evaluation Evaluation 8 8 10 minutes 10 minutes Presentation Assignment Assignment PST 05104 Pharmacology & Therapeutics 300 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Mechanism of Action of General Anaesthetics (40minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do general anaesthetics produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below General Anaesthetics are the drugs which produce reversible loss of all sensation and consciousness, or simply, a drug that brings about a reversible loss of consciousness General Anaesthetics are generally administered by an anesthesiologist in order to induce or maintain general anesthesia to facilitate surgery General anaesthetics are mainly inhalation or intravenous as shown in the table below; Inhalation: Inhalation: Inhalation: Intravenous: Intravenous: Gas: Gas: Inducing agents: Inducing agents: e.g Nitrous Oxide e.g Nitrous Oxide e.g Nitrous Oxide • Thiopentone, • Methohexitone sodium, • propofol • etomidate Volatile liquids: Volatile liquids: Volatile liquids: Benzodiazepines (slower acting): Benzodiazepines (slower acting): • Ether Ether • Diazepam • Halothane Halothane • Lorazepam • Enflurane Enflurane • Midazolam • Isoflurane Isoflurane • Desflurane Desflurane • Sevoflurane Sevoflurane Dissociative anaesthesia: Dissociative anaesthesia: e.g Ketamine e.g Ketamine Neurolept analgesia: Neurolept analgesia: e.g. Fentanyl e.g. Fentanyl PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics 301 301 NTA Level 5 Semester 1 Facilitator Guide Major targets of General Anaesthetics is ligand gated ion channels GABA-A, Cl¯ channel receptors which are found throughout the CNS Normally, GABA-A receptor mediates the effects of gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the brain When a general anaesthetic binds to this receptor, it causes conformational changes leading to opening of central pore and passing down of Cl- along concentration gradient The result is inhibitory effect which reduces the activity of neurones Therefore, General Anaesthetics bind with these channels and cause opening and potentiation of these inhibitory channels leading to inhibition and anaesthesia Fig 38. 2 Structure of GABAA receptor STEP 3: Drug Interactions Associated with General Anaesthetics (15minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are drug interactions associated with general anaesthetics drugs? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below PST 05104 Pharmacology & Therapeutics 302 NTA Level 5 Semester 1 Facilitator Guide Adrenergic Neurone Blockers: enhanced hypotensive effect when general anaesthetics given with Adrenergic Neurone Blockers Alpha-blockers: enhanced hypotensive effect when general anaesthetics given with Alpha-Blockers Aminophylline: increased risk of convulsions when Ketamine given with Aminophylline Analgesics: metabolism of etomidate inhibited by Fentanyl (consider reducing dose of etomidate); effects of thiopental possibly enhanced by Aspirin; effects of intravenous general anaesthetics and volatile liquid general anaesthetics possibly enhanced by Opioid Analgesics Angiotensin-II Receptor Antagonists: enhanced hypotensive effect when general anaesthetics given with Angiotensin-II Receptor Antagonists STEP 4: Side Effects of Local Anaesthetics (15minutes) The side effects of General Anaesthetics are as indicated in the tables below; Table 28.1; Intravenous Anaesthetic Agents Drug Speed of induction and Main unwanted effect(s) Main unwanted effect(s) Notes Notes recovery Propofol Fast onset, very fast Cardiovascular and Cardiovascular and • Rapidly metabolized recovery respiratory depression respiratory depression • Possible to use as • Possible to use as • Possible to use as • Possible to use as continuous infusion • Causes pain at injection site Thiopental Fast (accumulation Cardiovascular and Cardiovascular and • Largely replaced by occurs, giving slow respiratory depression respiratory depression propofol recovery) propofol recovery) • Causes pain at 'Hangover' • Causes pain at 'Hangover' injection site injection site • Risk of precipitating porphyria in susceptible patients Etomidate Fast onset, fairly fast Excitatory effects during Excitatory effects during • Less cardiovascular recovery induction and recovery induction and recovery and respiratory Adrenocortical Adrenocortical and respiratory Adrenocortical Adrenocortical depression than with suppression suppression depression than with suppression suppression thiopental • Causes pain at injection site Ketamine Slow onset, after effects • Psychotomimetic Produces good analgesia Produces good analgesia common during recovery effects following and amnesia and

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Antituberculosis Drugs Pharmacology and Therapeutics • Source Session/Topic 39 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 39: Pharmacodynamics of Antituberculosis Drugs Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe mechanism of action of Antituberculosis Drugs Describe drug interactions associated with Antituberculosis Drugs Describe side effects of Antituberculosis Drugs Describe contraindications of Antituberculosis Drugs Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks Introduction, Learning Tasks 2 2 45 minutes 45 minutes Presentation Mechanism of Action of Antituberculosis Mechanism of Action of Antituberculosis Mechanism of Action of Antituberculosis 2 2 45 minutes 45 minutes Presentation Drugs Drugs 3 3 20 minutes 20 minutes Presentation/ Drug Interactions Associated With Drug Interactions Associated With Drug Interactions Associated With 3 3 20 minutes 20 minutes brainstorming Antituberculosis Drugs Antituberculosis Drugs Antituberculosis Drugs brainstorming Antituberculosis Drugs Antituberculosis Drugs Antituberculosis Drugs 4 4 20 minutes 20 minutes Presentation Side Effects of Antituberculosis Drugs Side Effects of Antituberculosis Drugs Side Effects of Antituberculosis Drugs 5 5 20 minutes 20 minutes Presentation/ Contraindications of Antituberculosis Drugs Contraindications of Antituberculosis Drugs Contraindications of Antituberculosis Drugs 5 5 20 minutes 20 minutes Brainstorming Contraindications of Antituberculosis Drugs Contraindications of Antituberculosis Drugs Contraindications of Antituberculosis Drugs Brainstorming 6 6 05 minutes 05 minutes Presentation Key Points Key Points Key Points PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics PST 05104 Pharmacology & Therapeutics 308 308 308 NTA Level 5 Semester 1 Facilitator Guide NTA Level 5 Semester 1 Facilitator Guide 7 05 minutes Presentation Evaluation PST 05104 Pharmacology & Therapeutics 309 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Mechanism of Action of Antituberculosis Drugs (45 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How do Antituberculosis Drugs produce their pharmacological effects? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Isoniazid Isoniazid inhibits synthesis of mycolic acids, which are essential components of mycobacterial cell walls. Isoniazid is a prodrug that is activated by KatG, the mycobacterial catalase-peroxidase. The activated form of isoniazid forms a covalent complex with an acyl carrier protein (AcpM) and KasA, a beta-ketoacyl carrier protein synthetase, which blocks mycolic acid synthesis and kills the cell. Rifampin Rifampin binds to the β subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis Human RNA polymerase does not bind rifampin and is not inhibited by it. Rifampin is bactericidal for mycobacteria. It can kill organisms that are poorly accessible to many other drugs, such as intracellular organisms and those sequestered in abscesses and lung cavities Ethambutol Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall. PST 05104 Pharmacology & Therapeutics 310 NTA Level 5 Semester 1 Facilitator Guide Pyrazinamide Pyrazinamide is converted to pyrazinoic acid—the active form of the drug—by mycobacterial pyrazinamidase, which is encoded by pncA . The specific drug target is unknown, but pyrazinoic acid disrupts mycobacterial cell membrane metabolism and transport functions. STEP 3: Drug Interactions Associated with Antituberculosis Drugs (20 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are drug interactions associated with antituberculosis drugs? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below There is no serious interaction between ant tuberculosis drugs and other drugs except that rifampicin reduces plasma concentration of digoxin Absorption of isoniazid is reduced by antacids, Hepatotoxic of isoniazid is potentiated by general anaesthesia and its CNS toxicity is increased by cycloserine Pyrazinamide antagonizes effect of probenecid STEP 4: Side Effects of Antituberculosis Drugs (20 minutes) Side effects and adverse effects of antituberculosis drugs include: Rifampicin o Occasional adverse effects include rashes, thrombocytopenia, and nephritis. It may cause cholestatic jaundice and occasionally hepatitis o Rifampin commonly causes light-chain proteinuria Isoniazid side effects are dose related o They occur in high dose and may include nausea, vomiting, constipation, dry mouth; peripheral neuritis with high doses (pyridoxine prophylaxis, see notes above), optic neuritis, convulsions, psychotic episodes and vertigo Pyrazinamide o Major adverse effects of pyrazinamide include hepatotoxicity, nausea, vomiting, drug fever, and hyperuricemia o Hyperuricemia may provoke acute gouty arthritis PST 05104 Pharmacology & Therapeutics 311 NTA Level 5 Semester 1 Facilitator Guide Ethambutol; the most common serious adverse event is retro bulbar neuritis, resulting in loss of visual acuity and red-green color blindness Streptomycin is ototoxic and nephrotoxic o Vertigo and hearing loss are the most common side effects and may be permanent. o Toxicity is dose-related, and the risk is increased in the elderly o Toxicity can be reduced by limiting therapy to no more than 6 months whenever possible STEP 5: Contraindications of Antituberculosis Drugs (20 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are the contraindications of Antituberculosis Drugs? ALLOW few students to respond? WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below Rifampicin is contraindicated to patient with jaundice Isoniazid

NTA Level 5 • Semester 1 • PST05104 Pharmacodynamics of Antiarrythmic Drugs 315 Pharmacology and Therapeutics • Source Session/Topic 40 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 40: Pharmacodynamics of Antiarrythmic Drugs 315 PST 05104 Pharmacology & Therapeutics iv NTA Level 5 Semester 1 Facilitator Guide Background There is currently an ever-increasing demand for pharmaceutical personnel in Tanzania. This is due to expanding investment in public and private pharmaceutical sector. Shortage of trained pharmaceutical human resource contributes to poor quality of pharmaceutical services and low access to medicines in the country (GIZ, 2012). Through Public-Private-Partnership (PPP) the Pharmacy Council (PC) together with Development Partners (DPs) in Germany and Pharmaceutical Training Institutions (PTIs) worked together to address the shortage of human resource for pharmacy by designing a project named “Supporting Training Institutions for Improved Pharmaceutical Services in Tanzania‖ in order to improve quality and capacity of PTIs in training. CSSC prepared a Multi-actor Partnership (MAP) project proposal on how to sustain and strengthen health care in Tanzania through improvement of pharmaceutical training and an inter-institutional coordination of actors. This will harmonize and improve access to quality pharmaceutical service in Tanzania. The project has a various key stakeholders like; CSSC, NACTE, PC, TCU, CEDHA and Pharmaceutical Training Institutions (PTIs). Through this project, few PTIs will receive infrastructural improvements to increase the quantitative and qualitative capacities (CUHAS, RUCU and KSP). Furthermore this project will train Pharmaceutical tutors from different PTIs on teaching and assessment methods in Tanzania and thus improved health delivery through increased qualified human resource. It was also observed that in the previous stakeholder‘s meetings there was a need for the development of training manuals and assessment plans for NTA Level 5 & 6, in order to support the establishment and implementation of the curriculum in PTIs. During MAP kick-off workshop done in February 2018, Stakeholders agreed that there was a need for development of the said manuals and it was among the highest priority in Pharmacy education in Tanzania. Therefore this project aims at developing facilitator‘s guide and assessment plans for NTA Level 5 & 6. Pharmacy Council, CSSC and action medeor developed the Terms of Reference and selected a qualified service provider with experience in material development to develop the mentioned training manuals and assessment plan. Centre for Educational Development in Health Arusha (CEDHA) was selected and offered a contract to develop Facilitators guide for NTA level 5 & 6 and assessment plan. Centre for Educational Development in Health Arusha (CEDHA) was offered a leading role with the instructions to include experts who have developed teaching materials for NTA Level 4. These experts are primarily experienced pharmaceutical and non-pharmaceutical tutors. The mode of operation used by CEDHA to develop facilitators guide and assessment plan was participatory approach which included a number of activities through various workshops such as planning, and orientation of material development. After these preliminary PST 05104 Pharmacology & Therapeutics v NTA Level 5 Semester 1 Facilitator Guide workshops, experts developed materials individually and in-groups. Thereafter, developed draft materials were reviewed, edited and formatted and draft one was finalized and shared to stakeholders for inputs. Finally, CEDHA submitted the finalized Facilitator‘s guides and assessment plans for NTA level 5 and 6 to CSSC for endorsement, printing, dissemination and sharing with relevant authorities. There are 11 modules for NTA level 5 making 11 facilitator guides including one practicum guide. PST 05104 Pharmacology & Therapeutics vi NTA Level 5 Semester 1 Facilitator Guide PST 05104 Pharmacology & Therapeutics vii NTA Level 5 Semester 1 Facilitator Guide Acknowledgment The development of standardized training materials of a competence-based curriculum for pharmaceutical sciences has been accomplished through involvement of different stakeholders. Special thanks go to the Pharmacy Council for spearheading the harmonization of training materials in the pharmacy after noticing that training institutions in Tanzania were using different curricula and train their students differently. I would also like to extend my gratitude to Christian Social Service Commission (CSSC) for their tireless efforts to mobilize funds from development partners (German Ministry of Industry and action medeor). It is through the implementation of the Multi-Actors Partnership (MAP) project, CSSC has been able to provide the financial and technical support needed during the development of this training material. Many thanks go to the Centre for Educational Development in Health Arusha (CEDHA) experts on health material development and training who coordinated the development of these module sessions particularly Ms. Diana H. Gamuya for her commitment in coordinating and facilitating the planning and development to its completion. Particular acknowledgements are sent to Mr. Dickson Mtalitinya and Members from the secretariat of National Council for Technical Education (NACTE) for facilitating and providing their expertise to the success of this work. It will be unfair if I will not recognize the efforts and contributions of all CEDHA supportive staff that made this process a success; accountant, secretary, drivers and printers Finally, I very much appreciate the contributions of the tutors and content experts representing PTIs, hospitals, and other health training institutions. Their participation in meetings and workshops, and their input in the development of this training manual/facilitators guide have been invaluable. These participants are listed with our gratitude below: Ms. Elizabeth Shekalaghe Registrar, Pharmacy Council of Tanzania Registrar, Pharmacy Council of Tanzania Assistant Director Allied Health,MoHCDGEC Assistant Director Allied Health,MoHCDGEC MoHCDGEC MoHCDGEC Acting Principal, CEDHA Acting Principal, CEDHA Project Manager – MAP, CSSC Project Manager – MAP, CSSC CEDHA Ms. Diana H. Gamuya CEDHA SIBS Ms. Grace Mallange PC KSP CSSC Ms. Emily Mwakibolwa Pharmacy Council Pharmacy Council Pharmacy Council Pharmacy Council PST 05104 Pharmacology & Therapeutics viii NTA Level 5 Semester 1 Facilitator Guide Ms. Tumaini H. Lyombe Ms. Dilisi J. Makawia NACTE NACTE CEDHA CEDHA HKMU CUHAS CUHAS CUHAS CUHAS MUHAS MUHAS MUHAS TCHRT KSP KSP KSP RAS-KLM RuCU RuCU SIBS SIBS SIBS Director of Human Resources Development Ministry of Health, Community Development, Gender, Elderly